Second-trimester Maternal Serum Insulin-like Growth Factor Binding Protein 4 to Sex Hormone-binding Globulin Ratio as a Predictor of Spontaneous Preterm Birth: A Prospective Observation Study from North India

Background: The ratio of maternal serum insulin-like growth factor binding protein 4 (IGFBP-4) to sex hormone-binding globulin (SHBG) has emerged as a promising proteomic predictor, but validation in high-burden settings including India is limited. The aim of this study was to evaluate the predictive value of the second-trimester IGFBP-4/SHBG ratio for spontaneous preterm birth (PTB) and association with fetomaternal outcome. Methods: A prospective observational study was carried out over a period of 1 year. A total of 190 singleton pregnant women between 16 and 21 weeks of gestation were enrolled. Maternal serum IGFBP-4 and SHBG levels were measured by enzyme-linked immunosorbent assay (ELISA) technique using an ELISA kit as per the producer protocol. Participants were followed till delivery and categorized into Group A preterm (delivery <37 weeks, n = 54) and Group B term (delivery ≥37 weeks, n = 136). Predictive accuracy (AUROC) of the ratio for PTB was assessed. Fetomaternal outcomes were analyzed. Results: The PTB rate was 28.4%, and the second-trimester IGFBP-4/SHBG ratio was significantly higher in Group A than Group B (0.619 ± 0.399 vs. 0.191 ± 0.242; P < 0.001). ROC analysis for the ratio at enrollment yielded an AUC of 0.906 (95% confidence interval: 0.859-0.952). At a cutoff >0.188, the ratio showed 94.4% sensitivity and 79.4% specificity for predicting PTB. A raised baseline ratio was significantly associated with spontaneous preterm delivery (86.1% preterm vs. 37.8% term, P < 0.001), similarly low birth weight (74.7% vs. 36.0%, P < 0.001), low 5-min Apgar (10.1% vs. 0.0%, P = 0.001), and increased neonatal intensive care unit admission ( P = 0.031). Conclusion: The second-trimester maternal serum IGFBP-4/SHBG ratio is a highly sensitive and specific predictor for spontaneous PTB. It also correlates strongly with adverse neonatal outcomes.