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

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.