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

Glenn R. Markenson, George R. Saade, Louise C. Laurent, Kent D. Heyborne, Dean V. Coonrod, Corina N. Schoen, Jason K. Baxter, David M. Haas, Sherri Longo, William A. Grobman, Scott A. Sullivan, Carol A. Major, Sarahn M. Wheeler, Leonardo M. Pereira, Emily J. Su, Kim A. Boggess, Angela F. Hawk, Amy H. Crockett, Angela C. Fox, Ashoka PolpitiyaTracey C. Fleischer, Gregory C. Critchfield, Julja Burchard, J. Jay Boniface, Garrett K. Lam

Research output: Contribution to journalArticlepeer-review

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 (Proteomic Assessment of Preterm Risk study, NCT01371019) a preterm birth predictor comprising a ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin. OBJECTIVE: To determine the performance of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin 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 (Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor, NCT02787213) at 18 sites in the United States. Women had blood drawn at 170/7 to 216/7 weeks' gestation. For confirmation, we planned to analyze a randomly selected subgroup of women having blood drawn between 191/7 and 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 neonatal intensive care unit stay, and 4 represents perinatal mortality. RESULTS: A total of 5011 women were enrolled, with 847 included in this planned substudy analysis. There were 9 preterm birth cases at <320/7 weeks' gestation and 838 noncases at ≥320/7 weeks' gestation; 21 of 847 infants had neonatal composite morbidity and mortality index scores of ≥3, and 4 of 21 had a score of 4. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was substantially higher in both preterm births at <320/7 weeks' gestation and there were more severe neonatal outcomes. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was significantly predictive of birth at <320/7 weeks' gestation (area under the receiver operating characteristic curve, 0.71; 95% confidence interval, 0.55-0.87; P=.016). Stratification by body mass index, optimized in the previous validation study (22<body mass index≤37 kg/m2), resulted in an area under the receiver operating characteristic curve of 0.76 (95% confidence interval, 0.59-0.93; P=.023). The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio predicted neonatal outcomes with respective area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.57-0.77; P=.005) and 0.78 (95% confidence interval, 0.63-0.93; P=.026) for neonatal composite morbidity and mortality scores of ≥3 or 4. In addition, the ratio of insulin-like growth factor-binding protein 4 to sex hormone binding globulin significantly stratified neonates with increased length of hospital stay (log rank P=.023). CONCLUSION: We confirmed in an independent cohort the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin 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 ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin predictor may be to risk stratify patients for implementation of preterm birth preventive strategies and direct patients to appropriate levels of care.

Original languageEnglish (US)
Pages (from-to)100140
Number of pages1
JournalAmerican journal of obstetrics & gynecology MFM
Volume2
Issue number3
DOIs
StatePublished - Aug 1 2020

Keywords

  • biomarker
  • IGFBP4
  • insulin-like growth factor-binding protein 4
  • neonatal morbidity and mortality
  • pregnancy
  • prematurity
  • preterm birth
  • proteomics
  • sex hormone-binding globulin

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Performance of a proteomic preterm delivery predictor in a large independent prospective cohort'. Together they form a unique fingerprint.

Cite this