Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Full Report

The Expert Panel defined 14 critical questions for the literature search (Table 1–1) and the risk factors to be addressed (Table 1–2). The first phase of the evidence review focused on critical questions 1–9, which address the association between the development of atherosclerosis and the presence and intensity of CVD risk factors in childhood and adolescence. The second phase of the evidence review addressed critical questions 10–14, which aim to assess the evidence for the safety and efficacy of reduction of each risk factor and the impact of risk factor change on the atherosclerotic process.

In addition to the typical RCTs, systematic reviews, and meta-analyses, two additional types of studies were considered to provide evidence pertaining to the development of atherosclerosis. Longitudinal observational studies were included to assess the tracking of risk factors from youth to adulthood and the relationship of risk factors in youth to the development of atherosclerosis. From the many available observational studies in the literature, the Panel identified the 12 listed in Table 1–3 for inclusion in the evidence review. The panel used several criteria to evaluate which studies should be in the evidence review, including sample size, and for longitudinal studies the length of followup. In general, the studies were large, averaging more than 1,000 subjects. Smaller studies that had long-term followup allowing evaluation of the relationship between risk factors identified in infancy and early childhood and adolescent and adult endpoints were also included. In addition, natural history studies of genetic disorders known to alter CV risk status were included to provide models of the consequences of prolonged risk exposure or risk protection.

The Expert Panel selected a literature search start date of January 1,1985, roughly 5 years before the previous expert panel process that had generated guidelines for the management of cholesterol in childhood, the National Cholesterol Education Program's Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents, which was published in 1992.[1] From an initial group of more than 1 million titles published between January 1, 1985, and June 30, 2007, the search was refined to ultimately include 648 studies: 50 systematic reviews, 33 meta-analyses, 293 RCTs, 194 observational studies, and, in addition, 78 sets of guidelines relevant to pediatric CVD prevention, which were provided as reference material. Each of the first four listed types of studies underwent full text review and abstraction of critical information into evidence tables; each study was graded individually using a unique algorithm developed for these Guidelines. Details of the search methodology and the abstraction and individual study grading processes are provided in Appendix A. Methodology. The evidence tables are available electronically on the NHLBI Web site at http://www.nhlbi.nih.gov/health-pro/guidelines/current/cardiovascular-health-pediatric-guidelines/index.htm.

Expert Panel members were grouped into subcommittees to focus on specific risk factors according to their respective areas of expertise, with many Expert Panel members participating on more than one subcommittee. In addition, two oversight committees were formed: (1) a Science Team to ensure high scientific quality of the entire evidence review and Guidelines development process and (2) a Clinical Team to maintain the relevance of the recommendations to clinical practice throughout Guidelines development. The Science Team, led by Samuel S. Gidding, M.D., addressed the first nine critical questions and summarized the evidence for the origins of atherosclerosis in childhood and the evidence for the role of risk factors in the atherosclerotic process in Section II. State of the Science: Cardiovascular Risk Factors and the Development of Atherosclerosis in Childhood. For each risk factor, the Expert Panel provided an overview of the evidence, focusing on those studies it believed provided the most important information. These summaries are provided in the risk factor-specific sections of this document. Because of the volume and complexity of the literature review, specific information on every study is provided only in the evidence tables. The risk factor subcommittees critically evaluated the body of evidence relative to each risk factor, using an evidence grading system from the American Academy of Pediatrics (AAP) (Table 1–4).[2] As shown in Table 1–4, the AAP evidence grading system was modified to incorporate genetic natural history studies in the Grade B evidence category. Each risk factor subcommittee then formulated age-specific recommendations with grade and strength of recommendation assigned using the AAP grading system, based on consideration of the entire body of evidence used in developing each recommendation. The age categories corresponded with the system used by the AAP publication Bright Futures: Guidelines for Health Supervision of Infants, Children and Adolescents.[3] Each risk factor subcommittee reached internal consensus before presenting its recommendations to the full Expert Panel. The final recommendations were then reviewed and approved by the entire Expert Panel. Additional information on the Guidelines development process is provided in Appendix A. Methodology. A draft Guidelines document was reviewed by multiple professional societies and by many individuals within the National Institutes of Health, the Centers for Disease Control and Prevention, and relevant U.S. Department of Health and Human Services organizations. The Guidelines also underwent a 30-day public comment period. In total, individual responses were developed for more than 800 comments.

Section II. State of the Science: Cardiovascular Risk Factors and the Development of Atherosclerosis in Childhood summarizes all the evidence linking the presence of risk factors in childhood and adolescence to the presence and severity of the atherosclerotic process as assessed both pathologically and by imaging studies. An overview of the role of screening for CV risk factors in children is addressed in Section III. Screening for Cardiovascular Risk Factors. The next eight sections (IV–XI) address individual risk factors. Each risk factor section begins with a brief description of the current status of the risk factor in childhood and adolescence. Since this kind of information is often not available from studies that are included in evidence reviews, selected references are used to provide the context within which the recommendations were developed. This text is followed by the Expert Panel's written summary of the evidence review relative to the specific risk factor. As described above, Expert Panel members provided an overview of the evidence, focusing on those studies that in their expert opinions provide the most important information and identifying deficiencies in the evidence. Specific information on each study is provided in the evidence tables available through the NHLBI Web site at http://www.nhlbi.nih.gov/health-pro/guidelines/current/cardiovascular-health-pediatric-guidelines/index.htm. The conclusions of the Expert Panel's review of the evidence are then summarized, accompanied by the evidence grades and the strength of the recommendation. Each risk factor section ends with the Expert Panel's age-specific recommendations, accompanied by supportive actions, which represent suggestions developed by Expert Panel consensus to support implementation of the recommendations. The recommendations are integrated across risk factors and developmentally across age groups into the Integrated Cardiovascular Health Schedule (Section XV), which summarizes the age-specific recommendations for all of the risk factors. To optimize accessibility, references are grouped by risk factor and are listed sequentially at the end of each section. References from the evidence review are identified by the unique PubMed identifier (PMID) number that appears in bold text. Additional references do not include the PMID number.

By addressing the major population-based risk factors for CVD in a single evidence-based set of Guidelines, the aim is to support pediatric care providers in optimizing CV health in infancy, early childhood, and adolescence. By extending risk factor modification into childhood, our goal is to reduce the development of clinical CVD in the future lives of children.

Table 1–1. Development of the Evidence Base: Critical Questions

What is the evidence that atherosclerosis and atherosclerosis-related target organ damage begin in childhood? What is the evidence that the presence of risk factors in childhood affects the development and progression of atherosclerosis and atherosclerosis-related target organ damage during childhood? What is the evidence that the presence of risk factors in childhood affects the progression of atherosclerosis and atherosclerosis-related target organ damage in adulthood? What is the evidence that indicates the relative importance of each risk factor in the development and progression of atherosclerosis and atherosclerosis-related target organ damage in childhood? What is the evidence that racial or ethnic background, geographic region, or socioeconomic status affect cardiovascular (CV) risk factor status in childhood/adolescence? What is the evidence that risk factors cluster in childhood? What is the evidence that risk factor clustering is consistent in childhood? What is the evidence that risk factors present in childhood persist (i.e., track) into adulthood? What is the evidence that an increase in the number and/or intensity of risk factors in childhood alters (a) the development and progression of atherosclerosis and atherosclerosis-related target organ damage in childhood; (b) the development and progression of atherosclerosis and atherosclerosis-related target organ damage in adulthood; and/or (c) the development of clinical CV disease (CVD) in adulthood? What is the evidence that risk factors in childhood can be decreased? What is the evidence that a decrease in risk factors in childhood can be sustained? What is the evidence that a decrease in risk factors in childhood alters (a) the development and progression of atherosclerosis and atherosclerosis-related target organ damage in childhood; (b) the development and progression of atherosclerosis and atherosclerosis-related target organ damage in adulthood; and (c) the development of clinical CVD in adulthood? What is the evidence that acquisition of risk factors or risk behaviors can be prevented in childhood and adolescence? What is the evidence that preservation of a low-risk state from childhood, adolescence, or young adulthood to later adult life is associated with (a) decreased development/progression of atherosclerosis and atherosclerosis-related target organ damage and/or (b) decreased incidence of clinical CVD?

 

Table 1–2. Evaluated Risk Factors

 

Family history Age Gender Nutrition/ diet Physical inactivity Tobacco exposure Blood pressure Lipids Overweight/ Obesity Diabetes mellitus Predisposing conditions Metabolic syndrome Perinatal factors Inflammatory markers

 

Table 1–3. Selected Observational Studies

 

Abbreviation	Full Title
NHANES	National Health and Nutrition Examination Survey
Bogalusa	Bogalusa Heart Study
PDAY	Pathobiological Determinants of Atherosclerosis in Youth
Muscatine	Muscatine Study
Princeton	Princeton Lipid Research Clinics Follow-Up Study
Young Finns	Cardiovascular Risk in Young Finns Study
NGHS	National Heart, Lung, and Blood Institute Growth and Health Study
STRIP	Special Turku Coronary Risk Factor Intervention Project (observational followup from this randomized controlled trial)
CARDIA	Coronary Artery Risk Development in Young Adults Study
Minnesota	Minnesota Children's Blood Pressure Study
Beaver County	Beaver County Lipid Study
Fels	Fels Longitudinal Study

 

Table 1–4. Evidence Grading System

 

EVIDENCE QUALITY GRADES FOR THE BODY OF EVIDENCE

Grade	Evidence
A	Well-designed randomized controlled trials or diagnostic studies performed on a population similar to the guideline's target population
B	Randomized controlled trials or diagnostic studies with minor limitations; genetic natural history studies; overwhelmingly consistent evidence from observational studies
C	Observational studies (case-control and cohort design)
D	Expert opinion, case reports, or reasoning from first principles (bench research or animal studies)

 

GUIDELINE DEFINITIONS FOR EVIDENCE-BASED STATEMENTS

 

Statement Type	Definition	Implication
Strong recommendation	The Expert Panel believes that the benefits of the recommended approach clearly exceed the harms and that the quality of the supporting evidence is excellent (grade A or B). In some clearly defined circumstances, strong recommendations may be made on the basis of lesser evidence when high-quality evidence is impossible to obtain and the anticipated benefits clearly outweigh the harms.	Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present.
Recommendation	The Expert Panel feels that the benefits exceed the harms but the quality of the evidence is not as strong (grade B or C). In some clearly defined circumstances, recommendations may be made on the basis of lesser evidence when high-quality evidence is impossible to obtain and when the anticipated benefits clearly outweigh the harms.	Clinicians should generally follow a recommendation but remain alert to new information and sensitive to patient preferences.
Optional	Either the quality of the evidence that exists is suspect (grade D) or well-performed studies (grade A, B or C) show little clear advantage to one approach versus another.	Clinicians should be flexible in their decision-making regarding appropriate practice, although they may set boundaries on alternatives; patient and family preference should have a substantial influencing role.
No recommendation	There is both a lack of pertinent evidence (grade D) and an unclear balance between benefits and harms.	Clinicians should not be constrained in their decision-making and be alert to new published evidence that clarifies the balance of benefit versus harm; patient and family preference should have a substantial influencing role.

 

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REFERENCES

[1] NCEP Expert Panel of Blood Cholesterol Levels in Children and Adolescents. National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics 1992;89:495-501. (PM:1741227)

[2] American Academy of Pediatrics Steering Committee on Quality Improvement and Management. Classifying recommendations for clinical practice guidelines. Pediatrics 2004;114:874-877.

[3] Hagan JF, Duncan PM, eds. 2008. Bright Futures: Guidelines for Health Supervision of Infants, Children and Adolescents, Third Edition. Elk Grove Village, IL: American Academy of Pediatrics.

The risk factors considered in this analysis are listed in Table 2–1. Each risk factor exists within a behavioral, environmental, physiologic, and genetic context that provides the rationale for its consideration as a risk factor that could be used to identify persons who are at elevated risk or who may be the target of intervention. Included are conditions of life (family history, age, gender), measurable pathophysiologic risk factors (high blood pressure, lipids, overweight/obesity, diabetes mellitus), behavioral factors (tobacco exposure, nutrition/diet, physical inactivity), and emerging risk factors (metabolic syndrome, inflammatory markers, perinatal factors).

Table 2–1. Risk Factors for Cardiovascular Disease

Family history Age Gender Nutrition/diet Physical inactivity Tobacco exposure High blood pressure Blood lipids Overweight/obesity Diabetes mellitus and other predisposing conditions Metabolic syndrome Perinatal factors Inflammatory markers

Atherosclerotic vascular disease events—such as myocardial infarction, stroke, peripheral arterial disease, and ruptured aortic aneurysm—are the culmination of a lifelong disease process.[1],[2] Pathologically, the process begins with the accumulation of abnormal lipid in the carotid intima, a reversible stage, progressing to an advanced stage in which a core of extracellular lipid is covered by a fibromuscular cap, culminating in thrombosis, vascular rupture, or acute ischemic syndromes.[1] Although the advanced stages of atherosclerosis and related clinical events are observed almost exclusively in adults, the initial phases of this chronic process are observed in childhood, with early changes identified even in the fetus (Figure 2–1).[2],[3],[4]

Figure 2–1. Atherosclerosis: A Progressive Process

[[nid:824 view_mode=custom_size width=600 height=409]]

 

Figure 2–1 depicts the pathologic progression of atherosclerosis with aging, from no visible atherosclerosis at birth to the development of complex plaques with potential rupture and thrombosis in mid- to late adulthood. The process begins in the first decade of life when initial risk exposures occur. The progression of atherosclerosis is exacerbated and intensified by the presence of risk factors. The solid white line indicates clinical events as shown. Except in rare circumstances, atherosclerotic disease is subclinical for the first two to three decades of life.

 

Relationship of Risk Exposure to Atherosclerosis Development and Cardiovascular Events

The most important evidence for the relationship of childhood risk factors to CVD is the establishment of a direct relationship between risk exposure and events. This evidence is best obtained from long-term observational studies beginning in childhood, with risk factors measured and related to CVD outcomes later in life. Because of the time course of atherosclerosis, studies of 50 to 60 years' duration linking early risk to CV events are impractical, although studies exist in which risk was measured in early adulthood and outcomes were measured much later in life. Clinical trials of voluntary risk exposure, in which children would be randomized at birth to become, for example, chronic smokers, to determine the likelihood of future heart attack decades later, would be both impractical and unethical.

Thus, studies examining the clinical importance of CV risk in childhood must consider end points recognized as intermediate stages in the pathogenesis of CVD. This pathway is illustrated in Figure 2–2. Studies of this pathway include correlation analyses of risk factors measured either ante mortem or post mortem, with the extent of atherosclerosis at autopsy following accidental death early in life; longitudinal studies of individuals with specific genetic mutations that confer either lifelong risk exposure or protection; studies of individuals with risk assessed in childhood and subclinical measures of atherosclerosis (e.g., carotid intima media thickness (cIMT), coronary calcium measurements by computerized tomography assessed in young adulthood; studies of high-risk children who demonstrate cardiac or vascular end organ injury; and population-based studies demonstrating that the presence of risk factors in childhood predict risk in adulthood (tracking studies). Also relevant are studies of factors associated with the development of risk factors, such as a high-fat diet and a physically inactive lifestyle. The evidence review for these Guidelines includes examples of all of these study types.

Figure 2–2. Evidence Pathways Used in Developing Pediatric Cardiovascular Risk Reduction Guidelines

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Legend to Figure 2–2: This flow diagram depicts the timeline for development of cardiovascular (CV) risk, atherosclerosis, and CV events along a continuum extending from before birth to adult life. The studies composing the evidence pathway are displayed relative to this process. Studies describing environmental or behavioral factors that affect the process are shown on the left side, and potential pathophysiologic or medical actions are shown on the right. The complexity of the evidence development process is apparent in the multiple interrelationships between risk factors that change and evolve throughout the history of each individual from childhood to adulthood. Atherosclerosis develops more rapidly as the number and the intensity of risk factors increase.

Figure 2-2 Text Description

The figure is a flow chart with 11 labeled boxes linked by arrows. The chart flows in one direction with arrows pointing downward and lateral arrows to one or more boxes. Below, the flow chart is described as lists in which the possible next steps are listed beneath each box label.

1. Newborns at Risk
   1. Forward to Risk Factor (RF) Exposures
   2. Forward to RF Identification
   3. Forward to Children at Risk
2. Fetal Exposures
   1. Lateral to Newborns at Risk
3. Genetic Input
   1. Lateral to Newborns at Risk
4. Risk Factor (RF) Exposures:
   -Environment
   -Home
   1. Forward to Children at Risk
5. RF Identification
   1. Forward to Children at Risk
6. Children at Risk
   1. Forward to Lifestyle Interventions
   2. Forward to Intermediate Outcomes
   3. Forward to Pharmacologic Interventions
7. Intermediate Outcomes
   Atherosclerosis
   Subclinical Atherosclerosis
   End organ injury
   1. Lateral to Lifestyle Interventions
   2. Lateral to Pharmacologic Interventions
   3. Forward to Adults at Risk
8. Lifestyle Interventions
   1. Forward to Adults at Risk
   2. Lateral to Intermediate Outcomes
9. Pharmacologic Interventions
   1. Forward to Adults at Risk
   2. Lateral to Intermediate Outcomes
10. Adults at Risk
    1. Foward to Clinical Cardiovascular Disease Outcomes
11. Clinical Cardiovascular Disease Outcomes
    Morbidity Mortality Quality of Life

Considered collectively, these studies constitute an evidence chain, with the strength of the body of evidence represented in the evidence grades. Studies evaluated for the Guidelines may have examined single links in the chain of evidence, may have connected several links simultaneously, or may have evaluated the consequences of specific interventions for risk-benefit analysis. Although each study is graded individually in the evidence tables, the Expert Panel assigned summary grades for the body of evidence reviewed in developing each recommendation. The many evidence pathways pursued in preventive cardiology research and included in the evidence reviewed for the Guidelines are displayed in Figure 2–2. Some studies encompass the entire lifespan (e.g., natural history of familial hypercholesterolemia, relationship of low birth weight to CV mortality), whereas others examine the impact of interventions on intermediate outcomes (e.g., impact of cholesterol-lowering therapy on subclinical atherosclerosis, effect of exercise on CV risk factor development). The studies that make up the pathways in Figure 2–2 provide evidence addressing the key questions critical to this evidence review—including associations between exposures and outcomes, efficacy of screening for conditions of interest, the presence of adverse consequences of screening, the efficacy of interventions on outcomes, and the adverse consequences of interventions. This evidence inquiry is limited by the absence of reports of cost-effectiveness analyses of the screening and intervention strategies to lower CV risk in childhood. In contrast to adult guidelines, the challenge of preparing evidence-based guidelines for CV risk reduction in childhood is augmented by the scarcity of evidence pertaining to the impact of preventive interventions on mortality, morbidity, and quality of life.

Acute CV events in adults are the culmination of two processes: (1) the development and long-term progression of atherosclerosis and (2) a more acute thrombotic process associated with atherosclerotic plaque instability and rupture.[1] The pediatric component of this process is the development of atherosclerosis; thrombosis does not occur in the absence of the atherosclerotic substrate. With aging, the role of risk assessment changes. Prevention of atherosclerosis development receives greater emphasis in children and young adults. In older adults, importance is placed on factors associated with the progression of atherosclerosis and factors associated with acute events, such as predisposition to thrombosis or plaque instability.

SUMMARY OF THE EVIDENCE REVIEW OF PATHOLOGIC STUDIES OF ATHEROSCLEROSIS IN CHILDHOOD

Atherosclerosis at a young age was first identified in Korean War and Vietnam War casualties.[5],[6] Two major contemporary studies, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) and the Bogalusa Heart Study (Bogalusa), have subsequently demonstrated atherosclerosis, indicated by fatty streaks and more advanced lesions, in children, adolescents, and young adults who died as a result of unintentional injury. In the Bogalusa study, CV risk factors (lipids, blood pressure, body mass index (BMI), tobacco use) were measured as part of a comprehensive school-based epidemiologic study of a biracial community. Findings were related to atherosclerosis measured at autopsy after accidental death, and strong correlations were shown between the presence and intensity of risk factors and the extent and severity of atherosclerosis.[3],[7] In the PDAY study, risk factors and surrogate measures of risk factors were measured post mortem in 15- to 34-year-olds who died accidentally of external causes. Strong relationships were demonstrated between atherosclerotic severity and extent and the presence and intensity of known risk factors, including higher age, higher non-high-density lipoprotein cholesterol (non-HDL–C), lower HDL cholesterol (HDL–C), hypertension (determined by renal artery thickness), tobacco use (thiocyanate concentration), diabetes mellitus (glycohemoglobin), and obesity in males. There was a strikingly higher atherosclerotic severity and extent as the number of risk factors increased.[8],[9],[10],[11] An international study with more limited information on risk factors was consistent with these findings.[12]

Figure 2–3, from the PDAY study, shows the relationship between the number of identified CV risk factors and the pathologic lesions of atherosclerosis by age in the right coronary artery, using maps of arterial segments created by converting pathologically classified lesions to computerized images. These are displayed as prevalence maps of fatty streaks and raised lesions, with color intensity reflecting the density and grade of the lesions.[13] In 15- to 24-year-old subjects, the maps demonstrate the impact of increasing numbers of risk factors on both the presence and severity of the atherosclerotic process. Comparison with 25- to 34-year-olds shows the impact of both age and multiple risk factors. Risk, particularly the presence of multiple risk factors, accelerates the development of atherosclerosis. Finally, and most importantly, Figure 2–3 demonstrates that the absence of identified risk factors is associated with a virtual absence of advanced atherosclerotic lesions (American Heart Association Grades IV and V) in 15- to 34-year-olds.

Figure 2–3. Atherosclerosis Maps of the Right Coronary Artery

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These computerized images from the Pathobiological Determinants of Atherosclerosis in Youth study are prevalence maps of fatty streaks and raised lesions, with color intensity reflecting the density and grade of the lesions for the two age groups and the number of risk factors.

SOURCE: Edward E. Herderick and C. Alex McMahan for the Pathobiological Determinants of Atherosclerosis in Youth Study Group, unpublished observation.

Comparison of the PDAY cohort to population-based data on CV risk factors obtained concurrent with acquisition of PDAY specimens suggests that risk distribution of the PDAY cohort mirrors the general population, after adjustment for factors associated with premature death.[14] This comparison to a living cohort also suggests that the PDAY risk relationships are conservative; measuring risk post mortem adds additional variability to the plasma- and serum-based risk measures.

SUMMARY OF THE EVIDENCE REVIEW ON MEASURES OF END ORGAN INJURY AND ATHEROSCLEROSIS IMAGING STUDIES

Measures of subclinical atherosclerosis and end organ injury include the presence of coronary calcium on electron beam computerized tomography (EBCT) imaging, increased medial thickness of the carotid artery assessed with ultrasound (cIMT), reduced endothelium-dependent dilation of the brachial artery with ultrasound imaging (flow-mediated dilation (FMD)), and increased left ventricular mass (LVM) by cardiac ultrasound. In adolescents with familial heterozygous hypercholesterolemia (FH), studies have shown abnormal levels of coronary calcium, increased cIMT, and impaired FMD.[15],[16],[17] Children with hypertension have increased cIMT, increased LVM, and eccentric left ventricular geometry.[18],[19],[20] Children with type 1 diabetes mellitus (T1DM) have significantly abnormal FMD and, in some studies, increased cIMT. In addition, adverse interactions with hypertension, obesity, and a high-fat diet have been observed in children with T1DM.[21],[22],[23],[24],[25] Children and young adults with a family history of myocardial infarction have increased cIMT, higher prevalence of coronary calcium, and impaired FMD.[26],[27],[28],[29] Endothelial dysfunction has been demonstrated by ultrasound and plethysmography in association with cigarette smoking (passive and active) and obesity.[30], [31],[32],[33] In several randomized controlled trials, a change in FMD has been used to assess the response to an exercise intervention. [34],[35],[36] Left ventricular hypertrophy at levels associated with excess mortality in adults has been demonstrated in children with severe obesity and impaired glucose tolerance.[37]

Subclinical atherosclerosis imaging studies (coronary calcium by EBCT, cIMT) have been important in demonstrating the importance of childhood risk factors to future atherosclerosis. Four longitudinal studies have shown the relationships of risk factors measured in childhood and young adulthood—low-density lipoprotein cholesterol (LDL–C), non-HDL–C and serum apolipoproteins, obesity, hypertension, tobacco use, and diabetes—with measures of subclinical atherosclerosis in later adulthood.[38],[39],[40],[41],[42],[43],[44],[45],[46] In many of these studies, risk factors measured in childhood and adolescence were better predictors of adult atherosclerosis than were risk factors measured at the time of the subclinical atherosclerosis study.[38],[41],[42],[43],[45] In two of these cohorts, worsening risk status between the earliest and latest measurements was associated with increased evidence of the presence of atherosclerosis.[47],[48]

SUMMARY OF THE EVIDENCE REVIEW LINKING RISK FACTORS IN CHILDHOOD TO CLINICAL CARDIOVASCULAR DISEASE

The most important evidence relating risk in childhood to clinical CVD is the observed association of risk factors for atherosclerosis to clinically manifest CV conditions. Genetic disorders related to high cholesterol are the biologic model for risk factor impact on the atherosclerotic process. In homozygous hypercholesterolemia, where LDL–C levels exceed 800 mg/dL beginning in infancy, coronary events begin in the first decade of life, and lifespan is severely shortened. In heterozygous hypercholesterolemia, in which LDL–C levels are minimally 160 mg/dL and typically higher than 200 mg/dL beginning in infancy, 50 percent of men and 25 percent of women experience clinical coronary events by age 50 years.[49],[50] In contrast, genetic traits associated with low cholesterol are associated with longer life expectancy.[51] In the PDAY study, every increase in non-HDL–C of 30 mg/dL was associated with incremental increases in the extent and severity of atherosclerosis, including the presence of advanced lesions associated with clinical myocardial ischemia.[52] In natural history studies of diabetes mellitus, early CVD mortality is so consistently observed that the presence of diabetes mellitus is considered evidence of vascular disease in adults.[53] Consonant with this, in 15- to 19-year-olds in the PDAY study, the presence of hyperglycemia was associated with advanced atherosclerosis of the coronary arteries.[54],[55] In a 25-year followup, the presence of the metabolic syndrome risk factor cluster in children predicted clinical CVD in adults ages 30–48 years.[56] In the PDAY study, there is a strong relationship between abdominal aortic atherosclerosis and tobacco use.[12],[52] This aligns with the epidemiologic evidence of an observed attributable risk of 80 percent for tobacco use with the incidence of abdominal aortic aneurysms.

As described above, there is evidence to indicate that hypertension, dyslipidemia, diabetes, obesity, and cigarette smoking—established risk factors for CVD in adults—contribute to the early development of atherosclerosis, with the exception of two risk factors. The first is physical fitness. Studies directly relating fitness levels in childhood to future atherosclerosis have not been performed. However, longitudinal studies have shown that optimal CV risk profiles are seen in individuals who are consistently physically active.[57],[58],[59] Tracking of both sedentary and active behaviors is moderately strong from childhood to young adulthood, with the most consistent tracking seen for higher levels of physical activity at 9–18 years of age, predicting higher levels of physical activity later in life.[60],[61] The second risk factor is HDL–C. In adults, lower HDL levels are consistently shown to be associated with increased risk for CVD. In children, relationships between this risk factor and future atherosclerosis have been demonstrated, but the magnitude of the relationship is smaller than that shown in studies in adults.[38],[42],[52]

SUMMARY OF THE EVIDENCE REVIEW ON THE IMPACT OF RACIAL/ETHNIC BACKGROUND AND SOCIOECONOMIC STATUS IN CHILDHOOD ON THE DEVELOPMENT OF ATHEROSCLEROSIS

CVD has been observed in diverse geographic areas and in all racial and ethnic backgrounds. Cross-sectional research in children has shown differences by race and ethnicity and by geography for the prevalence of CV risk factors; these differences are often partially explained by differences in socioeconomic status (SES).[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72] No group within the United States is without a significant prevalence of risk. Several longitudinal cohort studies referenced extensively in these Guidelines (Bogalusa, PDAY, Coronary Artery Risk Development in Young Adults (CARDIA)) examine biracial populations, although longitudinal data for Hispanic, Native American, and Asian children are lacking. Clinically important differences in the prevalence of risk factors exist by race and gender, particularly with regard to tobacco use rates, obesity prevalence, hypertension, and dyslipidemia. In adults, the influence of obesity on CV risk may vary by ethnicity.[73] Low SES in and of itself confers substantial risk. Evidence is not adequate for the recommendations provided in these Guidelines to be specific to racial or ethnic groups or to SES.

SUMMARY OF THE EVIDENCE REVIEW ON THE IMPACT OF MULTIPLE RISK FACTORS IN CHILDHOOD ON THE DEVELOPMENT OF ATHEROSCLEROSIS

Although genetic dyslipidemias and diabetes mellitus are recognized as high-risk states, from a population standpoint, it is the clustering of multiple risk factors that is most commonly associated with premature atherosclerosis. As demonstrated in the PDAY, CARDIA, Young Finns, and Bogalusa studies and as shown in Figure 2–3, the presence of multiple risk factors is associated with striking evidence of an accelerated atherosclerotic process. The two most prevalent multiple risk combinations are tobacco use with one other risk factor[74] or the development of obesity, which often is associated with insulin resistance (as opposed to elevated blood sugar in adults), elevated triglycerides, reduced HDL–C, and elevated blood pressure. This latter combination, known as the metabolic syndrome in adults, has become increasingly prevalent in childhood. [67][75],[76],[77],[78],[79],[80],[81],[82],[83],[84],[85] Another risk factor that frequently occurs in combination is low cardiorespiratory fitness. This was identified in 33.6 percent of adolescents in the National Health and Nutrition Examination Survey from 1999 to 2002 and was inversely associated with overweight and obesity, elevated total cholesterol levels, higher systolic –C.[86]

The relationship of the current obesity epidemic in children to future CVD and diabetes in adulthood is considered one of the most important public health challenges in the United States, particularly given the fact that more than 30 percent of the U.S. pediatric population is above the 85th percentile of the age- and gender-specific BMI for the generation of the 1970s and 1980s, with Native Americans, Hispanics, and African Americans disproportionately affected.[87] There is ample evidence from both cross-sectional and longitudinal studies that obesity-related risk factor clustering exists in childhood and continues into adulthood. [57],[67],[78],[79],[82],[88],[89],[90],[91]

SUMMARY OF THE EVIDENCE REVIEW ON RISK FACTOR TRACKING

Tracking studies from childhood to adulthood exist for all the major risk factors, including obesity, dyslipidemia, diabetes, cigarette smoking, and hypertension. Obesity tracks more strongly than any other risk factor. Among the many studies demonstrating this tracking,[72],[92],[93],[94] one of the most recent is a report from the Bogalusa study, which followed more than 2,000 children from 5 to 14 years of age at initial evaluation to adult followup at a mean age of 27 years. Based on BMI percentiles derived from the study population, 84 percent of those with a BMI in the 95th to 99th percentiles as children were obese as adults.[95] For obesity, increased correlation is seen with increasing age at which the elevated BMI is obtained. For cholesterol and blood pressure, tracking correlation coefficients in the range of 0.4 have been reported and are consistent across many studies, correlating these measures in children 5 to 10 years of age with results 20 to 30 years later.[96],[97],[98],[99],[100],[101],[102],[103],[104] These data suggest that having cholesterol or blood pressure levels in the upper portion of the pediatric distribution makes having these as risk factors as adults likely but not certain. Individuals who develop obesity have been shown to be more likely to develop hypertension or dyslipidemia as adults.[72],[94] Tracking data on physical activity are more limited. Physical activity levels do track but not as strongly as the other risk factors.[60],[61], [105] Because of tobacco's addictive nature, its use often persists into adulthood, although approximately 50 percent of those who have ever smoked eventually quit.[106] T1DM is a lifelong condition. The insulin resistance of T2DM can be reduced by exercise, weight loss, and bariatric surgery, but the long-term outcome of T2DM diagnosed in childhood is not known.[107] As stated above, risk factor clusters, such as those seen with obesity and the metabolic syndrome, have been shown to track from childhood to adulthood.[67],[78],[79],[82],[88],[89],[90],[91]

CARDIOVASCULAR DISEASE PREVENTION BEGINNING IN CHILDHOOD

The rationale for these Guidelines derives from several factors:

• Atherosclerosis, the precursor of CV morbidity in later life, originates in childhood.
• Risk factors for the development of atherosclerosis can be identified in childhood.
• To a greater or lesser extent, risk factors track from childhood to adulthood.
• Safe and effective interventions exist to manage identified risk factors.

It is important to distinguish between the goals of prevention at young ages and such goals at older ages when atherosclerosis is well-established, morbidity already may exist, and the process is only minimally reversible (Figure 2–2). At middle age and older, the goals are to prevent clinical events from occurring and to minimize the risk of future events in those with existing morbidity. At a young age, historically there have been two goals of prevention: (1) prevent the development of risk factors (primordial prevention) and (2) recognize and manage those children and adolescents at high risk due to the presence of one severe risk factor or multiple risk factors (primary prevention). With the development of measures of subclinical atherosclerosis, left ventricular hypertrophy, and endothelial function, the potential to assess a third goal has emerged: documentation of the prevention of the early stages of atherosclerosis and other forms of CV pathology. It is well-established that a population that enters adulthood with lower risk will have less atherosclerosis and will collectively have lower CVD rates.[1] This concept is supported by research showing that (1) populations with low levels of CV risk factors have low CVD rates and that changes in risk in those populations are associated with changes in CVD rates; (2) control of risk factors in those populations leads to declines in CVD morbidity and mortality; and (3) individuals in those populations without childhood risk have minimal atherosclerosis at ages 30–34 years, absence of subclinical atherosclerosis as young adults, extended life expectancy, and a better of quality of life free from CVD.[1][107],[108],[109],[110],[111],[112]

Pediatric CVD prevention occurs in two settings: clinical practice and public health. These Guidelines focus on the clinical practice setting. That does not diminish the critical importance of public health measures to CVD prevention. For risk factors such as tobacco use and physical inactivity, public health measures are critical for risk reduction. For risk factors such as hypertension, diabetes mellitus, obesity, and dyslipidemia, public health measures will affect prevalence, but without medical recognition and treatment, effective risk reduction cannot occur.

The Pathway to Recommending Clinical Practice-Based Prevention

The most direct means of establishing evidence for active CVD prevention beginning at a young age would be to randomize young individuals with defined risks to treatment of CV risk factors or to no treatment and then to follow both groups over sufficient time to determine whether CV events are prevented without undue increase in morbidity arising from treatment. This direct approach is attractive because atherosclerosis prevention would begin at the earliest stage of the disease process, thereby maximizing benefit. Of course, this approach is as unachievable as it is attractive. Such a study would be extremely expensive and would require a high level of adherence and participant retention over several decades, during which time changes in environment and medical practice would diminish the relevance of the results. Many scenarios could arise in which the ethics of such a trial could be questioned, including undue exposure to risk in one of the trial arms, the discovery of novel treatments of improved efficacy during the conduct of the trial, environmental changes or shifts in priorities of the funding entity that complicate its completion, and the potential withholding of effective therapy to a generation of youths with identified risk who do not receive treatment.

The recognition that evidence from this direct pathway is unlikely to be obtained requires an alternate stepwise approach, linking segments of an evidence chain in a manner that serves as a sufficiently rigorous proxy for the causal inference of a clinical trial. Figure 2–2 demonstrates the components of this evidence chain, with links comprising a series of critical studies leading from risk beginning before birth, to risk acquisition during childhood, to risk modification by reduction strategies, and finally to clinical disease in adulthood. Studies evaluated for these Guidelines may examine single links in this evidence train, connect several links simultaneously, or evaluate the consequences of specific interventions to allow risk-benefit analysis. Some studies encompass the entire lifespan, whereas others examine the impact of interventions on intermediate states. Many of these evidence links come from the epidemiologic studies described in this entire section and provide answers to the first nine critical questions of the evidence review: atherosclerosis begins in childhood, atherosclerosis is related to risk factors that can be identified in childhood, and the presence of these risk factors in a given child predicts an adult with risk factors.

The remaining evidence links pertain to the determination of whether interventions that aim to reduce risk factors will have a health benefit and whether the risk and cost of interventions to reduce risk are outweighed by the reduction in CVD morbidity and mortality. These issues are captured in the critical questions related to intervention (see I. Introduction, Table 1–1, questions 9–14), which are addressed subsequently in the evidence review of each risk factor. The best evidence for answering these questions derives from randomized trials showing event reduction in adults, randomized trials in children showing risk reduction with change in subclinical measures of atherosclerosis or target organ damage and patient safety, genetic studies that provide a model for the adverse effects of sustained exposure to risk, and long-term observational studies demonstrating the benefit of maintenance of low risk on health and all-cause mortality. Recommendations to intervene must consider not only the relationship of the risk factor to future disease but also whether reduction of that risk factor will result in an appreciable decline in subclinical disease or in adverse clinical events with an acceptable safety profile. The presence of a risk factor may confer a high relative risk of a future CV event, but intervention may not be warranted if actual event rates in the next several decades are low; conversely, a lower relative risk may be acceptable for intervention if the likelihood of an adverse event related to that risk factor is high. The timing and safety profile of pharmacologic interventions are important considerations for CVD prevention. The lifetime risk of disease associated with high risk in childhood may identify candidates for more aggressive intervention.

Intervention planning must consider that each risk factor exists within an individual's unique combination of environmental, behavioral, physiologic, and genetic characteristics. This context determines the timing and type of intervention under consideration. A family history showing multiple members affected by clinical CVD at a young age suggests the need to investigate both genetic risk and toxic environmental exposure and to consider early risk reduction. For example, tobacco use is a behavior with significant environmental predictors. That this behavior is highly addictive means that the use of tobacco alone is an indication for smoking cessation counseling. In contrast, recommendations to treat elevated blood pressure are based on multiple elevated measures over time because of the intrinsic variability of blood pressure and the possibility of significant modification through diet and exercise. However, the presence of elevated blood pressure and evidence of target organ damage (i.e., left ventricular hypertrophy) prompt more aggressive intervention. The presence of multiple risk factors represents a powerful stimulus for accelerated atherosclerosis, and knowledge of this situation affects treatment decisions. As described throughout these Guidelines, recommended strategies for intervention should consider environmental, behavioral, physiologic, and genetic attributes, as well as the efficacy and safety of potential treatment modalities, in selecting the type and timing of any intervention and in measuring outcomes.

For certain behavioral risk factors, limitations in measurement and data collection make the establishment of a causal pathway between the risk factor and disease impossible. There is unlikely to be a study comparing the effect of a lifetime of whole-milk consumption with fat-free milk consumption, or a study comparing daily physical training for decades with a lifetime of inactive television watching on the amount of atherosclerosis or rates of myocardial infarction. What is important about diet and exercise in childhood is the relationship of healthful behaviors to the development of future risk factors, including obesity, diabetes mellitus, hypertension, and dyslipidemia. Consequently, recommendations must include studies that examine the impact of interventions on risk factor development and reduction rather than studies that only examine the effects on subclinical disease measures or clinical events.

Since risk levels in the preadolescent pediatric population with normal weight for height are generally below levels associated with CV events,[113] a critical component of pediatric CVD prevention is understanding those factors associated with the evolution from the low-risk state of childhood to the presence of risk in adulthood. The well-established factors on this environmental-behavioral axis are initiating tobacco use and becoming obese. Although the evidence for a heart healthy diet and physical activity in the treatment of established risk factors is strong, less strong but emerging evidence suggests that an energy-balanced, nutrient-dense diet and consistent routine levels of physical activity that promote physical fitness prevent risk factor acquisition over the course of decades. Given that at least 40 percent of the U.S. population currently experiences CVD and that maintaining a low-risk state prevents CVD most effectively, emphasis on healthful behaviors in children, in the absence of established risk factors, assumes added importance.1,2

A new consideration is the role of new noninvasive measures of cardiac and vascular injury in the evaluation of evidence. These include measurements of vascular functioning and arterial stiffness like FMD; noninvasive measures of atherosclerosis, such as cIMT and coronary artery calcium; and measures of cardiac characteristics, such as LVM by echocardiography. For adults, the primary use of these technologies has been in event prediction; that is, whether the presence of one of these markers increases the likelihood of a future CV event beyond that expected from conventional risk factor assessment. There remains considerable controversy over the clinical roles of these tests in adults. For children and adolescents, the role of these measurements may be different. Rather than predicting clinical events, future research may show that a positive test signals the transition to more advanced atherosclerosis or the presence of CV target organ damage. Studies of subclinical atherosclerosis and LVM have been important in establishing the relationship of risk in childhood to evidence of CV injury. Monitoring of LVM has been incorporated into treatment algorithms for hypertension in childhood.[113] However, only a few studies in the pediatric age group have used these measures as clinical end points. It is expected that research using these intermediate end points will be used to clarify knowledge gaps identified in the evidence review for these Guidelines; the clinical importance of these new studies in adults and children remains to be fully established.

Thus, for each risk factor discussed in the sections below, recommendations reflect a complex decision process that integrates the strength of the evidence with knowledge of the natural history of atherosclerotic vascular disease, estimates of intervention efficacy and risk, and the physician's responsibility to provide both health education and effective disease prevention and treatment. These recommendations for providers of health care to children will be most effective when complemented by a broader public health strategy, as discussed in Section XVI. Implications of the Guidelines for Public Policy.

The Childhood Medical Office Visit: the Ideal Setting for Cardiovascular Health Management

In the beginning of this section, the differences in goals for CV risk management in children and in adults were presented, along with the dual pediatric focus on primordial prevention (i.e., the prevention of risk factor development) and primary prevention (i.e., the management of specific identified risk factors). One cornerstone of pediatric care is placing clinical recommendations in a developmental context. As opposed to virtually universal recommendations that apply to nearly all adults, pediatric recommendations must consider not only the relationship of age to disease expression but also the ability of the child and the family to understand and implement medical advice and the safety of the intervention modality. For each risk factor, recommendations must be specific to age and developmental stage. Therefore, the Bright Futures concept of the American Academy of Pediatrics, in which age-specific prevention measures are embedded in routine pediatric care, is used to provide a framework for these Guidelines, with CV risk reduction recommendations specific for each age group.[114]

The concept of primordial prevention is a major theme in all pediatric care. Based on the results of the evidence review, the Guidelines provide recommendations for preventing the development of risk factors and optimizing CV health beginning in infancy. Pediatric care providers—pediatricians, family practitioners, nurses and nurse practitioners, physician assistants, and registered dietitians—are ideally positioned to reinforce these CV health behaviors as part of routine care. The Guidelines also offer specific guidance on primary prevention, with age-specific, evidence-based recommendations for individual risk factor detection. Management algorithms provide staged care recommendations for risk reduction within the pediatric care setting and identify risk factor levels requiring referral to a specialist. The Guidelines also identify specific medical conditions, such as diabetes and chronic kidney disease, which are associated with increased risk for accelerated atherosclerosis. Recommendations for ongoing CV health management for children and adolescents with these diagnoses are provided.

A second cornerstone of pediatric care is the provision of health education. In the U.S. health care delivery system, doctors and nurses are perceived as credible messengers for health information. Patients and families expect physicians, nurses, dietitians, and other health care providers and counselors to provide accurate health information. The childhood health maintenance visit provides a useful context for effective delivery of the CV health message. Providing health information alone is insufficient since reduction of CV risk typically requires behavioral changes by the child and/or the family. The office of the pediatric care provider provides an effective setting for the health care team to engage children and families in the initiation of behavior change to reduce the risk of CVD and promote lifelong CV health.

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Screening is common practice in regular pediatric care with age-based recommendations designed to identify conditions at appropriate times relative to both the disease process and the stage of growth and development. For example, the American Academy of Pediatrics recommends universal newborn screening for metabolic conditions, hemoglobinopathy, and hearing loss, and selective screening for elevated levels of lead in infancy and early childhood.[1] Although many screening programs have been widely adopted, they are not always evidence based. This section reviews the criteria for an effective screening program and provides discussions of both scientific and practical considerations involved in screening for CV risk factors in childhood.

Empirically, a recommendation for universal screening requires a high burden of proof. First, by definition, screening is performed on asymptomatic individuals. Second, all of the downstream consequences of screening, both beneficial and harmful, are important to consider; sometimes they are not obvious. Third, widespread screening programs are costly.

The highest quality evidence for establishing the utility of a screening program derives from randomized controlled trials (RCTs) of screening versus no screening. Such trials compare clinical outcomes among children randomly allocated to no screening with outcomes among children allocated to screening, followed by interventions among those with identified risk. For a CV risk factor screening trial, the children in both groups would be followed for decades to determine disease incidence, and the analysis would allow balancing of benefits, risks, and costs. For CV risk factors such as dyslipidemia, hypertension, and obesity, it is unlikely that such a large, long-term study will ever exist because of the time and costs involved, as well as the great degree of difficulty in achieving high levels of adherence and followup over decades. Furthermore, by the time substantial numbers of definitive end points occurred decades later, knowledge and technology most likely would have made the initial screening test obsolete. An RCT of CV risk factor screening with shorter term followup to examine change(s) in risk factor levels or surrogate outcomes (such as noninvasive measures of subclinical atherosclerosis) may be more feasible. However, like most surrogate measures and as described in the preceding Section II, subclinical measures of atherosclerosis do not perfectly predict clinical CVD outcomes.

One argument for screening is the knowledge that extreme elevations of risk factors are associated with early and severe clinical outcomes. For example, children with coarctation of the aorta have elevation of upper body blood pressure (BP) from infancy. When surgical repair of coarctation is delayed, early death from heart attack, stroke, and aortic rupture has been well-documented.[2] Similarly, in children with extreme elevations of low-density lipoprotein cholesterol (LDL–C) levels due to the rare inherited homozygous form of familial hypercholesterolemia, clinical CVD events begin as early as the first decade of life.[3]

The question that the Expert Panel faced is whether childhood screening to identify less severe forms of these risk factors is a useful strategy to prevent CVD events from occurring in middle-aged adults. Without definitive evidence from RCTs of screening programs, the Expert Panel was left to determine the wisdom of recommending screening in the face of suboptimal evidence but with knowledge that the atherosclerotic process begins in childhood and that the long time period required between screening during youth and clinical end points makes the most rigorous test of a CV risk factor screening program infeasible. In this situation, assessing the usefulness of screening involves evaluating alternative criteria, including attributes of the test, outcomes of interventions among children with actionable levels of test results, and the program as a whole.

TEST CHARACTERISTICS

Reproducibility

Lipids, BP, height, and weight are measurements with intrinsic biologic and measurement variability. For BP and total cholesterol (TC), LDL–C, and high-density lipoprotein cholesterol (HDL–C) levels, two or three measurements, taken several days to weeks apart, appear necessary to place most children in the categories of normal, borderline, or high with reasonable confidence.[4],[5] As described in Section X. Overweight and Obesity, height, weight, and body mass index (BMI) measurements are reliably reproducible, but measurements over time are needed to provide consistent information on growth trends and to determine whether there has been an inappropriate change in the BMI percentile relative to age- and gender-specific norms.

Validity/Accuracy

To be useful, a screening test must detect the condition of interest with sufficient reliability, sensitivity, and specificity to determine whether intervention is warranted or to mandate a second test to confirm the presence of the risk factor or disease. For most screening tests, the frequency of the screened condition is low, so even high sensitivity and specificity translate into a low positive predictive value—a consideration in screening for all rare conditions.[6] From a long-term perspective, this means that a majority of children with an identified CV risk factor in childhood will not develop premature CVD events (i.e., myocardial infarction, sudden cardiac death, or stroke by ages 50–60 years). Although counted statistically as false positives, pathology studies demonstrate that these individuals develop atherosclerosis faster than children with normal risk factor levels and are at increased risk for morbidity from a range of vascular complications (see Section II. State of the Science: Cardiovascular Risk Factors and the Development of Atherosclerosis in Childhood). The destructive effects of early heart attacks and strokes, the impact of multiple risk factors in increasing the risk for such events, and especially the potential to reduce the risk of sudden death as the first manifestation of early atherosclerotic CVD mean that decisionmakers might consider a lower positive predictive value for CV risk factor screening than for childhood screening for other disease processes. Specifically, because sudden cardiac death often occurs in asymptomatic individuals, the threshold for CV screening could be lower than that for diseases that always manifest with symptoms.

Risk factors that are considered to be most strongly associated with disease can nonetheless be suboptimal as screening tests. For example, adults with TC values in the highest fifth of the population distribution have approximately a threefold higher 10-year risk of fatal ischemic heart disease than adults in the bottom fifth of the distribution. Although this appears to be a strong association, assessing a screening test requires estimating the absolute risk for individuals rather than the relative risk. If one assumes that 5 percent of unaffected individuals will have TC levels in the top fifth of the distribution, a relative risk of 3 means that among these individuals, the test will detect only 15 percent of those destined to die from ischemic heart disease.[7] In fact, even a relative risk of 200 would increase this detection rate (i.e., the sensitivity) to just over 50 percent. In the case of a 10-year death rate of 1 percent, for every 100 persons identified with high cholesterol levels, only 3 would die of ischemic heart disease and the other 97 would be false positives. This example is simplistic since it does not take into account other coexisting risk factors for heart disease, other manifestations of vascular disease, or the fact that lifetime CVD risk is higher than a 10-year risk; however, it does convey the point that relying on relative risk can lead to overestimation of screening test performance. These considerations also underscore that, for maximal benefit, a strong population approach should accompany any high-risk approach to CVD prevention beginning in childhood.

Role of Selective Screening

Updating recommendations for lipid screening was one of the most important tasks for the Expert Panel. The original 1992 National Cholesterol Education Program (NCEP) report National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents (NCEP Pediatric Guidelines) recommended screening for elevated cholesterol levels only among children with either a family history of early CVD or elevated TC levels.[8] The rationale was that, compared with universal screening, this selective approach would identify the majority of children with elevated LDL–C levels by screening fewer individuals with similar benefits at lower costs, because a group with higher prevalence was being screened. As outlined in Section IX. Lipids and Lipoproteins, the evidence review indicates that office-based, family history-directed CV risk factor screening identifies significantly fewer children with abnormal LDL–C levels than would universal screening. When this evidence is combined with the knowledge that a complete family history is unavailable for many children, a family history-based screening approach for cholesterol does not appear to be effective. One caveat to this conclusion is that few data address whether family history-directed screening provides a useful approach for detecting extreme LDL–C levels (i.e., those high enough to warrant medication use). Also, as described in detail in Section IX. Lipids and Lipoproteins, most studies of medication use involve positive family history as an entry criterion, so that more research is needed about the efficacy of treatment among family history-negative children with elevated LDL–C.

The obesity epidemic makes more intensive lipid screening among overweight and obese children worthy of consideration, beyond the importance of identifying obesity as an independent risk factor for future CVD. As described in these Guidelines, particularly in Section X. Overweight and Obesity, evaluation of obese children will identify a large number with dyslipidemia, typically moderate to severe elevation of triglycerides (TG), mild elevation of LDL–C and reduced HDL–C, as well as elevated BP. A very small number also will have type 2 diabetes mellitus (T2DM). Primary treatment for any of these risk factors is weight control. TG levels in particular are very responsive to weight loss and to dietary change. HDL–C levels rise in response to regular exercise. As presented in Section IX. Lipids and Lipoproteins and in Section X. Overweight and Obesity, dietary change, exercise, and weight loss can contribute to normalization of lipid levels and BP and elimination of the metabolic abnormalities in T2DM. An unanswered question for both children and adults, however, is the extent to which treatment of the dominant lipid abnormalities associated with obesity will result in reduced risk of early CV events.

Acceptability

Obtaining risk factor measurements from children requires that testing be feasible and acceptable to parents and children. Measurement of length/height and weight are routine and well-accepted in pediatric care from birth onward. Measurement of BP, recommended for all children beginning at 3 years of age,[9] is also routine in most practices. Lipid testing requires a blood test and in the past has required overnight fasting. As described in detail in Section IX. Lipids and Lipoproteins, measuring non-HDL–C, which is accurate in the nonfasting state,[10] as the first step in lipid screening should be a major improvement in feasibility for clinical practice and acceptability to parents and children. Additional blood draws in the fasting state are needed to confirm initially abnormal levels; their acceptability to children and parents is an open question. Some older research suggests low compliance by parents and children with followup screening recommendations in real-world practice, but current data are sparse.[11]

Evaluation of Interventions among Children with Abnormal Risk Factors

As reviewed throughout these Guidelines, the major rationale for CV risk factor screening in youth, followed by treatment of abnormal levels, derives from knowledge that atherosclerosis begins in childhood and that its severity is greater in children with a higher burden of atherogenic risk factors. However, these observations do not directly address interventions to reduce this burden. A sine qua non of useful screening programs is that interventions based on abnormal screening results must be not only efficacious but also more efficacious than interventions that occur later in the disease process. If earlier interventions are not more efficacious than those initiated later in life, they incur cost and potential risk with no benefit. Studies in adults indicate that treating prehypertension with medication or lifestyle change is associated with a lower subsequent incidence of hypertension.[12],[13],[14] In children with coarctation of the aorta, long-term followup studies demonstrate that early surgical repair is associated with reduced incidence of subsequent CVD.[15] The extent to which efficacy of intervention in youth extends to primary and less severe hypertension is not known. For obesity and lipids, no studies directly address the benefits (or risks) of early childhood treatment over treatment later in life on clinical disease.

The case of heterozygous familial hypercholesterolemia (FH) provides partial proof of the concept that early reduction of risk factors may reduce future disease rates. Individuals with FH are at increased risk for early CVD because of elevated LDL–C levels from infancy. In natural history studies, 50 percent of males and 25 percent of females with FH develop clinical CVD by age 50 years.[16],[17] In RCTs among older children and adolescents with FH, statin treatment substantially lowers LDL–C levels and slows progression of atherosclerosis as assessed by noninvasive testing.[18] Although pediatric medication trials are of relatively short duration, they suggest that sustained LDL–C-lowering therapy in children with FH will lower the risk of early clinical CVD. By extension and by analogy with adult treatment guidelines, the Expert Panel recommends treating less extreme elevations of LDL–C in childhood, especially in the setting of multiple CV risk factors. The extent to which either lifestyle change or medication treatment of lipids in youth reduces the atherosclerotic burden or risk of CV events is not yet known, nor is the long-term safety of treatment with statins beginning in childhood, although published trials do not show any adverse impact on growth, pubertal maturation, or hormonal metabolism over several years (see Section IX. Lipids and Lipoproteins).

It is vital to know how well primary care clinicians can incorporate recommended screening programs, including testing and interventions, into routine practice. Unfortunately, evidence is meager regarding repeated testing strategies or the effectiveness or sustainability of interventions in real-world practices. Thus, the evidence review almost exclusively identified studies that addressed intervention efficacy in a research setting. Nevertheless, the Expert Panel anticipates that practices will be better equipped to adopt its recommendations in the future than they are today. The recommendations may very well effect changes in policy and systems, as well as additional research that will assist clinicians in overcoming current time, space, personnel, and reimbursement challenges.

Other Issues

A potential ancillary benefit of childhood CV risk factor screening is to alert older family members of the need to have their own risk factors checked, especially lipids. If they have not been screened previously, parents and grandparents of children with abnormal lipid values should have their own lipid levels checked by their primary care providers. Several studies have shown that first-degree relatives of children with elevated LDL–C levels have both higher LDL–C levels themselves and higher rates of CV events.[19],[20],[21]

It is also possible that knowledge of an abnormal risk factor in a child could spur lifestyle changes for the whole family. Many clinicians can cite anecdotes of families who made salutary changes after learning of a child's elevated cholesterol, BP, or BMI. However, the extent to which this phenomenon occurs is unclear, nor is it known whether this effect adds substantially to a concerted primordial prevention approach aimed at all children and families. Certainly, the literature is clear that, in general, knowledge alone is insufficient for effective behavior change.

FURTHER RESEARCH NEEDED

One of the most difficult issues to address in CV risk factor screening in childhood is the potential value of slowing or reversing atherosclerosis in its early stages. This issue is particularly important with respect to lipids. Statin treatment among high-risk adults reduces CV events within months of initiation.[22] However, statin therapy does not eliminate risk, and adult trials cannot include those who have already died of very early CV events, of which sudden death is a particular concern. Thus, an RCT of childhood CV risk factor screening and treatment of elevated levels with a noninvasive measure of atherosclerosis as the primary outcome is an appealing study design. This study design could apply to any of the childhood CV risk factors, not just elevated LDL–C. As described in the previous section, one caveat of using measures of subclinical atherosclerosis as end points is that, whether invasive or noninvasive, all of those measures are surrogates for the true outcome of clinical CV events. Trials with surrogate end points have sometimes led to misleading recommendations and harmful clinical practices.[23]

Through the assessment of benefit, risk, and cost, the science of clinical decisionmaking offers an alternative to large long-term trials for the evaluation of CV risk factor screening in children. A decision analytic framework allows modeling of the immediate and downstream consequences of assessing childhood risk factors and intervening among those with abnormal results. As with any analytic method, decision analysis has strengths and weaknesses. The most important attribute of decision analysis is to ask the right questions. In the case of childhood CV risk factor screening, one strength of decision analysis is the ability to compare a number of strategies, including no screening or intervention, primordial prevention approaches only, universal or selective screening at specific ages, and the marginal benefit of screening at younger versus older ages. If a model contains appropriate decision points and outcomes, it can be a valuable method for assessing effects on long-term health outcomes without having to wait decades. In such a model, empirical evidence drives the quantitative comparison of one decision versus another. A good decision analysis not only will point out where data are lacking but also, through sensitivity analysis, will identify the most important new data to collect. The cost to society at large will likely be a major factor in decisions regarding screening. When added to a decision analytic model, the costs of screening, followup, and intervention can lead to estimation of the cost-effectiveness of various screening strategies, and sensitivity analysis can show where variability in costs is meaningful or irrelevant. Cost-effectiveness can be a major driver of policy decisions to support prevention programs. For these reasons, well-considered cost-effectiveness analyses of childhood CV risk factor screening should be a priority for future research.

CONCLUSIONS

The Expert Panel recommends two complementary strategies to reduce future risk for clinical CVD. Primordial prevention seeks to prevent the acquisition of risk factors by optimizing CV health for all, beginning in infancy. Primary prevention requires screening to identify children at increased risk for CVD. This section focused on screening and reviewed the limitations of current knowledge within the requirements for a useful screening program. Taking these factors into account, the Expert Panel recommends routine measurement of length/height and weight beginning in infancy, with calculation of BMI annually beginning at age 2 years to identify growth trends; yearly assessment of BP from age 3 years; and universal screening for lipid abnormalities by a nonfasting non-HDL–C level at age 10 years. These screening strategies, described in detail in the respective risk factor sections of these Guidelines, will identify a relatively large number of children for whom the Expert Panel recommends intensified lifestyle intervention. Only a small number of children will require pharmacologic therapy. While they await the results of future research, the Expert Panel members conclude that recommending these assessments, followed by interventions as part of routine pediatric care, represents the best current primary prevention strategy to lower lifetime risk of atherosclerotic vascular disease.

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[21] Muratova VN, Islam SS, Demerath EW, Evans Minor V, Neal WA. Cholesterol screening among children and their parents. Prev Med 2001;33:1-6.

[22] Thavendirananthan P, Bagai A, Brookhart MA, Choudry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med 2006;166:2307-2313.

[23] CAST Investigators, DS Echt, PR Liebson, LB Mitchell, RW Peters, D Obias-Manno, AH Barker, D Arensberg, A Baker, L Friedman, HL Greene, ML Huther and DW Richardson, Mortality and morbidity in patients receiving encainide, flecainide or placebo. The Cardiac Arrhythmias Suppression Trial. N Engl J Med 1991; 324: 781–788.

BACKGROUND

A family history of CVD represents the net effect of shared genetic, biochemical, behavioral, and environmental components. In adults, epidemiologic studies have demonstrated that a family history of premature coronary heart disease in a first-degree relative—heart attack, treated angina, percutaneous coronary catheter interventional procedure, or coronary artery bypass surgery, stroke or sudden cardiac death in a male parent or sibling before age 55 years or a female parent or sibling before age 65 years—is an important independent risk factor for future CVD. The process of atherosclerosis is complex and involves many genetic loci and multiple environmental and personal risk factors. Nonetheless, from a sentinel study in this area, the presence of a positive parental history doubled baseline risk for CVD.[1] Offspring risk was strongly inversely related to the age of the parent at the time of the index event. The association of a positive family history with increased CV risk has been confirmed for men, women, and siblings and for different racial and ethnic groups.[2],[3],[4],[5],[6],[7],[8]

OVERVIEW OF THE EVIDENCE FOR IMPACT OF FAMILY HISTORY OF CARDIOVASCULAR DISEASE ON ATHEROSCLEROSIS IN CHILDREN AND ADOLESCENTS

In young subjects, autopsy findings and vascular function abnormalities have been correlated with a family history of premature coronary disease. In infants with a positive family history of early coronary disease, relative luminal narrowing has been demonstrated in the left and right coronary arteries at post mortem compared with infants without such a history.[9] A series of vascular studies have demonstrated subclinical abnormalities: Carotid intima-media thickness (cIMT) assessed by ultrasound has been shown to be increased in children, adolescents, and young adults with a parental history of myocardial infarction.[10],[11] Endothelium-dependent dilation of the brachial artery (FMD) is impaired in young subjects with a family history of premature coronary heart disease.[12] In a combined study, cIMT was significantly increased and FMD was significantly reduced in young healthy teenagers whose parents had experienced a myocardial infarction compared with controls with a negative family history.[13] Two generations of the Framingham Heart Study were evaluated for the presence of coronary artery and abdominal aortic calcification (AAC). A history of premature parental CVD and/or coronary artery disease (CAD) was significantly associated with the presence of coronary artery calcium in young- to middle-aged third-generation cohort subjects; AAC was associated only with parental coronary heart disease.[14] Although it has not been shown how arterial wall changes early in life relate to adult clinical disease, the presence of both structural and functional abnormalities of arterial function, combined with the large body of epidemiologic data, supports the concept that a positive family history of early CAD is an important independent risk factor for accelerated atherosclerosis.

OVERVIEW OF THE EVIDENCE FOR ASSOCIATION OF FAMILY HISTORY OF CARDIOVASCULAR DISEASE WITH ABNORMAL CARDIOVASCULAR RISK PROFILES IN CHILDREN AND ADOLESCENTS

In addition to its strength as an independent risk factor, the presence of a positive family history is associated with an unfavorable CV risk profile in the family constellation. In offspring, a parental history of early CVD has been shown to be associated with an adverse CV risk factor profile.[4] The Muscatine Study and the Bogalusa Heart Study both demonstrate that a history of coronary heart disease in parents is associated with unfavorable CV risk profiles in their children. In the Muscatine Study, selecting children with total cholesterol (TC) above the 95th percentile, identified a family group with increased coronary mortality.[15] When index cases were children who were consistently obese on three successive Muscatine surveys, the relative risk of dying from a CV cause was significantly increased for family members compared with lean and random group relatives.[16] From a cross-sectional analysis of more than 8,000 children in the Bogalusa study, offspring with a history of parental heart attack were significantly overweight after age 10 years and showed elevated levels of TC, low-density lipoprotein cholesterol (LDL–C), insulin, and glucose after age 17 years.[17] In a subsequent cohort study of children from the Bogalusa Study with a verified history of parental CAD, the adverse CV risk profile findings of the first study were confirmed: A positive family history was associated with obesity beginning in early childhood and with elevations of TC and LDL–C as well as glucose.[18] The association of a positive family history with an unfavorable CV risk profile suggests that both familial environmental influences and gene-environment interactions may underlie the increased risk associated with a positive family history.

OVERVIEW OF THE EVIDENCE FOR FAMILY HISTORY OF CARDIOVASCULAR DISEASE AND RISK REDUCTION IN CHILDREN AND ADOLESCENTS

The evidence review identified two randomized controlled trials in which the presence of familial CVD was a selection criterion. In a Norwegian study, young first-degree relatives of subjects with verified premature CAD were randomized to either a combined smoking cessation and low-fat diet modification or to usual care.[19] Outcome variables were smoking rates, lipid profiles, and a range of oxidative, inflammatory, and procoagulant markers. In the intervention group, there was a significant decrease in cholesterol and saturated fat intake with an associated decrease in LDL–C, oxidized LDL, and E-selectin, a vascular adhesion molecule. There was also a decrease in smoking in the intervention group, with an associated decrease in intercellular adhesion molecule-1. A second lifestyle intervention trial in Australian teenagers who were identified when a parent was hospitalized for treatment of angina or myocardial infarction showed minimal decreases in fat intake and serum cholesterol.[20]

If family history information is to be used to infer risk for CVD, reported information must be accurate. Unfortunately, even in subjects from established epidemiologic studies, the accuracy of reported family history for heart disease is variable. From the Framingham Heart Study, offspring reports of parental CVD and CV risk factors were compared with confirmed medical evidence of parental CV status.[21] Positive reports of high blood pressure, diabetes, and high cholesterol were accurate for mothers and fathers. By contrast, positive predictive values for a history of parental heart attack and stroke were low. Although this is partially due to the low prevalence of early onset heart disease in the Framingham population, it also reflects lack of awareness of parental disease. Since the Framingham cohort could be considered to represent a "best-case scenario" for the accuracy of parental CV history, inaccuracy is likely to be even more prevalent in the general population. One role for pediatric health care providers is to educate parents and families about the importance of complete and accurate family health history information. Life circumstances, such as divorce and geographic separation, can make learning about a family history difficult. Although there is nothing that can be done about missing family history information in adopted individuals, encouraging young parents to learn their own health history whenever possible, even when families are fragmented and family members are separated, should help improve future knowledge about this important risk factor.

Conclusions and Grading of the Evidence Review for the Role of Family History in Cardiovascular Health

• Overwhelmingly consistent evidence from observational studies strongly supports inclusion of a positive family history of early coronary heart disease in identifying children at risk for accelerated atherosclerosis and for the presence of an abnormal risk profile (Grade B).
• For adults, a positive family history is defined as a parent and/or sibling with a history of treated angina, myocardial infarction, percutaneous coronary catheter interventional procedure, coronary artery bypass grafting, stroke or sudden cardiac death before age 55 years in men or age 65 years in women. Because the parents and siblings of children and adolescents are usually young themselves, it was the Expert Panel's consensus that when evaluating family history in a child, history should also be ascertained for the occurrence of CVD in grandparents, aunts, and uncles, although the evidence supporting this is insufficient to date (Grade D).
• Overwhelmingly consistent evidence from observational studies shows that identification of a positive family history for CVD and/or CV risk factors should lead to evaluation of all family members, especially parents, for CV risk factors (Grade B).
• Family history evolves as a child matures, so regular updates are necessary as part of routine pediatric care (Grade D).
• Education about the importance of accurate and complete family health information should be part of routine care for children and adolescents. As genetic sophistication increases, linking family history to specific genetic abnormalities will provide important new knowledge about the atherosclerotic process (Grade D).

Table 4–1. Evidence-Based Recommendations for Use of Family History in Cardiovascular Health Care

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations; they are not graded.

Birth-18 years	Take detailed family history (FHx) of CVDa at initial encounter and/or at 3y, 9-11y & 18 y members	Grade B Recommend
Birth-18 years (cont.d)	If (+) FHx identified, evaluate patient for other CV risk factors, including dyslipidemia, hypertension, diabetes, obesity, history of smoking, and sedentary lifestyle
Birth-18 years (cont.d)	If (+) FHx and/or CV risk factors identified, evaluate family, especially parents, for CV risk factors	Grade B Recommend
Birth-18 years (cont.d)	Update FHx at each non-urgent health encounter	Grade D Recommend
Birth-18 years (cont.d)	Use FHx to stratify risk for CVD risk as risk profile evolves	Grade D Recommend
Birth-18 years (cont.d)	Supportive actions: Educate parents about the importance of FHx in estimating future health risks for all family members
18-21 years	Review FHx of heart disease with young adult patient	Grade B Strongly recommend
18-21 years (cont.d)	Supportive actions: Educate patient about family/ personal risk for early heart disease including need for evaluation for all CV risk factors

a Parent, grandparent, aunt, uncle, or sibling with heart attack, treated angina, CABG/stent/angioplasty, stroke, or sudden cardiac death at < 55 y in males, < 65 y in females

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REFERENCES

[1] Colditz GA, Rimm EB, Giovannucci E, Stampfer MJ, Rosner B, Willett WC. A prospective study of parental history of myocardial infarction and coronary artery disease in men. Am J Cardiol 1991;67(11):933-938.

[2] Myers RH, Kiely DK, Cupples LA, Kannel WB. Parental history is an independent risk factor for coronary artery disease: the Framingham Study. Am Heart J 1990;120(4):963-969.

[3] Sesso HD, Lee IM, Gaziano JM, Rexrode KM, Glynn RJ, Buring JE. Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women. Circulation 2001;104(4):393-398.

[4] Leander K, Hallqvist J, Reuterwall C, Ahlbom A, de Faire U. Family history of coronary heart disease, a strong risk factor for myocardial infarction interacting with other cardiovascular risk factors: Results from the Stockholm Heart Epidemiology Program (SHEEP). Epidemiology 2001;12:215-222.

[5] Jousilahti P, Puska P, Vartiainen E, Pekkanen J, Tuomilehto J. Parental history of premature coronary heart disease: an independent risk factor of myocardial infarction. J Clin Epidemiol 1996;49(5):497-503.

[6] Li R, Bensen JT, Hutchinson RG, Province MA, Hertz-Picciotto I, Sprafka JM, Tyroler HA. Family risk score of coronary heart disease (CHD) as a predictor of CHD: the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI family heart study. Genet Epidemiol 2000;18(3):236-250.

[7] Lloyd-Jones DM, Nam BH, D'Agostino RB Sr, Levy D, Murabito JM, Wang TJ, Wilson PW, O'Donnell CJ. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA 2004;291(18):2204-2211.

[8] Murabito JM, Pencina MJ, Nam BH, D'Agostino RB Sr, Wang TJ, Lloyd-Jones D, Wilson PW, O'Donnell CJ. Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults. JAMA 2005;294(24):3117-3123.

[9] Kaprio J, Norio R, Pesonen E, Sarna S. Intimal thickening of the coronary arteries in infants in relation to family history of coronary artery disease. Circulation 1993;87(6):1960-1968.

[10] Cuomo S, Guarini P, Gaeta G, De Michele M, Boeri F, Dorn J, Bond M, Trevisan M. Increased carotid intima-media thickness in children, adolescents, and young adults with a parental history of premature myocardial infarction. Eur Heart J 2002;23(17):1345-1350.

[11] Juonala M, Viikari JS, Rasanen L, Helenius H, Pietikainen M, Raitakari OT. Young adults with family history of coronary heart disease have increased arterial vulnerability to metabolic risk factors: the Cardiovascular Risk in Young Finns Study. Arterioscler Thromb Vasc Biol 2006;26(6):1376-1382. (PM:16614318)

[12] Clarkson P, Celermajer DS, Powe AJ, Donald AE, Henry RM, Deanfield JE. Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation 1997;96(10):3378-3383.

[13] Gaeta G, De Michele M, Cuomo S, Guarini P, Foglia MC, Bond MG, Trevisan M. Arterial abnormalities in the offspring of patients with premature myocardial infarction. N Engl J Med 2000;343(12):840-846.

[14] Parikh NI, Hwang S-J, Larson MG, Cupples A, Fox CS, Manders ES, Murabito JM, Massaro JM, Hoffmann U, O'Donnell CJ. Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham offspring and third generation cohorts. Circulation 2007;116:1473-1481.

[15] Schrott HG, Clarke WR, Wiebe DA, Connor WE, Lauer RM. Increased coronary mortality in relatives of hypercholesterolemic school children: the Muscatine study. Circulation 1979;59(2):320-326. (PM:758999)

[16] Burns TL, Moll PP, Lauer RM. Increased familial cardiovascular mortality in obese schoolchildren: the Muscatine Ponderosity family Study. Pediatrics 1992;89:262-268.

[17] Bao W, Srinivasan SR, Wattigney WA, Berenson GS. The relation of parental cardiovascular disease to risk factors in children and young adults. The Bogalusa Heart Study. Circulation 1995;91(2):365-371. (PM:7805239)

[18] Bao W, Srinivasan SR, Valdez R, Greenlund KJ, Wattigney WA, Berenson GS. Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease: the Bogalusa Heart Study. JAMA 1997;278(21):1749-1754. (PM:9388151)

[19] Tonstad S, Sundfor T, Seljeflot I. Effect of lifestyle changes on atherogenic lipids and endothelial cell adhesion molecules in young adults with familial premature coronary heart disease. Am J Cardiol 2005;95(10):1187-1191. (PM:15877991)

[20] Walker R, Heller R, Redman S, O'Connell D, Boulton J. Reduction of ischemic heart disease risk markers in the teenage children of heart attack patients. Prev Med 1992;21(5):616-629. (PM:1438110)

[21] Murabito JM, Nam BH, D'Agostino RB, Sr., Lloyd-Jones DM, O'Donnell CJ, Wilson PW. Accuracy of offspring reports of parental cardiovascular disease history: the Framingham Offspring Study. Ann Intern Med 2004;140(6):434-440.

BACKGROUND

These Guidelines provide evidence-based dietary recommendations to promote CV health and reduce CV risk that build on previous recommendations for adolescents and children 2 years and older that were established in the 2010 DGA.[1] The DGA provides science-based recommendations to promote health and reduce risk for chronic disease through diet and physical activity for members of the general public 2 years and older. The DGA is updated every 5 years: www.health.gov/dietaryguidelines. The recommendations in the DGA form the basis of Federal Government nutrition program and policy development. The 2010 DGA includes information from Dietary Reference Intake(DRI) reports of the Institute of Medicine (IOM); information from the DRIs also was accessed for this section. The 2010 DGA describe a healthy diet as one that:

• Emphasizes a variety of vegetables, fruit, whole grains, and low-fat dairy products
• Includes protein foods such as lean meats, poultry without skin, seafood, beans and peas, eggs, processed soy products, nuts, and seeds
• Is low in saturated fat and trans fat, cholesterol, sodium, and added sugar
• Stays within daily calorie limits

These new pediatric CV Guidelines not only build upon the recommendations for achieving nutrient adequacy in growing children as stated in the 2010 DGA but also add evidence regarding the efficacy of specific dietary changes to reduce CV risk from the current evidence review, for use by pediatric care providers in the care of their patients. Because the focus of these Guidelines is on CV risk reduction, the evidence review specifically evaluated dietary fatty acid and energy components as major contributors to hypercholesterolemia and obesity, as well as dietary composition and micronutrients as they affect hypertension. New evidence from multiple dietary trials addressing CV risk reduction in children provides important information for these recommendations.

ESTIMATED ENERGY REQUIREMENTS

The underlying premise of the 2010DGA is that foods, not supplements, should constitute the primary basis of a recommended eating plan for children and adolescents. The dietary recommendations of the 2010 DGA included all of the nutrients required for growth and health, balanced with energy requirements. On average, children need greater energy intake per kilogram of body weight than adults to accommodate the body's demands for growth, and this must be balanced with physical activity needs. The increasing prevalence of obesity in children reflects a chronic imbalance between energy intake and expenditure, where calorie intake is in excess of what is needed for normal growth. An emphasis of the DGA is the importance of achieving the appropriate energy balance at all ages. Calculations for recommended daily Estimated Energy Requirements (EER) (contained in the DRI) for children aged 2 and older by gender and age are provided in Table 5-1 as taken from the DGA.[1] Because the calculations provide estimates only, monitoring weight status and stage of growth are important considerations in estimating energy needs.

Table 5–1. Estimated Calorie Needs per Day by Age, Gender, and Physical Activity Levela

Estimated amounts of calories needed to maintain caloric balance for various gender and age groups at three different levels of physical activity. The estimates are rounded to the nearest 200 calories. An individual's calorie needs may be higher or lower than these average estimates.

Gender	Age (Years)	Calorie Requirements (kcals) by Activity Levelb: Sedentary	Calorie Requirements (kcals) by Activity Levelb: Moderately Active	Calorie Requirements (kcals) by Activity Levelb: Active
Child	2–3	1,000–1,200	1,000–1,400c	1,000–1,400c
Femaled	4–8	1,200–1,400	1,400–1,600	1,400–1,800
Femaled	9–13	1,400–1,600	1,600–2,000	1,800–2,200
Femaled	14–18	1,800	2,000	2,400
Femaled	19–30	1,800–2,000	2,000–2,200	2,400
Male	4–8	1,200–1,400	1,400–1,600	1,600–2,000
Male	9–13	1,600–2,000	1,800–2,200	2,000–2,600
Male	14–18	2,000–2,400	2,400–2,800	2,800–3,200
Male	19–30	2,400–2,600	2,600–2,800	3,000

a Based on Estimated Energy Requirements (EER) equations, using reference heights (average) and reference weights (health) for each age/gender group. For children and adolescents, reference height and weight vary. For adults, the reference man is 5 feet 10 inches tall and weighs 154 pounds. The reference woman is 5 feet 4 inches tall and weighs 126 pounds. EER equations are from the Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington (DC): The National Academies Press; 2002.

b Sedentary means a lifestyle that includes only the light physical activity associated with typical day-to-day life. Moderately active means a lifestyle that includes physical activity equivalent to walking about 1.5 to 3 miles per day at 3 to 4 miles per hour, in addition to the light physical activity associated with typical day-to-day life. Active means a lifestyle that includes physical activity equivalent to walking more than 3 miles per day at 3 to 4miles per hour, in addition to the light physical activity associated with typical day-to-day life.

c The calorie ranges shown are to accommodate needs of different ages within the group. For children and adolescents, more calories are needed at older ages. For adults, fewer calories are needed at older ages.

d Estimates for females do not include women who are pregnant or breastfeeding.

SOLID FATS AND ADDED SUGARS

Balancing energy intake with energy expenditure in a growing child is a complex process. Understanding the concepts of essential versus discretionary calories can assist pediatric care providers in guiding children and their families toward choosing nutrient-dense foods to maintain energy balance. Solid fats and added sugars (SOFAS) are always counted as "discretionary" or nonessential calories. Sources of SOFAS include "snack" foods, sugar-sweetened beverages, and desserts. Due to the sedentary behavior of most Americans, few such foods should be consumed, typically no more than 100–200 calories/day (kcal/d) as part of total energy intakefor the age group and physical activity level. To meet nutrient needs without overconsumption of calories (energy intake), meals and snacks need to be nutrient dense (high in nutrients) but as low as possible in saturated and trans fats and with little or no added sugars. Foods such as fat-free milk, fruits, vegetables, whole-grain breads, and low-sugar cereals exemplify this concept. Conversely, the sugar in sugar-sweetened beverages, the fat in whole milk (versus fat-free milk), the fat and added sugar in chocolate milk (versus fat-free unflavored milk), the fat in high-fat meats (versus lean meats), and the fat and sugar in cookies, cakes, pastries, granola bars, and sweetened cereals (versus unsweetened grain foods) are examples of sources of nonessential calories. Selecting nutrient-dense foods in each food group gives individuals an effective way to meet their nutrient needs without consuming excess calories. This approach can be adopted and maintained throughout life to prevent the development of overweight and obesity. Because the discretionary calorie concept is important but complex for most consumers, the Expert Panel emphasizes consuming mostly nutrient-dense foods for meals and snacks.

For growing children, the EER increases with age and with physical activity level, as do allowances for essential calories and discretionary calories, as shown in Figures 5–1 and 5–2. However, due to the low levels of physical activity common among most American children, the nonessential, discretionary calorie allowance is no more than 100–400 kilocalories, based on age and activity level. This is not sufficient to accommodate daily (or regular) consumption of whole milk, high-calorie/low-nutrient-dense snacks, or desserts and/or sugar-sweetened beverages (see Figures 5–1 and 5–2). Sedentary children who regularly consume energy-dense, nutrient-poor foods are at risk of developing overweight and obesity and having inadequate nutrition, despite high calorie intake.

[[nid:827 view_mode=custom_size width=600 height=439]]

Text description of Figure 5-1.

Figure 5-1. Estimated Energy Requirements (EER) and Discretionary Calorie Allowance by Level of Activity-(Boys)*

Boys	Essential Calories for CHILD 1-2	Discretionary Calories#	Total
2-3 sedentary	800	200	1,000
2-3 moderately active	1,000	200	1,200
2-3 active	1,200	200	1,400
4-8 sedentary	1,000	200	1,200
4-8 moderately active	1,400	200	1,600
4-8 active	1,650	300	2,000
9-13 sedentary	1,600	200	1,800
9-13 moderately active	1,900	300	2,200
9-13 active	2,200	400	2,600
14-18 sedentary	1,900	300	2,200
14-18 moderately active	2,300	400	2,700
14-18 active	2,550	650	3,200

# Discretionary calories for children aged 4-8 are based on recommended 2 servings of dairy/day.
* Adapted from Gidding et al. Circulation. 112(13). September 2005.

[[nid:828 view_mode=custom_size width=600 height=439]]

Text description of Figure 5-2.

Figure 5-2. Estimated Energy Requirements (EER) and Discretionary Calorie Allowance by Level of Activity-(Girls)*

Girls	Essential Calories for CHILD 1-2	Discretionary Calories#	Total
2-3 sedentary	800	200	1,000
2-3 moderately active	1,000	200	1,200
2-3 active	1,200	200	1,400
4-8 sedentary	1,000	200	1,200
4-8 moderately active	1,400	200	1,600
4-8 active	1,500	300	1,800
9-13 sedentary	1,450	150	1,600
9-13 moderately active	1,800	200	2,000
9-13 active	1,900	300	2,200
14-18 sedentary	1,600	200	1,800
14-18 moderately active	1,800	200	2,000
14-18 active	2,100	300	2,400

# Discretionary calories for children aged 4-8 are based on recommended 2 servings of dairy/day.
* Adapted from Gidding et al. Circulation. 112(13). September 2005.

Figures 5-1 and 5-2. Concept of discretionary calories by gender. As daily physical activity increases, more energy is needed for normal growth, unless the child is overweight or obese and may benefit from limited additional calorie intake as determined by the health care provider. For sedentary children, only small amounts of discretionary calories can be consumed before caloric intake becomes excessive. Discretionary calories represent snacks, desserts, sugar-sweetened beverages, and other nutrient-poor, energy-dense foods whose intake should not exceed the indicated allowances according to level of activity. In Figures 5-1 and 5-2, the discretionary calorie allowance for children ages 4-8 years is based on 2 servings of dairy per day. Mod Act indicates moderately active. Information is based on estimated calorie requirements and discretionary calories published in the Dietary Guidelines for Americans (2005).

FORMAT OF THE EVIDENCE REVIEW FOR NUTRITION AND DIET

The results of the evidence review addressing the role of nutrition and diet in promoting CV health are summarized below. The review encompassed 30 systematic reviews, 12 meta-analyses, 121 randomized controlled trials (RCTs), and 47 observational studies. Because of the large volume of studies reviewed and the diverse nature of the evidence, the Expert Panel provides an overview of the studies reviewed, highlighting those that in its view provide the most important information. Detailed information from each study has been extracted into the evidence tables and will be available at http://www.nhlbi.nih.gov/health-pro/guidelines/current/cardiovascular-health-pediatric-guidelines/index.htm. Results are presented here by dietary component and by age group and are summarized after each dietary component review. Some studies were not specific to the age groups addressed in these Guidelines; the Expert Panel used clinical judgment in determining how best to apply results from those studies to age-specific recommendations. At the end of each dietary component review, the results are summarized. The conclusions of the entire evidence review for diet and nutrition, with grades and age-specific recommendations, appear at the end of this section.

CURRENT DIETARY INTAKE IN CHILDREN AND ADOLESCENTS

Four epidemiologic studies evaluated overall dietary content for children and adolescents. The Bogalusa Heart Study is a major community-based cohort of more than 1,655 Black and White children and young adults in Bogalusa, Louisiana, that began in 1973 and still continues. Participants were originally examined at ages 5–17 years and were 52 percent female and 44 percent Black. The Bogalusa investigators developed and applied a scoring system based on consumption of nutrient-dense foods. Repeated cross-sectional surveys between 1989 and 2004 showed an overall decline in dietary quality, with a decrease in the consumption of nutrient-dense foods with increasing age. This was accompanied by extensive development of overweight and obesity in this cohort. At age 10 years, 50 percent of children had a good nutrient density score, but this dropped to only 19 percent by young adulthood.[2]

The Cardiovascular Risk in Young Finns study (Young Finns) is a multicenter longitudinal cohort study of CV risk from Finland, with 3,956 subjects enrolled at ages 3–18 years in 1980 and followed with serial lipid evaluation over time. Based on data from 21 years of followup, two major dietary patterns have been observed beginning in childhood: a "traditional" pattern characterized by high consumption of rye, potatoes, butter, sausages, milk, and coffee and a "health-conscious" diet that includes high consumption of vegetables, legumes and nuts, rye, cheese and other dairy products, and alcoholic beverages[3] At the latest followup, with subjects now ages 24–39 years, the traditional diet was significantly and independently associated with higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL–C) concentrations, apolipoprotein B (apoB), and C-reactive protein (CRP) in both genders, and with systolic BP and insulin levels among females. The health-conscious diet was inversely but not significantly associated with the same CV risk factors.[4]

The National Heart, Lung, and Blood Institute National Growth and Health Study (NGHS) enrolled 2,379 Black and White girls in three different U.S. cities at age 9 years and followed their nutrition, growth, and development over the next decade. Among adolescent girls older than age 10 years, lower parental educational attainment was associated with increased total fat, saturated fat, and cholesterol intake and decreased carbohydrate intake.[4] Dietary total and saturated fat intake decreased with increasing age, but less than half of White girls and less than one-third of Black girls met the 1992 National Cholesterol Education Program (NCEP) expert panel's recommendations for dietary fat intake: less than 30 percent of calories from fat and less than 10 percent from saturated fat. Independent of parental education, living in a two-parent household was associated with decreased fat and cholesterol intake and increased carbohydrate intake.[5] A dietary pattern characterized by high intake of fruits and vegetables, dairy products, and fiber-rich grains and low intake of sugar, fried foods, burgers, pizza, and total fat was associated with less adiposity (body mass index (BMI), percentage of body fat, and waist circumference) over 10-year followup; the difference was significant for White girls.[5]

A report from the Third National Health and Nutrition Examination Survey (NHANES III) (1988–1994) of more than 4,000 youths ages 8–18 years found that foods of low-nutrient density (snacks, desserts, etc.) contributed more than 30 percent of daily energy intake, with caloric sweeteners and desserts jointly contributing nearly 25 percent of daily caloric intake. Intake of food-based vitamins and minerals decreased as consumption of foods of low-nutrient density increased.[6]

OVERVIEW OF THE EVIDENCE BY DIETARY COMPONENT AND AGE GROUP

Milk and Other Beverage Intake

Age Birth to 12 Months: Human Milk

There is near universal agreement that human milk is the preferred complete nutrition source for healthy full-term newborns and infants for the first 6 months of life, with continued breastfeeding recommended until age 12 months. As recommended by the U.S. Surgeon General, World Health Organization (WHO), American Academy of Pediatrics (AAP), and American Academy of Family Practice (AAFP), human milk is the preferred primary source of nourishment in infancy. Human milk is a unique biological fluid that changes almost daily to meet the nutritional and immunologic needs of the growing infant. Human milk is high in fat (45–55 percent of total calories), saturated fat, and cholesterol. It provides a rich source of essential fatty acids linoleic acid (LA) and alpha linoleic acid (ALA) and long-chain polyunsaturated fatty acid (PUFA) derivatives arachidonic acid (AA) and docosahexaenoic acid (DHA).[7] Human milk supplies the fat-soluble vitamins A, D, E, and K as well as carotenoids and bioactive components, with protective functions ranging from immunoglobulins to oligosaccharides, enzymes, antienzymes, and adrenal steroids, although vitamin D levels are often inadequate. To prevent vitamin D deficiency, the AAP recommends supplementation with 400 international units per day (IU/d) for all children.[8] The new RDA for Vitamin D for those 1-70 years old is 600 IU/day.[9]

The evidence review for these Guidelines identified studies that examined the long-term CV benefits of breastfeeding, including possibly but not conclusively protective effects against obesity,[10] lower serum TC levels and decreased carotid intima-media thickness (cIMT) in adulthood,[11],[12] and a lower risk of type 2 diabetes mellitus (T2DM).[13] A meta-analysis of 37 studies compared the late effects of breastfeeding versus formula-feeding on TC levels in adolescents and adults.[11] In infancy, mean TC was higher in breast-fed versus formula-fed infants, but this difference disappeared in childhood and adolescence. Among adults, the TC level of those who had been breast-fed as infants was lower than the TC level of those who had been formula fed.

Ages Birth to 12 Months: Infant Formula

Infant formulas that meet regulatory requirements for quality and nutrient content are marketed in the United States and many other countries. These products are designed to support the normal growth and development of infants. Infant formula products currently marketed in the United States are iron fortified and contain mixtures of vegetable oils, including coconut, soy, high-oleic safflower, high-oleic sunflower, and/or palm olein, plus single-cell oils containing the two long-chain PUFAs DHA and AA. The DRI recommendations for nutrient intake by infants are based on the nutrient content of breast milk and include intake of essential fatty acids that are unsaturated, specifically ALA omega-3 and LA omega-6 fatty acids. The fat and cholesterol contents of infant formula were varied in several small short-term RCTs, with subsequent significant differences in intervention infants, compared with controls for TC, LDL–C, triglycerides (TG), and high-density lipoprotein cholesterol (HDL–C); there were no differences between groups in lipoprotein profiles postweaning.[14],[15],[16],[17]

Transition to Childhood: Ages 12 Months to 2 Years: Introduction of Cow's Milk

Vitamin-D-fortified cow's milk and other dairy products are excellent sources of calcium, magnesium, protein, and vitamin D. However, the dairy fat in whole cow's milk is a major source of atherogenic saturated fat, cholesterol, and calories and a poor source of the essential fatty acids LA and ALA.

Of particular relevance to the transition from breast milk or infant formula is the Special Turku Coronary Risk Factor Intervention Project (STRIP) in Finland. This important trial enrolled 1,062 healthy 7-month-old infants who were randomized to an intervention or a control group.[18] The intervention group families received repeated, individualized, nutritionist-delivered, low-saturated-fat counseling designed to achieve a diet with total fat of 30–35 percent of total kcal/d, a 1:1:1 intake ratio of saturated fatty acids (SFA)/monounsaturated fatty acids (MUFA)/PUFA/d, cholesterol intake of less than 200 milligrams per day (mg/d), protein 10–15 percent of total kcal/d, and carbohydrates 50–60 percent of total kcal/d. Until age 12 months, families were advised to continue with breast- or formula-feeding. After age 1 year, skim milk was recommended as the primary beverage; in the intervention group, parents were encouraged to supplement the diet as needed with soft margarines and vegetable oils until age 24 months to maintain adequate fat intake. The control group received basic health education and no instructions on the use of dietary fats.[18] The children then were followed with serial evaluations, with the first at age 13 months, including dietary assessment with 4-day dietary records, to midadolescence, with reported findings to age 14 years. The children have been assessed for lipid results every 2 years and for other nutrition-related measures at irregular intervals. From the first intervention assessment at age 13 months onward until age 14 years, children in the intervention group consumed less total and saturated fat, less cholesterol, and more carbohydrates and polyunsaturated fat than controls. The percentage of calories in the intervention group from total fat (saturated fat in parentheses) was 26 percent (9 percent) at age 13 months, 30 percent (11 percent) at age 24 months, 30 percent (12 percent) at age 4 years, 30 percent (12 percent) at age 7 years, and 30 percent (11 percent) at age 10 years.[19],[20],[21],[22],[23] These dietary fat changes translated to significantly lower TC and LDL–C levels until age 7 years; after age 7 years, the latter difference was significant only for boys.[22],[23] No harmful effects were reported on growth, micronutrient intake, development, or neurologic function.[24],[25] In a subgroup of 78 intervention children and 89 control children assessed at age 9 years, the intervention children had significantly lower insulin levels and lower homeostatic model assessment of insulin resistance (HOMA–IR) than control children.[26] At age 10 years, followup included about half of the original cohort, as initially predicted and powered. Results showed that 10.2 percent of girls in the intervention group were overweight, compared with 18.8 percent of controls (P = 0.04); there was no difference in overweight prevalence between groups among boys. There was no significant difference between intervention and control groups in weight for height or obesity at any single age, thus illustrating energy adequacy despite recommended reduced fat intake.[27] For this study, overweight was defined as weight for height greater than 20 percent and obesity greater than 40 percent above the mean weight for height for Finnish children. In a subgroup assessed at ages 7 and 9 years, intervention children also had higher nutrition knowledge scores.[28]

Intake of Other Beverages

Infancy/Early Childhood

Consumption of fruit juices, representing a "naturally sweetened" beverage, has increased over the past 30 years due to increased availability, accessibility, marketing, and convenience.[29] Young children tend to be the highest consumers of fruit juices, and some studies have noted associations between high juice consumption and obesity.[30],[31] Of note, juice intake was higher and the relationship between juice intake and obesity was strongest in low-income populations where children participated in public nutrition programs, such as the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) that provide vouchers for juice. Two longitudinal studies of children participating in the WIC Program found that the increased risk of obesity with increased juice intake was strongest among children who were already overweight.[30],[31] The AAP recommends that a serving of natural, unsweetened fruit juice be limited to 4–6 fluid ounces and that infants can receive 1 serving per day after age 6 months as part of a meal or snack. After infancy, children ages 1–6 years should receive no more than 1 serving of unsweetened fruit juice per day, and children ages 7–18 years should limit juice consumption to no more than 2 servings per day.[32] This evidence review identified no additional studies in this subject area for these age groups.

Later Childhood and Adolescence

The Centers for Disease Control and Prevention's (CDC's) 2007 Youth Risk Behavior Surveillance report found that only 19 percent of male teens and 9 percent of female teens consumed at least 3 glasses of milk per day.[33] In contrast, 39 percent of males and 29 percent of females consumed at least one 12-ounce can of soda per day, not including diet soda. Soft drink consumption in the United States has increased more than 300 percent over the past two decades; 56–85 percent of school-aged children consume at least one soft drink daily. The full impact on obesity and other CV risk factors from the displacement of calcium, vitamin D, protein, and other essential nutrients, combined with the increase in calories from sugar, is as yet unquantified. The NGHS (described previously) reported that higher consumption of sugar-sweetened beverages was associated with significantly lower milk consumption and that increased soda consumption predicted greater increases in BMI; BMI increased 0.01 unit for each 100 grams of soda consumed. Consumption of sugar-sweetened beverages was significantly associated with higher daily calorie intake. For every 100 grams of soda consumed, average daily calorie intake increased by about 82 calories.[34] A 2006 systematic review of sugar-sweetened beverage intake and weight gain included 21 (of 30) studies in children and adolescents.[35] The review concluded that greater consumption of sugar-sweetened beverages is significantly associated with both weight gain and obesity. Two RCTs reviewed in detail in Section X. Overweight and Obesity showed significant reductions in overweight and obesity when intake of sugar-sweetened beverages was limited.[36],[37]

Sports drinks represent a relatively new beverage category. By design, they contain higher amounts of sodium, refined carbohydrates (sugar), and calories than does water. No studies in this evidence review dealt with sports drinks, but information is provided because of their increasing consumption as a sugar-sweetened beverage and thus their potential impact on children's caloric intake. Originally developed and marketed for use by trained athletes during competition, sports drinks have been marketed to the general public and "casual athletes" in recent years. Consumption by children and adolescents is increasingly common, with or without accompanying physical activity. In one review of adolescents ages 11–18 years, 56.4 percent reported having consumed a sports drink during the previous week.[38] Research in adult athletes evaluated under conditions of prolonged exercise with or without heat stress indicates that beverages containing electrolytes are effective in maintaining plasma volume and preventing hyponatremia, compared with plain water.[39] Compared with water, drinks containing electrolytes and refined carbohydrates have been shown to improve performance in sustained exercise tasks lasting more than 45 minutes.[40] In studies of young adult competitive athletes, primarily males, sports drinks appear to be safe and effective during training and competition, especially in hot conditions.[41] Although it may be reasonable to extrapolate these benefits to adolescents exerting high levels of energy under similar conditions, the evidence review identified no research examining the effects of these drinks in children.

SUMMARY OF THE EVIDENCE REVIEW FOR MILK AND OTHER BEVERAGE INTAKE

• Human milk, as the primary source of nutrition in the first year of life, is associated with CV benefits on late followup in adult life.
• Results of the STRIP trial suggest that the fat content of cow's milk can be safely reduced in healthy infants when accompanied by counseling on nutrition quality and energy density, including attention to sufficient fat intake prior to age 2 years, with benefits on TC and LDL–C levels in boys and girls up to age 7 years and in boys through age 14 years, plus lower rates of obesity and insulin resistance.
• Increased sugar-sweetened beverage intake is associated with obesity in multiple reports.

OVERVIEW OF THE EVIDENCE FOR DIETARY FAT INTAKE

Background

The evidence that, in adults, a diet lower in fat is associated with reduced development of cardiovascular disease (CVD) originated with epidemiologic studies dating back half a century. Dietary fat intake (quantity) and fatty acid type regulate serum lipids in children as they do in adults, but fat intake may represent a major source of energy for children, especially infants and toddlers, whose volume capacity is limited. Energy density can be an important factor among finicky eaters whose total caloric needs may otherwise not be met. The original NCEP recommendations were published in 1992 and were based on evidence available at the time. The National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents recommended a diet with less than 30 percent of total calories from fat, less than 10 percent from saturated fat, and cholesterol intake <300 mg/d for all healthy U.S. children 2 years and older.[42] There is no biologic requirement for SFA, so the limits were intended to help reduce atherogenic risk without eliminating high-quality animal protein sources. The DRI recommendations promote the intake of essential fatty acids from unsaturated sources, specifically ALA and LA omega-6 fatty acids. The acceptable range for intake of LA is 5–10 percent of fat calories and for ALA is 0.6–1.2 percent of fat calories for children and adults. From the evidence review, dietary pattern studies in children and adolescents report that higher blood lipid levels are associated with higher total and saturated fat intake, just as in adults.[4],[5],[6],[7] The evidence review for these Guidelines also identified a series of studies focused on evaluating the safety of lower dietary fat and saturated fat content as well as the efficacy of such diets in lowering serum lipid levels and reducing obesity. Most important among these studies for the youngest age range is the STRIP trial, now with 14 years of followup.[18],[19],[20],[21],[22],[23] STRIP is the only trial examining and reporting health effects from a reduced saturated fat diet in normal children from infancy through adolescence. The STRIP trial and each of the other dietary fat interventions identified by the evidence review are described by age group below.

Infancy

Despite recommendations advocating breast milk or formula in infancy, a 2002 survey reported that 20 percent of toddlers had been fed whole cow's milk on a daily basis before age 12 months.[43] The consequences of whole-milk consumption by infants, with its high protein and sodium content and reduced LA content, have not been reported. In several RCTs with small study groups, the fat and cholesterol contents of infant formulas varied, with subsequent short-term changes in levels of TC, LDL–C, and TG in infancy, but no long-term differences in lipoprotein profiles were demonstrated on followup.[14],[14],[15],[16]

Infancy After Weaning

As described above, many of the data on the safety and efficacy of a diet low in saturated fat and cholesterol starting in infancy come from the STRIP study, in which 7-month-old Finnish infants were randomized into either (1) a group whose parents received counseling from a nutritionist for a diet with total fat of 30–35 percent of total kcal/d and with a 1:1:1 intake ratio of SFA/MUFA/PUFA per day, cholesterol intake <200 mg/d, protein 10–15 percent per day, and carbohydrates 50–60 percent per day or (2) a group whose parents received basic health education and no instructions on the use of fats.[18] From age 12 months onward, the primary beverage consumed by these children was skim milk. The children were followed with repeated dietary counseling and serial evaluations, including dietary assessment using 4-day diet records, the first at age 13 months and extending now into midadolescence.

Beginning at the age 13-month assessment and extending to age 14 years, children in the intervention group have consumed significantly less total and saturated fat and more carbohydrates and polyunsaturated fat, compared with children in the control group. The total fat content of the diet of the intervention children ranged from 26 to 30.5 percent throughout the 14-year followup period.[19],[20],[21],[22],[23] This compares with a significantly higher total fat intake of 28–33 percent in control subjects. Saturated fat intake among the intervention children was significantly lower, ranging from 9.5 percent to 11 percent, compared with 13–14 percent in control subjects. From age 13 months to age 14 years, those in the STRIP intervention group had lower TC and lower LDL–C than the control group; after age 7 years, the difference was only significant in males.[21],[22],[23] There were no differences in growth or in pubertal maturation between groups. In a substudy, serum stanol concentrations were measured to further assess the effect of replacing milk fat with vegetable fat. Campesterol and sitosterol levels were increased, but this was not associated with any change in the levels or production of cholesterol.[44] The lower total fat and saturated fat diet was associated with important CV health benefits, including the difference in serum lipids described above.[19],[20],[21],[22] Assessed at age 9 years, a subgroup of STRIP intervention children also had significantly lower insulin levels and lower HOMA–IR than control children.[26] Assessed for obesity measures at age 10 years, there were significantly more overweight females in the control group than in the intervention group; only two intervention females and one male were obese, compared with eight control females and one male.[27] For this study, overweight was defined as weight for height greater than 20 percent and obesity as greater than 40 percent above the mean for Finnish children. In a subgroup assessed at ages 7–9 years, intervention children had higher nutrition knowledge scores.[28] No harmful effects on nutrient adequacy, physiologic development, or neurologic function were seen over 14 years of followup in those who continued to be followed, representing more than half the original cohort and adequately powered to assess the planned outcome measures.[23],[24],[25]

Childhood and Adolescence

The Dietary Intervention Study in Children (DISC)[45] assessed the safety and efficacy of a reduced-fat dietary intervention among children with moderately elevated LDL–C levels between the 80th and 98th percentiles at baseline. Prepubertal boys (N = 362) and girls (N = 301) (initially ages 8–10 years) and their parents were randomized to either an ongoing, nutritionist-driven, individual and group intervention or a usual-care group in a six-center clinical trial. A behavioral-based, nutritionist-tailored intervention with monthly nutritionist visits and telephone followup was used to promote adherence to a diet similar to the NCEP Step II diet, with 28 percent of energy from fat, <8 percent from saturated fat, <9 percent from polyunsaturated fat, and cholesterol intake <150 mg/d. The control group received dietary literature only. At the 3-year followup, dietary total fat intake averaged 28.6 percent of calories, with a saturated fat intake of 10.2 percent of calories in the intervention group, significantly lower than in the usual-care group. This change was accompanied by small but significant mean differences in LDL–C levels (reduction from baseline of 15.4 mg per deciliter (mg/dL) in the intervention group versus a reduction of 11.9 mg/dL in the control group). Greater sexual maturation and BMI were found to increase the normal fall in LDL–C levels in both groups, which occurs during adolescence.[46] At followup after a mean of 7.4 years, children in the intervention group maintained significantly lower dietary intakes of total fat, saturated fat, and cholesterol, compared with children in the control group, but there was no longer a significant difference in LDL–C between the two groups. There were no differences in any of the safety measures, including height or depression scores.[47],[48]

A clinically initiated, home-based, parent-child autotutorial (PCAT) dietary education program directed at increasing dietary knowledge and reducing fat consumption and LDL–C levels was assessed in 174 boys and girls ages 4–10 years with borderline-high or high LDL–C.[49] Intervention families received individualized dietary recommendations to maintain a total dietary fat intake of less than 30 percent of calories and a saturated fat intake of less than 10 percent of calories and used tape-recorded nutrition messages to support appropriate dietary decisions between clinical visits. After 3 months, the PCAT group had significantly lower intakes of total and saturated fat and calories and lower LDL–C levels than an at-risk control group that received no intervention; there were no significant differences in dietary intake or lipid levels between PCAT and traditional dietary counseling. Results were maintained at 1-year followup.[50] Another office-based, 16-week nutritional education program effectively decreased intake of total fat, saturated fat, and cholesterol and significantly lowered TC and LDL–C levels.[51]

In prepubertal children with heterozygous familial hypercholesterolemia (FH), an RCT of 96 children ages 6–11 years tested a fat-restricted diet with 23 percent ±5 percent of energy from total fat, 8 percent ±2 percent from saturated fat, 5 percent ±1 percent from polyunsaturated fat, 8 percent ±2 percent from monounsaturated fat, 15 percent ±2 percent from protein, and 62 percent ±5 percent from carbohydrates, with a cholesterol intake of 67 mg ±28 mg/1,000 kcal, for 1 year. TC and LDL–C levels were lowered by 4.4 percent and 5.5 percent, respectively. HDL–C, TG, apoB, ferritin, weight for height, and height velocity were unchanged.[52]

The Child and Adolescent Trial for Cardiovascular Health (CATCH) was an RCT to examine the outcomes of a multilevel school-based intervention, including health behavior education and school environmental changes, in 56 intervention schools compared with 40 control schools; effects in 5,106 initially third-grade students from ethnically diverse backgrounds in California, Louisiana, Minnesota, and Texas were assessed.[53] In intervention schools, there were school food service modifications to lower fat and sodium content plus enhanced physical education and classroom health curricula, both with and without family education. Compared with control schools, children at intervention schools consumed significantly less total fat from cafeteria lunches (reduced from 38.9 percent to 31.9 percent of energy for the lunch meal only) and increased their amounts of vigorous physical activity. Due to limitations in the full collection of diet assessment methodology, whether total fat and saturated fat intakes per day were effectively reduced to NCEP guidelines levels of less than 30 percent and less than 10 percent of total calories, respectively, was only documented in a subsample.[54] However, after this 2.5-year intervention, there were no differences between the intervention and control schools regarding children's cholesterol levels, BP, or body size, nor were there any deleterious effects on growth or development.[55]

Of note, the evidence review for these Guidelines identified no RCT in which dietary fat intake of 30–35 percent was evaluated in children or adolescents. Even in the STRIP study, which focused on reducing saturated fat intake with dietary counseling for up to 30–35 percent of total calories from fat, total fat intake of the intervention group never exceeded 30.5 percent from ages 7 months to 14 years.[18],[19],[20],[21],[22],[23] Lower total fat intake with nutritionist-tailored diet interventions was associated with no adverse events under the conditions specified for each trial.

SUMMARY OF THE EVIDENCE REVIEW FOR DIETARY FAT INTAKE

• A diet with total fat at less than 30 percent of calories, saturated fat less than 10 percent of calories, and cholesterol intake <300 mg/d, as recommended in the 1992 National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents, is safe for healthy children; in one large trial, this kind of diet was initiated in infancy through tailored, nutritionist-delivered intervention and no harmful effects were reported throughout childhood into adolescence.
• Modifying the type and amount of fat intake in children's diets can be effectively accomplished by qualified ongoing nutritional guidance and behavioral counseling for parents and children, preferably along with environmental change.
• Dietary intervention studies in healthy children and in children with hypercholesterolemia using trained nutritionists safely achieved an average total fat intake of 28–30 percent of calories and an average saturated fat intake of 8–10 percent of calories.
• These levels of total fat and saturated fat intake were shown in RCTs to be associated with lower TC and LDL–C levels in intervention subjects, compared with control subjects.
• No harmful, adverse effects of restricting total or saturated fat intake at the levels described in the reviewed studies were demonstrated through several years of followup, with one RCT demonstrating no harm for as long as 14 years.
• This evidence review identified no studies evaluating trans fat intake in children.

OVERVIEW OF THE EVIDENCE FOR DIETARY CHOLESTEROL INTAKE

Cholesterol is found in the membranes of all cells and is the precursor of bile acids, sex hormones, vitamin D, and other essential biologic elements. Because of endogenous production, there is no dietary requirement for cholesterol.[56] However, dietary cholesterol is known to impact plasma lipids; it has been estimated that in adults on a 2,500 kcal/d diet, serum cholesterol will decrease by about 4 mg/dL for every 100 mg/d decrease in dietary cholesterol.[57] The 1992 National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents recommended that dietary cholesterol intake be limited to <300 mg/d in all children and to <200 mg/d in those with elevated LDL–C levels. From the NHANES surveys from the 1970s through 1994, mean dietary cholesterol intake in male and female children younger than age 13 years and in females through adolescence achieved the recommended level, averaging <300 mg/d. However, in males between ages 12 and 19 years, mean intake of cholesterol was 335 mg/d, exceeding the recommended 300 mg/d, regardless of racial/ethnic group.[58] This evidence review identified 15 RCTs that addressed dietary cholesterol in infancy, childhood, and adolescence. In several small short-term studies, the fat and cholesterol contents of infant formula varied, with subsequent changes in levels of TC, LDL–C, and TG in infancy, but there were no demonstrated long-term differences in lipoprotein profiles.[14],[15],[16],[17] The STRIP trial, described in detail above, enrolled 1,062 healthy infants who were randomized to either intervention or control groups beginning at age 7 months. In addition to the low-saturated-fat diet described above, the intervention group received repeated, individualized, nutritionist-delivered counseling to maintain a dietary cholesterol intake of <200 mg/d.18 The children were then followed with serial evaluations, including dietary assessment using 4-day food records, until early adolescence. Results demonstrate that from age 13 months onward, children in the intervention group consumed significantly less total fat, saturated fat, and cholesterol and had lower TC and LDL–C levels; after age 7 years, the difference in LDL–C levels was significant only among boys.[18],[19],[20],[21],[22],[23] No harmful effects were detected on growth, micronutrient intake, development, or neurologic function.[23],[24],[25] Benefits on CV risk factors, especially lipids, described in detail in the preceding section, were seen, continuing into adolescence.[18],[19],[20],[21],[22],[23],[26],[27]

The DISC trial[45] described in detail above, was an RCT to assess the safety and efficacy of a reduced-fat dietary intervention among children with elevated LDL–C levels (between the 80th and 98th percentiles) at baseline. The DISC trial used a behavioral-based, nutritionist-tailored intervention to promote adherence to a diet similar to the NCEP Step II diet, with 28 percent of energy from fat, <8 percent from saturated fat, <9 percent from polyunsaturated fat, and cholesterol intake <75 mg/1,000 kcal/d, not to exceed 150 mg/d. Based on multiple 24-hour dietary recalls, cholesterol intake was shown to decrease from a mean of 118 mg/100 kcal to 90 mg/100 kcal at 1-year followup; this difference persisted at evaluation 5 years postinitiation. At 3-year evaluation, LDL–C levels were significantly lowered in the intervention group, compared with the control group (reduction from baseline of 15.4 mg/dL versus 11.9 mg/dL, respectively); this difference was not sustained at 7-year followup. There were no differences between groups in the prespecified safety measures of height and serum ferritin.[46],[47]

In prepubertal children with heterozygous FH, an RCT of 96 children ages 6–11 years tested a fat- and cholesterol-restricted diet (23 percent ±5 percent of energy from total fat, 8 percent ±2 percent from saturated fat, 5 percent ±1 percent from polyunsaturated fat, 8 percent ±2 percent from monounsaturated fat,15 percent ±2 percent from protein, and 62 percent ±5 percent from carbohydrates with daily cholesterol intake of 67 ±28 mg/1,000 kcal).[52] After 1 year, TC and LDL–C levels decreased by 4.4 percent and 5.5 percent, respectively. HDL–C, TG, apoB, and ferritin levels, weight-for-height, and height velocity were unchanged.[52]

The PCAT dietary education program described previously was directed at increasing dietary knowledge, reducing fat consumption, and decreasing LDL–C levels in boys and girls ages 4–10 years with borderline-high or high LDL–C.[49] In addition to individualized dietary recommendations to maintain a total dietary fat intake at less than 30 percent of calories and saturated fat intake at less than 10 percent of calories, intervention families were trained to limit cholesterol intake to <300 mg/d. At baseline, cholesterol intake was well below the 300-mg goal in all subjects, averaging 156.5 ±6.6 mg/d in the intervention group and 178.4 ±7.7 mg/d in the control group. After 3 months, those in the PCAT intervention group had significantly lower intakes of total fat, saturated fat, cholesterol, and calories. Cholesterol intake averaged 133.2 ±8.0 mg/d in the intervention group but was unchanged at 173.1 ±8.2 mg/d in the control group. LDL–C levels decreased 10 mg/dL in intervention subjects and 3.4 mg/dL in control subjects. These results were maintained at 1-year followup.[50] Another office-based, 16-week nutritional education program similarly decreased intakes of dietary total fat, saturated fat, and cholesterol—the latter to <200 mg/d—with significant decreases in TC and LDL–C levels and no reported adverse outcomes.[51]

SUMMARY OF THE EVIDENCE REVIEW FOR DIETARY CHOLESTEROL INTAKE

• Usual mean dietary cholesterol intake by children and adolescent females fall below the level of 300 mg/d previously recommended by the NCEP Pediatric Panel as reported in the 1992 National Cholesterol Education Program: Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents; in adolescent males, mean dietary cholesterol intake exceeds this level.
• In multiple RCTs in children with hypercholesterolemia, dietary cholesterol intake has been safely decreased with nutritional counseling to <200 mg/d, with one study of healthy children beginning in infancy and followed up through childhood into adolescence.
• Combined with lower total fat and saturated fat intake, lower cholesterol intake was associated with significant reductions in serum TC and LDL–C levels in the RCTs that were conducted in children ranging from age 7 months to early adolescence.

OVERVIEW OF THE EVIDENCE REVIEW FOR INTERVENTIONS TO INCREASE FRUIT AND VEGETABLE INTAKE

Background

Consumption of fruits and vegetables is advocated in the U.S. Department of Agriculture (USDA) MyPlate.[59] Most fruits and vegetables are plentiful in micronutrients and low in energy density. Because of their high fiber content, some studies suggest that fruits and vegetables can also contribute to feelings of satiety without excessive energy intake. As described in the section on dietary patterns, higher intake of fruits and vegetables in epidemiologic studies has been associated with less adiposity and lower BP and cholesterol levels.[4],[5] The DGA concluded that some evidence exists to support the conclusion that there is an association between higher vegetable and fruit intake and less adiposity in children.[1] Despite the high nutrient value of fruits and vegetables, children have inadequate intake of fruits and vegetables. In a national survey from 1999 to 2002, only one-fourth of children ages 2–11 years were found to consume at least three servings per day of vegetables, and fewer than half consumed at least two fruit servings per day.[60] The Expert Panel focused its review on evidence supporting effective interventions to increase the intake of fruits and vegetables among children. None of the identified studies were interventions in children younger than age 4 years.

Childhood and Adolescence

Four systematic reviews and one meta-analysis addressed fruit and vegetable intake as primary outcome measures. The body of evidence presented here evaluates the effectiveness of various interventions on the consumption of fruits and vegetables, rather than evidence of the relationship between fruit and vegetable intake and CV risk factors. A 1998 meta-analysis[61] evaluated the results of 12 elementary-school-based studies (published between 1980 and 1996) on heart healthy eating behaviors, including fruit and vegetable intake. Three were RCTs, which were included in this evidence review.[62],[63],[64] The results translated into a weighted standard effect size of 0.24, suggesting that school-based programs have a small but significant effect on fruit and vegetable intake as part of a heart healthy eating pattern. A systematic review published in 2002 evaluated the efficacy of behavioral interventions to modify dietary fat intake and fruit and vegetable intake in children and adults in studies published between 1975 and 1999.[65] That review included four studies from this evidence review[55],[63],[65],[66],[67]and concluded that more than three-fourths of all studies reported significant increases in fruit and vegetable intake, averaging 0.6 more servings per day; studies in children were not reported separately. Interventions were reported to be more successful in populations identified as being at risk for or diagnosed with disease, suggesting that results in the healthy pediatric population might have been less significant. A 2005 systematic review[68] focused on studies in children ages 6–12 years published between 1990 and March 2005 and included four studies from this evidence review.[55],[66],[67],[69] The review concluded that availability, accessibility, and taste preferences were the determinants most consistently and positively related to higher consumption of fruits and vegetables. Among interventions, multicomponent school-based interventions were the most successful. The most recent systematic review from 2006 evaluated worldwide intervention studies (published any time before April 2004) designed to increase fruit and vegetable intake in children and adults.[70] A total of 15 studies focused on subjects ages 5–18 years; of these, 11 were RCTs, 10 of which were included in this evidence review.[55],[63],[65],[67],[71],[72],[73][74],[75] Overall, 10 of the 15 studies showed a significant positive effect, ranging from an increase of 0.3 to 0.99 servings per day. The evidence was strongest for multicomponent interventions.

As indicated by the findings of the systematic reviews, most intervention studies addressing enhanced fruit and vegetable intake used multicomponent school-based strategies. The types of interventions varied and included such approaches as multimedia games, traditional classroom instruction, reward systems, and computer-based education. Many studies focused on obesity and addressed lower fat intake, especially lower saturated fat intake, and/or increased physical activity in addition to increased intake of fruits and vegetables.[45],[73][74],[75] Several studies targeted parents, teachers, and food service workers as well as children.[53],[67],[72],[74] Most demonstrated a modest, often short-term increase in fruit and vegetable intake. The most successful interventions provided fruits and vegetables free of charge, added them routinely to school meals or in supplemental food packages to families, and/or included children in preparing or taste-testing fruits and vegetables. Accessibility and availability were important aspects of successful interventions, compared with educational interventions alone[55],[76],[77]; the latter tended to result in an increase in knowledge but no increase in intake of fruits and vegetables.[28],[72],[75],[78] A reward system in one study resulted in increased fruit and vegetable intake during the school lunch period.[79] However, these gains disappeared when the reward system was removed. A computer-game-based intervention was associated with better nutritional knowledge and better overall food choices than a conventional curriculum among students in the last three grades of primary school, but there was no significant impact on fruit and vegetable intake.[80]

SUMMARY OF THE EVIDENCE FOR INTERVENTIONS TO INCREASE FRUIT AND VEGETABLE INTAKE

• Intake of fruits and vegetables by children ages 5 years and older can be modestly increased through a variety of interventions, but almost all have been school based and have advocated a stronger parental component.
• Because most studies have addressed multiple aspects of dietary change and lifestyle modification, the independent effects of fruit and vegetable intake on child weight gain and BMI outcomes are often unclear.
• Providing more fruits and vegetables to children results in increased intake.
• Allowing children to prepare and taste fruits and vegetables enhances their acceptance of these foods.
• Interventions aimed at increasing children's nutritional knowledge less consistently result in an increase in children's intake of fruits and vegetables.
• Fruit and vegetable intake tends to decline as children reach the middle school and high school years.

OVERVIEW OF THE EVIDENCE FOR DIETARY FIBER INTAKE

Background

The DGA identified whole grains as an important source of fiber, which is a component of good nutrition.[1] Dietary fiber is the nondigestible carbohydrate component of plant foods that include fruits, vegetables, legumes, and nuts as well as whole grains. Functional or supplemental fiber refers to nondigestible, nonnutrient-contributing carbohydrate supplements, which have been shown to have some beneficial physiologic effects in adults but which are not required if dietary sources of fiber are adequate. Functional/supplemental fiber is addressed in the dietary supplements section below. The 2002/2005 IOM DRI report for residents of the United States and Canada specifically addressed dietary fiber intake as important for laxation, attenuation of blood glucose levels, and normalization of serum cholesterol levels in adults.[81] The DRI report includes specific recommendations for fiber intake in children beginning at age 12 months, extrapolated from adult levels. The evidence review for these Guidelines identified no studies of dietary fiber intake in young children.

Childhood and Adolescence

Past concerns that extreme high-fiber diets could cause excessive loss of calories, protein, and fat in growing children have been addressed in a series of reports demonstrating that high-fiber diets are associated with a more nutrient-dense eating pattern, whereas low-fiber diets are associated with lower nutrient density, higher calorie intake, and increased obesity.[82] From this evidence review, the Bogalusa Heart Study, described previously in this section, examined age and secular trends between 1976 and 1988 in dietary fiber intake by youths ages 10–17 years. Total dietary fiber intake, assessed by dietary recalls, was low, with a mean intake of 12 grams per day (g/d) or 5 g/1,000 kcal, with no change over the period of observation. When children were stratified by quartiles of fiber intake, the percentages of calories from dietary total fat and saturated fat were lower, and the percentage of calories from carbohydrates was higher in children with high fiber intakes.[83] The USDA Agricultural Research Service's Continuing Survey of Food Intake by Individuals (CFSII) (1994–1996, 1998) reported only slightly higher mean dietary fiber intakes for youths: 15.2 g/d and 17.7 g/d for males ages 9–13 and 14–18 years, respectively, and 12.9 g/d and 12.8 g/d for females ages 9–13 and 14–18 years, respectively.[84] A more recent report from the NHANES III of more than 4,000 youths ages 8–18 years found that dietary fiber intake was inversely related to low-nutrient-density food consumption: high dietary fiber intake was consistently associated with higher nutrient intake. Conversely, intake of vitamins and minerals decreased as consumption of low-nutrient-density foods increased.7 In another analysis based on data from the CFSII, children ages 2–5 years with high fiber intake were found to consume diets with higher nutrient density, compared with those with low fiber intake.[85]

The Avon Longitudinal Study of Parents and Children found a relationship between lower dietary intake of fiber and higher fat mass as assessed by dual energy densitometry.[86] At age 9 years, a high-calorie, low-fiber, low-fat diet score was correlated with a significantly higher odds ratio for greater adiposity. Analysis of NHANES data from 1999 to 2000 used popcorn consumption as a proxy for fiber intake. Among individuals older than 4 years, popcorn consumers had a 25 percent higher intake of whole grains and a 25 percent higher daily fiber intake, compared with nonconsumers.[87]

In the DRI, the recommended average daily intake of total fiber for children and adolescents is based on data for adults reporting that a preponderance of the evidence indicated that 14 g/1,000 kcal reduced the risk of coronary heart disease.[81] Extrapolating from this, the DRI recommended total dietary fiber intakes for each age and gender group of children and adolescents as a product of the median energy intake and this recommended total fiber intake (14 g/1,000 kcal). Thus, for children ages 1–3 years and 4–8 years, a total fiber intake of 19 g/d and 25 g/d, respectively, is recommended. For males ages 9–13 years, a total fiber intake of 31 g/d is recommended, increasing to 38 g/d for males ages 14–30 years. For females ages 9–30 years, a total fiber intake of 25–26 g/d is recommended. The AAP recommends more moderate goals for fiber intake for children, age plus 5 g/d for young children, increasing to an adult goal of 22 g/d at around age 15 years.[87] Dietary fiber should come from foods such as fruits, vegetables, whole grains, nuts, and legumes rather than from fiber supplements.

SUMMARY OF THE EVIDENCE REVIEW FOR DIETARY FIBER INTAKE

• Higher dietary fiber intake is associated with high-nutrient-dense diets in children and adolescents.
• Existing recommendations for dietary fiber intake are extrapolated from those for adults.
• Dietary fiber should come from foods such as fruits, vegetables, whole grains, nuts, and legumes rather than from fiber supplements.

OVERVIEW OF THE EVIDENCE FOR MULTICOMPONENT DIETARY INTERVENTIONS

Many studies have evaluated dietary obesity prevention interventions that focus on lowering fat intake and increasing fruit and vegetable intake. Most of these were school based and were designed to both improve nutrition and increase physical activity; these studies are described in Section VI. Physical Activity and Section X. Overweight and Obesity in these Guidelines.[71],[72],[73],[74],[80],[88],[89],[90],[91],[92] The age groups addressed ranged from preschoolers to teenagers and study sizes from 213 to more than 5,000 subjects. Most studies were successful in improving dietary quality, with small decreases in fat intake, small increases in fruit and vegetable intake, and small increases in physical activity; however, measures of obesity rarely changed. None of these studies focused on infancy or early childhood.

Later Childhood and Adolescence

The CATCH study described earlier in this section was the largest, most comprehensive, multicomponent CV health intervention ever conducted for middle-school-aged children. The 3-year study achieved significant improvement in diet (lower dietary saturated fat intake at the lunchtime meal) and physical activity (more time spent in vigorous physical activity) among children in intervention schools, compared with those in control schools.53,54,55 These beneficial changes, however, were not associated with any difference in lipid levels, the study's primary outcome. The CATCH study was not focused on obesity, and the improvements noted in lunchtime dietary intake had no significant impact on BMI, further illustrating the potential value of more comprehensive, family-based recommendations.

SUMMARY OF THE EVIDENCE FOR MULTICOMPONENT DIETARY INTERVENTIONS

Many studies have evaluated dietary interventions designed to improve CV risk factors in children, with a focus on lowering fat intake, increasing fruit and vegetable intake, and increasing physical activity levels. Most were successful in improving dietary quality, with small decreases in fat intake, small increases in fruit and vegetable intake, and small increases in physical activity; however, measures of CV risk factors, including BMI, blood lipids, and BP, did not change.

OVERVIEW OF THE EVIDENCE FOR Dietary Patterns

Background

Nutrients and food groups are not consumed in isolation but in combinations as part of a dietary pattern, a concept that has been shown to be useful in studying nutrition. From epidemiologic studies in adults, diets that are higher in fruits and vegetables and low-fat dairy foods and lower in prepared foods, salt/sodium, and saturated fat have been shown to be associated with reduced CV risk, including lower BP, optimal lipid profile patterns, and lower prevalence of obesity. Dietary pattern studies in adults have tested a Mediterranean-type diet and the Dietary Approaches to Stop Hypertension (DASH) diet. The former is a broadly defined diet that is high in fruits and vegetables, bread, potatoes, beans, nuts, and seeds, with olive oil and in some reports a high-linolenic-acid margarine as the primary fat sources, and low to moderate amounts of fish and poultry and little red meat. In adults, the Mediterranean diet has been shown to significantly decrease recurrent cardiac events when initiated after first myocardial infarction in adults.[93]

In the DASH intervention feeding trial in adults, a diet rich in fruits and vegetables, low-fat or fat-free dairy products, whole grains, fish, poultry, beans, seeds, and nuts substantially reduced both systolic and diastolic BPs among adults with stage 1 hypertension or prehypertension.[94] The DASH diet is also lower in sweets and added sugars, fats, and red meat than the typical U.S. diet. Although originally tested for effects on BP, consumption of the DASH diet was also associated with reduced total and saturated fat intake and a significant decrease in LDL–C level.[95] Reduced dietary sodium in addition to following the DASH diet achieved the largest BP reductions. [96] In observational studies, sustained adherence to a DASH-style diet has been shown to be associated with lower risk of coronary heart disease and stroke in both men and women on long-term followup.[97],[98] When tested in free-living conditions in adults, the Premier Research Group reported that a behavioral intervention, including the DASH dietary pattern along with other lifestyle changes to reduce BP—reduced dietary sodium, increased physical activity, and weight loss—resulted in increased intake of dietary fiber, weight loss, and reductions in BP and lipid levels among adults with prehypertension or hypertension.[99]

Childhood and Adolescence

The evidence review for these Guidelines identified no dietary pattern studies in infants, but such studies in older children have been emerging. As described previously, the Young Finns study, begun when subjects were ages 3–18 years, evaluated two major dietary patterns: a "traditional" pattern characterized by high consumption of rye, potatoes, butter, sausages, milk, and coffee and a "health-conscious" diet with high consumption of vegetables, legumes and nuts, cheese and other dairy products, and, in older subjects, alcoholic beverages.[4] At 21-year followup, with subjects then ages 24–39 years, the traditional diet was significantly and independently associated with higher TC and LDL–C levels, apo B, and CRP values in both genders and higher systolic BP and insulin levels among women; the health-conscious diet was associated with better CV risk status but the latter correlation did not achieve statistical significance.[4]

From the NGHS, a dietary pattern characterized by high intake of fruits and vegetables, low fat dairy products, and grains and low intakes of sugar, fried foods, burgers, and pizza was associated with less adiposity over 10-year followup.[6] From the Framingham Children's Study, data from 95 children ages 3–6 years at enrollment indicate that, in adolescence, those with consistently higher intakes of fruits and vegetables and dairy products had significantly lower systolic BP levels.[100]

An RCT of the DASH diet in 57 adolescents with prehypertension or hypertension found at 3-month followup that the DASH diet group had a significantly greater decrease in systolic BP associated with higher intakes of fruits, low-fat dairy products, potassium, and magnesium and a greater decrease in dietary total fat intake than the usual-care group.[101] There were no adverse effects.

SUMMARY OF THE EVIDENCE REVIEW FOR DIETARY PATTERNS

• There is emerging evidence in children and adolescents that a composite healthy eating pattern is feasible and is associated with reduced CV risk factors.
• The DASH dietary pattern was tested in only one RCT in adolescents, but the benefit may be extrapolated from studies in adults.

OVERVIEW OF THE EVIDENCE FOR INTAKE OF DIETARY SUPPLEMENTS

This evidence review identified several small studies that reported short-term effects of dietary supplements in children, often in the absence of dietary assessment data. Regardless, the findings are summarized below by age group for the purpose of providing available evidence on these topics as identified by the evidence review.

Infancy/Early Childhood

Fish Oil

To investigate whether maternal intake of n-3 long-chain PUFA during lactation or current macronutrient intake affects children's BP, mothers with low fish intake were randomized to receive fish oil or olive oil daily during the first 4 months of lactation.[102] At age 2.5 years, no significant effect of maternal fish oil intake on children's BP was detected.

Plant Sterols

The effect of replacing dietary fat with plant stanol ester was investigated in a subset of 6-year-old children from the STRIP study.[103],[104] TC and LDL–C levels decreased 5.4 percent and 7.5 percent, respectively, among children who consumed a plant stanol-enriched margarine, compared with placebo. There were no effects on HDL–C or TG values. These changes were accompanied by decreased cholesterol absorption. Safety was judged to be excellent. The presence of the apoE–4 variant did not affect the response to plant stanols.[105] There was no significant difference in cholesterol absorption between boys and girls, but there was a greater decrease in the LDL–C level in boys (9.1 percent) than in girls (5.8 percent). The plant stanol results were confirmed in a short-term study of U.S. preschool children.[106]

Calcium

In a study designed to evaluate whether there is an association between calcium intake and change in body fat in children ages 3–5 years, calcium supplementation did not reduce gain in fat mass when baseline calcium intake was adequate.[107]

Adolescence

Fiber Supplements

Evidence of the use of fiber supplements in children is limited. In a small, 2-month RCT of 60 overweight adolescents, no significant difference was noted in weight change among subjects who received a fiber supplement (glucomannan), compared with placebo; dietary fiber intake was not assessed. At followup, the glucomannan group had lower HDL–C levels and higher very-low-density lipoprotein and TG levels, compared with lower TG and LDL–C values in the placebo group, suggesting no benefit and a potentially adverse impact of the supplement.[108]

SUMMARY Of THE EVIDENCE FOR INTAKE OF DIETARY SUPPLEMENTS

• Evidence on the health effects of dietary supplements in children is limited.
• Short-term replacement of dietary fat with plant stanol ester in healthy children ages 2–6 years was safe and was associated with significantly decreased TC and LDL–C levels.
• In children ages 3–5 years, supplemental calcium did not reduce gain in fat mass when baseline intake of calcium was adequate in one study.
• Maternal fish oil supplementation during lactation in healthy infants was not associated with any differences in children's BP at age 2.5 years in one study.
• Very limited evidence regarding use of fiber supplements in children suggests no benefit and possible adverse effects.

DEVELOPMENT OF FOOD PREFERENCES AND EATING BEHAVIORS

The development of food preferences in childhood is important because early preference patterns have a long-term influence on dietary intake later in life.[109],[110] Research in this area generally does not include RCTs that address CV risk factors, and no studies were identified in this evidence review; however, because this is such an important precept, a brief review of knowledge in the area is provided below.

Children's food preferences develop from a complex interplay of innate, familial, and environmental factors. There are innate preferences for sweet and salty tastes demonstrated from early infancy, and genetic propensities toward certain food groups have been shown in twin studies.[111],[112],[113] One of the most important influences in the development of taste preferences is experience. Maternal diets have been shown to be experienced by the fetus and the breast-fed baby, and specific exposures have been shown to affect an infant's subsequent dietary preferences.[114] Repeated exposures to selected foods, including fruits and vegetables, in early infancy have been shown to be associated with acceptance and then preference for these foods. Between 5 and 14 exposures to a new food are needed to see increased preference in both infants and children.[115],[116] Some research indicates that acceptance of textured foods is determined by earlier experience.[117] Early exposure to culture-specific foods and dietary styles gives rise to subsequent differences in food preferences, evident in the widely varying food preferences of children in different cultures.[118]

Parents powerfully shape children's early experiences with food, deciding what foods are made available and accessible and determining quantities provided and eating patterns. Parents and siblings model eating behavior from birth onward, and parent-child and sibling similarities in food preferences and eating behavior have been described.[119],[120],[121],[122] In addition, parental feeding style, principally feeding restriction, has been suggested to enhance the appeal of energy-dense, nutrient-poor foods, leading to overeating of these foods when access is gained and potentially contributing to excess weight gain.[123],[124] Finally, exposure to television and its associated child-oriented food commercials has been associated with food choices and higher food intake.[125],[126]

In pediatric care, questions about feeding and diet are a dominant source of concern, especially in infancy. This period of opportunity allows pediatric care providers to introduce heart healthy, calorie-balanced eating patterns at a time when food preferences, eating patterns, and lifestyle behaviors are being formed. Routine, regularly scheduled well-child visits to the pediatric care provider allow for reinforcement of healthy eating patterns throughout childhood and into young adulthood.

Healthy Eating Behaviors

Background

A number of eating behaviors in children and adolescents may promote or detract from a healthy nutrition pattern. These include eating breakfast (both frequency and quality); eating meals with family members ("family dinner"); eating away from home, especially fast food; eating school lunch; and both quality of snack foods and frequency of snacking. In addition, during early childhood, the quality of the mother-child feeding interaction may affect future weight gain. The search strategy for the Expert Panel recommendations prioritized results from RCTs, but none were identified among children or adolescents for these eating behaviors. Thus, the Expert Panel carefully reviewed existing observational studies and extracted potentially useful findings. Limitations inherent in all observational studies include the inability to adequately control for confounding factors. Also, most of these studies are cross-sectional, thereby making it unclear whether an "exposure" causes an "outcome." The lack of high-quality evidence for these eating behaviors automatically requires that any resulting recommendations result from Expert Panel consensus, which is ranked lower than evidence-based recommendations. None of the reported studies addresses infancy or early childhood.

Childhood and Adolescence

Although the evidence in children is limited, eating breakfast may reduce excessive weight gain, hypothetically by enhancing satiety through high-fiber cereal and/or whole-grain intake, reducing hunger and overeating at lunchtime, and/or providing other foods as part of breakfast such as fruits or products that may contribute further to improved nutrition density while aiding appetite regulation. In adults, a small number of prospective observational studies and short-term RCTs suggest that eating breakfast may reduce weight or prevent weight gain.[127],[128],[129] In children and adolescents, prospective studies are few, and trials are lacking.[130],[131] In the NGHS, 2,379 White and Black girls were followed annually from ages 9 to 19 years. Frequency of breakfast eating declined with age. The number of days per week when breakfast was eaten was associated with higher calcium and fiber intakes and was predictive of lower BMI, but the independent effect of eating breakfast on BMI was not significant after parental educational attainment, overall energy intake, and physical activity were included in the analysis.[132] Eating breakfast may have beneficial effects on cognition and school performance.[130]

In some observational, primarily cross-sectional, studies of children and adolescents, eating dinner or other meals with one's family has been associated with more healthful dietary patterns. The few existing prospective studies suggest that increased frequency of family meals is associated with less excessive weight gain, but confounding is possible, and mechanisms are unclear.[133],[134],[135] In preschool children, the association of healthful diets with the greater frequency of eating dinner as a family was counteracted by a higher frequency of watching television during the meal.[136]

The existing literature conflates eating away from home, eating certain foods or nutrients (such as fried foods) away from home, and fast-food consumption. Furthermore, the definition of "fast food" is not entirely clear. Nevertheless, several cross-sectional and a small number of prospective studies suggest that eating foods away from home, especially from fast-food establishments, may contribute to excessive weight gain.[137],[138],[139] In a study of preschool children, each 1 hour per day increase in television/video watching was significantly associated with greater consumption of fast food.[140]

A few, mostly cross-sectional, studies correlate the intake of snack foods, which tend to be relatively low in dietary quality, or snacking behavior with weight status. In the few longitudinal studies available, however, evidence argues against a substantial effect of snack food consumption.134,[141],[142],[143] In a study of children age 3 years, daily hours of television viewing were significantly associated with higher intakes of sugar-sweetened beverages, fast food, red and processed meats, total energy intake, and percentage of energy intake from trans fats and lower intakes of fruits and vegetables, calcium, and fiber.[144]

PUBLIC HEALTH APPROACHES

Clinicians should be cognizant of public health approaches, such as the WIC Program and other school- and community-based programs, that have the potential to significantly affect children's dietary intakes. For additional information about public health approaches, readers are encouraged to consult The Guide to Community Preventive Services, coordinated by the CDC, which provides evidence-based reviews of public health approaches(http://www.thecommunityguide.org/index.html). Because public health initiatives have the potential to affect the nutrition of children and adolescents, these approaches are an important avenue for advocacy by pediatric care providers. Key issues are summarized below.

Because many U.S. children obtain a large proportion of daily energy in the school setting, changing children's eating habits and dietary intakes at school could potentially influence both nutrition and weight status, as well as CV risk factors such as hypertension and dyslipidemia. Indeed, many of the intervention studies described in this section are school based. Although foods and beverages served as part of the USDA-reimbursable school breakfast or school lunch programs must meet dietary standards, foods sold in the cafeteria in competition with school lunch or school breakfast, sold in vending machines or school stores, or sold for fundraising events are not required to meet these standards. Some States and local school districts have been successful in changing the school food environment and, thus, children's eating habits.[145] Preliminary evidence suggests that improved nutrition standards, in conjunction with increases in physical activity and education, have increased awareness and may have begun to affect students' overweight rates.[146],[147] A multicomponent school nutrition policy initiative randomized 10 schools in which at least 50 percent of students were eligible for free or reduced-price meals. After 2 years, among 1,349 initially fourth- through sixth-graders, there was a 50 percent reduction in the incidence of overweight, with significantly fewer children in the intervention schools than in the control schools becoming overweight. The prevalence of overweight was also lower in the intervention schools. No differences, however, were observed in the incidence, prevalence, or remission of obesity at 2-year followup.[148] The findings suggest to the Expert Panel that public health approaches to overweight may have significant impact but that more intensive intervention may be needed for obese children. In addition, public health approaches can increase supportive environments for fruit and vegetable intake.[149],[150] (Story 2008; CDC Guide to F&V 2010). Because public health initiatives have the potential to affect the nutrition of children and adolescents, this is an important avenue for advocacy by pediatric care providers.

CONCLUSIONS AND GRADING OF THE EVIDENCE REVIEW FOR DIET AND NUTRITION IN CARDIOVASCULAR RISK REDUCTION

The Expert Panel concluded that there is strong and consistent evidence that good nutrition beginning at birth has profound health benefits, with the potential to decrease future risk for CVD. The Expert Panel accepts the 2010 DGA as containing appropriate recommendations for diet and nutrition in children age 2 years and older. The recommendations in these Guidelines are intended for pediatric care providers to use with their patients to address CV risk reduction. The conclusions of the Expert Panel's review of the entire body of evidence in a specific nutrition area with grades are summarized below. The age- and evidence-based recommendations of the Expert Panel follow in Table 5–2. Where evidence is inadequate yet nutrition guidance is needed, recommendations for pediatric care providers are based on a consensus of the Expert Panel (Grade D).

In accordance with the Surgeon General's Office, the WHO, the AAP, and the AAFP, exclusive breast-feeding is recommended for the first 6 months of life. Continued breast-feeding is recommended to at least age 12 months, with the addition of complementary foods. If breast-feeding per se is not possible, feeding human milk by bottle is second best, with formula-feeding as the third choice.

• Long-term followup studies consistently demonstrate that infants who were breast-fed have sustained CV health benefits, including lower cholesterol levels, reduced prevalence of T2DM, lower measures of subclinical disease (e.g., cIMT), and possibly lower BMI in adulthood (Grade B).
• Ongoing nutrition counseling has been effective in helping children and families to adopt and sustain recommended diets for both nutrient adequacy and reducing CV risk (Grade A).
• Within appropriate age- and gender-based requirements for growth and nutrition, in normal children and in children with hypercholesterolemia, intake of total fat can be safely limited to 30 percent of total calories, saturated fat intake limited to 7–10 percent of calories, and dietary cholesterol limited to 300 mg/d. Under the guidance of qualified nutritionists, this dietary composition has been shown to result in lower TC and LDL–C levels, less obesity, and less insulin resistance (Grade A). Under similar conditions and with ongoing followup, these levels of fat intake may have similar effects starting in infancy (Grade B). Fats are important to infant diets due to their role in brain and cognitive development. Fat intake in infants younger than 12 months of age should not be restricted without medical indication.
• The remaining 20 percent of fat intake should comprise a combination of monosaturated and polyunsaturated fats (Grade D). Intake of trans fats should be limited as much as possible (Grade D).
• The current NCEP guidelines recommend that adults consume 25–35 percent of calories from fat. The 2010 DGA includes the IOM recommendation for 30–40 percent of calories from fat for ages 1–3 years, 25–35 percent of calories from fat for ages 4–18 years, and 20–35 percent of calories from fat for adults. For growing children, milk provides essential nutrients, including protein, calcium, magnesium, and vitamin D, that are not readily available elsewhere in the diet. Consumption of fat-free milk in childhood starting at age 2 years and through adolescence optimizes these benefits, without compromising nutrient quality while avoiding excess saturated fat and calorie intake (Grade A). Between ages 1 and 2 years, as children transition from breast milk or formula, milk reduced in fat (ranging from 2 percent milk to fat-free milk) can be used based on the child's growth, appetite, intake of other nutrient-dense foods, intake of other sources of fat, and risk for obesity and CVD. Milk with reduced fat should be used only in the context of an overall diet that supplies 30 percent of calories from fat. Dietary intervention should be tailored to each specific child's needs.
• Optimal intakes of total protein and total carbohydrates in children were not specifically addressed, but with a recommended total fat intake of 30 percent of energy, the Expert Panel recommends that the remaining 70 percent of calories include 15–20 percent from protein and 50–55 percent from carbohydrate sources (no grade). These recommended ranges fall within the acceptable macronutrient distribution range specified by the 2010 DGA: 10–30 percent of calories from protein and 45–65 percent of calories from carbohydrates for children ages 4–18 years.
• Sodium intake was not addressed by the evidence review for this section on nutrition and diet. From the evidence review for Section VIII. High Blood Pressure, lower sodium intake is associated with lower systolic and diastolic BPs in infants, children, and adolescents.
• Plant-based foods are important low-calorie sources of nutrients, including vitamins and fiber, in the diets of children; increasing access to fruits and vegetables has been shown to increase their intake (Grade A). However, increasing fruit and vegetable intake is an ongoing challenge.
• Reduced intake of sugar-sweetened beverages is associated with decreased obesity measures (Grade B). Specific information about fruit juice intake is too limited for an evidence-based recommendation. Recommendations for intake of naturally sweetened fruit juice (without added sugar) in infants are a consensus of the Expert Panel (Grade D) and are in agreement with those of the AAP.
• Per the 2010 DGA, energy intake should not exceed energy needed for adequate growth and physical activity. Calorie intake needs to match growth demands and physical activity needs. Estimated calorie requirements by gender and age group at three levels of physical activity from the 2010 DGA are shown in Table 5–1. For children of normal weight whose activity is minimal, most calories are needed to meet nutritional requirements, leaving only about 10 percent of calorie intake from discretionary sources (e.g., foods with added fat and sugar) (Grade D).
• Dietary fiber intake is inversely associated with energy density and with increased levels of body fat and is positively associated with nutrient density (Grade B). A daily total dietary fiber intake from food sources of at least age plus 5 g for young children up to 14 g/1,000 kcal for older children and adolescents is recommended (Grade D).
• The Expert Panel supports the recommendation of the AAP for vitamin D supplementation with 400 IU/d for all infants and 600 IU/day for children over 1 years old. No other vitamin, mineral, or dietary supplements are recommended (Grade D).
• Use of dietary patterns modeled on those shown to be beneficial in adults (such as the DASH pattern) is a promising approach to improving nutrition and decreasing CV risk (Grade B).
• All dietary recommendations must be interpreted by the pediatric care provider for each child and family to address individual diet and growth patterns and patient sensitivities such as lactose intolerance and food allergies (Grade D).

As stated above, these dietary recommendations to promote CV health in children under the care of pediatric care providers are based on the results of the evidence review and the population recommendations are consistent with the DGA. Graded, age-specific recommendations for pediatric care providers to use in reducing CV risk in their patients are summarized in Table 5–2 (CHILD 1) and are designed to support implementation of the findings of the evidence review. CHILD 1 is the first stage in dietary change for children with identified dyslipidemia, overweight and obesity, risk factor clustering, and high-risk medical conditions who may ultimately require more intensive dietary change. More intensive recommendations to be implemented if needed for children with these conditions appear in the designated sections of these Guidelines. CHILD 1 is also the recommended diet for children with a positive family history of early CV disease, dyslipidemia, obesity, primary hypertension, diabetes, or children exposure to smoking in the home. Any dietary modification must provide nutrients and calories needed for optimal growth and development. Likewise, recommended intakes are adequately met by a DASH-style eating plan, which emphasizes fat-free/low-fat milk and dairy products and increased intake of fruits and vegetables. This pattern has been modified for use in children age 4 years and older based on daily energy needs and is shown in Table 5–3 as one example of a heart healthy eating plan using the CHILD 1 recommendations.

Table 5–2. Evidence-Based Recommendations for Patients of Pediatric Care Providers: Cardiovascular Health Integrated Lifestyle Diet (CHILD 1)

CHILD 1 is the recommended first step diet for all children and adolescents at elevated cardiovascular risk.

Grades reflect the findings of the evidence review.
Recommendation levels the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations; they are not graded.

Birth - 6 months	Infants should be exclusively breast fed (no supplemental formula or other foods) until age 6 months.a	Grade B Strongly recommend
6 - 12 months	Continue breast-feedinga until at least age 12 months while gradually adding solids; transition to iron-fortified formula until 12 months if reducing breastfeeding	Grade B Strongly recommend
6 - 12 m (cont.d)	Fat intake in infants less than 12 months of age should not be restricted without medical indication.	Grade D Recommend
6 - 12 months (cont.d)	Limit other drinks to 100% fruit juice < 4 oz/d; No sweetened beverages; encourage water.	Grade D Recommend
12 - 24 months	Transition to reduced-fatb (2% to fat-free) unflavored cow's milkc (see Supportive Actions bullet 1)	Grade B Recommend
12 - 24 months (cont.d)	Limit/avoid sugar-sweetened beverage intake; encourage water	Grade B Strongly recommend
12 - 24 months (cont.d)	Transition to table food with:
12 - 24 months (cont.d)	Total fat 30% of daily kcal/EERd	Grade B Recommend
12 - 24 months (cont.d)	Saturated fat 8-10% of daily kcal/EER	Grade B Recommend
12 - 24 months (cont.d)	Avoid trans fat as much as possible	Grade D Strongly recommend
12 - 24 months (cont.d)	Monounsaturated and polyunsaturated fat up to 20% of daily kcal/EER	Grade D Recommend
12 - 24 months (cont.d)	Cholesterol < 300 mg/d	Grade B Strongly recommend
12 - 24 months (cont.d)	Supportive actions: The fat content of cow's milk to introduce at age 12-24 months should be decided together by parents and health care providers based on the child's growth, appetite, intake of other nutrient-dense foods, intake of other sources of fat, and potential risk for obesity and CVD. Limit 100 percent fruit juice (from a cup) no more than 4 oz/d Limit sodium intake Consider DASH-type diet rich in fruits, vegetables, whole grains, low-fat/fat-free milk and milk products; lower in sugar (Table 5-3)
2 -10 years	Primary beverage: Fat-free unflavored milk	Grade A Strongly recommend
2 -10 years (cont.d)	Limit/avoid sugar sweetened beverages; encourage water.	Grade B Recommend
2 -10 years (cont.d)	Fat content:
2 -10 years (cont.d)	Total fat 25-30% of daily kcal/EERd	Grade A Strongly recommend
2 -10 years (cont.d)	Saturated fat 8-10% of daily kcal/ EER	Grade A Strongly recommend
2 -10 years (cont.d)	Avoid trans fats as much as possible	Grade D Recommend
2 -10 years (cont.d)	Monounsaturated and polyunsaturated fat up to 20% of daily kcal/EER	Grade D Recommend
2 -10 years (cont.d)	Cholesterol < 300 mg/d	Grade A Strongly recommend
2 -10 years (cont.d)	Encourage high dietary fiber intake from foodse	Grade B Recommend
2 -10 years (cont.d)	Supportive actions: Teach portions based on EER for age/sex/age(Table 5-1) Encourage moderately increased energy intake during periods of rapid growth and/or regular moderate-to-vigorous physical activity Encourage dietary fiber from foods: Age plus 5 g/de Limit naturally sweetened juice (no added sugar) to 4 oz/d Limit sodium intake Support DASH-style eating plan as outlined below (Table 5-3)
11–21 years	Primary beverage: Fat-free unflavored milk	Grade A Strongly recommend
11–21 years (cont.d)	Limit/ avoid sugar sweetened beverages; encourage water.	Grade B Recommend
11–21 years (cont.d)	Fat content:
11–21 years (cont.d)	Total fat 25-30% of daily kcal/EERd	Grade A Strongly recommend
11–21 years (cont.d)	Saturated fat 8-10% of daily kcal/ EER	Grade A Strongly recommend
11–21 years (cont.d)	Avoid trans fat as much as possible	Grade D Recommend
11–21 years (cont.d)	Monounsaturated and polyunsaturated fat up to 20% Grade D of daily kcal/ EER	Grade D Recommend
11–21 years (cont.d)	Cholesterol < 300 mg/d	Grade A Strongly recommend
11–21 years (cont.d)	Encourage high dietary fiber intake from foodse	Grade B Recommend
11–21 years (cont.d)	Supportive actions: Teach portions based on EER for age/sex/activity (Table 5-2) Encourage moderately increased energy intake during periods of rapid growth and/or regular moderate to vigorous physical activity Advocate dietary fiber: Goal of 14 g/1,000 kcal e Limit naturally sweetened juice (no added sugar) to 4-6 oz/d Limit sodium intake Encourage healthy eating habits: Breakfast every day, eating meals as a family, limiting fast food meals. Support DASH-style eating plan as outlined below (Table 5-3)

a Infants that cannot be fed directly at the breast should be fed expressed milk. Infants for whom expressed milk is not available should be fed iron-fortified infant formula.
b Toddlers 12-24 m of age with a family history of obesity, heart disease, or high cholesterol, should discuss transition to reduced-fat milk with pediatric care provider after 12 months of age.
c Continued breast-feeding is still appropriate and nutritionally superior to cow's milk. Milk reduced in fat should be used only in the context of an overall diet that supplies 30% of calories from fat.
d EER = Estimated Energy Requirements/d for age/gender (Table 5-1)
e Naturally fiber-rich foods are recommended (fruits, vegetables, whole grains); fiber supplements are not advised. Limit refined carbohydrates (sugars, white rice, and white bread)

Table 5-3. DASH-Style Eating Plan: Servings per Day by Food Group and Total Energy Intake

(Table 5-1 provides Estimated Energy Requirements (EER) by age, gender, and activity level. EER and discretionary calorie allowance by age and level of activity for boys and girls are shown in Figures 5-1 and 5-2.)

Food Group	1,200 Calories	1,400 Calories	1,600 Calories	1,800 Calories	2,000 Calories	2,600 Calories	Serving Sizes	Examples and Notes	Significance of Each Food Group to the DASH Eating Plan
Grains*	4-5	5-6	6	6	6–8	10-11	1 slice bread 1 oz dry cereal** ½ cup cooked rice, pasta, or cereal**	Whole wheat bread and rolls, whole wheat pasta, English muffin, pita bread, bagel, cereals, grits, oatmeal, brown rice, unsalted pretzels and popcorn	Major sources of energy and fiber
Vegetables	3-4	3-4	3-4	4-5	4–5	5-6	1 cup raw leafy vegetable ½ cup cut-up raw or cooked vegetable ½ cup vegetable juice	Broccoli, carrots, collards, green beans, green peas, kale, lima beans, potatoes, spinach, squash, sweet potatoes, tomatoes	Rich sources of potassium, magnesium, and fiber
Fruits	3-4	4	4	4-5	4–5	5-6	1 medium fruit ¼ cup dried fruit ½ cup fresh, frozen, or canned fruit ½ cup fruit juice	Apples, apricots, bananas, dates, grapes, oranges, grapefruit, grapefruit juice, mangoes, melons, peaches, pineapples, raisins, strawberries, tangerines	Important sources of potassium, magnesium, and fiber
Fat-free or low-fat milk and milk products	2-3	2-3	2-3	2-3	2–3	3	1 cup milk or yogurt 1½ oz cheese	Fat-free milk or buttermilk, fat-free, low-fat, or reduced-fat cheese, fat-free/low-fat regular or frozen yogurt	Major sources of calcium and protein
Lean meats, poultry, and fish	3 or less	3-4 or less	3-4 or less	6 or less	6 or less	6 or less	1 oz cooked meats, poultry, or fish 1 egg–	Select only lean; trim away visible fats; broil, roast, or poach; remove skin from poultry	Rich sources of protein and magnesium
Nuts, seeds, and legumes	3 per week	3 per week	3-4 per week	4 per week	4–5 per week	1	1/3 cup or 1½ oz nuts 2 Tbsp peanut butter 2 Tbsp or ½ oz seeds ½ cup cooked legumes (dry beans and peas)	Almonds, filberts, mixed nuts, peanuts, walnuts, sunflower seeds, peanut butter, kidney beans, lentils, split peas	Rich sources of energy, magnesium, protein, and fiber
Fats and oils–	1	1	2	2-3	2-3	3	1 tsp soft margarine 1 tsp vegetable oil 1 Tbsp mayonnaise 2 Tbsp salad dressing	Soft margarine, vegetable oil (such as canola, corn, olive, or safflower), low-fat mayonnaise, light salad dressing	The DASH study had 27 percent of calories as fat, including fat in or added to foods
Sweets and added sugars	3 or less per week	3 or less per week	3 or less per week	5 or less per week	5 or less per week	– 2	1 Tbsp sugar 1 Tbsp jelly or jam ½ cup sorbet, gelatin 1 cup lemonade	Fruit-flavored gelatin, fruit punch, hard candy, jelly, maple syrup, sorbet and ices, sugar	Sweets should be low in fat

The Food and Drug Administration (FDA) and the Environmental Protection Agency are advising women of childbearing age who may become pregnant, pregnant women, nursing mothers, and young children to avoid some types of fish and shellfish and eat fish and shellfish that are low in mercury. For more information, call the FDA's food information line toll free at 1-888-SAFEFOOD or visit http://www.cfsan.fda.gov/~dms/admehg3.html.

* Whole grains are recommended for most grain servings as a good source of fiber and nutrients.

** Serving sizes vary between 1/2 cup and 1-1/4 cups, depending on cereal type. Check product's Nutrition Facts label.

– Because eggs are high in cholesterol, limit egg yolk intake to no more than four per week; two egg whites have the same protein content as 1 oz meat.

– Fat content changes serving amount for fats and oils. For example, 1 Tbsp regular salad dressing = 1 serving; 1 Tbsp low-fat dressing = 1/2 serving; 1 Tbsp fat-free dressing = zero servings. Abbreviations: oz = ounce; Tbsp = tablespoon; tsp = teaspoon.

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[104] Tammi A, Ronnemaa T, Valsta L, Seppanen R, Rask-Nissila L, Miettinen TA, Gylling H, Viikari J, Anttolainen M, Simell O. Dietary plant sterols alter the serum plant sterol concentration but not the cholesterol precursor sterol concentrations in young children (the STRIP study). Special Turku Coronary Risk Factor Intervention Project. J Nutr 2001;131:1942-1945. (PM:11435511)

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BACKGROUND

Physical activity is any bodily movement produced by contraction of skeletal muscle that increases energy expenditure above a basal level. Physical activity can be focused on strengthening muscles, bones, and/or joints, but because these Guidelines address CV health, the evidence review concentrated on aerobic activity. There is strong evidence for the beneficial effects of physical activity on the overall health of children and adolescents across a broad array of domains.[1] In the United States, 16.6 percent of total deaths have been attributed to the combination of a sedentary lifestyle and dietary factors.[2] The evidence review concentrated on the effects of physical activity on CV health where physical inactivity has been identified as an independent risk factor for coronary heart disease.[3],[4] Research on physical activity in children has explored three interdependent but distinct constructs: fitness, physical activity, and sedentary behavior. A comprehensive review of the independent role of each of these in CV health is beyond the scope of these Guidelines; specifically, the Expert Panel reviewed studies on physical activity and sedentary behavior but did not address research on fitness.

OVERVIEW OF THE EVIDENCE OF THE ASSOCIATION BETWEEN PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR AND CARDIOVASCULAR RISK FACTORS

Over the past several decades, there has been a decrease in the amount of time that children spend being physically active and a steady increase in the amount of time spent in sedentary activities. A recent systematic review indicates that contemporary youths watch 1.8–2.8 hours/day (h/d) of television, with 28 percent watching more than 4 h/d; boys average 60 minutes/day (min/d) playing video games compared with 23 min/d for girls; computer use increases with increasing age but averages 30 min/d across childhood. In this report, total screen time averaged 2.7–4.3 h/d.[5] From the current evidence review, multiple observational studies in children ages 4–18 years and young adults ages 19–21 years strongly link increased time spent in sedentary activities with reduced overall physical activity levels; disadvantageous lipid profile changes; higher systolic blood pressure (BP); increased levels of obesity and all of the obesity-related CV risk factors, including hypertension, insulin resistance, and type 2 diabetes mellitus, especially among male children and adolescents. Participation in routine physical activity, including team sports, is inversely associated with these same outcomes.[1],[6],[7],[8],[9],[10],[11],[12]

Longitudinal studies show that the most optimal CV risk profiles are seen in individuals who are consistently physically active.[6],[8],[13] In diverse populations, the tracking of both sedentary and active behaviors is moderately strong from childhood to young adulthood, with the most consistent tracking seen for higher levels of physical activity at ages 9–18 years, predicting higher levels of adult physical activity.[6],[9],[14],[15] Finally, health-enhancing and/or -compromising physical activity patterns, dietary choices, and smoking behaviors have consistently been shown to cluster together.[9],[10]

OVERVIEW OF THE EVIDENCE FOR INTERVENTIONS TO INCREASE PHYSICAL ACTIVITY AND/OR DECREASE SEDENTARY TIME

The Guidelines evidence review identified 6 systematic reviews, 3 meta-analyses, and 46 RCTs addressing physical activity and/or sedentary behavior. Many studies simultaneously addressed increasing physical activity, decreasing sedentary behavior, and improving nutrition and measured fitness, obesity, lipid profile, BP, and/or insulin resistance as outcomes. More than a third of the identified RCTs were conducted in school settings and were designed as multicomponent interventions addressing combinations of the physical activity regimen, time spent in physical activity, environmental factors, and/or training of supervisors. Of the school-based trials, most were successful in increasing time spent being physically active and/or in decreasing sedentary time during the intervention in either or both sexes.[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28] Late followup after completion of an intervention is unusual, but when available, has not shown sustained physical activity change.[29] School-based physical activity interventions have been shown to lower BP in children and adolescents[19] and to decrease total cholesterol (TC).[17],[27],[28] Such interventions occasionally have resulted in decreased measures of overweight and obesity,[21],[30] but more often, school-based physical activity trials that have been designed to address measures of obesity have been unsuccessful.[28],[31],[32]

Almost half of the physical activity RCTs have been relatively small studies in clinical research laboratory settings. Most were successful in increasing time spent being physically active and/or decreasing sedentary time during the intervention.[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47] Several RCTs demonstrated that making a favored sedentary activity contingent on increased physical activity was successful in increasing time spent being physically active and decreasing sedentary time,[33],[37],[40],[41],[42],[48] and one study applied this concept successfully in an Internet-based physical activity-contingent intervention.[49] Three of four studies set in daycare or community settings were successful in increasing physical activity and/or decreasing sedentary screen time.[50],[51],[52] Finally, one successful study was implemented through a primary care practitioner's office that used computerized telephone and mailed reminders.[53] Multiple physiologic outcomes were evaluated in these studies, many of which addressed prevention or treatment of obesity. The preponderance of the evidence indicates that increasing physical activity and decreasing sedentary time are associated with lower systolic and diastolic BP,[34],[38],[54],[55],[56] decreased measures of body fat,[21],[33],[34],[35],[36],[37],[42],[45],[46],[54],[55],[57] decreased body mass index (BMI) or percentage of overweight,[34],[35],[36],[39],[55],[56] improved fitness measures,[21],[35],[38],[39],[43],[44],[45],[47],[54],[55],[56],[58] lower TC,[36],[55] lower low-density lipoprotein cholesterol (LDL–C),[34] lower triglycerides (TG),[21],[34],[38],[55] higher high-density lipoprotein cholesterol (HDL–C),[44],[55] and decreased insulin resistance.[21],[34],[46],[54],[57] Several studies in obese children have evaluated vascular function and have shown significant increases in flow-mediated dilation and reduced carotid intima-media thickness after exercise interventions.[34],[43],[44],[47],[56],[58] No study reported any adverse CV outcome as a consequence of a physical activity intervention.

CONCLUSIONS AND GRADING OF THE EVIDENCE REVIEW FOR PHYSICAL ACTIVITY

Overall, the Expert Panel concluded that the evidence strongly supports the role of activity in optimizing CV health in children and adolescents.

• There is reasonably good evidence that physical activity patterns established in childhood are carried forward into adulthood (Grade C).
• There is strong evidence that increases in moderate to vigorous physical activity are associated with lower systolic and diastolic BPs, decreased measures of body fat, decreased BMI, improved fitness measures, lower TC, lower LDL–C, lower TG, higher HDL–C, and decreased insulin resistance in childhood and adolescence (Grade A).
• There is limited but strong and consistent evidence that physical exercise interventions improve subclinical measures of atherosclerosis (Grade B).
• Physical activity patterns, dietary choices, and smoking behaviors cluster together (Grade C).
• There is no evidence of harm associated with increased physical activity or limitation of sedentary activity in normal children (Grade A).
• There is strong evidence that physical activity should be promoted in schools (Grade A).

There is less specific information on the type and amount of physical exercise required for optimal CV health. Reported physical activity interventions from this evidence review ranged from 20 to 60 minutes, 2–5 times/week in children ages 3–17 years and included a wide variety of dynamic and isometric exercises. Extrapolating from these interventions which occurred in supervised settings to the real world of childhood and adolescence, the Expert Panel recommended at least 1 hour of moderate to vigorous physical activity every day of the week, with vigorous, intense physical activity on at least 3 of these days in agreement with the 2008 Physical Activity Guidelines for Americans from the U.S. Department of Health and Human Services. In working with children and families, the Expert Panel suggested that moderate to vigorous activity could be compared with walking briskly or jogging and that vigorous physical activity could be compared with running, playing singles tennis, or playing soccer. Similarly, reducing sedentary time is convincingly associated with a favorable CV profile, and the Expert Panel agreed with the recommendation from the American Academy of Pediatrics for limiting leisure screen time to no more than 1 to 2 hours of quality programming per day. The 2008 Physical Activity Guidelines for Americans was published after the evidence review for these Guidelines was completed and, therefore, cannot be formally included. However, the 2008 Physical Activity Guidelines is recommended to pediatric care providers as an extensive resource on physical activity recommendations for their patients and is available at http://ww.health.gov/paguidelines.

Pediatric care providers represent an important source of accurate information about physical activity recommendations for children and adolescents. However, information about how to optimize the adoption of these recommendations in a practice setting remains limited. The supportive actions included in Table 6–1 represent expert consensus suggestions from the Expert Panel to support implementation of the recommendations.

Table 6–1. Evidence-Based Physical Activity Recommendations for Cardiovascular Health

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations.

0-12 months	Parents should create an environment promoting and modeling physical activity and limiting sedentary time	Grade D Recommend
0-12 months (cont.d)	Supportive actions: Discourage TV viewing altogether.
1- 4 years	Unlimited active playtime in safe, supportive environment	Grade D Recommend
1- 4 years (cont.d)	Limit sedentary time, especially TV/ video	Grade D Recommend
1- 4 years (cont.d)	Supportive actions: For children < 2 years, discourage television viewing altogether. Limit total media time to no more than 1-2 hours of quality programming per day No TV in child's bedroom Encourage family activity at least once a week Counsel routine activity for parents as role models for children
5 - 10 years	Moderate to vigorous physical activity* every day	Grade A Strongly Recommend
5 - 10 years (cont.d)	Limit daily leisure screen time (TV/video/computer)	Grade B Strongly Recommend
5 - 10 years (cont.d)	Supportive actions: Prescribe moderate to vigorous activity* 1 h/d with vigorous intensity physical activity** on 3 d/wk Limit total media time to no more than 1-2 hours of quality programming per day No TV in child's bedroom Take activity and screen time history from child once a year Match physical activity recommendations with energy intake Recommend appropriate safety equipment relative to each sport Support recommendations for daily physical education in schools
11 -17 years	Moderate to vigorous physical activity* every day	Grade A Strongly Recommend
11 -17 years (cont.d)	Limit leisure time TV/video/computer use	Grade B Strongly Recommend
11 -17 years (cont.d)	Supportive actions: Encourage adolescents to aim for 1 h/d of moderate to vigorous daily activity*, with vigorous intense physical activity** on 3 d/wk Encourage no TV in bedroom Limit total media time to no more than 1-2 hours of quality programming per day Match activity recommendations with energy intake Take activity and screen time history from adolescent at health supervision visits Encourage involvement in year-round, physical activities Support continued family activity once a week and/or family support of adolescent's physical activity program Endorse appropriate safety equipment relative to each sport.
18 - 21 years	Moderate to vigorous physical activity* every day.	Grade A Strongly Recommend
18 -21 years (cont.d)	Limit leisure time TV/video/computer.	Grade B Strongly Recommend
18 -21 years (cont.d)	Supportive actions: Support goal of 1 h/d of moderate to vigorous daily activity with vigorous intense physical activity on 3 d/wk Recommend that combined leisure screen time not exceed 2 h/d Take activity and screen time history at health supervision visits Endorse involvement in year-round, lifelong physical activities

*Examples of moderate to vigorous physical activities are are walking briskly or jogging.
**Examples of vigorous physical activities are running, playing singles tennis or soccer.

---

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[20] Simon C, Wagner A, Platat C, Arveiler D, Schweitzer B, Schlienger JL, Triby E. ICAPS: a multilevel program to improve physical activity in adolescents. Diabetes Metab 2006;32(1):41-49. (PM:16523185)

[21] Robinson TN. Reducing children's television viewing to prevent obesity: a randomized controlled trial. JAMA 1999;282(16):1561-1567. (PM:10546696)

[22] McKenzie TL, Nader PR, Strikmiller PK, Yang M, Stone EJ, Perry CL, Taylor WC, Epping JN, Feldman HA, Luepker RV, Kelder SH. School physical education: effect of the Child and Adolescent Trial for Cardiovascular Health. Prev Med 1996;25(4):423-431. (PM:8818066)

[23] Salmon J, Ball K, Crawford D, Booth M, Telford A, Hume C, Jolley D, Worsley A. Reducing sedentary behaviour and increasing physical activity among 10-year-old children: overview and process evaluation of the 'Switch-Play' intervention. Health Promot Int 2005;20(1):7-17. (PM:15668218)

[24] Prochaska JJ, Sallis JF. A randomized controlled trial of single versus multiple health behavior change: promoting physical activity and nutrition among adolescents. Health Psychol 2004;23(3):314-318. (PM:15099173)

[25] Pate RR, Ward DS, Saunders RP, Felton G, Dishman RK, Dowda M. Promotion of physical activity among high-school girls: a randomized controlled trial. Am J Public Health 2005;95(9):1582-1587. (PM:16118370)

[26] Hopper CA, Munoz KD, Gruber MB, Nguyen KP. The effects of a family fitness program on the physical activity and nutrition behaviors of third-grade children. Res Q Exerc Sport 2005;76(2):130-139. (PM:16128481)

[27] Harrell JS, McMurray RG, Bangdiwala SI, Frauman AC, Gansky SA, Bradley CB. Effects of a school-based intervention to reduce cardiovascular disease risk factors in elementary-school children: the Cardiovascular Health in Children (CHIC) study. J Pediatr 1996;128(6):797-805. (PM:8648539)

[28] Fardy PS, White RE, Haltiwanger-Schmitz K, Magel JR, McDermott KJ, Clark LT, Hurster MM. Coronary disease risk factor reduction and behavior modification in minority adolescents: the PATH program. J Adolesc Health 1996;18(4):247-53. (PM:8860788)

[29] Kelder SH, Mitchell PD, McKenzie TL, Derby C, Strikmiller PK, Luepker RV, Stone EJ. Long-term implementation of the CATCH physical education program. Health Educ Behav 2003;30(4):463-475. (PM:12929897)

[30] Eliakim A, Makowski GS, Brasel JA, Cooper DM. Adiposity, lipid levels, and brief endurance training in nonobese adolescent males. Int J Sports Med 2000;21(5):332-337. (PM:10950441)

[31] Sallis JF, McKenzie TL, Alcaraz JE, Kolody B, Hovell MF, Nader PR. Project SPARK. Effects of physical education on adiposity in children. Ann N Y Acad Sci 1993;699:127-36. (PM:8267303)

[32] Reilly JJ, Kelly L, Montgomery C, Williamson A, Fisher A, McColl JH, Lo Conte R, Paton JY, Grant S. Physical activity to prevent obesity in young children: cluster randomised controlled trial. BMJ 2006;333(7577):1041. (PM:17028105)

[33] Roemmich JN, Gurgol CM, Epstein LH. Open-loop feedback increases physical activity of youth. Med Sci Sports Exerc 2004;36(4):668-673. (PM:15064595)

[34] Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast W. Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program. J Am Coll Cardiol 2006;48(9):1865-1870. (PM:17084264)

[35] Epstein LH, Valoski AM, Vara LS, McCurley J, Wisniewski L, Kalarchian MA, Klein KR, Shrager LR. Effects of decreasing sedentary behavior and increasing activity on weight change in obese children. Health Psychol 1995;14(2):109-115. (PM:7789345)

[36] Nemet D, Barkan S, Epstein Y, Friedland O, Kowen G, Eliakim A. Short- and long-term beneficial effects of a combined dietary-behavioral-physical activity intervention for the treatment of childhood obesity. Pediatrics 2005;115(4):e443-e449. (PM:15805347)

[37] Faith MS, Berman N, Heo M, Pietrobelli A, Gallagher D, Epstein LH, Eiden MT, Allison DB. Effects of contingent television on physical activity and television viewing in obese children. Pediatrics 2001;107(5):1043-1048. (PM:11331684)

[38] Kang HS, Gutin B, Barbeau P, Owens S, Lemmon CR, Allison J, Litaker MS, Le NA. Physical training improves insulin resistance syndrome markers in obese adolescents. Med Sci Sports Exerc 2002;34(12):1920-1927. (PM:12471297)

[39] Epstein LH, Paluch RA, Gordy CC, Dorn J. Decreasing sedentary behaviors in treating pediatric obesity. Arch Pediatr Adolesc Med 2000;154(3):220-226. (PM:10710017)

[40] Saelens BE, Epstein LH. Behavioral engineering of activity choice in obese children. Int J Obes Relat Metab Disord 1998;22(3):275-277. (PM:9539197)

[41] Goldfield GS, Kalakanis LE, Ernst MM, Epstein LH. Open-loop feedback to increase physical activity in obese children. Int J Obes Relat Metab Disord 2000;24(7):888-892. (PM:10918536)

[42] Goldfield GS, Mallory R, Parker T, Cunningham T, Legg C, Lumb A, Parker K, Prud'homme D, Gaboury I, Adamo KB. Effects of open-loop feedback on physical activity and television viewing in overweight and obese children: a randomized, controlled trial. Pediatrics 2006;118(1):e157-e166. (PM:16818530)

[43] Watts K, Beye P, Siafarikas A, O'Driscoll G, Jones TW, Davis EA, Green DJ. Effects of exercise training on vascular function in obese children. J Pediatr 2004;144(5):620-625. (PM:15126996)

[44] Kelly AS, Wetzsteon RJ, Kaiser DR, Steinberger J, Bank AJ, Dengel DR. Inflammation, insulin, and endothelial function in overweight children and adolescents: the role of exercise. J Pediatr 2004;145(6):731-736. (PM:15580192)

[45] Epstein LH, Wing RR, Penner BC, Kress MJ. Effect of diet and controlled exercise on weight loss in obese children. J Pediatr 1985;107(3):358-361. (PM:4032130)

[46] Shaibi GQ, Cruz ML, Ball GD, Weigensberg MJ, Salem GJ, Crespo NC, Goran MI. Effects of resistance training on insulin sensitivity in overweight Latino adolescent males. Med Sci Sports Exerc 2006;38(7):1208-1215. (PM:16826016)

[47] Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS. Effects of diet and exercise on obesity-related vascular dysfunction in children. Circulation. 2004;109(16):1981-1986. (PM:15066949)

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[50] Robinson TN, Killen JD, Kraemer HC, Wilson DM, Matheson DM, Haskell WL, Pruitt LA, Powell TM, Owens AS, Thompson NS, Flint-Moore NM, Davis GJ, Emig KA, Brown RT, Rochon J, Green S, Varady A. Dance and reducing television viewing to prevent weight gain in African-American girls: the Stanford GEMS pilot study. Ethn Dis 2003;13(1 Suppl 1):S65-S77. (PM:12713212)

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BACKGROUND

Tobacco dependence is responsible for approximately 4 million annual deaths worldwide. Moreover, in utero exposure to tobacco products, involuntary tobacco smoke exposure (secondhand smoke), and tobacco use directly impair the health of fetuses, infants, children, and adolescents. Based on an analysis of published causes of death, tobacco use is the leading actual cause of death in the United States.[1] The evidence that tobacco use is harmful and addictive is unequivocal.[2],[3],[4],[5],[6] In childhood, nicotine is highly addicting, with symptoms of tobacco dependence demonstrated after only brief intermittent use.[7] Current cigarette use among high school students declined from 1997 to 2003, but rates have been stable since, through 2007.[8] From a public health standpoint, the need to reduce tobacco exposure is sufficiently compelling that a role for pediatric health care providers is essential.

A clinical practice guideline update from the U.S. Public Health Service published in May 2008 systematically reviewed almost 9,000 publications and concluded that smoking prevention and cessation interventions are effective in adults.[9],[10] However, different approaches may be needed for children and adolescents. Physicians who care for children are well-positioned to provide tobacco use prevention and treatment interventions for their patients. Youth interventions should target parents as well as their children, since parental smoking is both a risk factor for child smoking and a source of secondhand smoke exposure.

OVERVIEW OF THE EVIDENCE FOR PREVENTION OF TOBACCO EXPOSURE

From the evidence review relative to environmental smoke exposure, a moderate number of studies address the efficacy of physician-based interventions to alter parental smoking habits.[11] A 2003 systematic review included 19 studies published through October 2001 that tested interventions to reduce tobacco smoke exposure in children; 6 of these were part of the evidence review for these Guidelines.[12] Only four interventions were judged to be effective: Three involved intensive counseling in a clinical setting, and one used a curricular approach in a school setting. The reviewers concluded that there was good evidence that brief informational interventions were ineffective and found limited support for intensive counseling in primary care. The evidence review for these Guidelines identified eight randomized controlled trials (RCTs), three of which showed a significant decrease in children's smoke exposure.[13],[14],[15],[16],[17],[18],[19],[20] An intervention in low-income families in a primary care setting used motivational interviewing with informational materials supplied to controls; at 6-month followup, household nicotine levels were significantly lower in the intervention group.[17] In low-income families, seven counseling sessions delivered over 3 months were effective in significantly decreasing maternal smoking rates by self-report and children's urine cotinine concentrations.[18] In a pediatric clinic setting, a brief motivational interview followed by up to three telephone counseling calls in the following 3 months showed significantly higher maternal abstinence rates at 3- and 12-month followups.[16] Studies with unsuccessful interventions used tobacco exposure demonstrations,[13] a home-based intervention by lay community health advisors,[15] and a physician-delivered report of infant urine cotinine results, with mailed information on decreasing smoke exposure.[13] The Special Turku Coronary Risk Factor Intervention Project, a Finnish study that successfully reduced saturated fat intake beginning in infancy, with followup for more than a decade, showed no differences in parental smoking between the intervention and control groups despite repeated lifestyle counseling that included an antitobacco message.[14] Two pediatric care provider studies specifically addressed smoking cessation in mothers following the birth of a child.[16],[19] As in the obstetrical literature, these were effective in achieving smoking cessation during pregnancy, but after 6–12 months, there was no evidence for postnatal effect. Overall, interventions to decrease environmental smoke exposure carried out in pediatric care settings have shown mixed results, with some evidence that intensive counseling can be effective.

Office-based counseling directed at children and adolescents for prevention of tobacco use has been a mainstay in pediatric preventive care. Although contact with preadolescents and adolescents in primary care is sporadic, pediatricians and family physicians retain a critical voice in conveying health information to children and their parents. Counseling with regard to the adverse effects of tobacco products does improve patient knowledge.[2],[3],[5] The evidence review identified two major systematic reviews for consideration. A 2003 systematic review of smoking prevention interventions delivered by health care providers included four studies, of which only one showed a significant effect on prevention of smoking initiation.[21] A 2007 systematic review of family-based programs for smoking prevention identified 14 RCTs for review.[22] Four of the nine that tested a family intervention against a control group had significant positive effects, whereas only one of the five that tested a family intervention against a school-based intervention had a significant positive outcome. None of the six that compared the incremental effects of a family plus a school program with a school program alone had significant positive effects. Overall, a significantly lower rate of smoking initiation was achieved in approximately 40 percent of interventions. The amount of implementer training and the quality of the implementation were related to positive outcomes, but the number of sessions was not. Use of biomarkers of tobacco exposure in addition to self-report of tobacco use provided no consistent benefit. In an RCT, a pediatric practice-based smoking prevention and cessation program that used a combined provider- and peer-delivered intervention was effective in preventing initiation of smoking at 1-year evaluation.[23]

Studies of the benefits of office-based counseling on smoking reduction have yielded conflicting results. A 2006 Cochrane Collaboration review of the effectiveness of strategies to achieve smoking cessation in adolescents identified 15 trials for inclusion. The review found that interventions that used pharmacologic aids were ineffective, but those that used the stages of change approach and/or motivational interviewing did achieve statistically significant positive results at 6-month followup.[24] A randomized trial of more than 2,500 adolescents, both smokers and nonsmokers, in 7 large pediatric and family practice departments of a group health maintenance organization combined 30-second clinician advice, a 10-minute interactive computer program, a 5-minute motivational interview, and telephone booster sessions. At followup more than 6 months later, the abstinence rate was significantly higher in the intervention group compared to the control group.[25] In adolescent smokers, brief counseling by providers in an emergency department was associated with an increase in quit attempts by adolescent smokers.[26] A recent combined provider- and peer-delivered intervention set in pediatric practice settings increased abstinence rates among smokers at 6-month but not at 12-month followup.[23]

School-based smoking prevention programs have achieved modest success, although there, too, results have been inconsistent, and evidence of long-term benefits is often unavailable.[27],[28],[29],[30],[31] Two systematic reviews provide important perspectives. A 2006 Cochrane review identified 23 high-quality RCTs of school-based programs to prevent smoking initiation.[32] The interventions included providing information, social influence approaches, social skills training, and community approaches. Information alone was ineffective, but the combined social influences and social skills interventions were moderately effective in approximately half of the trials. A 2005 systematic review focused on long-term followup of school-based smoking prevention. Of eight studies that were reviewed, only one showed decreased smoking prevalence in the intervention group at longer than 1-year followup.[33]

Pharmacotherapies (i.e., nicotine replacement and medication) have been proven to aid in smoking cessation in adults. Some RCTs have demonstrated the safety of the nicotine patch and nicotine gum, as well as bupropion in adolescent smokers, but cessation results are inconsistent.[34],[35] Overall, such studies performed in young smokers have shown that pharmacotherapies were not successful.[24],[36]

Public health measures have been the most effective methods to prevent and limit tobacco use. Successful strategies include taxation of tobacco products, clean indoor air legislation, and counteradvertising against tobacco products.[2] Regulatory efforts and activities as well as efforts to promote clean indoor air in homes, automobiles, and schools all have been shown to have positive effects on tobacco smoke exposure and tobacco use.[33],[37]

CONCLUSIONS AND GRADING OF THE EVIDENCE REVIEW ON PREVENTION OF TOBACCO EXPOSURE

Among all the known risk factors for CVD, the dichotomy between known benefits of risk elimination and the paucity of evidence for effective interventions to achieve risk reduction in pediatric care provider settings is greatest for tobacco exposure. The quality of the evidence regarding the harm of smoking and the benefits of passive smoke exposure avoidance, smoking prevention, and smoking cessation is uniformly Grade A. The reason that evidence grades in the recommendations are less than Grade A reflects the lack of existing evidence on interventions impacting smoking behaviors in specific pediatric age groups as opposed to the collective evidence.

• Good-quality interventions in pediatric care settings to decrease children's environmental smoke exposure have shown mixed results (Grade B).
• Intervention studies to prevent smoking initiation have had moderate success, although long-term results are limited (Grade B).
• Practice-based interventions to achieve smoking cessation in adolescents have had moderate success with limited long-term followup (Grade B).
• School-based smoking prevention programs have been moderately successful, with limited long-term followup (Grade B).

Although the evidence base in support of an office-based approach to tobacco intervention is moderate and at times mixed, the evidence that cigarette use is harmful and addictive is unequivocal. From a public health standpoint, the need to reduce tobacco exposure is sufficiently compelling that a role for pediatric health care providers is essential. The lack of harm associated with such interventions and the importance of communicating the message of risk associated with tobacco provide the rationale for supporting "Strongly recommend," despite the lack of conclusive evidence that office-based interventions reliably reduce tobacco initiation or smoking cessation. Physicians and nurses who care for children are well-positioned to provide intervention to patients who smoke. The Expert Panel believes that such providers should routinely identify patients who smoke using the medical history. Patients should be explicitly informed about the addictive and adverse health effects of tobacco use. By using the 5A questions (Ask, Advise, Assess, Assist, Arrange), providers can assess their patients' readiness to quit and assist in providing resources to support smoking cessation efforts. Information about telephone quit lines (e.g., 1-800-QUIT-NOW), community cessation programs, and pharmacotherapy should also be made available.

As described, practice-based interventions to decrease environmental smoke exposure have shown mixed results. Nonetheless, the Expert Panel believes that pediatric care providers should identify parents and other caregivers who smoke and explicitly recommend that children not be exposed to tobacco smoke in the home, in automobiles, and in any other space where exposure can occur. For the parent who smokes, information provided should include statements about health benefits to the individual, child, and/or fetus, as well as referral to smoking cessation care providers.

Prenatal tobacco exposure is addressed separately in Section XIII. Perinatal Factors. Pediatric care providers should identify mothers who use tobacco and should deliver explicit counseling to these mothers to quit smoking before pregnancy, not smoke during pregnancy, and remain smoke free after the baby's birth. Such counseling has been shown to be effective during pregnancy, but postpregnancy recidivism is high.

The Expert Panel strongly recommends that pediatric care providers deliver a clear and repeated antismoking and smoking cessation message. When possible, primary care providers should attempt to integrate more intensive approaches to tobacco use prevention and cessation in their practices. Only a small number of studies have demonstrated that pharmacotherapies (i.e., nicotine replacement and medication) have been effective in supporting smoking cessation efforts in adolescents. Nonetheless, pediatricians may wish to acquire experience using these therapies or identify another health care professional with such experience for referral.

Tobacco use is considered in risk stratification algorithms in individuals with hypercholesterolemia, hypertension, and diabetes mellitus. Treatment thresholds for pharmacologic treatment of elevated cholesterol and hypertension are lower with tobacco use, and treatment goals may be more aggressively pursued in active smokers.

Public health measures have been effective in preventing and limiting tobacco use. Pediatricians need to be involved in advocacy for such regulatory efforts, as well as in school- and community-based efforts to prevent the initiation of smoking and to promote effective cessation strategies.

Table 7–1. Evidence-Based Recommendations to Prevent Tobacco Exposure

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations

Prenatal	Obtain smoking history from mothers, then provide explicit smoking cessation message before and during pregnancy	Grade A Strongly recommend
Prenatal (cont.d)	Supportive actions: Identify resources to support maternal smoking cessation efforts. Advocate for school and community-based smoke free interventions See Section XIII. Perinatal Factors
0-12 months; 1-4 years	Promote a smoke-free home environment	Grade B Strongly recommend
0-12 months; 1-4 years (cont.d)	Reinforce this message at every encounter, including urgent visits for respiratory problems	Grade C Recommend
0-12 months; 1-4 years (cont.d)	Supportive actions: Provide information about health benefits of a smoke-free home to parents and children Advocate for school- and community-based smoke-free interventions
5-10 years	Obtain smoke exposure history from child, including personal history of tobacco use.	Grade C Recommend
5-10 years (cont.d)	Counsel patients strongly about not smoking, including providing explicit information about the addictive and adverse health effects of smoking	Grade C Recommend
11-17 years; 18-21 years	Obtain personal smoking history at every non-urgent health encounter	Grade B Strongly Recommend
11-17 years; 18-21 years (cont.d)	Explicitly recommend against smoking	Grade B Strongly Recommend
11-17 years; 18-21 years (cont.d)	Provide specific smoking cessation guidance	Grade B Strongly Recommend
11-17 years; 18-21 years (cont.d)	Supportive actions: Use 5A questions to assess readiness to quit Establish your health care practice as a resource for smoking cessation Provide quit line number Identify community cessation resources Provide information about pharmacotherapy for cessation Advocate for school and community-based smoke-free interventions

 

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[35] Moolchan ET, Robinson ML, Ernst M, Cadet JL, Pickworth WB, Heishman SJ, Schroeder JR. Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Pediatrics 2005;115(4):e407-e414. (PM:15805342)

[36] Roddy E, Romilly N, Challenger A, Lewis S, Britton J. Use of nicotine replacement therapy in socioeconomically deprived young smokers: a community-based pilot randomised controlled trial. Tob Control 2006;15(5):373-376. (PM:16998171)

[37] Sowden AJ, Arblaster L. Mass media interventions for preventing smoking in young people. Cochrane Database Syst Rev 2000;(2):CD001006.

BACKGROUND

In 2004, an NHLBI Task Force published The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Fourth Report).[1] This report was based on a complete review of the current evidence on BP management up to that time and included detailed recommendations for diagnosing and managing high BP throughout childhood. Those expert consensus recommendations were used as the basis for the recommendations for this section of these Guidelines. The review of the science was considered complete until 2003, when the review of the Fourth Report ended. Therefore, the evidence review on high BP for these Guidelines was limited to studies published between January 1, 2003, and June 30, 2007,with the addition of selected studies through June 30, 2008, identified by the Expert Panel that met all the criteria for inclusion. Repeating the review performed by the Fourth Report Task Force was not believed to be either necessary, given the relatively short time since publication of the Fourth Report, or to be a judicious use of the resources available for the development of these Guidelines. The randomized controlled trials (RCTs) identified from 2003 to 2008 for this evidence review were graded individually and can be viewed in the evidence tables, which will be available at http://www.nhlbi.nih.gov/health-pro/guidelines/current/cardiovascular-health-pediatric-guidelines/index.htm.

OVERVIEW OF THE EVIDENCE ON TREATMENT OF HIGH BLOOD PRESSURE IN CHILDREN AND ADOLESCENTS

The evidence review for the defined period identified 9 observational studies, 13 RCTs, and 3 meta-analyses. Eight RCTs evaluated medications for hypertension control that had not previously been studied in childhood: amlodipine, felodipine, fosinopril, lisinopril, losartan, metoprolol, and valsartan.[2],[3],[4],[5],[6],[7],[8],[9] Each of these medications was found to be well-tolerated for relatively short periods in children from ages 6 to 17 years, but primarily in adolescents. Most of the trials lasted 3–8 weeks; 1 trial for adolescents lasted 52 weeks. One trial evaluated valsartan in children ages 1–5 years, but data on the use of other drugs in younger children are lacking. All studies tended to determine tolerability and efficacy on reducing BP levels. In one study, African American children were found to require greater doses of fosinopril to obtain the same BP control as Caucasian children.[4]

Several studies addressed the roles of diet and lifestyle as they relate to BP. A meta-analysis of RCTs testing reduction of salt intake on BP in children and adolescents found that a modest reduction in salt intake did decrease BP, with a significant effect size of -1.17 millimeters of mercury (mmHg) for systolic BP and -2.47 mmHg for diastolic BP in children ages 8–16 years who were normotensive or had high normal BP. The meta-analysis included three trials in infants; results for this age group indicated that salt reduction decreased systolic BP by 2.47 mmHg.[10] In the Coronary Artery Risk Development in Young Adults study, higher intake of plant foods (whole grains, fruits, vegetables) and lower intake of meat products were associated with lower BP on a population basis among individuals ages 18–30 years.[11] An RCT of the Dietary Approaches to Stop Hypertension (DASH) diet was conducted in 57 adolescents with prehypertension or hypertension. At 3-month follow up, the DASH group had a significantly greater decrease in systolic BP, associated with higher intake of fruits and vegetables and low-fat dairy products and lower intake of total fat, than did the usual-care group. In the intervention group, intake of potassium and magnesium was significantly higher than in usual-care controls, but there was no difference in sodium intake.[12] Another RCT found that a 4-month transcendental meditation intervention was effective in lowering BP assessed by ambulatory BP monitoring of African American adolescents with high-normal baseline BP measurements at 8-month followup.[13]

Four studies evaluated the late effects of feeding style in infants. A 6-year followup of an RCT in infants showed that increased intake of polyunsaturated fatty acids (PUFA) in infant formula was associated with a significantly lower BP than a standard formula-fed control group; in a breast-fed reference group, diastolic BP was significantly lower than in the nonsupplemented group but did not differ from the PUFA-supplemented group.[14] Maternal fish oil supplementation in lactating mothers was not associated with any difference in BP or pulse wave velocity at 2.5-year followup compared with either a control group whose mothers received olive oil or a breast-fed reference group.[15] In small-for-gestational-age babies, a nutrient-enriched diet that promoted more rapid weight gain in infancy was associated with higher BP in childhood 6–8 years later.[16] In a meta-analysis of 15 studies, breastfeeding in infancy was found to be associated with lower BP at followup 3–60 years later, with a small but significant effect size for both systolic and diastolic BP.[17]

A series of epidemiologic studies provide important information. Long-term followup studies suggest that low birth weight is inversely associated with BP later in adult life[18] and that differences in birth weight may explain the origin of "Black/White" differences in BP.[19] A weighted analysis of BP data from national surveys in 8- to 17-year-olds obtained from 1963 to 2002 demonstrated that BP, prehypertension, and hypertension trended downward from 1963 to 1988 but upward thereafter.[20] At least part of this increase was explained by the rise in obesity, with the upward shift in BP occurring approximately 10 years after the upward trend in the prevalence of obesity. There were racial/ethnic differences, with non-Hispanic Blacks and Mexican Americans showing a greater prevalence of hypertension and prehypertension than non-Hispanic Whites and males showing a greater prevalence than females. BP variability was assessed in an analysis of longitudinal data from the National Childhood Blood Pressure database.[21] Among subjects designated as having prehypertension at baseline, 14 percent of boys and 12 percent of girls had hypertension 2 years later. Among subjects classified as hypertensive at baseline, 31 percent of boys and 26 percent of girls were still hypertensive after 2 years, and 47 percent of boys and 26 percent of girls were in the prehypertension category. Baseline BP z-score, baseline body mass index (BMI), and change in BMI were significant independent determinants of subsequent BP. Finally, a meta-analysis of 50 cohort studies confirmed that BP consistently tracks from childhood into adulthood, with the strength of tracking increasing with baseline age and decreasing with followup length.[22]

CONCLUSIONS OF THE EVIDENCE REVIEW UPDATE: 2003–2008

• The evidence review for the defined time period resulted in no major changes in the approach to BP evaluation and management.
• In epidemiologic surveys of children and adolescents over the past 20 years, BP levels are increasing, and the prevalences of hypertension and prehypertension are increasing; these findings are explained partially by the rise in obesity.
• Prehypertension progresses to hypertension at the rate of approximately 7 percent per year; hypertension persists in almost one-third of boys and one-fourth of girls on 2-year longitudinal followup.
• From the evidence review, both breastfeeding and supplementation of formula with PUFA in infancy are associated with lower BP at followup.
• A DASH-style diet—which is rich in fruits, vegetables, low-fat or fat-free dairy products, whole grains, fish, poultry, beans, seeds, and nuts and lower in sweets and added sugars, fats, and red meats than the typical American diet—is associated with lower BP, as in adults. The Cardiovascular Health Integrated Lifestyle Diet (CHILD 1) combined with the DASH eating plan (described in Section V. Nutrition and Diet) is an appropriate diet for children that meets the DASH study and Dietary Guidelines for Americans 2010 (2010 DGA) nutrient goals.
• Lower dietary sodium intake is associated with lower BP levels in infants, children, and adolescents.
• Losartan, amlodipine, felodipine, fosinopril, lisinopril, metoprolol, and valsartan can be added to the list of medications that are tolerated over short periods, and can reduce BP in children from ages 6 to 17 years but predominantly is effective in adolescents. For African American children, greater doses of fosinopril may be needed for effective BP control. Trial durations, however, were short, and long-term safety is still in question. Antihypertensive medications are shown in Table 8–5.
• In one study in small-for-gestational-age babies, a nutrient-enriched diet that promoted rapid weight gain was associated with higher BP on followup in late childhood. This potential risk should be considered when such diets are selected in the clinical setting.
• In one study, transcendental meditation has been shown to effectively lower BP in nonhypertensive adolescents.

RECOMMENDATIONS

Recommendations regarding BP are all graded as expert opinion (Grade D) since they are based on the expert consensus conclusions of the Fourth Report.

The current recommendations focus on a developmental approach to the prevention of cardiovascular disease (CVD) by appropriate identification and amelioration of risk factors during routine pediatric care. For BP, the Fourth Report provided an algorithm and flow diagram to assist clinicians in identifying hypertension in children.[1] For these Guidelines, these recommendations are stratified to provide age-appropriate approaches that are congruent with the risk factor recommendations in other sections; this is reflected in Table 8–1 and in revised algorithms (Figures 8–1 and 8–2). The BP norms for age, gender, and height are shown in Tables 8–3 and 8–4 and are taken directly from the Fourth Report.

For children from birth to age 3 years:

• Routine measurement of BP is not recommended. Blood pressure should be measured when there is a suspicion of renal disease, coarctation of the aorta, or other condition that may be associated with BP elevation. Conditions under which children younger than age 3 years should have BP measured are listed in Table 8–2.
• In these young patients, auscultation of BP is often quite difficult, so measurement with an oscillometric device using an appropriate size cuff is acceptable. The state of the infant or young child (e.g., sleeping, quiet, fussing, crying) is very important in the interpretation of BP measurement.
• For younger patients, treatment of high BP is often directed at the underlying cause, since primary hypertension is uncommon.

For children, ages 3–11 years:

• Routine measurement of BP during health care visits is recommended. This is true of visits for health maintenance and for visits when the child is ill.
• Auscultation should be the method of choice for confirmation of elevated BP measurements using an oscillometric device. The BP percentiles from the Fourth Report based on age, gender, and height percentiles should be used to categorize BP as prehypertension or Stage 1 or Stage 2 Hypertension (Tables 8–3 and 8–4). BP elevation must be persistent to be considered hypertension; the process for establishing the BP category is outlined in Table 8–1 and in Figures 8–1 and 8–2.
• In this age group, obesity is an increasingly important cause of BP elevation. When obesity is present, therapy should first be directed at improving diet and physical activity behaviors. This age group offers the opportunity to intervene early in the process of obesity development, allowing the clinician to focus on weight maintenance while the child grows, as opposed to weight loss. It also provides an important opportunity to introduce the DASH-style diet, which is described in Section V. Nutrition and Diet, as an example of CHILD 1. The DASH diet focuses on increased fruits and vegetables, low-fat dairy products, and whole-grain foods and meets all nutrient and energy requirements for children in this age range. Dietary sodium intake should also be limited.
• BP category-specific management is outlined in Table 8–1 and Figure 8–2.

For adolescents, ages 12–17 years:

• The approach to the evaluation of BP is similar to that of children ages 3 to younger than 12 years, but the prevalence of primary hypertension is much more common, and obesity is a major concern as an underlying factor. As shown in Tables 8–3 and 8–4, the percentiles of the Fourth Report should be used to evaluate BP.
• Adolescents with obesity are at risk of type 2 diabetes mellitus. Diabetes is a condition for which more aggressive BP lowering is recommended; this is described in Section XI. Diabetes Mellitus and Other Conditions Predisposing to the Development of Accelerated Atherosclerosis, which addresses the management of children with high-risk conditions.
• In this age group, the level of BP indicating prehypertension is at least 120/80, the same as that for adults. This is because the 90th percentile for adolescents is higher than 120/80 for most ages and height percentiles.
• For adolescents with increased BMI and elevated BP, weight loss is the cornerstone of therapy. Both dietary and physical activity behaviors should be addressed, aiming for appropriate energy balance, lower dietary sodium, and a DASH-like dietary pattern. Recommendations for the management of obesity are outlined in Section X. Overweight and Obesity.
• BP category-specific management is outlined in Figures 8–1 and 8–2 and in Table 8–1.

For young adults, ages 18–21 years:

• Adult cut points for BP in this age group are used to define hypertension, as per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines.[23]
• In this age range, institution of the adult DASH diet is recommended for individuals with prehypertension or hypertension, as is reduction of dietary sodium. Overweight continues to be a major concern in this age group; weight reduction should be promoted through enhanced energy expenditure coupled with reduced energy intake. Physical activity should be promoted, since moderate-to-vigorous physical activity reduces BP levels in adults.
• The management of hypertension is as described in JNC 7.[23]

For all age groups, the assessment of left ventricular mass (LVM) by echocardiography is recommended as the best method to assess hypertensive target organ disease. Assessment should be done for patients with stage 2 hypertension and those with persistent stage 1 hypertension. Evaluation of LVM may be helpful in establishing the need for pharmacologic treatment of hypertension.

Table 8–5 shows medications that have been used to achieve BP control in children and adolescents. At present, no data support the use of specific antihypertensive agents for specific age groups, and long-term safety data are not available.

Table 8–1 Age-Specific Recommendations for Blood Pressure (BP) Measurement and Diagnosis of Hypertension

BP recommendations are based on The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Fourth Report), with the evidence review updated from 2003.

Recommendations are all graded as expert opinion (Grade D) as they are based on the expert consensus conclusions of the Fourth Report.

Birth-3 years	No routine BP measurement Measure BP if history (+) for neonatal complications, congenital heart disease, urinary/ renal abnormality, solid-organ transplant, malignancy, drug Rx, or condition known to raise BP or increase intracranial pressure (Table 8-2) If BP > 90th %ile by oscillometry, confirm by auscultation –If BP confirmed – 90th %ile, initiate evaluation for etiology and treatment per algorithm. (Figure 8-2)
3-11 years	Annual BP measurement in all, interpreted for age/sex/height per Tables 8-3 and 8-4 below BP < 90th %ile, repeat in 1 year BP – 90th %ile: Repeat BP X 2 by auscultation Average replicate measurements – Re-evaluate BP category – If BP confirmed – 90th %ile, < 95th %ile = Prehypertension (HTN) Recommend weight management if indicated Repeat BP in 6 months – If BP – 95th %ile, < 99th %ile + 5mmHg Repeat BP in 1-2 weeks, average all BP measurements" Re-evaluate BP category BP confirmed – 95th %ile, < 99th %ile + 5 mmHg = Stage 1 HTN Basic work-up per figure 8-2 – If BP – 99th %ile + 5 mmHg Repeat BP by auscultation X 3 at that visit, average all BP measurements Re-evaluate BP category BP confirmed – 99th %ile + 5 mmHg = Stage 2 HTN Refer to pediatric HTN expert within 1 week OR Begin BP treatment and initiate basic work-up, per Figure 8-2.
12-17 years	Annual BP measurement in all, interpreted for age/sex/height per Tables 8-3 and 8-4 below BP < 90th %ile, counsel on CHILD 1 diet, activity recommendations, and repeat BP in 1 year BP – 90th %ile or > 120/80: Repeat BP X 2 by auscultation Average replicate measurements – Re-evaluate BP category – If BP confirmed – 90th %ile, < 95th %ile or – 120/80 = Pre-HTN CHILD 1 diet, activity recommendations, weight management if indicated Repeat BP in 6 months – If BP – 95th %ile, < 99th %ile + 5mmHg Repeat BP in 1-2 weeks, average all BP measurements Re-evaluate BP category BP confirmed – 95th %ile, < 99th %ile + 5 mmHg = Stage 1 HTN Basic work-up per Figure 8-2 – If BP – 99th %ile + 5 mmHg Repeat BP by auscultation X 3 at that visit, average all BP measurements Re-evaluate BP category BP confirmed – 99th %ile + 5 mmHg = Stage 2 HTN Refer to pediatric HTN expert within 1 week OR Begin BP treatment and initiate work-up, per Figure 8-2
18-21 years	Measure BP at all health care visits BP – 120/80 to 139/89 = Pre-HTN BP – 140/90 to 159/99 = Stage 1 HTN BP – 160/100 = Stage 2 HTN Evaluation/ Treatment per JNC recommendations[23]

 

Table 8–2. Conditions Under Which Children < 3 Years Old Should Have BP Measured

 

• History of prematurity, very low birth weight, or other neonatal complication requiring intensive care
• Congenital heart disease (repaired or unrepaired)
• Recurrent urinary tract infections, hematuria, or proteinuria
• Known renal disease or urologic malformations
• Family history of congenital renal disease
• Solid-organ transplant
• Malignancy or bone marrow transplant
• Treatment with drugs know to raise BP
• Other systemic illnesses associated with hypertension (neurofibromatosis, tuberous sclerosis, etc.)
• Evidence of increased intracranial pressure

Figure 8-1. Blood Pressure (BP) Measurement and Categorization

[[nid:829 view_mode=custom_size width=600 height=459]]

Figure 8-1 Description

The figure is a flow chart with 21 labeled boxes linked by arrows. The chart is in one direction with all arrows pointing downward to one or more boxes.

Below the flow chart is described as lists in which the possible next steps are listed beneath each box label.

1. Select appropriate BP cuff size. Meaure BP at each well child visit over 3 years of age* (auscultatory method preferred)
   1. Forward to Measure HT, WT & calculate BMI
2. Measure HT, WT & calculate BMI
   1. Foward to Determine BP category for age, HT, gender (Tables 8-3 & 8-4)
3. Determine BP category for age, HT, gender (Tables 8-3 & 8-4)
   Determine BMI category for age and gender (CDC growth charts)
   1. Forward to <90%ile (normal)
   2. Forward to – 90th%ile or 120/80 mmHg to < 95th% (preHTN)
   3. Forward to – 95th%ile < 99th% + 5 mmHg (stage 1)
   4. Forward to – 99th%ile + 5 mmHg (stage 2)
4. <90th%ile (normal)
   1. Forward to Normotensive
   2. Forward to Repeat BP at next visit, plus
   3. Forward to Educate on CHILD-1– activity levels**
5. – 90th%ile or 120/80 mmHg to < 95th% (preHTN)
   1. Foward to Repeat by auscultation if performed with oscillometric device
6. – 95th%ile < 99th% + 5 mmHg (stage 1)
   1. Foward to Repeat by auscultation if performed with oscillometric device
7. – 99th%ile + 5 mmHg (stage 2)
   1. Foward to Repeat by auscultation if performed with oscillometric device
8. Repeat by auscultation if performed with oscillometric device
   1. Forward to Average replicate BP measurements at initial visit
9. Average replicate BP measurements at initial visit
   Re-evaluate BP category
   1. Forward to Pre-Hypertensive
   2. Forward to Stage 1 Hypertension
   3. Forward to Stage 2 Hypertension
10. Pre-Hypertensive
    1. Forward to Repeat BP in 6 months
11. Stage 1 Hypertension
    1. Forward to Repeat BP in 1-2 weeks
12. Stage 2 Hypertension
    1. Forward to Evaluate or refer for treatment within 1 week
13. Repeat BP in 6 months, plus
    1. Forward to CHILD-1–/activity education** &/or Weight management***
14. Repeat BP in 1-2 weeks
    Average BP over all 3 visits, plus
    1. Forward to CHILD-1–/activity education** &/or Weight management***
15. Evaluate or refer for treatment within 1 week, plus
    1. Forward to CHILD-1–/activity education** &/or Weight management***
16. CHILD-1–/activity education** &/or Weight management***
17. CHILD-1–/activity education** &/or Weight management***
18. CHILD-1–/activity education** &/or Weight management***

Figure 8-1 Legend:
* See Table 1;
– Cardiovascular Health Integrated Lifestyle Diet - Section V. Nutrition and Diet;
** Section VI. Physical Activity;
*** Section X. Overweight and Obesity

Figure 8-2. Blood Pressure (BP) Management by Category

[[nid:830 view_mode=custom_size width=600 height=489]]

Figure 8-2 Description

The figure is a flow chart with 29 labeled boxes linked by arrows. The chart is in one direction with all arrows pointing downward to one or more boxes.

Below the flow chart is described as lists in which the possible next steps are listed beneath each box label.

1. Determine BP category from average of replicate readings at multiple visits (see measurement algorithm)
   1. Forward to Normotensive
   2. Forward to Pre-Hypertension
   3. Forward to Stage 1 Hypertension
   4. Forward to Stage 2 Hypertension
2. Normotensive
   1. Forward to Assess other CV risk factors
3. Pre-Hypertension
   1. Forward to Assess other CV risk factors*
4. Stage 1 Hypertension
   1. Forward to Basic Work-up: Medical/Family/Sleep Hx, PEx, CBC, renal panel, U/A, Renal/Cardiac U/S, lipids, glucose
5. Stage 2 Hypertension
   1. Forward to Basic Work-up: &/or refer to Ped HTN expert for extended work-up
6. Assess other CV risk factors, plus
   1. Forward to CHILD-1–/Activity Education**
7. Assess other CV risk factors*, plus
   1. Forward to CHILD-1–/activity education** &/or Weight management***
8. Basic Work-up: Medical/Family/Sleep Hx, PEx, CBC, renal panel, U/A, Renal/Cardiac U/S, lipids, glucose, plus
   1. Forward to CHILD-1–/activity education** &/or Weight management***
9. Basic Work-up: &/or refer to Ped HTN expert for extended work-up
   1. Primary or Secondary HTN, forward to Anti-HTN Drug +/- Rx for 20 cause + Weight management*** &/or CHILD-1–/activity education**
10. CHILD-1–/Activity Education**
    1. Forward to Re-evaluate at next visit
11. CHILD-1–/activity education** &/or Weight management***
    1. Forward to Monitor Q 6 Mo
12. CHILD-1–/activity education** &/or Weight management***
    1. Primary HTN No LVH, Forward to Monitor Q3 to 6 Months
    2. Secondary HTN or LVH, Forward to Rx for 20 cause + Anti-HTN Drug
13. Anti-HTN Drug +/- Rx for 20 cause + Weight management*** &/or CHILD-1–/activity education**
    1. Forward to Follow until BP controlled, Q 1-2 wks
14. Monitor Q 6 Mo
    1. Forward to Re-evaluate BP cagegory**
15. Monitor Q 3 to 6 Months
    1. Forward to Re-evaluate BP cagegory
16. Rx for 20 cause + Anti-HTN Drug
    1. Forward to Monitor Q 3-6 Months
17. Follow until BP controlled, Q 1-2 wks
    1. Monitor Q 1-3 Months
18. Re-evaluate BP Category**
    1. <90th %ile, 90<95th%ile (–95th%ile – Stage 1 W/U) –95th%ile, forward to Consider basic W/U + cardiac U/S for TOD*
19. Re-evaluate BP category
    1. Forward to Anti-HTN Drug if no improvement
20. Monitor Q3-6 Months
    1. Forward to Consider re-evaluation of BP Category if BP well controlled, –BMI or s/p Rx for 20 cause
21. Monitor Q 1-3 Months
    1. Forward to Consider re-evaluation of BP Category if BP well controlled, –BMI or s/p Rx for 20 cause
22. Consider basic W/U + cardiac U/S for TOD*
    1. Forward to Monitor Q 6 Mo
23. Anti-HTN Drug if no improvement
    1. Forward to Continue moderate follow-up
24. Consider re-evaluation of BP Category if BP well controlled, –BMI or s/p Rx for 20 cause
    1. Forward to Continue moderate follow-up
    2. Forward to Continue close follow-up
25. Re-evaluate at next visit
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
26. Monitor Q 6 Mo
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
27. Continue moderate follow-up
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
28. Continue close follow-up
    1. Forward to GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage
29. GOAL BP: <95th%ile for age/sex/HT, <90th %ile if CKD, DM, Target Organ Damage

Figure 8-2 Legend:
* Work up for target organ damage (TOD)/ LVH if obese or (+) for other CV risk factors;
– Cardiovascular Health Integrated Lifestyle Diet; See Section V. Nutrition and Diet;
** Activity Education. See Section VI. Physical Activity;
*** Weight management. See Section X. Overweight and Obesity.

Table 8-3. Blood Pressure (BP) Norms for Boys by Age and Height Percentiles (%iles)

Age, y	BP %ile	SBP, mm Hg, %ile of Height, 5th	SBP, mm Hg, %ile of Height, 10th	SBP, mm Hg, %ile of Height, 25th	SBP, mm Hg, %ile of Height, 50th	SBP, mm Hg, %ile of Height, 75th	SBP, mm Hg, %ile of Height, 90th	SBP, mm Hg, %ile of Height, 95th	DBP, mm Hg, %ile of Height, 5th	DBP, mm Hg, %ile of Height, 10th	SBP, mm Hg, %ile of Height, 25th	SBP, mm Hg, %ile of Height, 50th	SBP, mm Hg, %ile of Height, 75th	DBP, mm Hg, %ile of Height, 90th	DBP, mm Hg, %ile of Height, 95th
1	50th	80	81	83	85	87	88	89	34	35	36	37	38	39	39
1	90th	94	95	97	99	100	102	103	49	50	51	52	53	53	54
1	95th	98	99	101	103	104	106	106	54	54	55	56	57	58	58
1	99th	105	106	108	110	112	113	114	61	62	63	64	65	66	66
2	50th	84	85	87	88	90	92	92	39	40	41	42	43	44	44
2	90th	97	99	100	102	104	105	106	54	55	56	57	58	58	59
2	95th	101	102	104	106	108	109	110	59	59	60	61	62	63	63
2	99th	109	110	111	113	115	117	117	66	67	68	69	70	71	71
3	50th	86	87	89	91	93	94	95	44	44	45	46	47	48	48
3	90th	100	101	103	105	107	108	109	59	59	60	61	62	63	63
3	95th	104	105	107	109	110	112	113	63	63	64	65	66	67	67
3	99th	111	112	114	116	118	119	120	71	71	72	73	74	75	75
4	50th	88	89	91	93	95	96	97	47	48	49	50	51	51	52
4	90th	102	103	105	107	109	110	111	62	63	64	65	66	66	67
4	95th	106	107	109	111	112	114	115	66	67	68	69	70	71	71
4	99th	113	114	116	118	120	121	122	74	75	76	77	78	78	79
5	50th	90	91	93	95	96	98	98	50	51	52	53	54	55	55
5	90th	104	105	106	108	110	111	112	65	66	67	68	69	69	70
5	95th	108	109	110	112	114	115	116	69	70	71	72	73	74	74
5	99th	115	116	118	120	121	123	123	77	78	79	80	81	81	82
6	50th	91	92	94	96	98	99	100	53	53	54	55	56	57	57
6	90th	105	106	108	110	111	113	113	68	68	69	70	71	72	72
6	95th	109	110	112	114	115	117	117	72	72	73	74	75	76	76
6	99th	116	117	119	121	123	124	125	80	80	81	82	83	84	84
7	50th	92	94	95	97	99	100	101	55	55	56	57	58	59	59
7	90th	106	107	109	111	113	114	115	70	70	71	72	73	74	74
7	95th	110	111	113	115	117	118	119	74	74	75	76	77	78	78
7	99th	117	118	120	122	124	125	126	82	82	83	84	85	86	86
8	50th	94	95	97	99	100	102	102	56	57	58	59	60	60	61
8	90th	107	109	110	112	114	115	116	71	72	72	73	74	75	76
8	95th	111	112	114	116	118	119	120	75	76	77	78	79	79	80
8	99th	119	120	122	123	125	127	127	83	84	85	86	87	87	88
9	50th	95	96	98	100	102	103	104	57	58	59	60	61	61	62
9	90th	109	110	112	114	115	117	118	72	73	74	75	76	76	77
9	95th	113	114	116	118	119	121	121	76	77	78	79	80	81	81
9	99th	120	121	123	125	127	128	129	84	85	86	87	88	88	89
10	50th	97	98	100	102	103	105	106	58	59	60	61	61	62	63
10	90th	111	112	114	115	117	119	119	73	73	74	75	76	77	78
10	95th	115	116	117	119	121	122	123	77	78	79	80	81	81	82
10	99th	122	123	125	127	128	130	130	85	86	86	88	88	89	90
11	50th	99	100	102	104	105	107	107	59	59	60	61	62	63	63
11	90th	113	114	115	117	119	120	121	74	74	75	76	77	78	78
11	95th	117	118	119	121	123	124	125	78	78	79	80	81	82	82
11	99th	124	125	127	129	130	132	132	86	86	87	88	89	90	90
12	50th	101	102	104	106	108	109	110	59	60	61	62	63	63	64
12	90th	115	116	118	120	121	123	123	74	75	75	76	77	78	79
12	95th	119	120	122	123	125	127	127	78	79	80	81	82	82	83
12	99th	126	127	129	131	133	134	135	86	87	88	89	90	90	91
13	50th	104	105	106	108	110	111	112	60	60	61	62	63	64	64
13	90th	117	118	120	122	124	125	126	75	75	76	77	78	79	79
13	95th	121	122	124	126	128	129	130	79	79	80	81	82	83	83
13	99th	128	130	131	133	135	136	137	87	87	88	89	90	91	91
14	50th	106	107	109	111	113	114	115	60	61	62	63	64	65	65
14	90th	120	121	123	125	126	128	128	75	76	77	78	79	79	80
14	95th	124	125	127	128	130	132	132	80	80	81	82	83	84	84
14	99th	131	132	134	136	138	139	140	87	88	89	90	91	92	92
15	50th	109	110	112	113	115	117	117	61	62	63	64	65	66	66
15	90th	122	124	125	127	129	130	131	76	77	78	79	80	80	81
15	95th	126	127	129	131	133	134	135	81	81	82	83	84	85	85
15	99th	134	135	136	138	140	142	142	88	89	90	91	92	93	93
16	50th	111	112	114	116	118	119	120	63	63	64	65	66	67	67
16	90th	125	126	128	130	131	133	134	78	78	79	80	81	82	82
16	95th	129	130	132	134	135	137	137	82	83	83	84	85	86	87
16	99th	136	137	139	141	143	144	145	90	90	91	92	93	94	94
17	50th	114	115	116	118	120	121	122	65	66	66	67	68	69	70
17	90th	127	128	130	132	134	135	136	80	80	81	82	83	84	84
17	95th	131	132	134	136	138	139	140	84	85	86	87	87	88	89
17	99th	139	140	141	143	145	146	147	92	93	93	94	95	96	97

SD = standard deviation
The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean.

Table 8–4. Blood Pressure (BP) Norms for Girls by Age and Height Percentiles (%iles)

Age, y	BP %ile	SBP, mm Hg, %ile of Height, 5th	SBP, mm Hg, %ile of Height, 10th	SBP, mm Hg, %ile of Height, 25th	SBP, mm Hg, %ile of Height, 50th	SBP, mm Hg, %ile of Height, 75th	SBP, mm Hg, %ile of Height, 90th	SBP, mm Hg, %ile of Height, 95th	DBP, mm Hg, %ile of Height, 5th	DBP, mm Hg, %ile of Height, 10th	SBP, mm Hg, %ile of Height, 25th	SBP, mm Hg, %ile of Height, 50th	SBP, mm Hg, %ile of Height, 75th	DBP, mm Hg, %ile of Height, 90th	DBP, mm Hg, %ile of Height, 95th
1	50th	83	84	85	86	88	89	90	38	39	39	40	41	41	42
1	90th	97	97	98	100	101	102	103	52	53	53	54	55	55	56
1	95th	100	101	102	104	105	106	107	56	57	57	58	59	59	60
1	99th	108	108	109	111	112	113	114	64	64	65	65	66	67	67
2	50th	85	85	87	88	89	91	91	43	44	44	45	46	46	47
2	90th	98	99	100	101	103	104	105	57	58	58	59	60	61	61
2	95th	102	103	104	105	107	108	109	61	62	62	63	64	65	65
2	99th	109	110	111	112	114	115	116	69	69	70	70	71	72	72
3	50th	86	87	88	89	91	92	93	47	48	48	49	50	50	51
3	90th	100	100	102	103	104	106	106	61	62	62	63	64	64	65
3	95th	104	104	105	107	108	109	110	65	66	66	67	68	68	69
3	99th	111	111	113	114	115	116	117	73	73	74	74	75	76	76
4	50th	88	88	90	91	92	94	94	50	50	51	52	52	53	54
4	90th	101	102	103	104	106	107	108	64	64	65	66	67	67	68
4	95th	105	106	107	108	110	111	112	68	68	69	70	71	71	72
4	99th	112	113	114	115	117	118	119	76	76	76	77	78	79	79
5	50th	89	90	91	93	94	95	96	52	53	53	54	55	55	56
5	90th	103	103	105	106	107	109	109	66	67	67	68	69	69	70
5	95th	107	107	108	110	111	112	113	70	71	71	72	73	73	74
5	99th	114	114	116	117	118	120	120	78	78	79	79	80	81	81
6	50th	91	92	93	94	96	97	98	54	54	55	56	56	57	58
6	90th	104	105	106	108	109	110	111	68	68	69	70	70	71	72
6	95th	108	109	110	111	113	114	115	72	72	73	74	74	75	76
6	99th	115	116	117	119	120	121	122	80	80	80	81	82	83	83
7	50th	93	93	95	96	97	99	99	55	56	56	57	58	58	59
7	90th	106	107	108	109	111	112	113	69	70	70	71	72	72	73
7	95th	110	111	112	113	115	116	116	73	74	74	75	76	76	77
7	99th	117	118	119	120	122	123	124	81	81	82	82	83	84	84
8	50th	95	95	96	98	99	100	101	57	57	57	58	59	60	60
8	90th	108	109	110	111	113	114	114	71	71	71	72	73	74	74
8	95th	112	112	114	115	116	118	118	75	75	75	76	77	78	78
8	99th	119	120	121	122	123	125	125	82	82	83	83	84	85	86
9	50th	96	97	98	100	101	102	103	58	58	58	59	60	61	61
9	90th	110	110	112	113	114	116	116	72	72	72	73	74	75	75
9	95th	114	114	115	117	118	119	120	76	76	76	77	78	79	79
9	99th	121	121	123	124	125	127	127	83	83	84	84	85	86	87
10	50th	98	99	100	102	103	104	105	59	59	59	60	61	62	62
10	90th	112	112	114	115	116	118	118	73	73	73	74	75	76	76
10	95th	116	116	117	119	120	121	122	77	77	77	78	79	80	80
10	99th	123	123	125	126	127	129	129	84	84	85	86	86	87	88
11	50th	100	101	102	103	105	106	107	60	60	60	61	62	63	63
11	90th	114	114	116	117	118	119	120	74	74	74	75	76	77	77
11	95th	118	118	119	121	122	123	124	78	78	78	79	80	81	81
11	99th	125	125	126	128	129	130	131	85	85	86	87	87	88	89
12	50th	102	103	104	105	107	108	109	61	61	61	62	63	64	64
12	90th	116	116	117	119	120	121	122	75	75	75	76	77	78	78
12	95th	119	120	121	123	124	125	126	79	79	79	80	81	82	82
12	99th	127	127	128	130	131	132	133	86	86	87	88	88	89	90
13	50th	104	105	106	107	109	110	110	62	62	62	63	64	65	65
13	90th	117	118	119	121	122	123	124	76	76	76	77	78	79	79
13	95th	121	122	123	124	126	127	128	80	80	80	81	82	83	83
13	99th	128	129	130	132	133	134	135	87	87	88	89	89	90	91
14	50th	106	106	107	109	110	111	112	63	63	63	64	65	66	66
14	90th	119	120	121	122	124	125	125	77	77	77	78	79	80	80
14	95th	123	123	125	126	127	129	129	81	81	81	82	83	84	84
14	99th	130	131	132	133	135	136	136	88	88	89	90	90	91	92
15	50th	107	108	109	110	111	113	113	64	64	64	65	66	67	67
15	90th	120	121	122	123	125	126	127	78	78	78	79	80	81	81
15	95th	124	125	126	127	129	130	131	82	82	82	83	84	85	85
15	99th	131	132	133	134	136	137	138	89	89	90	91	91	92	93
16	50th	108	108	110	111	112	114	114	64	64	65	66	66	67	68
16	90th	121	122	123	124	126	127	128	78	78	79	80	81	81	82
16	95th	125	126	127	128	130	131	132	82	82	83	84	85	85	86
16	99th	132	133	134	135	137	138	139	90	90	90	91	92	93	93
17	50th	108	109	110	111	113	114	115	64	65	65	66	67	67	68
17	90th	122	122	123	125	126	127	128	78	79	79	80	81	81	82
17	95th	125	126	127	129	130	131	132	82	83	83	84	85	85	86
17	99th	133	133	134	136	137	138	139	90	90	91	91	92	93	93

SD = standard deviation
The 90th percentile is 1.28 SD, the 95th percentile is 1.645 SD, and the 99th percentile is 2.326 SD over the mean.

Table 8-5. Anti-hypertensive Medications with Pediatric

Angiotensin-converting enzyme (ACE) inhibitor

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Angiotensin-converting enzyme (ACE) inhibitor	Benazepril	0.2 mg/kg/day up to 10 mg/day	0.6 mg/kg/day up to 40 mg/day	qd	Randomized controlled trial	Yes
Angiotensin-converting enzyme (ACE) inhibitor	Captopril	0.3-0.5 mg/kg/dose (>12 months)	6 mg/kg/day	tid	Randomized controlled trial, Case series	No
Angiotensin-converting enzyme (ACE) inhibitor	Fosinopril**	Children >50 kg: 5-10 mg/day	40 mg/day	qd	Randomized controlled trial	Yes
Angiotensin-converting enzyme (ACE) inhibitor	Lisinopril**	0.07 mg/kg/day up to 5 mg/day	0.6 mg/kg/day up to 40 mg/day	qd	Randomized controlled trial	Yes
Angiotensin-converting enzyme (ACE) inhibitor	Quinapril	5-10 mg/day	80 mg/day	qd	Randomized controlled trial, Expert opinion	No

Comments§ All ACE inhibitors are contraindicated in pregnancy; females of childbearing age should use reliable contraception. Check serum potassium and creatinine periodically to monitor for hyperkalemia and azotemia. Cough and angioedema are reportedly less common with newer members of this class than with captopril. Benezapril and lisinopril labels contain information on the preparation of a suspension; captopril may also be compounded into a suspension. FDA approval for ACE inhibitors with pediatric labeling is limited to children –6 years of age and to children with creatinine clearance –30 mL/min/1.73m2. Initial dose of fosinopril of 0.1 mg/kg/day may be effective, although African American patients may require a higher dose.

Angiotensin-receptor blocker (ARB)

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Angiotensin-receptor blocker (ARB)	Irbesartan	6-12 years: 75-150 mg/day; –13 years: 150-300mg/day	300 mg/day	qd	Case series	Yes
Angiotensin-receptor blocker (ARB)	Losartan**	0.7 mg/kg/day up to 50 mg/day	1.4 mg/kg/day up to 100 mg/day	qd-bid	Randomized controlled trial	Yes
Angiotensin-receptor blocker (ARB)	Valsartan**	5-10 mg/day 0.4 mg/kg/day	40-80 mg/day 3.4 mg/kg/day	qd	Randomized controlled trial	No

Comments§ All ARBs are contraindicated in pregnancy; females of childbearing age should use reliable contraception Check serum potassium and creatinine periodically to monitor for hyperkalemia and azotemia. Losartan label contains information on the preparation of a suspension. FDA approval for ARBs is limited to children –6 years of age and to children with creatinine clearance –30 mL/min/1.73m2 .

Alpha- and beta-antagonist

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
alpha- and beta-antagonist	Labetalol	1-3 mg/kg/day	10-12 mg/kg/day up to 1,200 mg/day	bid	Case series, Expert opinion	No

Comments§ Asthma and overt heart failure are relative contraindications. Heart rate is dose limiting. May impair athletic performance in athletes. Should not be used in insulin-dependent diabetics.

Beta-antagonist

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
beta-antagonist	Atenolol	0.5-1 mg/kg/day	2 mg/kg/day up to 100 mg/day	qd-bid	Case series	No
beta-antagonist	Bisoprolol/ HCTZ	2.5-6.25 mg/day	10/6.25 mg/day	qd	Randomized controlled trial	No
beta-antagonist	Metoprolol**	Children >6 years: 1 mg/kg/day (12.5-50 mg/day)	2 mg/kg/day up to 200 mg/day	bid	Case series	Yes***
beta-antagonist	Propranolol	1-2 mg/kg/day	4 mg/kg/day up to 640 mg/day	bid-tid	Randomized controlled trial, Expert opinion	Yes

Comments§ Noncardioselective agents (propranolol) are contraindicated in asthma and heart failure. Heart rate is dose limiting. May impair athletic performance in athletes. Should not be used in insulin-dependent diabetics. A sustained-release, once-daily formulation of propranolol is available.

Calcium channel blocker

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Calcium channel blocker	Amlodipine**	Children 6-17 years: 2.5 mg/day	5 mg/day	qd	Randomized controlled trial	Yes
Calcium channel blocker	Felodipine	2.5 mg/day	10 mg/day	qd	Randomized controlled trial, Expert opinion	No
Calcium channel blocker	Isradipine	0.15-0.2 mg/kg/day	0.8 mg/kg/day up to 20 mg/day	tid-qid	Case series, Expert opinion	No
Calcium channel blocker	Extended-release nifedipine	0.25-0.5 mg/kg/day	3 mg/kg/day up to 120 mg/day	qd-bid	Case series, Expert opinion	No

Comments§ Amlodipine and isradipine can be compounded into stable extemporaneous suspensions. Felodipine and extended-release nifedipine tablets must be swallowed whole. Isradipine is available in both immediate-release and sustained-release formulations; sustained release form is dosed qd or bid. May cause tachycardia. Doses up to 10 mg of amlodipine have been evaluated in children. Contraindicated for children <1 year of age.

Central alpha-agonist

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Central alpha-agonist	Clonidine	Children –12 years: 0.2 mg/day	2.4 mg/day	bid	Expert opinion	Yes

Comments§ May cause dry mouth and/or sedation. Transdermal preparation is available. Sudden cessation of therapy can lead to severe rebound hypertension.

Diuretic

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Diuretic	HCTZ	1 mg/kg/day	3 mg/kg/day up to 50 mg/day	qd	Expert opinion	Yes
Diuretic	Chlorthalidone	0.3 mg/kg/day	2 mg/kg/day up to 50 mg/day	qd	Expert opinion	No
Diuretic	Furosemide	0.5-2.0 mg/kg/ dose	6 mg/kg/day	qd-bid	Expert opinion	`No
Diuretic	Spironolactone	1 mg/kg/day	3.3 mg/kg/day up to 100 mg/day	qd-bid	Expert opinion	No
Diuretic	Triamterene	1-2 mg/kg/day	3-4 mg/kg/day up to 300 mg/day	bid	Expert opinion	No
Diuretic	Amiloride	0.4-0.625 mg/kg/day	20 mg/day	qd	Expert opinion	No

Comments§ All patients treated with diuretics should have electrolytes monitored shortly after initiating therapy and periodically thereafter. Useful as add-on therapy in patients being treated with drugs from other drug classes. Potassium-sparing diuretics (spironolactione, triamterene, amiloride) may cause severe hyperkalemia, especially if given with ACE inhibitor or ARB. Furosemide is labeled only for treatment of edema but may be useful as add-on therapy in children with resistant hypertension, particularly in children with renal disease. Chlorthalidone may precipitate azotemia in patients with renal diseases and should be used with caution in those with severe renal impairment.

Peripheral alpha-antagonist

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Peripheral alpha-antagonist	Doxazosin	1 mg/day	4 mg/day	qd	Expert opinion	No
Peripheral alpha-antagonist	Prazosin	0.05-0.1 mg/kg/ day	0.5 mg/kg/day	tid	Expert opinion	No
Peripheral alpha-antagonist	Terazosin	1 mg/day	20 mg/day	qd	Expert opinion	No

Comments§ May cause first-dose hypotension.

Vasodilator

Class	Drug	Initial Dose*	Maximal Dose	Dosing Interval	Evidence–	FDA–
Vasodilator	Hydralazine	0.75 mg/kg/day	7.5 mg/kg/day up to 200 mg/day	qid	Expert opinion	Yes
Vasodilator	Minoxidil	Children <12 years: 0.2 mg/kg/ day; children > 12 years: 5 mg/day	Children <12 years: 50 mg/day; children –12 years: 100 mg/day	qd-tid	Case series, Expert opinion	Yes

Comments§ Tachycardia and fluid retention are common side effects. Hydralazine can cause a lupus-like syndrome in slow acetylators. Prolonged use of minoxidil can cause hypertrichosis. Minoxidil is usually reserved for patients with hypertension resistant to multiple drugs.

RCT = randomized controlled trial
CS = case series
EO = expert opinion
* The maximal recommended adult dose should not be exceeded in routine clinical practice.
– Level of evidence on which recommendations are based.
– U.S. Food and Drug Administration (FDA) -approved pediatric labeling information is available for treatment of hypertension. Recommended doses for agents with FDA-approved pediatric labels contained in this table are the doses contained in the approved labels. Even when pediatric labeling information is not available, the FDA-approved label should be consulted for additional safety information.
§ Comments apply to all members of each drug class except where otherwise stated.
** Indicates drug added since The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (2004).
*** Study did not reach primary end point (dose response for reduction in systolic blood pressure). Some prespecified secondary end points demonstrated effectiveness.

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