Second trimester quad test for fetal down syndrome screening as a predictor of spontaneous preterm birth in a developing country: a population-based study

To evaluate the association between second-trimester serum biomarkers of Quad test (comprising alpha-fetoprotein (AFP), free β-hCG, unconjugated estriol (uE3), and inhibin-A (IhA)) and spontaneous preterm birth, and to develop a predictive model based on Quad test analysis. A cohort study was conducted using a prospectively collected database of singleton pregnancies undergoing routine Quad test screening. Serum biomarker levels were adjusted for covariates and expressed as multiples of the median. Pregnancy outcomes were followed up. Logistic regression was used to assess associations and construct a prediction model for spontaneous preterm birth, with predictive performance evaluated using ROC curve analysis. Internal validation was performed using bootstrapping methods. A total of 44,132 pregnancies were analyzed. Elevated AFP, β-hCG, and inhibin-A levels, together with reduced uE3, were significantly associated with an increased risk of preterm birth, with stronger associations observed for early preterm birth. The combined Quad test prediction model yielded an AUC of 0.682 (95% CI: 0.664–0.699) for predicting early preterm birth, but showed lower performance for overall preterm birth (AUC 0.564; 95% CI: 0.552–0.573). Quad test biomarkers are significantly associated with spontaneous preterm birth, particularly early preterm birth. Although predictive accuracy is limited, the Quad test may serve as a cost-free adjunct for identifying women at increased risk, thereby supporting counseling and early detection, especially in resource-limited settings.