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To examine the potential role of maternal serum level of adiponectin in the first trimester of pregnancy in the prediction of neonatal macrosomia.Maternal serum adiponectin concentration was measured in a case–control study of singleton pregnancies at 11 to 13 weeks' gestation, which included 50 cases that subsequently delivered macrosomic neonates with birth weight above the 95th percentile for gestation at delivery and 300 controls who delivered appropriate for gestational age neonates. The median multiple of the median (MoM) serum adiponectin in the two outcome groups was compared and the bivariate Gaussian distributions were simulated in a screened population of 33 344 pregnancies to estimate the performance of screening for macrosomia by a combination of maternal characteristics and obstetric history with serum adiponectin.In the macrosomic group the median serum adiponectin [0.82, interquartile range (IQR): 0.56–1.02 MoM] was significantly lower than in the non-macrosomic controls (1.02, IQR: 0.70–1.29 MoM; p = 0.001). The estimated detection rate of macrosomia, at fixed false positive rate of 10%, from maternal characteristics and obstetric history was 34.6% and this increased to 38.2% with the addition of serum adiponectin.Maternal serum adiponectin at 11 to 13 weeks is a useful biomarker for early prediction of macrosomia. Copyright © 2011 John Wiley & Sons, Ltd.