Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery

Abstract

Objectives: Since pregnancies with a male fetus have higher perinatal complications attributed to placental dysfunction, including severe pre-eclampsia and intrauterine growth restriction, the objective of our study was to formally evaluate placental pathology for a placental origin of these sex-specific differences.

Design: Retrospective study at Mount Sinai Hospital in Toronto, Canada. Identification of 262 singleton pregnancies affected by severe pre-eclampsia and/or intrauterine growth restriction who delivered between 22 and 32 weeks' gestation from 2000 to 2010. Detailed placental pathology was reviewed, and data from 140 pregnancies with male fetuses were compared with 122 pregnancies with female fetuses. A comparison group of 40 unaffected pregnancies who delivered in the same gestational range was used to determine baseline rates of placental pathology.

Main outcome measured: Detailed placental pathology, including placental development/differentiation, velamentous umbilical cord insertion, maternal-fetal interface pathology, villous infarction, hemorrhagic lesions, villous development, and fetal vascular under-perfusion.

Results: Impaired placental development and differentiation was equally common amongst males (73/140, 52.1%) and females (69/122, 56.6%). Male placentas exhibited significantly higher rates of chronic deciduitis (17.9% vs. 9.0%; relative risk [RR] 1.98, 95% confidence interval [CI] 1.02-3.86) and velamentous umbilical cord insertion (9.5% vs. 1.7%; RR 5.66, 95% CI 1.30-24.6), and a significantly lower frequency of villous infarction (55.4% vs. 73.7%; RR 0.75, 95% CI 0.62-0.90) than female placentas. No significant differences were noted for other lesions.

Conclusions: Fetal sex exerts a differential effect on the placental pathology that mediates severe pre-eclampsia and/or IUGR. Placental pathology at birth may provide insight into the mechanisms linking adverse in utero events with long-term adult disease since, for example, a male tendency to an inflammatory pathology at the maternal-fetal interface may be linked to the excess risk of coronary artery disease.