Study of first-trimester serum levels of Beta-hCG and PAPP-A as a screening test for fetal development of intrauterine growth restriction

Abstract

Objective: To evaluate the association between first-trimester serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (b-hCG) and the development of intrauterine growth restriction (IUGR), in order to assess their utility in early screening for improved perinatal outcomes. Methods: A retrospective case-cohort study was conducted at Marqués de Valdecilla University Hospital in 2021, including 119 pregnancies with IUGR and a randomly selected subcohort of 383 pregnancies from the same population. Serum levels of PAPP-A and b-hCG were analyzed both as continuous variables and as categorical variables based on population-specific percentiles (< 10th and < 5th). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for relevant maternal and obstetric covariates. Results: Lower PAPP-A levels were significantly associated with an increased risk of IUGR, both as a continuous variable (OR = 0.50; 95% CI: 0.34-0.76, p = 0.001) and when categorized below the 10th percentile (OR = 4.01; 95% CI: 1.78-9.01, p < 0.001) and 5th percentile (OR = 4.45; 95% CI: 1.57-12.63, p = 0.005). b-hCG showed no association when analyzed continuously (p = 0.164), but values below the 10th percentile were significantly associated with IUGR (OR = 4.45; 95% CI: 1.97-10.04, p < 0.001). No reliable estimate could be obtained at the 5th percentile due to the small number of cases. Conclusion: Incorporating PAPP-A and b-hCG into first-trimester screening protocols could enable earlier identification of pregnancies at risk of IUGR, facilitating timely interventions and potentially improving maternal and neonatal outcomes. These findings support the clinical utility of these biomarkers in routine obstetric care.