IL-1RA Autoantibodies Detected at 15 Weeks Associate with 2.3-Fold Higher Preterm Birth Odds in Multi-Cohort Analysis

The study tracked immune profiles from pre-pregnancy through 15-week samples in fertility patients and statewide screening archives. Women with subsequent preterm birth showed expanded autoreactivity and specifically elevated anti-IL-1RA antibodies that remove inhibition of IL-1β-driven inflammation known to promote uterine contractions. Mouse injection of the antibody reproduced placental damage and elevated maternal IL-1β matching human preterm histology.

This observational design links a measurable immune signal to preterm risk but cannot establish causation or rule out reverse causality from subclinical placental injury. Prior cytokine studies in smaller cohorts reported similar IL-1 pathway activation yet lacked the broad antibody screening that isolated IL-1RA as the dominant target here. Confounding by maternal age or prior preterm history was partially addressed through cohort matching.

Next steps require prospective validation of a screening threshold and randomized trials of IL-1 pathway modulators begun before 20 weeks. Large biobanks with serial sampling will be needed to determine whether the antibody signature precedes or follows early placental stress.