BACKGROUND: Leptin is an adipocyte-secreted hormone that regulates energy homeostasis, while its role in fetal programming remains poorly understood. We aimed to evaluate the effect of maternal weight status on cord blood leptin levels and their combined effect on fetal growth.METHODS: We included 638 mother-child pairs from the prospective mother-child cohort 'Rhea' study in Crete, Greece with singleton pregnancies, providing cord blood serum samples for leptin analysis and complete data on birth outcomes. Multivariable logistic and linear regression models were used adjusting for confounders. Generalised additive models were used to explore the form of the relationship between cord leptin and continuous birth outcomes.RESULTS: Log cord leptin was positively associated with birthweight {β-coef: 176.5 [95% confidence interval (CI): 133.0, 220.0] }, ponderal index (β-coef: 1.0 [95% CI: 0.6, 1.4] ) and gestational age (β-coef: 0.7 [95% CI: 0.5, 0.8] ). Excessive weight gain during pregnancy was associated with a threefold increased risk for cord hyperleptinaemia {relative risk (RR): 3.0, [95% CI: 1.5, 6.3] }. Maternal pre-pregnancy overweight/obesity [body mass index (BMI) ≥25 kg/m(2) ] increased the risk of giving birth to a hyperleptinaemic neonate (RR: 2.1 [95% CI: 1.4, 3.2] and the effect of log leptin on birthweight (β-coef: 219.1 [95% CI: 152.3, 285.9] compared with women with a BMI <25 kg/m(2) (β-coef: 150.5 [95% CI: 93.1, 207.9].CONCLUSIONS: Higher cord blood leptin levels are associated with increased size at birth and gestational age, while maternal pre-pregnancy BMI and weight gain during pregnancy represent significant indicators of cord blood leptin.