Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis

Abstract

Background: : Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy.

Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy.

Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02-1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17-1.59).

Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE.

Keywords: ALSPAC; Sexual dimorphism; placenta; pre-eclampsia; sex ratio.

Figure 1.

Associations between fetal sex and overall PE between female and male pregnancies Results from random-effects models. Data reflect Odds ratios (95% Confidence Interval) in which female preeclampsia (PE) is compared to male PE.

Figure 2.

Associations between fetal sex and term de novo PE between female and male pregnancies Results from random-effects models. Data reflect Odds ratios (95% Confidence Interval) in which female term preeclampsia (PE) is compared to male term PE. Term PE was defined as gestational age ≥ 37+0 weeks at delivery.

Figure 3.

Associations between fetal sex and preterm de novo PE between female and male pregnancies Results from random-effects models. Data reflect Odds ratios (95% Confidence Interval) in which female preterm preeclampsia (PE) is compared to male preterm PE. Preterm PE was defined as gestational age < 37+0 weeks at delivery.

Figure 4.

Associations between fetal sex and very preterm de novo PE between female and male pregnancies Results from random-effects models. Data reflect Odds ratios (95% Confidence Interval) in which female very preterm preeclampsia (PE) is compared to male very preterm PE. Very preterm PE was defined as gestational age < 34+0 weeks at delivery.