Fetal sexual dimorphism and preeclampsia among twin pregnancies

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

We conducted a retrospective cohort study of 1,032 twin pregnancies between 2011 - 2022 using data from a perinatal database that recruits participants from three hospitals in Houston, TX. We categorized pregnancies based on fetal sex pairings into female/female, male/male, and female/male. Pregnancies with a female/female fetal sex 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 (RR) and 95% confidence interval (CI) for the association between fetal sex pairs and HDP.

Adjusted models of female/male fetal sex pairs were associated with preterm preeclampsia (RR 2.01, 95% CI 1.15-3.53) relative to those with female/female fetuses. No associations with other HDP were observed among pregnancies with male/male fetal sex compared to 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.