The Preterm Prediction Study: Toward a multiple-marker test for spontaneous preterm birth

OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic mar kers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those markers individually and in c ombination for an association with spontaneous preterm birth at < 32 and < 35 weeks gestational age. STUDY DESIGN: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontane ous preterm birth at < 32 weeks and 127 women with a spontaneous preterm bi rth at < 35 weeks were compared with results from matched-term control subj ects. RESULTS: In the univariate analysis, the most potent markers that are assoc iated with spontaneous preterm birth at < 32 weeks by odds ratio were a pos itive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and < 10th percentile cervical length (odds ratio, 5.8), and in serum, > 90th percent iles of alpha -fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and > 75th percentile of granulocyte colony-stimulating facto r (odds ratio, 5.5). Results for spontaneous preterm birth at < 35 weeks we re generally similar but not as strong. Univariate and multivariate logisti c regression analyses demonstrated little interaction among the tests in th eir association with spontaneous preterm birth. Combinations of the 5 marke rs were evaluated for their association with < 32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% Cl, 6.4-93.4). Among the case patients, 59% had greater than or equal to2 positive test r esults versus 2.4% of control subjects (odds ratio, 56.5; 95% Cl, 7.1-451.7 ). If a cutoff of 3 positive test results was used, 20% of case patients an d none of the control subjects had positive test results (P < .002). With t he use of only the 3 serum tests (alkaline phosphatase, alpha -fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 8 1 % of cases versus 22% of control subjects (odds ratio, 14.7; 95% Cl, 5.0- 42.7). For spontaneous preterm birth at < 35 weeks gestation, any 2 positiv e tests identified 43% of cases and 6% of control subjects (odds ratio, 11. 2; 95% Cl, 4.8-26.2). CONCLUSION: Overlap among the strongest biologic markers for spontaneous pr eterm birth is small. This suggests that the use of tests such as maternal serum alpha -fetoprotein, alkaline phosphatase, and granulocyte colony-stim ulating factor as a group or adding their results to fetal fibronectin test and cervical length test results may enhance our ability to predict sponta neous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.