Fetal Sex-Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period

Problem: Several pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences. Method of study: Using maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum. Results: Male fetal sex was associated with higher levels of proinflammatory cytokines (G-CSF, IL-12p70, IL-21, and IL-33) and angiogenic factors (PlGF and VEGF-A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL-5, IL-9, IL-17, and IL-25). IL-27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex-based difference in analyte concentrations at the postpartum measurement. Conclusion: Women carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus.