The role of maternal age, markers of ultrasound, sFlt-1 and CA125 serum levels in the prediction of miscarriage: Study acronym: MIS-CARE (markers of ultrasound, immunologic and serum factors in the comprehensive analysis of the risks for early pregnancy loss).

OBJECTIVE: To evaluate the effectiveness of combining sociodemographic factors, circulating endothelial growth factor-1 (sFlt-1), cancer antigen 125 (CA125), placental growth factor (PLGF), along with ultrasound measurements of crown-rump length (CRL), and fetal heart rate (FHR) in assessing the risk of spontaneous abortion, and to develop a predictive model for miscarriage risk.

METHODS: Between 2020 and 2023, we conducted a prospective observational study involving 235 pregnancies. Participants were divided into 2 groups - viable pregnancies and miscarriage before the 14th week of gestation. We recruited all patients at 6.0 to 6.6 weeks of gestation. At that point, demographic data was collected, and the first measurements of CRL and FHR were performed. Blood samples were taken for sFlt-1, PLGF, and CA125 analysis. Consequent visits were appointed every 2 weeks, which included a US scan and repeated blood serum tests. The outcome variable was early pregnancy loss, defined by the occurrence of spontaneous abortion (SA) before 14 weeks of gestation.

RESULTS: Our study has shown that in cases with first-trimester pregnancy loss, the FHR and sFlt-1 were consistently decreased, while MA and CA125 were increased. We observed that a combination of MA, FHR, CRL, CA125, and sFlt-1 can reliably identify singleton pregnancies at risk of spontaneous abortion before 14 weeks of gestation. Each additional variable substantially improved the prediction characteristics, suggesting a good stepwise discriminatory performance of the overall model. The combination of all variables achieved a DR of 73,53 %, and more importantly - clinically feasible Positive Predictive Value (PPV) of 75,81 %, and high Negative Predictive Value (NPV = 94,75 %) levels.

CONCLUSION: Combining maternal age, FHR, CA125, and sFlt-1 can reliably identify singleton pregnancies at risk of spontaneous abortion before the 14th week of gestation. To our best knowledge, this is the first SA prediction model combining CA125 and sFlt-1 serum markers with well-established US modalities and demographic characteristics. External validation would be required before adopting the proposed prediction model in clinical practice.