Abstract
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, 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 evaluated 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 timing of hormone exposure. First-trimester estrone was 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 = 0.47, 95% CI: 0.03, 0.86) in both sexes. First-trimester estrone and estradiol and first- and third-trimester 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; Estradiol: β = -4.36, 95% CI: -7.62, -1.11; 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.