Objective: The aim of this study was to investigate the association of the first trimester screening variables nuchal translucency (NT), pregnancy associated plasma protein (PAPP-A), and free beta-human chorionic gonadotrophin (βhCG) and birth weight, with a focus on the prediction of macrosomia. Methods: The database of our Fetal Medicine Unit was searched for all singleton pregnancies, who underwent first trimester Down syndrome screening. Live born infants born at term without chromosomal or structural defects from non-diabetic mothers constituted the study population. Birth weight percentiles were corrected for gestational age at delivery, parity, and gender. Macrosomia was defined as birth weight ≥95th centile. Results: We included 6503 fetuses. Multivariate analysis demonstrated that birth weight centile was positively correlated with NT multiples of the median (MoM), PAPP-A MoM, and maternal body mass index, and it was negatively correlated with smoking. An NT ≥95th centile was present in 315 fetuses (4.8%). Although median birth weight centile was not significantly different between cases with NT ≥95th centile and those <95th (P54 vs P52), a birth weight >95th centile was more common (11% vs 7%) in the presence of NT ≥95th centile. Pregnancy associated plasma protein was elevated (≥95th centile) in 303 cases (7.9%). Median birth weight was higher (P56 vs P51, P=0.03) in case of elevated PAPP-A compared with PAPP-A <95th centile. There was a trend toward higher macrosomia rate in case of PAPP-A ≥95th centile (7.4% vs 6.3%, P=0.07). Area under the receiver operating characteristics (ROC) curve for the prediction of macrosomia (birth weight ≥95th centile) by NT MoM, PAPP-A MoM, maternal body mass index, and maternal smoking was 0.64 (P<0.001). Conclusions: First trimester PAPP-A MoM and NT MoM are significantly related to birth weight centiles. Enlarged NT is associated with macrosomia.