The utility of biomarkers in the prediction of preterm birth: A nested case control study of the ASPIRIN trial

Introduction and Aim: Adverse pregnancy outcomes (APO’s-preterm birth, foetal growth restriction and hypertensive disorders of pregnancy (HDP)) are the primary drivers of perinatal mortality. C-Reactive Protein, Anti-Mullerian Hormone (AMH) and Alpha-FetoProtein (AFP) have shown promise in predicting these APO’s. Aim of this present work is to validate the predictive ability of these biomarkers to identify women at risk for preterm birth. Materials and Methods: A nested observational case-control study was performed drawing nulliparous pregnant women between 10 to 13 weeks and 17 to 21 weeks of gestation in nulliparous women randomized to aspirin or placebo as part of the ASPIRIN (Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas) trial. Results: A total of 126 women with these APO’s and 143 controls were selected for analyte analysis. None of the chosen analytes were found to predict preterm birth before 37 weeks or HDP. AFP obtained between 10 to 13 weeks, was able to moderately discriminate against women who had a preterm birth prior to 34 weeks (C-statistic 0.65- 95% CI 0.55 to 0.78). No other analytes were found to be predictive of preterm birth prior to 34 weeks. Conclusion: Elevated Alpha-FetoProtein early in pregnancy is associated with early preterm birth (PTB) and may be a marker of Aspirin efficacy.