Sex‐specific associations between hypertensive disorders in pregnancy and fetal and placental weight

ABSTRACT Importance Hypertensive disorders in pregnancy (HDPs) are common and increase the risk of maternal and fetal morbidity and mortality. HDPs may impact fetal growth; however, sex‐specific effects have been understudied. Objective To examine whether sex‐specific differences exist in the association between HDPs and birthweight and placental weight. Methods A birth cohort based in Detroit, Michigan, was utilized ( n = 1258). HDPs and birthweight were abstracted from medical records; placental weight was obtained from placental pathology reports. Linear regression was used to model sex‐specific associations, after multiple imputation, confounder adjustment, and inverse probability weighting to account for selection bias. Results The primary analysis included all pregnancies ( n = 853), while the secondary analysis included those sent for placental pathology, reflective of complicated pregnancies ( n = 165). In the primary analysis subset, males of mothers with gestational hypertension had birthweight Z‐scores that were on average 0.90 standard deviations higher, but this association was not found among females (interaction P = 0.019; male β [95% confidence interval {CI}]: 0.90 [0.28, 1.52]; female β [95% CI]: −0.12 [−0.65, 0.41]). However, in the subset of complicated pregnancies, female mothers with gestational hypertension also had reduced birthweight (interaction P = 0.013; male β [95% CI]: 1.50 [0.15, 2.86]; female β [95% CI]: −1.14 [−2.13, −0.16]). For fetoplacental weight ratio, any HDP was associated with a lower ratio among females only (interaction P = 0.028; male β [95% CI]: −0.04 [−0.71, 0.64]; female β [95% CI]: −0.95 [−1.57, −0.33]). Interpretation Male fetuses may prioritize growth, whereas females may prioritize placental development when exposed to HDPs.