Beyond Human Chorionic Gonadotropin: The Role of Growth Differentiation Factor-15 and Insulin-like Growth Factor-binding Protein-7 in the Pathogenesis of Hyperemesis Gravidarum

Abstract

Objective: To evaluate the levels of serum growth differentiation factor 15 and insulin-like growth factor binding protein-7 in pregnant women with hyperemesis gravidarum and healthy matched pregnant controls, and their
independent and combined discriminatory value

Study Design: Prospective case-control study
Place and Duration of Study: This study was conducted at the Department of Obstetrics and Gynecology, Alzahraa Teaching Hospital, Najaf city, Iraq from May 2026 to July 2026.

Methodology: The study included 60 women who had hyperemesis gravidarum and 60 healthy pregnant controls of similar gestational age (6-16 weeks). To diagnose hyperemesis gravidarum, the patient had to have weight loss ≥5%, ketonuria ≥2+, dehydration and a PUQE-24 score ≥8.Serum growth differentiation factor 15 and insulin-like growth factor binding protein-7 were quantified by sandwich enzyme-linked immunosorbent assay. Diagnostic performance was measured using Receiver Operating Characteristic curve analysis and logistic regression adjusted for gestational age, maternal age, parity and body mass index.

Results: The median value of growth differentiation factor 15 was significantly greater in hyperemesis gravidarum (4,277 pg/mL) than controls (1,785 pg/mL; p<0.001). Median insulin-like growth factor binding protein-7 was also elevated (124.0 vs. 67.5 ng/mL; p<0.001). Growth differentiation factor 15 was positively correlated with the PUQE-24 score (Spearman r=0.58; p<0.001). The combined growth differentiation factor 15 + insulin-like growth factor binding protein-7 adjusted model achieved AUC=0.949 (95% CI: 0.897-0.987). There was no significant difference between groups (p=0.34) for serum human chorionic gonadotropin.

Conclusion: The levels of growth differentiation factor 15 and insulin-like growth factor binding protein-7 are significantly higher in HG and show good combined diagnostic accuracy. The absence of a difference in serum
human chorionic gonadotropin between groups corroborates the finding that growth differentiation factor 15, instead of human chorionic gonadotropin, is the more important hormone involved in hyperemesis gravidarum.