First-trimester β-hCG, PAPP-A, and NLR in relation to preeclampsia and perinatal outcomes: A case-control study

ObjectiveTo examine whether first-trimester PAPP-A, free β-hCG, NLR, and PLR are associated with subsequent development of PE, and among women with PE, whether these biomarkers are associated with adverse perinatal outcomes.MethodsIn this retrospective case-control study, we analyzed 350 primigravid women, including 175 with PE (cases) and 175 with uncomplicated pregnancies (controls). All participants had singleton gestations and available first-trimester (11 + 0 to 13 + 6 weeks) serum measurements of PAPP-A, free β-hCG, and complete blood count. Univariable and multivariable logistic regression models assessed associations of biomarkers with PE and, separately among PE cases, with the composite adverse perinatal outcome. Receiver operating characteristic (ROC) curve analysis quantified discriminative performance.ResultsIn multivariable analysis, first-trimester free β-hCG (OR = 1.358, 95% CI 1.206-1.530), PAPP-A (OR = 0.756, 95% CI 0.691-0.828), and NLR (OR = 1.655, 95% CI 1.214-2.256) were associated with PE. The combined model including these three markers showed improved discrimination for PE (AUC=0.793) compared with any marker alone. Among women with PE, higher β-hCG (OR = 1.489, 95% CI 1.242-1.784), elevated NLR (OR = 1.562, 95% CI 1.075-2.268), and lower PAPP-A (OR = 0.794, 95% CI 0.696-0.906) were associated with the adverse composite outcome in multivariable analysis. The multivariable model including these markers demonstrated an AUC of 0.804 for discrimination of the adverse composite outcome.ConclusionsFirst-trimester levels of PAPP-A, free β-hCG, and NLR may be associated with the subsequent development of PE and with adverse perinatal outcomes among affected women. These findings suggest potential biological relevance but do not establish clinical utility and should be interpreted with caution given the observational study design.