Prospective evaluation of associations between prenatal cortisol and adulthood coronary heart disease risk: the New England family study.

Objective: Increasing evidence suggests that early life factors may influence coronary heart disease (CHD) risk; however, little is known about the contributions of prenatal cortisol. Objectives were to prospectively assess the associations of maternal cortisol levels during pregnancy with offspring's 10-year CHD risk during middle age.

Methods: Participants were 262 mother-offspring dyads from the New England Family Study. Maternal free cortisol was assessed in third-trimester maternal serum samples. Ten-year CHD risk was calculated in offspring at a mean age of 42 years, using the validated Framingham risk algorithm incorporating diabetes, systolic and diastolic blood pressure, total and high-density lipoprotein cholesterol, smoking, age, and sex.

Results: In multivariable-adjusted linear regression analyses adjusted for age and race/ethnicity, high versus low maternal cortisol tertile was associated with 36.7% (95% confidence interval [CI] = 8.4% to 72.5%) greater mean 10-year CHD risk score in women. There was no association in men (-2.8%, 95% CI = -23.8% to 24.0%). Further adjustment for in utero socioeconomic position showed 26.1% (95% CI = -0.5% to 59.9%) greater CHD risk in women. Adjustment for maternal age and size for gestational age had little effect on findings.

Conclusions: Maternal prenatal cortisol levels were positively associated with 10-year CHD risk among female, and not male, offspring. Adjusting for socioeconomic position during pregnancy reduced effect size in women, suggesting that it may be a common prior factor in both maternal cortisol and CHD risk. These findings provide evidence that targeting mothers who have elevated prenatal cortisol levels, including elevated cortisol in the setting of low socioeconomic position, may potentially reduce long-term CHD risk in their offspring.