ArticleCureus2026
Utility of First-Trimester Combined Screening Markers for Identifying Pregnancy at Increased Risk of Fetal Chromosomal Abnormalities.
Article in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background First-trimester combined screening using biochemical and ultrasonographic markers is widely employed for early identification of pregnancies at increased risk for fetal screening-based high risk status. However, contemporary Indian data evaluating the performance of these screening markers and their follow-up outcomes remain limited. Objectives To evaluate the association of maternal clinico-demographic characteristics and first-trimester biochemical and ultrasonographic markers with chromosomal anomaly risk status and to assess follow-up outcomes of high-risk pregnancies. Methods This retrospective cross-sectional analytical study included 164 pregnant women who underwent first-trimester aneuploidy screening between 11 and 13+6 weeks of gestation at a tertiary care centre. Maternal demographic characteristics, biochemical markers [free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A)], and ultrasonographic parameters [nuchal translucency (NT) and crown-rump length (CRL)] were analysed. Statistical analyses included Fisher's exact test, Fisher-Freeman-Halton exact test, Mann-Whitney U test, Spearman's correlation analysis, and receiver operating characteristic (ROC) curve analysis to evaluate the discriminatory performance of biochemical markers for identifying pregnancies classified as high risk by first-trimester screening. Results Of the 164 participants, 10 (6.1%) were classified as high risk for chromosomal anomalies. Maternal clinico-demographic variables showed no significant association with high risk of chromosomal anomaly, except for the gravida category (p=0.026). High-risk pregnancies demonstrated significantly higher free β-hCG levels and free β-hCG multiples of the median (MoM) values and significantly lower PAPP-A and PAPP-A MoM values compared with low-risk pregnancies (all p<0.01). NT thickness also differed significantly between groups (p=0.042), whereas CRL showed no significant difference. ROC analysis demonstrated good predictive performance for free β-hCG MoM (AUC=0.76, p=0.006), while low PAPP-A MoM showed excellent discriminatory performance after inversion of direction [area under the curve (AUC)=0.937], indicating a strong association with screening-based high-risk status. All 10 high-risk pregnancies underwent non-invasive prenatal testing (NIPT); one pregnancy had a high-risk NIPT result that was subsequently confirmed by amniocentesis as a chromosomal anomaly, resulting in medical termination of pregnancy. Conclusion Combined first-trimester screening using free β-hCG, PAPP-A, and ultrasonographic assessment effectively identified pregnancies at increased screening risk for fetal chromosomal abnormalities. These findings should be interpreted cautiously because only one chromosomal abnormality was confirmed.
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