Prediction of birth weight small for gestational age with and without preeclampsia by angiogenic markers: an Odense Child Cohort study

Purpose: To investigate the predictive performance of placental growth factor (PlGF) and soluble FMS-like kinase 1 (sFlt-1) on birth weight and small for gestational age (SGA), in a large, population-based cohort. Methods: Women enrolled in the population-based, prospective Odense Child Cohort Study with early (GA n = 1937) were included. The association between log-transformed values of the biomarkers and birth weight Z-score was studied using multivariate regression models. The prediction of SGA overall, and in women developing preeclampsia, by biomarkers was evaluated using receiver operating characteristic analyses. Results: No substantial associations between early pregnancy biomarkers and SGA were seen. PlGF measured in late pregnancy demonstrated the strongest association with birth weight Z-score (adjusted β-coefficient = 0.43 [95%CI = 0.35; 0.50]). The area under curve (AUC) for predicting SGA was higher for sFlt-1/PlGF compared to sFlt-1 (0.74 versus 0.63, p = .006) and reached excellent prediction for SGA after preeclampsia (AUC 0.94). Optimal sFlt-1/PlGF ratio cut-offs had higher negative predictive value (NPV) and positive predictive value (PPV) for SGA (cut-off > 5.0; NPV = 99.1%, PPV = 5.4%) compared to each marker individually. Conclusion: The sFlt-1/PlGF ratio is a potential predictor of SGA in population-based screening, particularly when preeclampsia is also present.