Abstract

Prenatal exposure to maternal stress may be associated with coronary heart disease (CHD) risk, however few studies have direct measures of in utero stress (e.g. maternal cortisol levels) and offspring adulthood CHD risk factors. Increased prenatal stress during the third trimester was hypothesized to be associated with an increase in 10-year CHD risk in middle-aged offspring. Participants were 282 offspring from the New England Family Study. Third trimester maternal serum samples, collected between 1959 and 1966, were analyzed for maternal free cortisol. The validated Framingham Risk Algorithm calculated the 10-year risk score in offspring using the CHD risk factors: blood pressure, total cholesterol, HDL cholesterol, diabetes, smoking, age, and sex. Multiple linear regression, stratified by sex, assessed associations between ordinal tertiles of maternal cortisol and the natural log of the 10-year CHD risk score, adjusting for offspring’s age, race, body mass index (BMI), and in utero socioeconomic index (SEI). In females, maternal cortisol was positively associated with log 10-year CHD risk score (β=0.34, 95% CI: 0.12, 0.56, comparing highest to lowest maternal cortisol tertile), adjusting for age and race. Adjustment for SEI slightly attenuated effect size (β=0.26, 95% CI: 0.02, 0.50). Further adjustment for BMI attenuated effect size (β=0.14, 95% CI: -0.06, 0.35). Maternal cortisol was not significantly associated with CHD risk score among males. In conclusion, higher prenatal levels of maternal cortisol were positively associated with calculated 10-year CHD risk among middle-aged female offspring. Adjusting for offspring adulthood BMI substantially reduced effect size, suggesting in may be a mediating mechanism. Associations were not observed in males. Additional research is needed to these replicate results and to better understand mechanisms involved, including gender differences.

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