Gender differences of placental dysfunction in severe prematurity

Objective Rates of several obstetric complications have been reported to vary with fetal gender. We investigated whether a sex difference exists in findings at placental histology of extreme prematurity. Design Case-control study. Setting University Hospital. Population Four hundred and thirty-seven consecutive deliveries before 32 weeks of gestation of singleton, liveborn, non-anomalous infants. Methods Obstetric, neonatal and placental histologic findings were compared between male (n= 232) and female (n= 205) neonates. Main outcome measures Histologic evidence of acute placental inflammation, uteroplacental vascular pathology, intraplacental vascular pathology and chronic placental inflammation. Results Male fetuses had similar racial distributions, rate of nulliparity, maternal age, gestational age at delivery, placental weight and fetoplacental weight ratio as female fetuses, but higher birthweight centiles (41 [27] vs 33 [26]). Placental histology showed no association between fetal gender and lesions of acute inflammation (P= 0.08), intraplacental vascular pathology (P= 0.16) or uteroplacental vascular pathology (P= 0.83). However, lesions of chronic inflammation had a significantly higher score in male than in female fetuses (P= 0.001). When we examined the distribution of chronic placental inflammation, significantly more severe lesions were noted in male than in female fetuses at the implantation site (i.e. the area of interstitial trophoblast invasion of the maternal decidua and maternal endovascular trophoblast remodelling), than within the placental villi (chronic villitis) or in the amniochorionic membranes (where interstitial trophoblast invasion is minimal). Conclusion In premature deliveries at <32 weeks, male fetal gender is associated with placental lesions suggestive of a maternal immune response against the invading interstitial trophoblast. The immunologic basis of these findings deserves further studies.