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Original Studies |
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Gunma, Japan
Address all correspondence and requests for reprints to: Akira Harigaya, M.D., Department of Pediatrics, Gunma University School of Medicine, 3–39-15 Showa-machi, Maebashi, Gunma, 371, Japan. E-mail: ahariga{at}news.sb.gunma-u.ac.jp
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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One hundred sixteen Japanese infants were divided into term (n = 91) and preterm groups (n = 25). Term infants were divided into 3 subgroups: birth weight appropriate for gestational age (AGA) (n = 44), birth weight large for gestational age (LGA) (n = 28), and birth weight small for gestational age (SGA) (n = 19). Longitudinal changes in the concentration of serum leptin after birth were examined in 48 infants. The serum leptin concentration was determined by RIA.
No significant difference in leptin levels between cord sera and infants’ sera obtained within the first 6 h of life (n = 28) was observed. Within the first 6 h of life, the concentration of serum leptin in LGA infants (12.8 ± 10.2 ng/mL) and SGA infants (1.6 ± 1.1 ng/mL) was significantly higher and lower, respectively, than that in the AGA infants (4.4 ± 3.0 ng/mL) (P < 0.01). A significant positive correlation was found between the leptin concentration within 6 h of life and birth body weight (r = 0.59, P < 0.01). After birth, the concentration of leptin in LGA and AGA infants significantly decreased to the level in SGA infants within 48 h of delivery (P < 0.05). After 48 h of life, no significant differences in the concentration of leptin were observed among the three groups, and low levels continued to 7 days of age.
These findings indicate that serum level of leptin correlates with fetal body weight gain.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Fat deposition in the fetus in the third trimester increases markedly (9). The mechanism of adiposity and physiological roles of leptin in the fetus have yet to be elucidated. In the present study, whether or not the concentration of serum leptin correlates with growth in utero was investigated, in addition to how leptin levels change in the first few days after birth.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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One hundred sixteen Japanese infants were examined. All subjects were born in our hospital between March and December 1996, and the study was limited to infants for whom informed consent could be obtained. Neonates with dysmorphic features, major congenital malformations, intrauterine infections, organic disorders, or chromosomal disorders were excluded. The infants were divided into term (n = 91) and preterm groups (n = 25). Term infants were divided into 3 subgroups: birth weight appropriate for gestational age (AGA) (n = 44), birth weight large for gestational age (LGA) (n = 28), and birth weight small for gestational age (SGA) (n = 19). The body weight of all preterm infants was appropriate for gestational age (AGA). Gestational ages were determined from the last menstrual period of the mother and confirmed by antenatal ultrasonic measurement of the biparietal diameter. Ten mothers who delivered LGA infants had diabetes mellitus (DM) (5 had gestational DM, 4 had noninsulin-dependent DM, 1 had insulin-dependent DM). The Ponderal Index was used for nutritional assessment of the neonate (9). The Ponderal Index was calculated as follows: Ponderal Index = body weight (g)/[body length (cm)]3 x 100. Twenty-five healthy adults (13 males and 12 females), age 31.4 ± 4.7 yr with body mass index 18–25 kg/m2, served as a control.
Blood sampling and examination of serum concentration of leptin and insulin
Twenty-eight samples of cord blood (20 AGA, 6 LGA, and 2 SGA) taken from the 91 term infants were obtained from the umbilical vein immediately after birth. In the 116 infants, venous bloods were obtained within 6 h after birth from antecubital vein. In 48 infants subjected to a longitudinal study of serum leptin levels, venous bloods were obtained from each infant, sometimes at random, at from 2 to 7 days of life, in addition to the sample taken within 6 h after birth. Sera were obtained by centrifugation, immediately frozen, and stored at -20 C until assay. The serum leptin concentration was determined by RIA (Linco Research, St. Louis, MO). The coefficient values of inter- and intraassays were 4.2% and 3.8%, respectively. The detection limit was 0.5 ng/mL. Serum insulin levels were measured using a commercialized enzyme immunoassay kit.
Statistical analysis
All data are expressed as mean ± SD. Differences between groups were tested using the Mann-Whitney test for unrelated samples and the Wilcoxon test for paired samples. Linear regression analysis was used to evaluate correlation. Variance analysis was used to determine significant differences among the groups.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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. No statistically significant
difference in the concentration of leptin was found between these two
samples. Thus, for the remainder of this study, the serum concentration
of leptin within 6 h of life was assumed to reflect the levels in
fetal circulation.
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. The placental
weight and Ponderal Index of the LGA group were significantly higher
than those of the AGA group. Although no statistically significant
differences were found among the three groups with respect to serum
insulin levels, the LGA group had slightly higher insulin levels.
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. The serum leptin levels in term AGA
infants (4.4 ± 3.0 ng/mL) were significantly lower than those of
normal adults in our laboratory (16.9 ± 10.9 ng/mL). The serum
leptin concentration in LGA (12.8 ± 10.2 ng/mL) and SGA infants
(1.6 ± 1.1 ng/mL) was significantly higher and lower,
respectively, than that in AGA infants (P < 0.01).
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. The concentration of
leptin in LGA and AGA infants was initially higher than that in the SGA
infants and dramatically decreased within 48 h of delivery. These
changes in the LGA and AGA infants were statistically significant
(P < 0.05). In contrast, the serum concentration of
leptin in SGA infants did not change significantly in the first 7 days
after birth. After 48 h of life, no significant difference in the
serum leptin concentration was found between the three groups, and low
levels continued to at least 7 days of age.
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, A).
In term and preterm AGA infants (n = 69), leptin levels within
6 h of life positively correlated with gestational age (r =
0.50, P < 0.01; Fig. 4, B).
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In term AGA infants, the concentration of serum leptin within 6 h of birth in males (n = 25) and females (n = 19) was 4.0 ± 2.7 and 5.0 ± 3.3 ng/mL, respectively. Therefore, no statistically significant gender effect was observed.
No statistically significant correlation between the concentration of leptin and insulin was observed (data not shown).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The total amount of body fat is less in SGA infants and greater in LGA infants compared with AGA infants (10). In addition, although body length was determined in 80 term infants in the present study, the Ponderal Index, which is considered useful for assessment of the nutritional state of infants (9), was higher in the LGA group. Thus, we believe that the concentration of serum leptin within 6 h of life closely correlates with the amount of adipose tissue in infants. Linear regression analysis demonstrated there was a significant positive correlation between blood leptin levels and body weight at birth. These results are compatible with the recent reports (11, 12, 13), in which the leptin levels in cord blood correlated positively with birth weight. In a normal pregnancy, the fetal body components grow proportionally, which suggests the presence of fetal feedback and regulatory systems for fetal growth. However, these systems have yet to be elucidated. The findings of the present study indicate that leptin may be involved in one of these systems. A recent study has indicated that a low serum concentration of leptin leads to a reduction in energy expenditure through the increase in neuropeptide Y concentration in the hypothalamus (5). Conversely an increase in the levels of leptin increases energy expenditure (6). Because the energy balance in a growing fetus must be positive, a low concentration of serum leptin is physiologically suitable for fetal growth. In Pima Indians, subjects prone to weight gain initially have lower plasma leptin concentrations than weight- and body composition-matched subjects who maintain a stable weight (14). This data indicates that a relatively low plasma leptin concentration may play a role in the development of obesity in Pima Indians and that the mechanism may be similar to weight gain in the fetus. In addition, to maintain the increase in body mass, a positive feedback system may be operating. In some individuals in the LGA infants, the serum levels of leptin were low and overlapped with those in the SGA infants. Although the reason for this overlapping is unknown, the same phenomenon is found in obese adults. Leptin concentration heterogeneity is known to exist between individuals with the same body mass indes. Some obese patients have extremely high leptin levels, whereas others have levels similar to those seen in lean subjects. One possible explanation for this heterogeneity is that individuals with high plasma levels of leptin are clinically different from individuals with low blood leptin concentrations, resulting in different response to leptin.
In the present study, within 48 h of delivery, the serum leptin concentration in the LGA and AGA infants dramatically decreased to the low levels observed in the SGA infants regardless of birth body weight. One possible explanation for this phenomenon is that the nutritional state reflects the leptin concentration. After delivery, infants can not take full nutrition for several days. In human adults, serum leptin levels rapidly and drastically decrease during fasting in obese and normal subjects (15), suggesting that leptin release is regulated by factors other than changes in body fat mass. An alternative explanation is that the origin of leptin in fetal blood may be placental or maternal blood. A recent abstract reported that leptin messenger RNA was expressed in the placenta (16). However, no reports detailing leptin transference from the mother to the fetus through the placenta have been published.
The effect of gender on leptin concentration has received considerable attention. Although an earlier study did not find a gender effect on leptin levels in human adults (3), such an effect independent of body fat has been detected in another study (17). In the present study, gender had no effect on the concentration of serum leptin in term AGA infants.
Received March 28, 1997.
Accepted July 8, 1997.
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