First-Trimester Maternal Serum Biomarkers for Prediction of Pre-eclampsia: A Prospective Observational Study

Low PAPP-A and PlGF levels, along with elevated AFP, may indicate a higher risk for pre-eclampsia in the first trimester, but further validation is necessary before clinical application.

Summary and findings

This study evaluated the association of first-trimester maternal serum biomarkers with the prediction of pre-eclampsia (PE) in pregnant women. A total of 300 women were enrolled, and those who developed PE showed higher AFP and lower PAPP-A and PlGF concentrations. The combination of these biomarkers demonstrated a high discriminatory performance for predicting PE.

Abstract

Abstract Objective To evaluate the association and predictive performance of first-trimester maternal serum biomarkers—alpha-fetoprotein (AFP), free β-human chorionic gonadotropin (fβ-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF)—for the prediction of pre-eclampsia (PE) and to assess their relationship with adverse maternal and perinatal outcomes. Methods This prospective observational study was conducted over 18 months at the Department of Obstetrics and Gynecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, in collaboration with the Department of Pathology. Pregnant women with singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation were enrolled following written informed consent. Maternal characteristics and mean arterial pressure were recorded, and serum AFP, fβ-hCG, PAPP-A, and PlGF were measured using DELFIA technology. Biomarker concentrations were expressed as multiples of the median (MoM), with adjustment for relevant maternal and pregnancy characteristics. Participants were followed prospectively until delivery. The primary outcome was development of PE. Receiver operating characteristic analysis was used to assess the discriminatory performance of individual biomarkers and predefined biomarker combinations. Multivariable logistic regression was performed to evaluate associations between biomarker abnormalities and subsequent PE. Results Among 300 enrolled women, 38 (12.7%) developed PE. Compared with women who did not develop PE, those who developed PE had higher mean AFP MoM (1.42 ± 0.24 vs. 1.01 ± 0.15, p < 0.001) and lower mean PAPP-A MoM (0.72 ± 0.16 vs. 1.12 ± 0.20, p < 0.001) and PlGF concentrations (98 ± 35 vs. 158 ± 42 pg/mL, p < 0.001). The discriminatory performance was highest for PlGF (AUC 0.90, 95% CI 0.84–0.95), followed by PAPP-A (AUC 0.86, 95% CI 0.79–0.91) and AFP (AUC 0.81, 95% CI 0.74–0.87). The combination of AFP, PAPP-A, and PlGF demonstrated an AUC of 0.94 (95% CI 0.89–0.97), with a sensitivity of 95.1% and specificity of 87.7%. Free β-hCG showed limited discriminatory performance (AUC 0.61, 95% CI 0.52–0.70). In multivariable analysis, low PAPP-A (< 0.85 MoM), low PlGF (< 120 pg/mL), and elevated AFP (> 1.25 MoM) were associated with increased odds of subsequent PE, with adjusted odds ratios of 3.72 (95% CI 1.87–7.41), 4.65 (95% CI 2.29–9.40), and 2.58 (95% CI 1.34–4.99), respectively. Conclusion In this single-center prospective cohort, first-trimester low PAPP-A and PlGF and elevated AFP were associated with subsequent development of PE. The combination of AFP, PAPP-A, and PlGF showed good discriminatory performance and may have potential for early risk stratification. However, the findings should be interpreted as internally derived estimates, and external validation in larger, multicenter populations is required before routine clinical implementation. The influence of aspirin prophylaxis initiated following first-trimester risk assessment should also be considered when interpreting these findings.

Limitations

Not reported in abstract.

Elsewhere in the HCG (Human Chorionic Gonadotropin) corpus