| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Articles |
INSERM U-457 (D.J., J.L., C.L.-M., P.C.) and Obstetric Department (J.F.O.), Hôpital R. Debré, Paris, France
Address all correspondence and requests for reprints to: Delphine Jaquet, M.D., INSERM U-457, Hôpital Robert Debré, 48 boulevard Sérurier, 75019 Paris, France.
Abstract
The aim of this study was to investigate the ontogeny of serum leptin concentrations during the second half of gestation and at birth in small for gestational age and normal fetuses and newborns. Serum leptin concentrations were measured in arterial cord blood of fetuses (n = 79) and newborns (n = 132), with or without intrauterine growth retardation, at 18–42 weeks gestation. Serum leptin was detectable in fetal cord blood in all subjects as early as 18 weeks gestation. Leptin levels dramatically increased after 34 weeks gestation. In newborns, serum leptin concentrations were positively correlated with body weight (P < 0.001) and body mass index (P < 0.001). Newborns with intrauterine growth retardation had significantly lower serum leptin values (P < 0.001) than those with normal growth, and leptin levels were only positively correlated with body mass index (P < 0.001). These results suggest that the development of adipose tissue and the accumulation of fat mass are the major determinants of fetal and neonatal serum leptin levels. In addition, a gender difference, with higher leptin concentrations in female fetuses, was observed during the last weeks of gestation and was confirmed at birth regardless of growth status, suggesting that a sexual dimorphism already exists in utero.
LEPTIN, the product of the ob gene, is an hormone secreted by adipocytes (1). It regulates body weight through a negative feedback signal between the adipose tissue and the hypothalamic centers of satiety (2), thereby causing a decrease in food intake (3, 4, 5) and an increase in body temperature and energy expenditure (3, 4). In obese or normal weight children, as in adults, serum leptin concentrations closely correlate with body weight and percentage of body fat (6, 7). Girls consistently demonstrate higher serum leptin levels than boys, and this gender difference persists into adulthood (6, 7). Unlike adults, children need a positive energy balance for growth and development. Serum leptin concentrations decrease during pubertal development independent of adiposity, and it was hypothesized that children have a relative leptin resistance for their dynamic energy needs (6).
Several recent studies have demonstrated a positive correlation between leptin concentrations in cord blood and body weight at birth (8, 9, 10). A sexual dimorphism, with higher concentrations in female newborns, was observed in one of those studies (9), although this observation was not confirmed by others (10).
The last trimester of gestation is of considerable importance for the growth and development of adipose tissue, with an exponential accumulation of fat mass (11). However, the accumulation of fat mass is dramatically reduced in fetuses and newborns with intrauterine growth retardation (IUGR) (11). At birth, body fat mass was less than 3% of the total body weight in newborns with IUGR vs. 15% in newborns with normal growth (12).
The aim of this work was to study the ontogeny of serum leptin concentrations in human fetuses during the second half of gestation and in normal newborns. We also investigated the impact of IUGR on the variations in serum leptin in human fetuses and newborns.
Subjects and Methods
Study populations
Human fetuses. The population studied included 79 patients
referred for cordocentesis at different gestational ages (Table 1
) for karyotypic determination,
suspicion of malformation, or growth retardation. Gestational age
(18–38 weeks) was determined from the date of the last menstrual
period and was confirmed by early ultrasound scan. At the time of
cordocentesis, fetal growth was evaluated by ultrasonography, using
biparietal and abdominal diameters and femur length measurement.
Fetuses were classified in the IUGR group when at least 2 of these 3
measurements were below the 10th percentile, using the ultrasound data
growth curves (13). IUGR was later confirmed if birth weight was below
the 10th percentile for gestational age, according to the French growth
standard curves of Leroy (14). According to this classification, the
study group included 22 fetuses with IUGR and 57 with normal growth.
Informed consent for the study was obtained from all mothers.
|
. Sixty-two had normal intrauterine
growth according to the French growth standard curves of Leroy (14),
and 70 had IUGR, with a birth weight below the third percentile by
these standards. Gestational age (37–42 weeks) was determined in the
two groups from the date of the last menstrual period and was confirmed
by early ultrasound scan. Five milliliters of arterial cord blood were
collected at birth after obtaining maternal consent.
|
Serum leptin measurement
All serum samples were stored at -20 C until assayed. Serum leptin concentrations were measured using a specific RIA (Linco Research, St. Charles, MO) as previously described by Maffei et al. (15). The sensitivity of the assay was 0.4 ng/mL, with intra- and interassay coefficients of variation at 2.3 ng/mL of 5.2% and 8.7%, respectively.
Statistical analysis
Results are expressed as the mean ± 1 SD or as median values and ranges for continuous variables.
Given the non-Gaussian distribution of serum leptin concentrations in the study population, nonparametric tests were used for statistical analysis. A Mann-Whitney test was performed for comparison of leptin concentrations between genders, between newborns and fetuses, or between other studied groups. The Spearman rank correlation was used for testing correlations between leptin concentrations and other continuous variables in univariate analysis.
For the multivariate analysis, 1/leptin concentration was used as the dependent variable to normalize the distribution. A model was tested, including four explanatory variables (weight, gestational age, gender, and placental weight). The same model was also tested when body mass index was used instead of weight.
No significant differences was found in the serum leptin concentrations between fetuses with or without malformation. Therefore, congenital abnormality was not taken into account in the subsequent analysis.
Results
Effect of gestational age
The variations in serum leptin concentrations during development
were first studied in the combined populations of fetuses and newborns
(n = 79 and 132, respectively). Data plotted according to
gestational age with respect to IUGR status are shown in Fig. 1. All subjects had detectable serum
leptin concentrations as early as 18 weeks gestation. Before 34 weeks
gestation, the serum leptin concentration remained low (median, 0.61
ng/mL; range, 0.41–6.5 ng/mL). From that stage onward, a dramatic
increase in the serum leptin concentration was observed through the end
of gestation regardless of growth status (median, 3.5 ng/mL; range,
0.7–39 ng/mL).
|
).
|
In the fetuses, no significant association was found between serum
leptin concentrations and the three parameters used to define growth
status: biparietal and abdominal diameters and femur length measured by
ultrasound (data not shown). Conversely, a significant positive
correlation was observed at birth between serum leptin concentrations
and both body weight (r = 0.46; P 
0.001) and
body mass index (r = 0.51) (P < 0.001) (Table 3
).
The effect of IUGR, as defined in Subjects and Methods, was
tested on the study population. In the fetuses before 34 weeks
gestation, serum leptin values were not statistically different between
IUGR (n = 21) and normal growth fetuses (n = 50; median, 0.58
vs. 0.61 ng/mL; P = 0.09). No difference
could be found in the fetuses aged 34–38 weeks because of the small
number of subjects studied (1 vs. 8). At birth, serum leptin
concentrations were significantly lower in newborns with IUGR than in
those with normal growth (median, 2.3 vs. 5.70 ng/mL;
P 0.001; Fig. 2).
|
Effect of gender
At an early stage, no difference in serum leptin concentrations
between males and females was observed before 34 weeks gestation. From
the age of 34 weeks, female leptin values (median, 5.18 ng/mL; range,
1.73–5.47 ng/mL) tended to be higher than male values (median, 1
ng/mL; range, 0.8–4.980 ng/mL) without reaching significance
(P = 0.053). At birth, serum leptin values in female
newborns were insignificantly higher than those in males (median, 4.2
vs. 2.7 ng/mL; P = 0.08), as shown in Fig. 3.
|
This analysis was performed only in newborns with normal growth
(n = 62). Serum leptin values were significantly correlated with
placental weights (r = 0.303; P = 0.017; Table 3).
Multivariate analysis
Multivariate analysis was performed only in newborns in whom a significant effect of gestational age, weight, gender, and placental weight was detected in univariate analysis. To test the independent effects of these covariates on leptin levels, a model including the four parameters was tested using the inverse of leptin levels as the dependent variable.
Serum leptin concentrations remained independently and significantly correlated to body weight (P = 0.014) after adjustment for the other covariates. The gender effect was also independently significant (P = 0.03). Gestational age (P = 0.16) and placental weight (P = 0.96) did not show an independent effect on serum leptin after adjustment for the other covariates. Introduction of BMI instead of weight did not change the model (P = 0.006).
In the subgroup of newborns with IUGR, an independent and significant association between body mass index (P = 0.03) and gender (P = 0.009) with serum leptin concentrations was observed. The other parameters did not remain significantly correlated with serum leptin values after adjustment for the other covariates.
Body mass index, reflecting fat mass, and gender are, therefore, the strongest predictors of serum leptin levels.
Discussion
One of the major findings of this study is that leptin was detectable in fetal cord blood as early as 18 weeks gestation. Schrubing et al. previously demonstrated that leptin present in cord blood is likely to be synthesized and secreted by the fetus in an autonomous fashion based on the lack of correlation between maternal and fetal leptin values (10). The presence of fetal synthesis and secretion of leptin at this time, suggested by our results, is consistent with the onset of adipose tissue development during the second trimester of gestation (16). However, it is well known that accumulation of fat and growth of adipose tissue increase in an exponential manner in the last weeks of gestation (11). These observations could explain the low leptin concentrations found in our study before 34 weeks gestation. A more sensitive assay would be required to analyze more precisely the putative variations in leptin concentrations during this period.
The increase in serum leptin concentrations in cord blood is consistent with the known exponential increase in fat mass (115%) during the last trimester of gestation (17). This hypothesis is supported by the strong association between leptin concentrations and body weight or body mass index at birth. It is also supported by the difference in serum leptin values between newborns with or without IUGR. Previous studies have demonstrated that the fat mass accumulated during the last trimester of gestation is dramatically reduced in fetuses or newborns with IUGR (11, 12). In our study, we found significantly reduced leptin concentrations in small for gestational age newborns but not in the fetuses less than 34 weeks of age. Moreover, in newborns with IUGR, there a was positive correlation between serum leptin concentrations and body mass index, reflecting fat mass, but not with body weight. All of these data suggest that leptin synthesis and secretion are, rather, associated with the development and growth of adipose tissue than with antenatal development per se. Likewise, the difference in leptin values between normally grown and small for gestational age fetuses and newborns is at least in part explained by the difference in fat mass accumulation. However, we cannot exclude other factors linked to intrauterine malnutrition that might be better clarified when leptin regulation during fetal life will be better understood.
The increase in serum leptin values after 34 weeks gestation was observed independently of growth status and suggests that other minor parameters could be involved in fetal leptin synthesis and secretion. The small number of fetuses aged 34–38 weeks in our study does not allow us to determine the effect of delivery, which could be a stimulatory factor by itself.
Unlike Schrubing et al., we did not find a significant and independent correlation between placental weight and serum leptin values. This result together with the absence of correlation between maternal and fetal serum leptin concentrations (10) suggest that fetal leptin synthesis and secretion could be dependent only on the fetus.
As in children (6, 7) and consistent with a recent study in newborns (9), our results show a gender difference, independent of growth status, with higher serum leptin values in females; this difference is present at birth and probably by the end of gestation. The presence of a sexual dimorphism in leptin concentrations in the newborn has been debated. Schrubing et al. (10), and others (18) did not find any differences in leptin concentrations between male and female newborns. These conflicting results could be explained by the wide and variable distributions of leptin values observed in each study. Sexual dimorphism appears at the end of gestation in concert with the exponential growth of adipose tissue. Nevertheless, the highly significant gender effect present in newborns with IUGR suggests that gender could act on the serum leptin concentration by itself rather than through a gender difference in fat distribution during this period.
In summary, leptin is present in fetal cord blood at the end of the first half of gestation, and leptin values increase at the end of gestation. In addition, a strong effect of IUGR on leptin was observed at birth, but not in early stage gestation fetuses. Taken together, these data suggest that, as in children and adults, variations in serum leptin concentrations are more dependent on the development and growth of the adipose tissue and the accumulation of fat mass than other developmental factors during gestation.
In the light of our results, investigation of the variations in leptin concentrations during the first years of life, especially during the catch-up growth period observed in infants born with IUGR, may be of considerable interest in understanding the specific function of leptin during this period of positive energy needs.
Acknowledgments
The authors acknowledge the contribution of the nursing staff at the delivery room of R. Debré Hospital (Paris, France).
Footnotes
1 Supported by a fellowship from Novo Nordisk (France). 
Received September 30, 1997.
Revised December 10, 1997.
Accepted December 30, 1997.
References
This article has been cited by other articles:
 |
|
 |
|
  J. A. Duffield, T. Vuocolo, R. Tellam, B. S. Yuen, B. S. Muhlhausler, and I. C. McMillen Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1413 - R1419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Forhead, C. A. Lamb, K. L. Franko, D. M. O'Connor, F. B. P. Wooding, R. L. Cripps, S. Ozanne, D. Blache, Q. W. Shen, M. Du, et al. Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestation J. Physiol., May 1, 2008; 586(9): 2393 - 2403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kyriakakou, A. Malamitsi-Puchner, H. Militsi, T. Boutsikou, A. Margeli, D. Hassiakos, C. Kanaka-Gantenbein, I. Papassotiriou, and G. Mastorakos Leptin and adiponectin concentrations in intrauterine growth restricted and appropriate for gestational age fetuses, neonates, and their mothers Eur. J. Endocrinol., March 1, 2008; 158(3): 343 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Troisi, N. Potischman, and R. N. Hoover Exploring the Underlying Hormonal Mechanisms of Prenatal Risk Factors for Breast Cancer: A Review and Commentary Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1700 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. O'Connor, D. Blache, N. Hoggard, E. Brookes, F. B. P. Wooding, A. L. Fowden, and A. J. Forhead Developmental Control of Plasma Leptin and Adipose Leptin Messenger Ribonucleic Acid in the Ovine Fetus during Late Gestation: Role of Glucocorticoids and Thyroid Hormones Endocrinology, August 1, 2007; 148(8): 3750 - 3757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Dabelea The Predisposition to Obesity and Diabetes in Offspring of Diabetic Mothers Diabetes Care, July 1, 2007; 30(Supplement_2): S169 - S174. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Saenger, P. Czernichow, I. Hughes, and E. O. Reiter Small for Gestational Age: Short Stature and Beyond Endocr. Rev., April 1, 2007; 28(2): 219 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-M. Alexe, G. Syridou, and E. Th. Petridou Determinants of Early Life Leptin Levels and Later Life Degenerative Outcomes Clin. Med. Res., December 1, 2006; 4(4): 326 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. SECKL and M. J. MEANEY Glucocorticoid "Programming" and PTSD Risk Ann. N.Y. Acad. Sci., July 1, 2006; 1071(1): 351 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I C McMillen, L J Edwards, J Duffield, and B S Muhlhausler Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction, March 1, 2006; 131(3): 415 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. C. McMillen, C. L. Adam, and B. S. Muhlhausler Early origins of obesity: programming the appetite regulatory system J. Physiol., May 15, 2005; 565(1): 9 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. Mcmillen and J. S. Robinson Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming Physiol Rev, April 1, 2005; 85(2): 571 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tenhola, P. Halonen, J. Jaaskelainen, and R. Voutilainen Serum markers of GH and insulin action in 12-year-old children born small for gestational age Eur. J. Endocrinol., March 1, 2005; 152(3): 335 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Collinson, S. Moore, M. O'Connell, C. Charalambos, and A. Prentice Developmental changes in leptin as a measure of energy status in human infants in a natural ecologic setting Am. J. Clinical Nutrition, February 1, 2005; 81(2): 488 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Edwards, J. R. McFarlane, K. G. Kauter, and I. C. McMillen Impact of periconceptional nutrition on maternal and fetal leptin and fetal adiposity in singleton and twin pregnancies Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2005; 288(1): R39 - R45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. SECKL and M. J. MEANEY Glucocorticoid Programming Ann. N.Y. Acad. Sci., December 1, 2004; 1032(1): 63 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Ng, C. H. Lee, C. W. K. Lam, E. Wong, I. H. S. Chan, and T. F. Fok Plasma Ghrelin and Resistin Concentrations Are Suppressed in Infants of Insulin-Dependent Diabetic Mothers J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5563 - 5568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.S.J. Yuen, P.C. Owens, M.E. Symonds, D.H. Keisler, J.R. McFarlane, K.G. Kauter, and I.C. McMillen Effects of Leptin on Fetal Plasma Adrenocorticotropic Hormone and Cortisol Concentrations and the Timing of Parturition in the Sheep Biol Reprod, June 1, 2004; 70(6): 1650 - 1657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. El-Haddad, M. Desai, D. Gayle, and M. G. Ross In Utero Development of Fetal Thirst and Appetite: Potential for Programming Reproductive Sciences, April 1, 2004; 11(3): 123 - 130. [Abstract] [PDF]
|
|
|
|
|
|
B. S. Muhlhausler, C. T. Roberts, B. S. J. Yuen, E. Marrocco, H. Budge, M. E. Symonds, J. R. McFarlane, K. G. Kauter, P. Stagg, J. K. Pearse, et al. Determinants of Fetal Leptin Synthesis, Fat Mass, and Circulating Leptin Concentrations in Well-Nourished Ewes in Late Pregnancy Endocrinology, November 1, 2003; 144(11): 4947 - 4954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pighetti, G. A. Tommaselli, A. D'Elia, C. Di Carlo, A. Mariano, A. Di Carlo, and C. Nappi Maternal Serum and Umbilical Cord Blood Leptin Concentrations With Fetal Growth Restriction Obstet. Gynecol., September 1, 2003; 102(3): 535 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Veening, M. M. van Weissenbruch, and H. A. Delemarre-van de Waal Glucose Tolerance, Insulin Sensitivity, and Insulin Secretion in Children Born Small for Gestational Age J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4657 - 4661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takahashi, Y. Yokoyama, I. Kawabata, S. Iwasa, and T. Tamaya Leptin as an Acute Stress-Related Hormone in the Fetoplacental Circulation Obstet. Gynecol., October 1, 2002; 100(4): 655 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.S. Muhlhausler, C.T. Roberts, J.R. McFarlane, K.G. Kauter, and I.C. McMillen Fetal Leptin Is a Signal of Fat Mass Independent of Maternal Nutrition in Ewes Fed at or above Maintenance Energy Requirements Biol Reprod, August 1, 2002; 67(2): 493 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Ehrhardt, A. W. Bell, and Y. R. Boisclair Spatial and developmental regulation of leptin in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1628 - R1635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Reis, D. D'Antona, and F. Petraglia Predictive Value of Hormone Measurements in Maternal and Fetal Complications of Pregnancy Endocr. Rev., April 1, 2002; 23(2): 230 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Forhead, L. Thomas, J. Crabtree, N. Hoggard, D. S. Gardner, D. A. Giussani, and A. L. Fowden Plasma Leptin Concentration in Fetal Sheep during Late Gestation: Ontogeny and Effect of Glucocorticoids Endocrinology, April 1, 2002; 143(4): 1166 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Beringue, B. Blondeau, M. C. Castellotti, B. Breant, P. Czernichow, and M. Polak Endocrine Pancreas Development in Growth-Retarded Human Fetuses Diabetes, February 1, 2002; 51(2): 385 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Coutant, F. Boux de Casson, O. Douay, E. Mathieu, S. Rouleau, F. Beringue, P. Gillard, J. M. Limal, and P. Descamps Relationships between Placental GH Concentration and Maternal Smoking, Newborn Gender, and Maternal Leptin: Possible Implications for Birth Weight J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4854 - 4859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T K Hytinantti, M Juntunen, H A Koistinen, V A Koivisto, S-L Karonen, and S Andersson Postnatal changes in concentrations of free and bound leptin Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2001; 85(2): F123 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lepercq, J.-C. Challier, M. Guerre-Millo, M. Cauzac, H. Vidal, and S. Hauguel-de Mouzon Prenatal Leptin Production: Evidence That Fetal Adipose Tissue Produces Leptin J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2409 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Laml, O. Preyer, I. Schulz-Lobmeyr, E. Ruecklinger, B. W. Hartmann, and P. Wagenbichler Umbilical Venous Leptin Concentration and Gender in Newborns Reproductive Sciences, April 1, 2001; 8(2): 94 - 97. [Abstract] [PDF]
|
|
|
|
 |
|
 S. K. Fried, M. R. Ricci, C. D. Russell, and B. Laferrere Regulation of Leptin Production in Humans J. Nutr., December 1, 2000; 130 (12): 3127S - 3131S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Henson and V. D. Castracane Leptin in Pregnancy Biol Reprod, November 1, 2000; 63(5): 1219 - 1228. [Abstract] [Full Text]
|
|
|
|
|
|
P C Ng, C W K Lam, C H Lee, G W K Wong, T F Fok, E Wong, K C Ma, and I H S Chan Leptin and metabolic hormones in infants of diabetic mothers Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2000; 83(3): 193F - 197. [Abstract] [Full Text]
|
|
|
|
|
|
P C Ng, C W K Lam, C H Lee, G W K Wong, T F Fok, I H S Chan, K C Ma, and E Wong Leptin and metabolic hormones in preterm newborns Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2000; 83(3): 198F - 202. [Abstract] [Full Text]
|
|
|
|
|
|
B. Lonnerdal and P. J Havel Serum leptin concentrations in infants: effects of diet, sex, and adiposity Am. J. Clinical Nutrition, August 1, 2000; 72(2): 484 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.G. Lea, D. Howe, L.T. Hannah, O. Bonneau, L. Hunter, and N. Hoggard Placental leptin in normal, diabetic and fetal growth-retarded pregnancies Mol. Hum. Reprod., August 1, 2000; 6(8): 763 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. HORLICK, M. ROSENBAUM, M. NICOLSON, L. S. LEVINE, B. FEDUN, J. WANG, R. N. PIERSON Jr., and R. L. LEIBEL Effect of Puberty on the Relationship between Circulating Leptin and Body Composition J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2509 - 2518. [Abstract] [Full Text]
|
|
|
|
|
|
T. Hytinantti, H. A Koistinen, V. A Koivisto, S.-L. Karonen, E.-M. Rutanen, S. Andersson;, A. BEREZIN, and M. MELO Increased leptin concentration in preterm infants of pre-eclamptic mothers Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2000; 83(1): 13F - 16. [Abstract] [Full Text]
|
|
|
|
|
|
O. Ogueh, S. Sooranna, K. H. Nicolaides, and M. R. Johnson The Relationship between Leptin Concentration and Bone Metabolism in the Human Fetus J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1997 - 1999. [Abstract] [Full Text]
|
|
|
|
|
|
