658: Prediction of pregnancy outcomes from serum and clinical factors in women receiving 17-alpha hydroxyprogesterone caproate (17-OHPC)

Abstract

We sought to improve prediction of spontaneous preterm birth (SPTB) and delivery gestational age (GA) in women with a prior SPTB receiving 17-OHPC by combining clinical factors with novel serum biomarkers. This is a secondary analysis of a prospective observational study of 5,501 women with singleton gestations at 11 US sites with the aim of developing SPTB biomarkers. For this analysis, we included women with a prior SPTB who received 17-OHPC; this subset was excluded from the parent analysis a priori. All preterm birth (PTB) cases were subject to expert adjudication masked to proteomic results. Medically indicated PTB were excluded. Targeted mass spectrometry quantified peptides from 63 proteins in serum drawn at 170/7 - 246/7 weeks. Clinical and proteomic profiles were examined to identify predictors of delivery GA (Outcome #1) and SPTB (Outcome #2). We evaluated models for correlation with delivery GA and AUC for SPTB prediction. Regularized regression selected significant predictors and Kaplan-Meier analysis estimated survival curves. ANOVA was used to compare models. Unsupervised hierarchical clustering was used to explore biological pathways of predictive peptides. 80 women met inclusion criteria. Serum was collected at a median of 4 (IQR 3 - 6) weeks after 17-OHPC initiation. Delivery was at a median of 37.6 (IQR 35 - 39) weeks; 42.5% had recurrent SPTB. In clinical-only models, education (<high school; mean effect -18 days) and cervical length (<25mm; mean effect -16 days) were associated with outcomes (Table). In peptide-only models, complement factor B (CFAB) and inhibin beta C chain (INHBC) peptides were the best predictors of delivery GA (Outcome #1). Each 2-fold increase in peptide levels prolonged GA by 6 (CFAB) and 26 (INHBC) days. The clinical + peptide models improved delivery GA and SPTB prediction compared to clinical-only models (Figure). CFAB alone also improved recurrent SPTB prediction over clinical-only models (Outcome #2). CFAB and INHBC clustered in a group of 10 inflammatory/stress proteins. Adding serum peptides to clinical risk factors improves prediction of delivery GA and recurrent SPTB in high-risk women receiving 17-OHPC. Outcomes in these women may be related to inflammatory mediators measurable in serum in mid-trimester prior to onset of clinical symptoms.View Large Image Figure ViewerDownload Hi-res image Download (PPT)