The association between pre-pregnancy and first-trimester hair cortisol and preterm birth: a causal inference model

Adverse life events and chronic psychological distress before and during pregnancy have frequently been associated with preterm birth but the biological underpinnings remain unclear. We investigated the association between corticosteroid levels in pre-pregnancy and first-trimester hair and the risk of preterm birth. We followed N=1,807 pregnant women from a prospective pre-birth cohort study in Lima, Peru. Hair samples were taken at the end of the first pregnancy trimester. The two most proximal 3 cm segments to the scalp (representing pre-pregnancy and first-trimester) were analyzed to obtain hair cortisol and cortisone concentrations (HCC and HCNC). Preterm birth was defined as birth<37 completed gestational weeks. We constructed four generalized propensity scores for pre-pregnancy and first-trimester HCC and HCNC to create corresponding inverse probability weights before fitting marginal structural models for estimating the effect of HCC and HCNC on preterm birth risk. Pre-pregnancy Log HCC was not independently associated with preterm birth risk (RR=0.97; 95%CI: 0.79, 1.19), nor was pre-pregnancy Log HCNC (RR=0.84; 95%CI: 0.58, 1.20). In the first trimester, a one SD increase in Log HCC was associated with a 37% increased risk of preterm birth (95%CI: 1.11, 1.69), whereas Log HCNC was not significantly associated with preterm birth risk (RR=1.20; 95%CI: 0.87, 1.65). Our findings show that chronic corticosteroid levels in early pregnancy are causally linked to preterm birth risk in pregnant Peruvian women. This finding contributes to understanding the biological underpinnings of preterm birth better to enhance its prevention.