Objective. Leptin is a highly hydrophilic protein that circulates in plasma as a 16-kDa protein. It is produced in adipose tissue and also recently described to be synthesized by placental tissue. Plasma concentration of leptin is positively correlated to body fat mass, and administration of recombinant leptin to mice indicates that leptin participates in the regulation of food intake and energy expenditure. Leptin may have a role during initiation of human pubertal development. Gender differences have been reported among adults as well as among children, even after correction for body fat content. Little is known about variation in leptin levels during pregnancy or the level or function of leptin in the growing fetus and infants. The aim of the present study was to examine plasma concentration of leptin in pregnant women and their newborn infants during the first 3 months of life, and to relate plasma leptin concentration to body weight and gender during this period.

Materials and Methods. Among 609 women recruited to study the effect of very long-chain n-3 fatty acids during pregnancy, 180 women were selected to study leptin as well. The women were all healthy and nulli- or primiparas, and 16% were smokers. The study was randomized and double-blinded, and the participants received either 10 mL of cod liver oil (Peter Möller, avd.av Orkla ASA, Oslo, Norway) daily or the same amount of corn oil. Blood samples were taken from the mothers during pregnancy in weeks 18 and 35, and from the umbilical cord and from 4- and 14-week-old infants. The mothers' body mass index (BMI) at 18 and 35 weeks of pregnancy was calculated by using body weight recorded within 1 week or, if this was missing, by using means from weights at the closest time points before and after the sampling. The infants were weighed and measured at local health care centers. Plasma leptin concentration was measured by radio immunoassay (Linco Research, St Charles, MO) using recombinant125I-leptin as tracer.

Results. We found no differences between the group receiving cod liver oil and the group receiving corn oil in any of the measured variables; thus, the groups are treated statistically as one. Leptin concentration in maternal plasma increased during pregnancy from 15.5 ± 9.0 μg/L (n = 175) in week 18 to 17.7 ± 10.7 μg/L (n = 166) in week 35. Mothers, pregnant with female fetuses (n = 77), had a significant increase in plasma leptin concentration, from 15.5 ± 8.8 μg/L (n = 83) at 18 weeks to 18.5 ± 10.9 μg/L (n = 80) at 35 weeks of pregnancy, whereas in mothers pregnant with male fetuses, the increase was insignificant (15.4 ± 9.3 μg/L (n = 92) to 17.0 ± 10.5 μg/L (n = 86). BMI increased during the same time period, from 24.2 ± 3.3 kg/m2  to 27.8 ± 3.8 kg/m2  (n = 174). There was a significant correlation between BMI and plasma leptin concentration at 18 weeks (r = 0.54, n = 169) and at 35 weeks (r = 0.45, n = 160), but we found no change in the relative leptin concentration (plasma leptin concentration/BMI) from week 18 to week 35. We found no significant difference between smokers and nonsmokers in plasma leptin concentration, neither at 18 nor 35 weeks of pregnancy. Gender differences in plasma leptin concentration was present already at birth in umbilical cord plasma (10.8 ± 9.2 μg/L for girls [n = 65] vs 7.6 ± 6.6 μg/L for boys [n = 74]). We also observed gender differences in plasma leptin concentration at 4 weeks (3.9 ± 1.8 μg/L,n = 68 vs 3.2 ± 1.8 μg/L, n = 71) and 14 weeks of age (4.9 ± 2.1 μg/L, n = 61 vs 4.1 ± 3.1 μg/L, n = 73). Plasma leptin levels at 4 and 14 weeks were lower than the level in umbilical cord plasma (n = 101). An increase in plasma leptin concentration was observed from 4 to 14 weeks of age, both for girls (n = 48) and for boys (n = 60). Leptin concentration in umbilical cord plasma correlated with birth weight (r = 0.44, n = 139), and there was significant correlation (r = 0.23, n = 124) between leptin in plasma and body weight at 14 weeks of age. We observed no correlation between maternal leptin concentration at 35 weeks of pregnancy and the birth weight of the neonates or the leptin levels in umbilical cord plasma.

Conclusion. The leptin levels of the mothers increased during pregnancy and correlated to BMI, but the relative leptin concentration (plasma leptin concentration/BMI) did not change. Our findings demonstrate that gender differences in plasma leptin concentrations already are present at birth. A reduction of 61% in plasma leptin concentration was found from birth to 4 weeks of age. The increase in plasma leptin concentration from 4 to 14 weeks of age can be explained by the increase in weight during the same period. Together with the recent observation that leptin mRNA is expressed in placenta, our present results indicate that placenta may contribute to the high level of leptin found in umbilical cord plasma and suggest a role for leptin in intrauterine growth and development.

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