Performance of a proteomic preterm delivery predictor in a large independent prospective cohort

Abstract Background Preterm birth remains a common and devastating complication of pregnancy. There remains a need for effective and accurate screening methods for preterm birth. Using a proteomic approach, we previously discovered and validated (PAPR study-NCT01371019) a preterm birth predictor comprising a ratio of insulin-like growth factor-binding protein 4/sex hormone-binding globulin (IBP4/SHBG). Objective To determine the performance of IBP4/SHBG to predict both spontaneous and medically indicated very preterm births, in an independent cohort distinct from the one in which it was developed. Study Design This was a prospective observational study (TREETOP-NCT02787213) at eighteen US sites. Women had blood drawn at 170/7 – 216/7 weeks. For confirmation, we planned to analyze a randomly selected subgroup of women having blood drawn between 191/7-206/7 weeks gestation, with the results of the remaining study participants blinded for future validation studies. Serum from participants was analyzed by mass spectrometry. Neonatal morbidity and mortality were analyzed using a composite score by a method from the PREGNANT trial (NCT00615550-Hassan et al.). Scores of 0-3 reflect increasing numbers of morbidities or length of NICU stay, and 4 represents perinatal mortality. Results A total of 5,011 women were enrolled, with 847 included in this planned sub-study analysis. There were 9 preterm birth cases Conclusion We confirmed, in an independent cohort, the IBP4/SHBG ratio as a predictor of very preterm birth, with additional prediction of increased length of neonatal hospital stay, and increased severity of adverse neonatal outcomes. Potential uses of the IBP4/SHBG predictor may be to risk-stratify patients for implementation of preterm birth preventive strategies and direct patients to appropriate levels of care.