Utility of First-Trimester Combined Screening Markers for Identifying Pregnancy at Increased Risk of Fetal Chromosomal Abnormalities.

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.