Placenta. 2026 Sep 9;183:136-143. doi: 10.1016/j.placenta.2026.09.002. Online ahead of print.
ABSTRACT
BACKGROUND: Fetal sex influences placental development and immune regulation. Although sex-related differences in placental vascular pathology have been described, their influence on intra-amniotic inflammation and placental inflammatory responses in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) remains poorly understood.
OBJECTIVE: To determine whether fetal sex is associated with differences in the intensity of the intra-amniotic inflammatory response, the distribution of intra-amniotic categories defined according to the presence or absence of microbial invasion of the amniotic cavity and intra-amniotic inflammation, acute placental inflammatory lesions, and short-term neonatal outcomes in PPROM.
STUDY DESIGN: This retrospective cohort study included 852 singleton pregnancies complicated by PPROM between 23 + 0 and 36 + 6 weeks of gestation that underwent transabdominal amniocentesis. Pregnancies complicated by maternal hypertensive disorders or diabetes mellitus were excluded from the analysis. The intra-amniotic inflammatory response was assessed by amniotic fluid interleukin-6 levels. Placental inflammatory lesions were evaluated according to the histopathological criteria described by Salafia et al. RESULTS: The distribution of intra-amniotic categories (P = 0.28) and amniotic fluid interleukin-6 levels did not differ between pregnancies carrying female and male fetuses. The prevalence of most acute placental inflammatory lesions was comparable between the groups. However, pregnancies carrying female fetuses had a higher prevalence of early-stage funisitis (11% vs. 5%; P = 0.002). Female newborns also had a higher prevalence of bronchopulmonary dysplasia (7% vs. 3%; P = 0.002).
CONCLUSION: In PPROM, fetal sex was not associated with differences in the intra-amniotic environment. However, female fetuses exhibited a higher prevalence of early-stage funisitis, suggesting that fetal sex may modulate the earliest histopathological manifestation of the fetal inflammatory response despite comparable intra-amniotic inflammatory exposure.
PMID:42732680 | DOI:10.1016/j.placenta.2026.09.002
