Maternal cortisol output in pregnancy and newborn telomere length: Evidence for sex-specific effects

Newborn telomere length is a potential biomarker of the effects of maternal-fetal processes on offspring long-term health. A number of maternal psychosocial and environmental factors in pregnancy (e.g., stress, health, socioeconomic status) have been associated with shortened telomere length at birth. The physiological mechanisms responsible for potential effects of maternal factors on newborn telomere length have yet to be identified. Indirect evidence suggests that disruptions in maternal hypothalamic-pituitary-adrenal (HPA) axis functioning in pregnancy may be involved. Studies are needed that test whether maternal HPA axis functioning in pregnancy is associated with newborn telomere length. This study examined whether maternal HPA axis functioning across pregnancy, reflected in hair cortisol collected within one week after delivery, predicted newborn telomere length assessed from leukocyte cord blood collected at birth among 93 sociodemographically diverse mother-infant dyads. We further tested whether associations between maternal hair cortisol and newborn telomere length differed by infant sex, given documented sex differences in prenatal environmental exposure effects on offspring health, patterns of cortisol exposure during gestation, and telomere biology across the lifespan. In a multi-group structural equation modeling analysis that accounted for cortisol exposures across trimesters, maternal cortisol levels in pregnancy were not associated with newborn telomere length in the sample as a whole. However, significant sex differences emerged, with a significant positive association among females and a lack of a significant association among males. In addition, analyses revealed that cortisol levels were higher across trimesters among mothers of male infants than mothers of female infants. The results suggest that functioning of the maternal HPA axis in pregnancy may differ by fetal sex and have sex-specific effects on newborn telomere biology. These findings have implications for understanding the mechanisms by which maternal psychosocial and environmental exposures influence newborn telomere length and for elucidating mechanisms contributing to sex disparities in health.