Prediction of Small for Gestational Age and Growth-Restricted Neonates at 35 to 36 Weeks of Gestation: A Multicenter Cohort Study

Abstract

Background and Objectives: Third-trimester screening is widely used to identify small for gestational age (SGA) and fetal growth restriction (FGR), but optimal models and timing remain under investigation. This study aimed to assess the performance of combined maternal factors and biomarkers, including ultrasound estimated fetal weight (EFW), Doppler indices, mean arterial pressure (MAP), and angiogenic biomarkers, for predicting SGA neonates after a routine 35-36 weeks' scan in an unselected population. Materials and Methods: We conducted a retrospective cohort study in three Spanish centers offering universal third-trimester ultrasound. Logistic regression analyses were carried out to predict birthweight < 10th and <5th percentile using maternal characteristics and medical history, EFW, MAP, Doppler indices, and the angiogenic biomarkers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Using a 10-fold cross-validation, we estimated the area under the receiver operating characteristic curve (AUC), detection rates (DRs), false-positive rates (FPRs), and their corresponding screen-positive rates (SPRs). External validation was performed using an independent cohort. Results: Among 3992 pregnancies, the DR of ultrasound alone for birthweight <10th percentile was 47.9% (95% CI: 44.0 to 51.9), with an FPR of 7.3%. Adding maternal factors increased DR to 57.0% (95% CI: 53.0 to 60.9) at 10% FPR and to 83.0% (95% CI: 79.9 to 85.9) at 30% FPR. Similarly, the DR of ultrasound alone for birthweight < 5th percentile was 48.4% (95% CI: 43.1 to 53.6), with an FPR of 4.5%. Adding maternal factors increased DR to 65.7 (95% CI: 60.5 to 70.5) at 10% FPR and to 88.2 (95% CI: 84.4 to 91.3) at 30% FPR. The inclusion of MAP, Doppler, and biomarkers provided marginal additional gains, particularly for <5th percentile prediction. To achieve a DR > 80%, an SPR of approximately 40% was required. Performance improved when focusing on neonates born before 38 weeks, with a DR of 77.5 (95% CI: 68.6 to 84.9) at 10% FPR for SGA < 10th percentile. However, less than 40% of screen-positive women remained undelivered by 40 weeks, limiting the number requiring further surveillance. Conclusions: A third-trimester screening at 35-36 weeks using maternal characteristics and EFW identifies most SGA neonates, particularly those delivering before 38 weeks. Even including other biomarkers, an SPR of about 40% should be necessary to achieve a high DR. However, less than 40% of the women would remain undelivered before a subsequent follow-up is required.