The Preterm Prediction Study:: The value of serum alkaline phosphatase, α-fetoprotein, plasma corticotropin-releasing hormone, and other serum markers for the prediction of spontaneous preterm birth

OBJECTIVE: High levels of a number of analytes are found in maternal blood; alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women. STUDY DESIGN: We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at <35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, a-fetoprotein, corticotropin-releasing hormone, and 5 other analytes. RESULTS: Alkaline phosphatase, a-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatese at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at <35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 8.3 (range, 2.2-30.9) and for spontaneous preterm birth at <35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-re leasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at <35 weeks, with an odds ratio 3.4 (range, 1.0-10.9). CONCLUSION: Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at <35 weeks.