Work

Development and internal validation of early- and mid-pregnancy prediction models for macrosomia in nulliparous singleton pregnancies

Year: 2026

Type: preprint

Abstract: Purpose Macrosomia is associated with adverse maternal and neonatal outcomes, but early risk stratification remains challenging. Most existing prediction approaches rely on later-pregnancy ultrasound measurements, limiting opportunities for earlier preventive counseling and monitoring. Methods In this secondary analysis of the prospective nuMoM2b cohort in the United States, we included 6,371 nulliparous singleton pregnancies selected for available periconceptional diet and ultrasound data at Visits 2 and 3. We developed visit-updated multivariable logistic regression models for birthweight >4000 g and >4500 g using routinely available maternal characteristics, anthropometry, periconceptional diet, and serial ultrasound measurements, with sensitivity analyses using large-for-gestational-age birthweight. Model performance was assessed by repeated stratified cross-validation and compared with World Health Organization fetal growth chart-based ultrasound percentile benchmarks, emphasizing the estimated fetal weight percentile as the most clinically familiar proxy. Results Birthweight >4000 g and >4500 g occurred in 7.9% and 1.2% of pregnancies, respectively. Models updated with later pregnancy information achieved the best discrimination, with an area under the receiver operating characteristic curve of 0.73 for birthweight >4000 g and 0.82 for birthweight >4500 g. In this selected analytic cohort, the early-pregnancy model based on maternal data alone provided moderate discrimination (0.63 and 0.72, respectively), although lower than the strongest third-trimester WHO fetal growth chart-based ultrasound percentile benchmarks. Conclusion Within this selected cohort, routinely available early-pregnancy maternal characteristics and anthropometry provided moderate risk stratification for macrosomia, and later ultrasound measurements improved performance further. Estimates for birthweight >4500 g require caution given the 77 events. External validation is required before clinical implementation. What this study adds to the clinical work Routinely available early-pregnancy maternal characteristics and anthropometry provided moderate risk stratification for macrosomia in nulliparous singleton pregnancies. Visit-updated models incorporating later ultrasound measurements improve discrimination further and may help refine surveillance during pregnancy.

Source: medRxiv

DOI: 10.64898/2026.10.29.26366704