(1075) Male fetal sex associated with maternal respiratory failure in infection: a health records-based cohort study

Pregnancy is an immunologically complex state, requiring maternal adaptations to both tolerate the semi-allogeneic fetus and protect the dyad from infections. Biological evidence suggests that pregnancies carrying a male fetus may have altered inflammatory responses to immune challenges. We aimed to assess the impact of fetal sex on severe maternal respiratory morbidity as a proxy for severe immune response in pregnancies complicated by viral and/or bacterial infections.acute re

Study Design:

This is a retrospective cohort study of pregnant individuals with a live singleton birth and known fetal sex occurring at two large academic medical centers in Boston between January 2020 and July 2023. We examined features associated with maternal respiratory failure (ICD-10 J96.*) or acute respiratory distress syndrome (ARDS, ICD-10 J80.*) in individuals with a diagnosis of viral respiratory infection (SARS-CoV-2, influenza, parainfluenza, rhinovirus, adenovirus), disseminated varicella, pneumonia, or upper urinary tract infection/pyelonephritis during pregnancy. The primary exposure of interest was fetal sex. Multiple logistic regression was used to assess maternal and fetal factors associated with maternal respiratory failure/ARDS.

Results:

3,903 pregnant individuals met inclusion criteria. Of 33 individuals with respiratory failure/ARDS, 26 (79%) had a male fetus, compared with 1,993/3,870 (52%) in those without respiratory failure/ARDS; unadjusted odds ratio (OR) 3.5, 95% CI: 1.8-6.8 (Fig. 1A). Male sex, pre-existing airway disease, and presence of a hypertensive disorder were significantly associated with maternal respiratory failure/ARDS in a logistic regression model (Fig. 1B); adjusted OR male sex: 4.5, 95% CI: 3.5-5.6, p< 0.001.

Conclusion:

In this large retrospective cohort, male sex was a significant risk factor for severe maternal respiratory morbidity following both respiratory and urinary tract infections. These data add to the growing literature that fetal sex plays an important role in modulating the maternal immune response.