AbstractObjectivesTo examine the relationship between newborn birth weight and first‐trimester uterine artery (UtA) pulsatility index (PI), maternal characteristics, serum pregnancy‐associated plasma protein‐A (PAPP‐A), free β‐human chorionic gonadotropin (β‐hCG) and fetal nuchal translucency (NT) thickness. We also examined the results of screening for large‐for‐gestational‐age (LGA) neonates by an integrated first‐trimester approach incorporating these parameters.MethodsWe evaluated maternal characteristics, fetal NT, PAPP‐A, free β‐hCG and UtA‐PI in 2097 singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. Linear models based on quasi Akaike's Information Criterion were used to determine the best predictive model for fetal birth weight. The patient‐specific risk of delivering an LGA infant was derived from multiple logistic regression analysis and the performance of screening was determined by receiver–operating characteristics curve analysis.ResultsThe best predictive models for fetal birth weight included UtA‐PI, PAPP‐A, NT, parity, maternal age, smoking status, weight, height and free β‐hCG. In pregnancies delivering LGA newborns compared with non‐LGA pregnancies, PAPP‐A and NT thickness were significantly increased (P = 0.016 and 0.001, respectively) and UtA‐PI was significantly decreased (P = 0.011). A combination of maternal factors with PAPP‐A, fetal NT and UtA‐PI identified 34.4% of LGA newborns for a false‐positive rate of 10%.ConclusionsThis study showed an association between newborn birth weight and maternal factors, and first‐trimester PAPP‐A, β‐hCG, fetal NT and UtA‐PI. Together, these factors can be used to identify over a third of pregnancies that will deliver LGA infants. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.