Analysis of first-trimester maternal serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels as a potential non-invasive biomarker for fetal aneuploidy and NTDs
Restricted accessResearch articleFirst published online March, 2026
Analysis of first-trimester maternal serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels as a potential non-invasive biomarker for fetal aneuploidy and NTDs
Chromosomal abnormalities and congenital anomalies have huge impact on infant mortality and morbidity. The combined incidence affects approximately 1 per 1000 pregnancies. Current diagnostic modalities include ultrasonography and biomarkers like Beta hCG, PAPP-A and Alpha fetoprotein which have limitations due to their varied sensitivity and specificity in aneuploidy and NTD detection. PCSK9, a proprotein converters appears to have an escalating role in neurogenesis, neuronal differentiation and neurological diseases apart from its role in lipid metabolism. This study estimates serum PCSK9 levels in pregnant women with normal gestation and those with high risk for Aneuploidy and NTDs.
Methods
This prospective case control study included 40 pregnant women with high risk of aneuploidy and NTDs (cases) diagnosed by prenatal screening with ultrasonography findings, Beta HCG, PAPP-A and 40 pregnant women with a healthy singleton pregnancy (controls). Statistical analyses were performed in SPSS software version 16. Fetal and maternal characteristics, serum Beta HCG, PAPP-A, PCSK-9 and aneuploidy risk scores were compared between two groups.
Results
This study observed significant difference in Beta HCG, PAPP-A and PCSK9 levels between the groups (P < .05). The PCSK9 levels were lower in cases [82.95 (70.41–90.74)] than control group [123.84 (102.515–152.70)]. PCSK9 levels <96.8 ng/mL had an 85% sensitivity and specificity. Further PCSK9 correlated with Trisomy 21 risk score and Beta HCG (P < .05).
Conclusions
Maternal serum PCSK9 is decreased in high-risk pregnancy during first trimester. With 85% sensitivity, the marker could be a reliable screening tool during prenatal screening which needs further validation.
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