Preterm birth is the principal contributor to neonatal death and morbidity worldwide. We previously described a plasma cell-free RNA panel that between 16 and 20 weeks of pregnancy had potential to predict spontaneous preterm birth (sPTB) ≤ 32 weeks caused by preterm labor (PTL) or preterm premature rupture of membranes (PPROM). The present study had three objectives: (1) estimate the RNA panel prognostic accuracy for PTL/PPROM ≤ 32 weeks in a larger series; (2) improve accuracy by adding clinical characteristics to the predictive model; and (3) examine the association of the RNA panel with preeclampsia. We studied 289 women from Memphis TN prospectively sampled 16.0-20.7 weeks and found: (1) PSME2 and Hsa-Let 7g were differentially expressed in cases of PTL/PPROM ≤ 32 weeks and together provided fair predictive accuracy with AUC of 0.76; (2) combining the two RNAs with clinical characteristics improved good predictive accuracy for PTL/PPROM ≤ 32 weeks (AUC 0.83); (3) NAMPT and APOA1 were differentially expressed in women with 'early-onset preeclampsia' (EOP) and together provided good predictive accuracy with AUC of 0.89; and (4) combining the two RNAs with clinical characteristics provided excellent predictive accuracy (AUC 0.96). Our findings suggest an underlying common pathophysiological relationship between PTL/PPROM ≤ 32 weeks and EOP and open inroads for the prognostication of high-risk pregnancies.
Keywords: early onset preeclampsia; extreme prematurity; plasma RNA; plasma transcriptome; preeclampsia; preterm birth; preterm labor; prognostication; screening.