IGFBP-1 combined with CHRDL1 in mid-pregnancy serum for predicting fetal growth restriction in late pregnancy among women with gestational hypertension: a prospective nested case-control study.

OBJECTIVE: To investigate the association between mid-pregnancy serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) and chordin-like 1 (CHRDL1) and the occurrence of fetal growth restriction (FGR) in late pregnancy among women with gestational hypertension (GH).

METHODS: This prospective nested case-control study was conducted within an established cohort of pregnant women with GH from January 2021 to January 2025. A total of 731 singleton pregnant women with GH at 20-24 gestational weeks were enrolled and followed up by dedicated nurses (those lost to follow-up were contacted at least three times) until late pregnancy (≥28 weeks), with 711 completing the entire follow-up. Based on prenatal ultrasound diagnosis, 106 cases of FGR were identified. These cases were individually matched in a 1:2 ratio (matching factors: maternal age, pre-pregnancy body mass index (BMI), and parity) with 212 controls selected from women without FGR, resulting in a final nested case-control sample of 318 participants. Fasting serum samples were collected at 20-24 weeks of gestation, and IGFBP-1 and CHRDL1 levels were measured by enzyme-linked immunosorbent assay (ELISA). FGR occurrence was assessed based on estimated fetal weight (EFW) monitored by B-ultrasound. Spearman's correlation analysis evaluated associations between mid-pregnancy serum concentrations of IGFBP-1 and CHRDL1 with EFW. Conditional logistic regression identified determinants of FGR development in late pregnancy within the GH cohort. The discriminative performance of mid-pregnancy serum IGFBP-1 and CHRDL1 for late-pregnancy FGR prediction was assessed using receiver operating characteristic (ROC) curve analysis.

RESULTS: Among 731 pregnant women with GH, 20 (2.74%) were lost to follow-up, and 711 completed the entire follow-up; of these, 106 (14.91%) developed FGR. Following 1:2 matching with 212 controls, 318 participants were included in the nested analysis. Serum levels of IGFBP-1 and CHRDL1 were significantly higher in the FGR group compared with the control group (both p < 0.001). The two biomarkers were positively correlated with each other (r = 0.455, p < 0.05) and negatively correlated with EFW (r = -0.335, -0.304, both p < 0.05). Conditional logistic regression analysis revealed that elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), IGFBP-1, and CHRDL1 were independent risk factors for FGR, while elevated triglycerides (TG) were protective factors. ROC curve analysis demonstrated that the area under the curve (AUC) for IGFBP-1 and CHRDL1 alone in predicting FGR was 0.734 (95%CI: 0.677-0.791) and 0.704 (95%CI: 0.645-0.762), respectively; the combined AUC was 0.801 (95%CI: 0.750-0.852).

CONCLUSIONS: Elevated serum IGFBP-1 and CHRDL1 levels in mid-pregnancy are independent risk factors for FGR in late pregnancy among women with GH. The combination of these two biomarkers demonstrates favorable predictive value, providing an actionable biomarker panel for early identification of high-risk populations in clinical practice, enabling intensified monitoring and intervention initiation at 20-24 weeks of gestation, and ultimately improving perinatal outcomes.