Impact of fetal sex on first trimester markers of placental development and pregnancy outcome: a prospective cohort study

Background: Placental development, maternal adaptations to pregnancy, and birth outcomes appear to differ based on fetal sex. The aim of this prospective cohort study was to investigate first trimester markers of feto-placental development and birth outcomes in a large population of healthy women with autologous pregnancies according to fetal sex. Methods: Healthy women with singleton pregnancies were enrolled at 11-13+6 weeks. At enrollment, maternal blood sample was collected for placental marker (Pregnancy Associated Plasma Protein A, free β-Human Chorionic Gonadotropin (HCG)), and ultrasound assessed mean pulsatility index of uterine arteries (UtA PI), placental volume and crown-rump length (CRL). Multi-adjusted generalized linear models were used to evaluate the associations between fetal sex, first trimester feto-placental markers, and pregnancy outcomes. Results: Among 1052 pregnancies (523 male, 529 female), female fetuses showed lower first trimester mean UtA PI (β = -0.10 (95 % CI -0.16; 0.03), p < 0.01) and CRL (β = -0.49 (95 % IC -0.96; 0-04), p < 0.05), and higher free-β-hCG (β = 19.8 (95 % IC 13.8-25.8), p < 0.001) in multi-adjusted models. Female sex was associated with a 69 % lower risk of preterm delivery. Male fetuses showed higher birth weight (p < 0.001). After excluding women undergoing a planned cesarean section, male fetuses showed lower arterial cord pH values regardless of the delivery mode (β = -0.21; 95 %IC: -0.40; -0-01, p < 0.05). Conclusions: The present study highlights crucial differences in prenatal development and placentation between male and female fetuses, leading to significant differences in pregnancy duration and response to labor stress.