The Role of Prenatal Maternal Sex Steroid Hormones in Weight and Adiposity at Birth and Growth Trajectories During Infancy

Objective : Intrauterine factors can impact fetal and child growth and may underlie the developmental origins of childhood obesity. Sex steroid hormone exposure during pregnancy is a plausible target because of the impact on placental vascularization, nutrient transportation, bone growth, adipogenesis, and epigenetic modifications. In this study we assessed maternal sex steroid hormones in each trimester in relation to birthweight, neonatal adiposity, and infant growth trajectories, and evaluate sensitive windows of development. Methods : Participants from a prospective pregnancy cohort who delivered at term were included in the analysis (n=252). Estrone, estradiol, and estriol, as well as total and free testosterone throughout gestation were assessed using high-performance liquid chromatography and tandem mass spectrometry. Path analyses were used to assess the direct associations of sex steroid hormones in each trimester with birth outcomes and infant growth trajectories (birth to 12 months) adjusting for covariates and considering moderation by sex. Results : The associations between prenatal sex steroid hormones and fetal/infant growth varied by sex and hormone assessment timing. First trimester estrone were associated with higher birthweight z-scores (β=0.37, 95%CI: 0.02, 0.73) and truncal skinfold thickness (TST) at birth (β=0.94, 95%CI: 0.34, 1.54) in female infants. Third trimester total testosterone was associated with higher TST at birth (β=0.61, 95%CI: 0.02, 1.21) in male infants. First trimester estrone/estradiol and first and third trimesters testosterone were associated with lower probabilities of high stable weight trajectory compared to low stable weight trajectory (Estrone: β=-3.87, 95%CI: -6.59, -1.16; First trimester testosterone: β=-3.53, 95%CI: -6.63, -0.43; Third trimester testosterone: β=-3.67, 95%CI: -6.66, -0.69) during infancy in male infants. Conclusions : We observed associations between prenatal sex steroid hormone exposure and birthweight, neonatal adiposity and infant growth that were sex and gestational timing dependent. Our findings suggest further investigation on additional mechanisms linking prenatal sex steroid exposure and fetal/postnatal growth is needed.