ObjectiveTo assess the relationship between maternal corticotropin-releasing hormone (CRH) levels in second trimester sera, and the risk of preterm delivery in an ethnically heterogeneous sample of pregnant women.MethodsThis nested case-control study included two case groups (97 women who delivered before 35 weeks' gestation, 144 who delivered at 35–36 weeks' gestation), and a control group (244 women who delivered at or after 37 weeks' gestation) frequency matched by ethnicity (black, white) and by alpha-fetoprotein levels (normal, unexplained high). Corticotropin-releasing hormone was evaluated in stored maternal sera collected at 15–19 weeks' gestation from cases and controls.ResultsDelivery before 35 weeks' gestation was associated positively with a second trimester, ethnic-specific CRH above 1.5 multiples of the median in white women [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1, 5.1] and black women (OR 5.0, 95% CI 1.8, 13.3). Sensitivity was 29% in whites and 41% in blacks; specificity was 84% in whites and 80% in blacks. We estimated the positive and negative predictive values to be 6% and 97%, respectively, in white women, and 16% and 93%, respectively, in black women. It was also noted that, within case and control groups, black women had consistently lower CRH levels than white women.ConclusionFactors that lead to a premature increase in placental CRH production and are associated with an increased risk of preterm birth are evident as early as 15–19 weeks' pregnancy. When considering potential links between stressors, placental changes, CRH levels, and preterm birth, it might be important to stratify or adjust for ethnicity.