Predicting risk of preterm delivery by second-trimester measurement of maternal plasma corticotropin-releasing hormone and α-fetoprotein concentrations

OBJECTIVE: Many women who have preterm labor have abnormally high plasma concentrations of the placental peptide corticotropin-releasing hormone and the fetal product alpha-fetoprotein in early pregnancy. This study was designed to evaluate the ability of these biochemical tests and a clinical risk factor score to prospectively discriminate pregnancies at high risk for preterm delivery. STUDY DESIGN: Eight hundred sixty women were studied prospectively from the early second trimester until delivery. A risk factor score for preterm delivery was calculated from the clinical history and maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations were measured by radioimmunoassay between 17 and 30 weeks' gestation. The risk factor score, corticotropin-releasing hormone concentration, and alpha-fetoprotein concentration for each woman were expressed as individual odds or likelihood ratios for preterm delivery and as a combined risk estimate derived from the 3 tests. RESULTS: Sixty women had preterm deliveries (n = 37 spontaneous labor, n = 23 planned deliveries), and these women had significantly higher concentrations of corticotropin-releasing hormone (median 1.92 multiples of the median) and alpha-fetoprotein (median 1.32 multiples of the median) than did women with term deliveries (median 1.00 multiples of the median, P < .001 for both tests), with these abnormalities being evident from early in the second trimester. The risk factor score was greater than or equal to 10 in 28% of women with preterm delivery and 7% of women with term delivery. The combination of all 3 markers resulted in a higher detection rate and a higher positive predictive value than the risk factor score, corticotropin-releasing hormone concentration, or a-fetoprotein concentration alone, correctly discriminating 37% of women who would have preterm deliveries with a false-positive rate of 5%. The positive predictive value was also 37% (odds of being affected given a positive result were 1:1.7). CONCLUSIONS: The combination of measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoptotein concentrations in the second trimester with risk factor scoring provides a more accurate indicator of the risk of preterm delivery than does risk factor scoring alone. This method of risk assessment may therefore be of use in targeting prevention strategies.