Evaluating <scp>microRNA</scp> ‐720 and <scp>microRNA</scp> ‐1275 as Noninvasive Specific Test Compared With Maternal Serum Alpha‐Fetoprotein and Three‐Dimensional Ultrasound to Diagnose Fetal Neural Tube Defects

BACKGROUND: Neural tube defects (NTDs) are common congenital anomalies of the central nervous system and are associated with substantial fetal and neonatal morbidity and mortality. Although maternal serum alpha-fetoprotein (MSAFP) and ultrasonography (US) are routinely used for prenatal screening, small or atypical lesions may be missed. Circulating microRNAs have emerged as promising noninvasive biomarkers in prenatal diagnosis. AIM: To calibrate the diagnostic utility of circulating microRNA-720 and microRNA-1275 for prenatal detection of fetal NTDs and to compare their performance with MSAFP and two- and three-dimensional US. METHODS: This case-control study included 48 pregnant women undergoing second-trimester screening (15-22 weeks of gestation), divided into 24 cases with fetal NTDs and 24 controls with normal fetuses. All participants underwent detailed two- and three-dimensional US evaluation and MSAFP measurement. Circulating microRNA-720 and microRNA-1275 expression levels were quantified using real-time quantitative polymerase chain reaction, and diagnostic performance was assessed using receiver operating characteristic curve analysis. RESULTS: MicroRNA-720 was significantly upregulated and microRNA-1275 significantly downregulated in NTD-affected pregnancies compared with controls (p < 0.001). Both microRNAs showed high diagnostic accuracy. Expression levels varied among NTD subtypes, with the highest microRNA-720 levels observed in acrania, followed by encephalocele and spina bifida. MSAFP levels were also significantly higher in cases than in controls (p < 0.001). CONCLUSION: Circulating microRNA-720 and microRNA-1275 are promising noninvasive biomarkers that provide a molecular layer of validation for fetal NTDs. They may complement established tools by providing additional diagnostic confidence, particularly in cases with borderline biochemical profiles.