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The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6 Ϯ 0.6 ng/mL; p Ͻ 0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p Ͻ 0.001) and fetal weight (p Ͻ 0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p Ͻ 0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p Ͻ 0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p Ͻ 0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress. Abbreviations AGA, appropriate for gestational age IUGR, intrauterine growth restricted LGA, large for gestational age GDM, gestational diabetes mellitus PI, pulsatility index FHR, fetal heart rate FBS, fetal blood sampling Leptin is a circulating polypeptide hormone expressed abundantly in the adipose tissue (1) that regulates body weight and energy expenditure through a negative feedback signal between the adipose tissue and the hypothalamic centers of satiety (2). In humans, there is a positive correlation between leptin and body fat content or body mass index (BMI), with a sexual dimorphism in its regulation at the same level of fatness or BMI, and significantly higher concentrations in females than in males (3, 4). Moreover, leptin deficiency is accompanied by reduced fertility in ob/ob female mice and leptin treatment restored fertility along with decreased dietary intake, body weight, and fat mass (5). Recently, these data have been confirmed in a 9-y-old girl with congenital leptin deficiency treated with recombinant leptin that lead to a sustained reduction in body weight and percent body fat, which was associated with an increase in gonadotropin concentrations and pulsatility (6).Leptin concentrations have been measured in cord blood of newborn infants and a significant relationship has been reported with fetal weight (7-11). Both fetal and placental pr...

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