Exposure to hypertensive disorders, gestational diabetes, or preterm birth in the womb may leave lasting effects on the heart and blood vessels, long before symptoms of cardiovascular disease appear.
Study: Adverse Pregnancy Outcomes and Cardiovascular Health Among Offspring in Early Adulthood. Image credit: fizkes/Shutterstock.com
A recent study published in the journal JAMA Network Open suggests poorer cardiovascular health in young adult offspring of mothers who experienced adverse pregnancy outcomes. The association was most pronounced for hypertensive disorders of pregnancy (HDP).
Pregnancy complications linked to future heart disease
Adverse pregnancy outcomes (APOs), including HDP, gestational diabetes (GD), and preterm birth (PTB), occur in almost a quarter of pregnancies in the US, and their rates are rising. They are associated with an elevated risk of maternal cardiovascular disease in later life, such as metabolic disease, coronary artery disease, acute coronary syndrome events, and premature death. However, their influence on the offspring's cardiovascular health remains unclear.
In-womb conditions linked to adult cardiovascular disease
Over three decades ago, researchers proposed that low birth weight was associated with an increased risk of ischemic heart disease in adult life. This gave rise to the Developmental Origins of Health and Disease paradigm, which traced long-term health conditions to exposures during critical early developmental periods, particularly in utero.
This is supported by the findings of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, where HDP, GD, and cardiometabolic risk factors during pregnancy were linked to poorer CVH in the offspring, as measured in early adolescence.
Diverse US birth cohort examined into young adulthood
The current study included 1,333 mother-child dyads followed into young adulthood, with cardiovascular assessments performed at approximately 22 years of age, beginning at the child's birth. The researchers aimed to look at how APOs were linked to cardiovascular health and early arterial injury in young adult offspring.
The study used data from the Future of Families and Child Well-Being Study and Future of Families - Cardiovascular Health Among Young Adults study, conducted in 20 US 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. About 51 % were Black, 28 % Hispanic, and 17 % White.
The mothers were assessed for pregnancy outcomes, including HDP, GD, and PTB, based on pregnancy records. The CVH of the offspring at 22 years was evaluated using the American Heart Association’s Life’s Essential 8 (LE8) score, clinically determined cardiovascular risk factors, and carotid ultrasonography to assess arterial injury.
The LE8 score is a composite cardiovascular health score calculated from diet quality, physical activity, sleep, tobacco exposure, body mass index (BMI), lipids, glycated hemoglobin (HbA1c), and blood pressure. A higher score indicates 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 educational status. GD exposure was more common among offspring born to older mothers, and PTB among those born to mothers who smoked cigarettes during pregnancy.
Pregnancy complications linked to poorer metabolic health outcomes
After adjusting for confounding factors, HDP exposure was associated with less favorable CVH measures, such as a mean increase of 2.8 kg/m² in BMI. The diastolic blood pressure was higher by an average of 2.3 mm Hg, and HbA1c by 0.2 percentage points.
There was no overall association between HDP and the LE8 score, but the sleep score was higher by 7.7 units. Conversely, HDP was associated with poorer component scores for several components, including the BMI, blood glucose, and blood pressure, indicating worse CVH.
PTB was associated with higher HbA1c and a poorer LE8 glucose component score, indicating worse glucose-related cardiovascular health. GD exposure was associated with a poorer blood pressure score.
Pregnancy complications linked to early arterial vessel damage
HDP exposure was associated with a mean increase of 0.02 mm in maximum and mean carotid intima-media thickness. GD exposure was also associated with higher maximum and mean carotid intima-media thickness, although not with other arterial injury markers. The authors compare this to 3-5 years of vascular aging, with the risk of premature death, heart attack, or stroke, among younger adults, increasing by 34 % per 0.1-mm rise in thickness. The authors suggest that this could be due to endothelial dysfunction and impaired vascular function.
Meanwhile, the carotid grayscale median was 3.7 units lower among individuals exposed to HDP, consistent with greater lipid-rich arterial changes.
Further analyses confirmed that most associations involving HDP, as well as the association between PTB and HbA1c, remained consistent even after accounting for fetal growth patterns at birth. However, associations involving GD became weaker, suggesting that fetal growth may partly explain these findings.
Shared genes and behaviors may drive cardiovascular risk
The authors suggest several mechanisms that may help explain these associations: common genetic factors, shared health behaviors, social context influencing health, and inflammation and oxidative stress pathways. Transgenerational behaviors and genes could also contribute to the risk of CVH being shared across generations, accounting for APOs in the mothers and arterial injury in the offspring.
Study limitations
The analysis was based on a large and diverse sample, but reported a low APO prevalence because the parent study excluded many mother-infant pairs with complications. Being observational, it cannot produce causal inferences. Third, evolving guidelines could have led to incorrect estimates of some APOs, especially GD.
Each exposure involved only a small sample, which might have prevented the identification of some associations. Also, the researchers did not adjust their estimates for the probability of error arising from testing multiple hypotheses, potentially increasing the likelihood of false positives.
Pregnancy health may shape offspring heart health decades later
Taken together, these findings suggest that exposure to APOs, particularly HDP, may be associated with poorer cardiovascular health markers and early arterial injury in young adult offspring. According to the authors, this suggests that “optimizing pregnancy health may support offspring CVH into early adulthood.”
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