Novel First-Trimester Prediction Model for Any Type of Preterm Birth Occurring before 37 Gestational Weeks in the Absence of Other Pregnancy-Related Complications Based on Cardiovascular Disease-Associated MicroRNAs and Basic Maternal Clinical Characteristics

The goal of the study was to establish an efficient first-trimester predictive model for any type of preterm birth before 37 gestational weeks (spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM)) in the absence of other pregnancy-related complications, such as gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age. The retrospective study was performed in the period from 11/2012 to 3/2020. Peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group with 80 singleton term pregnancies was selected on the basis of equal sample-storage time. A combination of only six microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p; AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut-off > 0.652) could predict preterm delivery before 37 gestational weeks in early stages of gestation in 52.83% of pregnancies with a 10.0% FPR. This predictive model for preterm birth based on aberrant microRNA expression profile was further improved via implementation of maternal clinical characteristics (maternal age and BMI at early stages of gestation, infertility treatment with assisted reproductive technology, occurrence of preterm delivery before 37 gestational weeks in previous pregnancy(ies), and presence of any kind of autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, type 1 diabetes mellitus, or other autoimmune disease)). With this model, 69.81% of pregnancies destined to deliver before 37 gestational weeks were identified with a 10.0% FPR at early stages of gestation. When other clinical variables as well as those mentioned above—such as positive first-trimester screening for early preeclampsia with onset before 34 gestational weeks and/or fetal growth restriction with onset before 37 gestational weeks using the Fetal Medicine Foundation algorithm, as well as positive first-trimester screening for spontaneous preterm birth with onset before 34 gestational weeks using the Fetal Medicine Foundation algorithm—were added to the predictive model for preterm birth, the predictive power was even slightly increased to 71.70% with a 10.0% FPR. Nevertheless, we prefer to keep the first-trimester screening for any type of preterm birth occurring before 37 gestational weeks in the absence of other pregnancy-related complications as simple as possible.