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The Influence of Early Programming in the Development of Cardiovascular, Lung, Blood, and Sleep Disorders
September 27, 2005
The National Heart, Lung, and Blood Institute convened a Working Group on September 27, 2005, in Bethesda, Maryland to assess and identify opportunities for research on how the intrauterine environment affects the development of heart, lung, blood, and sleep disorders later in life. Experts in developmental biology, developmental physiology, animal models, and in cardiovascular, lung, and blood diseases were invited to participate. The working group meeting was preceded by a workshop, The Intrauterine Environment: Long Term Consequences for Obesity and Metabolic Disorders sponsored by four NIH institutes (NIDDK, NHLBI, NICHD, and NIEHS), which focused on the effect of maternal diabetes and obesity on metabolic diseases in their offspring and augmented the ensuing working group discussion.
Epidemiologic observations by David Barker in the late1980s indicated that babies born before World War II in Hertfordshire, England, who had low birth weights, entered adulthood with an increased risk of cardiovascular disease (CVD). The "Barker Hypothesis" suggests that changes in the intrauterine environment can alter organ development and "program" physiological systems in the developing fetus, leading to an increased risk for a wide variety of diseases later in life. The WG discussed the need for more data on basic biological mechanisms to better understand how intrauterine challenges modify and program: (1) development of organ systems (heart, systemic vasculature, brain, placental vasculature, and kidney), (2) specific physiological pathways, and (3) phenotypes and gene-environment interactions. They discussed the importance of determining critical times during development when an organ system is susceptible to intrauterine challenges and of elucidating mechanisms that increase vulnerability. Identifying biomarkers (maternal and fetal) is also necessary for validating clinical manifestations and for developing early interventions. Alterations in placenta and placental signaling were discussed, since changes in the placenta itself, and in the placental barrier, milieu, and vasculature during intrauterine challenges may well determine the functionality of organs and cardiovascular or lung vulnerability.
The Working Group indicated that better clinical endpoints are needed. Other measurements of neonatal body composition (e.g., adiposity) and the metabolic and endocrine milieu, in addition to birth weight, might turn out to be good predictors of CVD in adulthood. New epidemiological studies are needed because the current state of knowledge is based on old data that may have little relevance to today's situation. In recent decades, the incidence and prevalence of obesity, diabetes, peripheral vascular disease, pre-hypertension, hypertension, and dyslipidemias, as well as bio-behavioral stress and depression have increased in the general population and, particularly, in women. Therefore, new research and approaches on preventing and treating these CVD risk factors are needed.
The Working Group made the following prioritized recommendations:
The Working Group also made some recommendations in areas outside the mission of the NHLBI:
Cristina Rabadan-Diehl, Ph.D., NHLBI, NIH
Working Group Members
Chair: Peter Nathanielsz, Ph., M.D., D.Sc., University of Texas Health Science Center
Last updated: February 13, 2006