Clinical validation of a proteomic biomarker threshold for increased risk of spontaneous preterm birth and associated clinical outcomes: A replication study

Julja Burchard, Ashoka D. Polpitiya, Angela C. Fox, Todd L. Randolph, Tracey C. Fleischer, Max T. Dufford, Thomas J. Garite, Gregory C. Critchfield, J. Jay Boniface, George R. Saade, Paul E. Kearney

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Preterm births are the leading cause of neonatal death in the United States. Previously, a spontaneous preterm birth (sPTB) predictor based on the ratio of two proteins, IBP4/SHBG, was validated as a predictor of sPTB in the Proteomic Assessment of Preterm Risk (PAPR) study. In particular, a proteomic biomarker threshold of −1.37, corresponding to a ~two-fold increase or ~15% risk of sPTB, significantly stratified earlier deliveries. Guidelines for molecular tests advise replication in a second independent study. Here we tested whether the significant association between proteomic biomarker scores above the threshold and sPTB, and associated adverse outcomes, was replicated in a second independent study, the Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TREETOP). The threshold significantly stratified subjects in PAPR and TREETOP for sPTB (p = 0.041, p = 0.041, respectively). Application of the threshold in a Kaplan– Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (p < 001, p = 0.0016) and rate of hospital discharge for both neonate (p < 0.001, p = 0.005) and mother (p < 0.001, p < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (p = 0.0083,) and 7.4-fold higher (p = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes.

Original languageEnglish (US)
Article number5088
JournalJournal of Clinical Medicine
Volume10
Issue number21
DOIs
StatePublished - Nov 1 2021

Keywords

  • Biomarkers
  • IBP4
  • Preterm birth
  • SHBG

ASJC Scopus subject areas

  • Medicine(all)

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