Doctor listens to baby’s heartbeat with stethoscope while examining pregnant woman.

Studies address link between rising U.S. maternal deaths and heart disease

Sleep apnea, obesity, race among the risk factors for pregnancy-related complications

During the last few decades, maternal deaths — long considered a critical marker of the health of a nation — have been declining in much of the world. But in the United States, the maternal death rate has increased an estimated 58% since 1990. The increase has been so significant that the U.S. now has the dubious distinction of having the highest maternal death rate of any industrialized nation.

Researchers say they are working to explain exactly why pregnant women in this country have outcomes that are so much worse than in others, but mounting evidence points to cardiovascular disease (CVD) as the main culprit. CVD is a group of disorders that damage the heart and blood vessels and can lead to complications such as heart attack and stroke. Studies estimate that CVD accounts for about 33%— a third—of maternal deaths. Being African American, older (age 35 and above), and having obesity boosts the risk of pregnancy-related CVD, although it can occur in women with no obvious preexisting conditions or risk factors, researchers say.

NHLBI researchers and others who are studying the link between maternal deaths and heart disease are hoping to help change that. Their review of research on the topic, which was recently detailed in a special issue of the Journal of Women’s Health (JWH) focusing on maternal mortality and morbidity, explores current understanding and promising research to reverse the trend. But health disparities demonstrating worse outcomes for some groups continue to persist, especially for racial and ethnic minorities.

“It is well-known that pregnancy acts as a stress test for the cardiovascular system in that it can reveal hidden signs of preexisting cardiovascular disease,” said Jasmina Varagic, M.D., Ph.D., the lead author of one of the JWH review papers, entitled Maternal Morbidity and Mortality: Are We Getting to the “Heart” of the Matter? Varagic is program director of the Vascular Biology and Hypertension Branch in NHLBI’s Division of Cardiovascular Sciences.

Researchers are investigating the mechanisms behind pregnancy-related CVD to find ways to prevent or treat the condition. “The good news is that some clues are starting to emerge,” Varagic said.

She noted that researchers are making inroads into the causes of two important pregnancy complications in particular: preeclampsia, or high blood pressure during pregnancy, and peripartum cardiomyopathy, a form of heart failure that can occur during pregnancy and after giving birth, and is characterized by enlargement and weakening of the heart. Scientists have identified several blood biomarkers associated with these conditions that hold promise for helping identify these conditions early.

Researchers are studying, for example, novel biomarkers such as sFlt-1, a protein whose high levels have been associated with the development of preeclampsia. Another is placental growth factor (PlGF), a protein whose low levels have been linked to the same condition. These biomarkers may even act as targets for treatments, Varagic said.

In their review article, Varagic and her coauthors noted that adverse pregnancy outcomes like preeclampsia, cardiomyopathy, preterm birth, and pregnancy loss can also impact a woman’s long-term health. Studies show, for example, that women who are diagnosed with preeclampsia have a two- to four-times higher risk of future CVD than those who do not have this condition. This long-term impact reinforces the need to better understand and control CVD risk factors in pregnant women, the researchers said.

Another critical factor linked to the rise in maternal deaths is race. African American women, for example, are three times more likely to die from pregnancy and childbirth as white women, while American Indian/Alaska Native women are two times more likely, according to the Centers for Disease Control and Prevention. White, Asian, and Latina women have much lower rates of pregnancy-related deaths.

“We don’t know precisely why health disparities in maternal health exist,” said Patrice Desvigne-Nickens, M.D., co-author of the JWH paper on maternal mortality and a medical officer in the Heart Failure and Arrhythmia Branch in NHLBI’s Division of Cardiovascular Sciences. “But we do know that racial and ethnic minorities and older women tend to have cardiovascular risk factors that predispose them to adverse pregnancy outcomes.”

Risk factors such as hypertension, obesity, and physical inactivity can be present before pregnancy, she noted. Other adverse factors collectively called social determinants of health include living on a low income, having less education, experiencing impaired access to care, and being less able to find and use information that can inform health-related decision-making. There’s also bias in medical treatment as well as racial discrimination, all of which contribute to stress and adverse pregnancy outcomes, Desvigne-Nickens added.

“The good news is that conventional cardiovascular risk factors can be modified by women and their healthcare providers working together,” she said. “Together, they have the opportunity to reduce cardiovascular risks and improve outcomes before, during, and after pregnancy.” Additional research to address social determinants of health to reduce disparities and improve health equity is also needed, Desvigne-Nickens said.

A related article in the JWH issue addressed the link between pregnancy-related CVD and sleep apnea, a serious condition that causes repeated episodes of partial or complete airflow blockage during sleep. It is accompanied by drops in blood oxygen levels and stress on the cardiovascular system. Studies indicate that women are more susceptible to sleep apnea during pregnancy due to factors including weight gain, hormonal changes, and increased nasal congestion. Importantly, several findings show that sleep apnea is associated with an increased risk of maternal cardiovascular complications such as preeclampsia and gestational diabetes.

African Americans are at higher risk for developing sleep apnea than other groups, which suggests the disorder may be contributing to health disparities associated with CVD outcomes. The contribution of sleep apnea to disparities in maternal health outcomes is an area that needs further exploration, researchers say.

“Evaluating women for sleep problems is not standard practice in obstetrics medicine. If a woman has sleep apnea, it’s likely to be overlooked,” noted Aaron Laposky, Ph.D., study co-author and program director of Sleep and Neurobiology at the NHLBI’s National Center on Sleep Disorders Research. The paper was co-authored by Victoria Pemberton, MS, RNC, a program officer and researcher in NHLBI’s Division of Cardiovascular Sciences.

“We hope that recent accumulation of research findings will increase awareness that sleep apnea is a risk factor for maternal cardiovascular disease and adverse pregnancy outcomes,” Laposky said.

Snoring and gasping for air during sleep can indicate sleep apnea. The condition is most often treated with a continuous positive air pressure (CPAP) machine, a device that delivers air through a mask to keep the airway open when worn during sleep. Clinical trials are underway to determine whether treating sleep apnea during pregnancy reduces the risk of CVD. Women who are pregnant and have symptoms of sleep apnea should bring up the issue with their physician, the researchers said.

NHLBI’s Varagic also encourages women to try to develop healthier lifestyles. This includes eating a healthy diet, getting regular physical activity, maintaining a normal weight, addressing sleep-disordered breathing, and seeing doctors regularly, she said.

“The pregnancy and post-pregnancy periods offer a window of opportunity to educate women about their cardiovascular risks,” Varagic said, noting that prevention and early screening may hold the key to stopping the alarming surge in maternal deaths in this country.