Exposure to hypertensive disorders, gestational diabetes, or premature birth in utero can leave lasting effects on the heart and blood vessels long before symptoms of cardiovascular disease appear.
Study: Adverse pregnancy outcomes and cardiovascular health in early adult offspring. Image credit: fizkes/Shutterstock.com
Recent research published in journals JAMA network open Our findings suggest that young adult offspring of mothers who experience adverse pregnancy outcomes have worse cardiovascular health. This association was most pronounced in hypertensive syndrome of pregnancy (HDP).
Pregnancy complications related to future heart disease
Adverse pregnancy events (APOs), including HDP, gestational diabetes (GD), and preterm birth (PTB), occur in nearly one-quarter of pregnancies in the United States, and the rate is increasing. These are associated with an increased risk of maternal cardiovascular disease later in life, including metabolic disease, coronary artery disease, acute coronary syndromes, and early death. However, their effects on offspring cardiovascular health remain unclear.
Intrauterine conditions associated with adult cardiovascular disease
More than 30 years ago, researchers proposed that low birth weight is associated with an increased risk of ischemic heart disease in adulthood. This has given rise to the developmental origins of health and disease paradigm, which tracks long-term health status from exposures during critical early developmental periods, particularly in utero.
This is supported by results from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, which showed that HDP, GD, and cardiometabolic risk factors during pregnancy are associated with lower CVH in offspring, as measured during early adolescence.
Studying diverse birth cohorts in the United States into young adulthood
The current study included 1,333 mother-infant pairs who were followed into young adulthood, with cardiovascular evaluations performed from the child’s birth until approximately age 22 years. The researchers aimed to examine how APO is associated with cardiovascular health and early arterial damage in young adult offspring.
The study used data from the Family Futures and Child Well-Being Study and the Family Futures – Youth Cardiovascular Health Study, which were conducted in 20 U.S. cities from February 1998 to September 2000. In the maternal cohort, the mean age at birth was 25 years. Of the offspring, 55% were female. Approximately 51% were black, 28% were Hispanic, and 17% were white.
Mothers were assessed for pregnancy outcomes including HDP, GD, and PTB based on pregnancy records. Children’s CVH at age 22 years was assessed using the American Heart Association Life’s Essential 8 (LE8) score, clinically determined cardiovascular risk factors, and carotid ultrasound to assess arterial injury.
The LE8 score is a composite cardiovascular health score calculated from diet quality, physical activity, sleep, smoking exposure, body mass index (BMI), lipids, glycated hemoglobin (HbA1c), and blood pressure. Higher scores indicate better CVH.
Overall, 128 offspring (10%) were exposed to HDP, 137 (10%) to PTB, and 67 (5%) to GD. HDP was more common among mothers with lower levels of education. GD exposure was more common among children born to older mothers, and PTB was more common among children born to mothers who smoked cigarettes during pregnancy.
Pregnancy complications are associated with poor metabolic health
After adjusting for confounders, HDP exposure was associated with less favorable CVH measures, including an average 2.8 kg/m increase in BMI. Diastolic blood pressure averaged 2.3 mm Hg and HbA1c was 0.2 percentage points higher.
There was no overall association between HDP and LE8 scores, but sleep scores were 7.7 units higher. Conversely, HDP is associated with lower scores on several factors such as BMI, blood glucose, and blood pressure, indicating worse CVH.
PTB is associated with elevated HbA1c and reduced LE8 glucose component scores, indicating worsened glucose-related cardiovascular health. Exposure to GD was associated with lower blood pressure scores.
Pregnancy complications related to early arterial vascular injury
HDP exposure was associated with an average increase of 0.02 mm in maximum and mean carotid intima-media thickness. GD exposure was also associated with increases in maximum and mean carotid intima-media thickness, but not with other arterial injury markers. The authors compared this to three to five years of vascular aging, and found that the risk of premature death, heart attack, and stroke in young adults increases by 34% for every 0.1 mm increase in thickness. The authors suggest that this may be due to endothelial dysfunction and vascular dysfunction.
On the other hand, the median gray scale of the carotid arteries was 3.7 units lower in HDP-exposed individuals, consistent with greater changes in lipid-rich arteries.
Further analysis confirmed that most associations related to HDP, as well as those between PTB and HbA1c, remained consistent even after accounting for fetal growth patterns at birth. However, the association with GD was weakened, suggesting that fetal growth may partially explain these findings.
Common genes and behaviors may drive cardiovascular risk
The authors suggest several mechanisms that may help explain these associations: common genetic factors, common health behaviors, social contexts that influence health, and inflammatory and oxidative stress pathways. Transgenerational behaviors and genes may also contribute to the risk of CVH that is shared across generations, contributing to maternal APO and offspring arterial damage.
Research limitations
Although this analysis was based on a large and diverse sample, APO prevalence was reported to be low because the parent study excluded many mother-infant pairs with complications. Being observational, it cannot generate causal inferences. Third, evolving guidelines may lead to inaccurate estimates of some APOs, especially GD.
Each exposure included only a small sample, which may have prevented the identification of some associations. The researchers also did not adjust their estimates of the probability of error resulting from testing multiple hypotheses, which could increase the chance of false positives.
Health during pregnancy may affect heart health in offspring decades later
Taken together, these findings suggest that exposure to APO, particularly HDP, may be associated with reduced cardiovascular health markers and early arterial damage in young adult offspring. According to the authors, this suggests that “optimizing health during pregnancy may support CVH in offspring into early adulthood.”
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