MicroRNAs isolated from peripheral blood in the first trimester predict spontaneous preterm birth

OBJECTIVE: To predict spontaneous preterm birth among pregnant women in an African American population using first trimester peripheral blood maternal immune cell microRNA. STUDY DESIGN: This was a retrospective nested case-control study in pregnant patients enrolled between March 2006 and October 2016. For initial study inclusion, samples were selected that met the following criteria: 1) singleton pregnancy; 2) maternal body mass index (BMI) <30 kg/m(2); 3) blood sample drawn between 6 weeks to 12 weeks 6 days gestation; 4) live born neonate with no detectable birth defects. Using these entry criteria, 486 samples were selected for study inclusion. After sample quality was confirmed, 139 term deliveries (38–42 weeks) and 18 spontaneous preterm deliveries (<35 weeks) were selected for analysis. Samples were divided into training and validation sets. Real time reverse transcription quantitative polymerase chain reaction (rt-qPCR) was performed on each sample for 45 microRNAs. MicroRNA Risk Scores were calculated on the training set and area-under-the-curve receiver-operating-characteristic (AUC-ROC) curves were derived from the validation set. RESULTS: The AUC-ROC for the validation set delivering preterm was 0.80 (95% CI: 0.69 to 0.88; p = 0.0001), sensitivity 0.89, specificity of 0.71 and a mean gestational age of 10.0 ±1.8 weeks (range: 6.6–12.9 weeks). When the validation population was divided by gestational age at the time of venipuncture into early first trimester (mean 8.4 ±1.0 weeks; range 6.6–9.7 weeks) and late first trimester (mean 11.5±0.8 weeks; range 10.0–12.9 weeks), the AUC-ROC scores for early and late first trimester were 0.79 (95% CI: 0.63 to 0.91) and 0.81 (95% CI: 0.66 to 0.92), respectively. CONCLUSION: Quantification of first trimester peripheral blood MicroRNA identifies risk of spontaneous preterm birth in samples obtained early and late first trimester of pregnancy in an African American population.