Fetal Sexual Dimorphism and Preeclampsia Among Twin Pregnancies

In singleton pregnancies, fetal sexual dimorphism has been observed in hypertensive disorders of pregnancy, particularly preeclampsia, a morbid syndrome that increases the risk of adult-onset cardiovascular disease for mothers and their offspring. However, few studies have explored the effect of fetal sex on hypertensive disorders of pregnancy among twin pregnancies.

We conducted a retrospective cohort study of 1032 twin pregnancies between 2011 and 2022 using data from a perinatal database that recruits participants from 3 hospitals in Houston, TX. We categorized pregnancies based on fetal sex pairings into female/female, male/male, and female/male. Pregnancies with female/female pairs were used as our reference group. Our primary outcomes included gestational hypertension, preeclampsia, superimposed preeclampsia, and preeclampsia subtyped by gestational age of delivery. A modified Poisson regression model with robust error variance was used to calculate the relative risk and 95% CI for the association between fetal sex pairs and hypertensive disorders of pregnancy.

Adjusted models of female/male pairs were associated with preterm preeclampsia (relative risk, 2.01 [95% CI, 1.15-3.53]) relative to those with female/female pairs. No associations with other hypertensive disorders of pregnancy were observed among pregnancies with male/male pairs compared with those with female/female fetal sex pairs.

We found some evidence of sexual dimorphism for preterm preeclampsia among female/male twin pairs. Additional research is needed to understand what biological mechanisms could explain these findings.