INFLAMMATORY CYTOKINES DURING PREGNANCY PREDICT POSTPARTUM ANXIETY: FINDINGS FROM A PROSPECTIVE PREGNANCY COHORT

Abstract Background Studies have linked inflammation with both depression and anxiety disorders. Pregnancy confers large- scale immune changes, and elevated inflammatory cytokines (particularly IL-1b and IL-6) during pregnancy have been associated with postpartum depression. However, the relationship between pregnancy cytokines and postpartum anxiety has not been thoroughly explored. Methods We included 716 participants from Generation C, a prospective pregnancy cohort in New York City (recruited from April 2020 - February 2022). Anxiety symptoms were assessed 1-8 months postpartum via the Generalized Anxiety Disorder (GAD) questionnaire. Cytokine levels were measured in blood from routine draws throughout pregnancy. Using quantile regressions, the relationship between cytokine levels (log-transformed) and continuously measured postpartum anxiety symptoms was investigated separately for 4 cytokines (IL-6, IL-17A, IL-1b, and CRP). The analyses were adjusted for maternal race/ethnicity, maternal education, parity, SARS-CoV-2 infection status during pregnancy, and GAD response timing. Results Participants' mean age was 33.0 (SD=4.91). 74 (10.34%) individuals were Asian, 85 (11.87%) were,192 (26.82%) Hispanic, and 327 individuals (45.67%) were white. Mean GAD score was 2.9 (SD=3.6), and 43 (6%) participants scored above the clinical cutoff (>10) for moderate/high anxiety. After adjustment, IL-17A was significantly associated with increased GAD score at the 75% quantile (b=0.70, SE=0.24, p=0.004). IL-6, IL-1b and CRP were not significantly associated with postpartum anxiety. Conclusion These findings suggest a significant link between pregnancy inflammation and postpartum anxiety among those experiencing the highest anxiety symptoms. While specific mechanisms require further exploration, this relationship not only advances our understanding of postpartum mental health but may also encourage investigation into novel applications of anti-inflammatory medications in the field of psychiatry.