Warsy A. S, Habib Z, Addar M, Sooad Al-Daihan, Alanazi M. Maternal Leptin and Glucose: Effect on the Anthropometric Measurements of the Saudi Newborn. Biomed Pharmacol J 2011;4(2)

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Manuscript received on :October 20, 2011
Manuscript accepted on :December 24, 2011
Published online on: 30-11-2015

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Arjumand S. Warsy¹, Zeinab Habib², Mohammad Addar², Sooad Al-Daihan¹ and Mohammad Alanazi¹

¹Department of Biochemistry, College of Science. ²Department of Ob/Gyn., College of Medicine, King Saud University, Riyadh Saudi Arabia.

Abstract

To investigate the influence of maternal leptin and glucose on umbilical cord leptin levels and anthropometric measures in Saudi newborn. Maternal blood samples (10ml) were drawn in ACD tubes and umbilical cord blood was collected from 151 mothers at the time of delivery of full term normal infants, at King Khalid University Hospital (KKUH), Riyadh. Informed consent was recorded for each female. Maternal height (ht), weight (wt), age and baby’s length and weight were recorded and ponderal index (wt/ht3), wt/ht ratio and body mass index (wt/ht2) were calculated. Leptin level was estimated in plasma by RIA. Maternal blood glucose level was estimated using an autoanalyser at the KKUH Laboratory in a blood sample collected in fluoride tube. Maternal and umbilical cord blood leptin levels were compared and correlated. Maternal leptin, glucose, weight and BMI were correlated with each other and with the anthropometric variables of the baby. Maternal leptin levels were significantly higher (19.79± 13.84 ng/ml) compared to the umbilical cord blood (10.36 ± 8.08 ng/ml) leptin (P<0.0001). No significant differences were seen in umbilical cord leptin from male and female babies. Similarly, maternal leptin level did not differ for male and female babies. Maternal leptin correlated with maternal weight (r=0.310; p=0.0001) and maternal BMI (r=0.254; p=.006). It also correlated positively with umbilical cord leptin (r= 0.287; p=0.0001), but not with baby’s weight or BMI or ponderal index. Maternal glucose level showed a strong positive correlation with umbilical cord leptin (r=0.435; p=0.0001) and the baby’s weight (r=0.307; p=0.008), BMI (r=0.334; p=0.004) and ponderal index (r=0.324; p=0.005). However, umbilical cord leptin correlated significantly with the weight of the baby (r=0.330; p=0.0001) wt/ht (r=0.182; p=0.034) and ponderal index (r=0.209; p=0.015) . In two large-for-gestational age babies (>4 kg), the leptin level was significantly higher (>25 ng/ml) compared to the rest of the normal-for-gestational age babies. The results of this study discard the hypothesis of a non-communicating two-compartment model of feto-placental leptin regulation and shows that maternal leptin level correlates with umbilical cord leptin. It is not affected by weight and BMI in the mothers but increases significantly as the maternal blood glucose level increases. This may be one of the causes for large babies in diabetic mothers.

Keywords

Leptin; Body Mass Index; Obesity; Cord Blood; Pregnancy

Introduction

Leptin is the protein product of the obesity gene and is synthesised in the adipose tissues and placenta1-2. It seems to function as a link between adiposity, satiety and activity and regulates body weight and energy expenditure through central nervous system feedback mechanism3-4.  Since its discovery in 1994, extensive studies have been carried out on leptin both in animals and humans and have provided new insight in weight regulation and obesity development5-6. Studies have shown that leptin synthesis starts in utero and circulating leptin levels may provide a growth promoting signal for fetal development during late pregnancy [7]. Umbilical cord leptin levels are generally lower than adult levels [8-9] and play a role in regulation of infancy weight gain10-11.

A strong correlation has been demonstrated between umbilical cord leptin concentration and birth-weight reflecting a close relationship between leptin, birth-weight and body fat mass in newborn infants12-15.  Hence leptin is considered as a possible growth factor in intrauterine fetal development (16). Some studies report similar levels of leptin in male and female newborn infants9, while others show higher levels in female newborns compared to male newborns17-20. Other contradictory reports regarding effect of gender of the baby on the leptin level of the mother also exist in the literature18-20. It is shown that both leptin and insulin like growth factor are independent predictors of fetal growth21 and are low in pregnancies with growth restriction22-23. The umbilical cord leptin is restricted in several conditions and is considered as a marker of intrauterine growth restriction23. Variable leptin levels are reported in different pathological states such as diabetes mellitus and hypertension24-25. It is also regarded as a potential marker of placental insufficiency26.

In an attempt to study maternal leptin and glucose levels at the time of delivery and to investigate correlation between maternal leptin level, umbilical cord leptin levels and anthropometric measures in the new born, we carried out this study on healthy Saudi mother/baby pairs at the time of normal full term delivery.

Materials and Methods

One hundred and fifty one (151) randomly selected healthy mother/newborn pairs at delivery of full term infants were included in this study. The study was approved by the ethical committee of the institution. All females signed an inform consent. The age, parity, height (length of baby), weight was recorded and body mass index (BMI) was calculated using the formula:

Ponderal index (wt/ht3) (Kg/m3) and ratio of weight (kg) / height (m) were also calculated for the baby.

Ten ml blood was drawn by venepuncture from healthy females having normal deliveries of live born babies at full term. In addition, blood sample was collected from umbilical cord at birth, immediately after delivery from the placental end (discarding the first 2 mls) after early ligation of the cord and after raising the baby to the level of the placenta to avoid feto-placental transfusion and vice versa.

The blood was centrifuged at 1000 RPM for ten minutes and the plasma was carefully removed from the cells and stored frozen at –70OC until required for analysis. Leptin level in the maternal plasma and umbilical cord plasma was determined by radioimmunoassay (RIA) using kits from Linco. Glucose was estimated using autoanalysers at KKUH hospital Lab.

The data obtained were entered on the computers and analyzed using SPSS (version 15) program for windows. Correlations studies and regression analysis were carried out using the General Linear Model Program. The relationship between leptin and anthropometric parameters was assessed by Pearson’s and Spearman correlation. Students ‘t’ test was applied to determine the significance of the difference between any two groups and between different parameters. P value < 0.05 was considered statistically significant.

Results

Demographic details of the mothers are presented in Table 1. The gestational age, birth-weight, birth length of the newborns were 36 – 42 weeks, 3.20 ± 0.524 kg and 0.486 ± 0.024 cm. The mean, standard deviation, standard error of the mean (SEM) values for maternal age, leptin, weight, height, BMI and glucose, umbilical cord leptin, baby’s length, weight, BMI, wt/ht and ponderal index are presented in Table 2.

Table 1: Mother’s Demographic Data

Table 2: Age, leptin and anthropometric measures in the mothers and their babies

Mean value of leptin was significantly higher in the mothers compared to the cord blood leptin level and the difference in the level of leptin in maternal blood and the cord blood was highly significant (p<0.0001). In the mothers the lowest leptin level was 1.0 ng/ml and highest was 64.6 ng/ml compared to 0.6 ng/ml and 49.0 ng/ml, respectively, in the cord blood, as shown in the frequency distribution histogram (Figure 1). The male babies were separated from the female babies and the leptin levels and anthropometric values were separately analysed for each gender, and the results are presented in Table 3.  No significant differences were seen in values of these parameters in male and female infants.

Fig. 1: Frequency distribution histogram of (a) maternal leptin and (b) umbilical cord leptin Click here to View figure

Table 3: Levels of leptin and anthropometric

*The difference in the results in the male and female babies is not statistically significant.

Correlation studies were conducted and Pearson correlation coefficient was obtained between the maternal parameters, the umbilical cord leptin and the anthropometric variables of the baby and Table 4 presents the Pearson correlation coefficient (r) and p value between the different correlated parameters (p<0.05). Maternal age was seen as an important factor affecting the weight and BMI of the mother and umbilical cord leptin (r=0.229; p=0.005). Maternal leptin correlated positively with maternal weight, BMI, and umbilical cord leptin (p<0.0001). Figure 2 presents the positive and significant correlation between maternal and umbilical cord leptin (r=0.287; p=0.0001). No correlation was seen with any of the anthropometric measures of the baby. Maternal glucose correlated significantly with umbilical cord leptin and baby’s weight, BMI and ponderal index. Figure 3 presents the significant increase in umbilical cord leptin level with increase in maternal glucose. The babies with the highest leptin were born to the mothers with high blood glucose level. Umbilical cord leptin showed a significant correlation with weight of the baby, weight/height ratio and ponderal index (p <0.05).

Table 4: Correlation between leptin, weight, glucose and BMI in mothers and their babies

*Statistically significant
r = Pearson correlation coefficient

Fig. 2: Correlation between maternal and umbilical cord leptin Click here to View figure

Fig. 3: Correlation between maternal glucose and babies BMI Click here to View figure

Mothers who delivered male babies (no.= 68) were separated from those who delivered female babies (no.=83) and leptin level in the two groups was calculated separately (Table 5). The former group had slightly higher mean leptin (20.53 ng/ml) compared to the latter (19.13 ng/ml) but the difference was not statistically significant (p>0.05).

 Table 5: Value of maternal leptin, weight, BMI and glucose

Discussion

During the last decade several studies have been carried out on umbilical cord leptin in an attempt to elucidate its role in fetal growth and development 8,11-14. All studies have shown that leptin is present in umbilical cord blood and its levels vary depending on several factors.  These include the fetal body weight27, ponderal index28, BMI29, fetal gender18,20,28, and maternal illnesses24,25,30,31. Several studies have shown that the level of umbilical cord leptin is significantly lower than the maternal leptin10, though a few studies have reported umbilical cord leptin level to be the same as adult level32. Our study on healthy Saudi full-term maternal/baby pairs has confirmed the presence of leptin in umbilical cord blood which shows a wide range of distribution both in maternal plasma and umbilical cord sample. This study has also shown that the mean umbilical cord leptin is significantly lower compared to the maternal leptin level (p<0.0001) and there is a statistically significant positive correlation between the maternal and umbilical cord leptin.  Studies report that leptin level increases in maternal blood during pregnancy and plays an important role in providing a growth-promoting signal for fetal growth and metabolism and fetal fat mass during pregnancy19,20,33,34. In addition, it is confirmed that placenta is one of the major sources of leptin production, however, the level of leptin in umbilico-placental circulation is independent of the weight of placenta10,29,35.  It has been suggested that during pregnancy, placental production of leptin is one major source of higher levels in maternal circulating leptin other than maternal gain of fat mass34. Data obtained in pregnant females has reinforced the idea that circulating leptin may provide a growth promoting signal for fetal development during late pregnancy10 and that an ‘adipo-insular axis’ exists and is functional before 34 weeks of gestation35.The results of this study show a close and statistically significant correlation between umbilical cord leptin and the birth weight, weight/height ratio, ponderal index of the baby. However, no differences were seen in the umbilical cord leptin level of the male and female babies. This is in agreement with several other studies that report no gender differences at birth in leptin levels37-39, though in some studies newborn females have been reported to have higher cord blood leptin compared to the male newborns17,18, 20,39,40. Hytinantti et al.,30 showed that leptin correlates with adiposity at birth in females, but not in male newborn infants. This led to the suggestion that sexual dimorphism in adipose tissues already exists in intero28. In adult females there is significantly higher leptin levels compared to the males and extent of adiposity and BMI seem to be important determinants of adult leptin level41. However, it is not clear why in some studies there are no differences in the leptin levels of umbilical cord blood of male and female newborns, while in others the difference is statistically significant. This point requires further more carefully controlled larger investigations to identify the possible factors which predispose to such differences in different studies.  In addition, there are reports in literature, of differences in leptin levels of mothers depending on the gender of the baby38. In this study on Saudis, we did not encounter any difference in the maternal leptin level depending on the gender of the baby. This point also requires further clarification.The umbilical cord leptin levels are reported to be higher in large for gestational age infants compared to the appropriate for gestational age infants41-44 and it is suggested that fatness of the fetus is the major determinant of circulating leptin levels45. In addition, it is confirmed that circulating leptin concentration relates to the intrauterine growth pattern. A very high umbilical cord leptin has been considered as an independent risk factor for fetal macrosomia46.  In our study there were 2 babies over 4 kg in weight and their leptin levels were significantly higher (>25 ng/ml) than the infants less then 4 kg in weight.Maternal health also plays a role in altering umbilical cord leptin level, where higher leptin levels have been demonstrated in the newborn infants of diabetic mothers and mothers with preeclampsia24,25,30,31, thus suggesting that any condition leading to intrauterine growth changes would also result in variation in umbilical cord leptin levels47. Interestingly, glucose level in the maternal plasma showed a significant correlation with umbilical cord leptin, baby weight, BMI and ponderal Index. Though the women included in this study were now diabetic, but elevation was glucose occurred in some near the time of delivery and this glucose level showed a significant correlation with the anthropometric measures in the baby.In this study we correlated the maternal leptin level in healthy females with the umbilical cord leptin, and observed a positive correlation. This finding is in disagreement with some of the previous reports which show that maternal leptin does not correlate with umbilical leptin level10,38. However, maternal leptin level can be considered as a reliable marker of fetal growth, while umbilical cord leptin correlates positively with fetal growth in all studies reported so far11.   The lack of correlation between maternal and cord blood leptin level seen in some studies had led to a hypothesis of a non-communicating, two compartment model of feto-placental leptin regulation, which our study refutes.In conclusion, the results of our study refute the hypothesis of a non-communicating two-compartment model of feto-placental leptin regulation and shows that umbilical cord leptin level correlates with maternal leptin level significantly. In addition, the in utero production of leptin is not influenced by the gender of the baby, but correlates positively with birth weight, height, BMI and ponderal index of the baby.  Thus, both umbilical cord leptin, and the maternal leptin, may be an important factor for growth of the fetus.

Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the research group project No. RGP-VPP-068″

Disclosure of Competing Interests

Authors declare that they do not have any competing interests with any group.

Authors’ Contributions¹

ASW designed the experiment, analyzed the data and wrote the manuscript. ²ZB and MA collected samples from their patients and contributed to discussion of results and preparation of the manuscript. SD and MA helped in data analysis, discussion of results and preparation of the manuscript. All authors read and approved the final manuscript.

References

• Cinti S, Frederick RC, Zingaretti MC et al. Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue. Endocrinology 138: 797-804 (1997).
• Klein S, Coppack SW, Mohamed-Ali V, Landt M. Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes, 45: 984-7 (1996).
• Campfield LA, Smith FJ & Bum P. The OB protein (leptin) – A link between adipose tissue mass and central neural networks. Hormone and Metabolic Research 28: 619-632 (1996).
• Sinha M, Opentanova I, Ohannesian JP, Kolackzinski JW, Heiman M, Hale J, Becker G, Bowsher R, Stephens T & Caro JF. Evidence of free and bound leptin in human circulation: studies in lean and obese subjects and during short-term fasting. Journal of Clinical Investigation 98: 1277-1282 (1996).
• Remesar X, Rafecas I, Femandez-Lopez JA and Alemany M. Leptin. Medicinal Research Reviews 17: 225-234 (1997)
• Pelleymounter M. Leptin and the physiology of obesity. Current Pharmaceutical Design 3: 85-98 (1997).
• Schulz S, Hackel C, Weise W. Hormonal regulation of neonatal weight: placental leptin and leptin receptors: BJOG 107(12): 1486-91 (2000).
• Papadopoulou FG, Mamopoulos AM, Triantos A, Constantinidis TC, apadimas J, Assimakopoulos EA, Koliakos G, Mamopoulos M. Leptin levels in maternal and cord serum: relationship with fetal development and placental weight. J Matern Fetal Med 9(5): 298-302 (2000).
• Kirel B, Tekin N, Tekin B, Kilic FS, Dogruel N, Aydogdu SD. Cord blood leptin levels: relationship to body weight, body mass index, sex and insulin and cortisol levels of maternal-newborn pairs at delivery. J Pediatr Endocrinol Metab 13(1): 71-7 (2000)
• Hytinantti T, Koistinen HA, Koivisto VA, Karonen SL, Andersson S. Changes in leptin concentration during the early postnatal period: adjustment to extrauterine life? : Pediatr Res 45(2) 197-201 (1999).
• Karakosta P, Chatzi L, Plana E, Margioris A, Castanas E, Kogevinas M. Leptin levels in cord blood and anthropometric measures at birth: a systematic review and meta-analysis. Paediatr Perinat Epidemiol. 25(2):150-63 (2011).
• Tung WK, Lin SJ, Hwang YS, Wu CM, Wang YH, Tsai WH. Association of cord plasma leptin with birth size in term newborns. Pediatr Neonatol.;50(6):255-60 (2009)
• Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal Tsai PJ, Yu CH, Hsu SP, Lee YH, Chiou CH, Hsu YW, Ho SC, Chu CHadiposity. Clin Endocrinol (Oxf). 61(1): 88-93 (2004).
• Oktem O, Dedeoðlu N, Oymak Y, Sezen D, Köksal L, Pekin T, Gökaslan H, Kavak ZN. Maternal serum, amniotic fluid and cord leptin levels at term: their correlations with fetal weight. J Perinat Med. 32(3):266-71 (2004).
• Karowicz-Biliñska A.Leptin concentration in women with normal pregnancy and intrauterine growth retardation. Ginekol Pol. 75(1): 10-4 (2004).
• Ben X, Qin Y, Wu S Placental leptin correlates with intrauterine fetal growth and development]. Zhonghua Yi Xue Za Zhi. 81(8):489-92 (2001).
• Jahan S, Zinnat R, Hassan Z, Biswas KB, Habib SH. Gender differences in serum leptin concentrations from umbilical cord blood of newborn infants born to nondiabetic, gestational diabetic and type-2 diabetic mothers. Int J Diabetes Dev Ctries. 29(4):155-8 (2009).
• Okereke NC, Uvena-Celebrezze J, Hutson-Presley L, Amini SB, Catalano PM. The effect of gender and gestational diabetes mellitus on cord leptin concentration. Am J Obstet Gynecol.187(3): 798-803 (2002).
• Inoue M, Itabashi K, Nakano Y, Nakano Y, Tobe T. High-molecular-weight adiponectin and leptin levels in cord blood are associated with anthropometric measurements at birth. Horm Res. 70(5):268-72 (2008).
• Laml T, Preyer O, Schulz-Lobmeyr I, Ruecklinger E, Hartmann BW, Wagenbichler P. Umbilical venous leptin concentration and gender in newborns. J Soc Gynecol Investig. 8(2): 94-7 (2001).
• Pighetti M, Tommaselli GA, D’Elia A, Di Carlo C, Mariano A, Di Carlo A, Nappi C. Maternal serum and umbilical cord blood leptin concentrations with fetal growth restriction. Obstet Gynecol. 102(3):535-43 (2003).
• Mise H, Yura S, Itoh H, Nuamah MA, Takemura M, Sagawa N, Fujii S. The relationship between maternal plasma leptin levels and fetal growth restriction. Endocr J. 54(6):945-51 (2007).
• Nezar MA, el-Baky AM, Soliman OA, Abdel-Hady HA, Hammad AM, Al-Haggar MS. Endothelin-1 and leptin as markers of intrauterine growth restriction. Indian J Pediatr. 76(5): 485-8 (2009).
• Silva NY, Tennekoon KH, Senanayake L, Karunanayake EH. Cord blood leptin levels in normal pregnancies, pregnancy induced hypertension and gestational diabetes mellitus. Ceylon Med J.53(3):79-82 (2008).
• Vela-Huerta MM, San Vicente-Santoscoy EU, Guizar-Mendoza JM, Amador-Licona N, Aldana-Valenzuela C, Hernnández J. Leptin, insulin, and glucose serum levels in large-for-gestational-age infants of diabetic and non-diabetic mothers. J Pediatr Endocrinol Metab. 21(1):17-22 (2008).
• Lepercq J, Guerre-Millo M, André J, Caüzac M, Hauguel-de Mouzon S. Leptin: a potential marker of placental insufficiency. Gynecol Obstet Invest. 55(3):151-5 (2003).
• Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, Dunger DB. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. J Clin Endocrinol Metab 84(3): 1145-8 (1999).
• Yang SW, Kim SY. The relationship of the levels of leptin, insulin-like growth factor-I and insulin in cord blood with birth size, ponderal index, and gender difference. J Pediatr Endocrinol Metab 13(3): 289-96 (2000).
• Lin KC, Hsu SC, Kuo CH, Zhou JY Difference of plasma leptin levels in venous and arterial cord blood: relation to neonatal and placental weight. Kaohsiung J Med Sci 15(12): 679-85 (1999).
• Hytinantti T, Koistinen HA, Koivisto VA, Karonen SL, Rutanen EM, Andersson S. Increased leptin concentration in preterm infants of pre-eclamptic mothers. Arch Dis Child Fetal Neonatal Ed 83(1): F13-6 (2000).
• Persson B, Westgren M, Celsi G, Nord E, Ortqvist E. Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers. Horm Metab Res 31(8): 467-71 (1999).
• Harigaya A, Nagashima K, Nako Y, Morikawa A. Relationship between concentration of serum leptin and fetal growth. J Clin Endocrinol Metab 82(10): 3281-4 (1997).

33- Herrera E, Lasuncion MA, Huerta L, Martin-Hidalgo A.Plasma leptin levels in rat mother and offspring during pregnancy and lactation., Biol Neonate 78(4): 315-20 (2000).

• Lin KC.Increase of maternal plasma leptin concentrations during pregnancy: comparison with nonpregnant women. : Kaohsiung J Med Sci 15(11): 640-5 (1999).
• Schubring C, Kiess W, Englaro P, Rascher W, Dotsch J, Hanitsch S, Attanasio A, Blum WF.Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight. J Clin Endocrinol Metab 82(5): 1480-3 (1997).
• Ng PC, Lam CW, Lee CH, Wong GW, Fok TF, Wong E, Chan IH, Ma KC. Changes of leptin and metabolic hormones in preterm infants: a longitudinal study in early postnatal life. Clin Endocrinol (Oxf) 54(5): 673-80 (2001).
• Ertl T, Funke S, Sarkany I, Szabo I, Rascher W, Blum WF, Sulyok E. Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone. Biol Neonate 75(3):167-76 (1999);
• Laml T, Hartmann BW, Ruecklinger E, Preyer O, Soeregi G, Wagenbichler P. Maternal serum leptin concentrations do not correlate with cord blood leptin concentrations in normal pregnancy. J Soc Gynecol Investig 8(1): 43-7 (2001).
• Helland IB, Reseland JE, Saugstad OD, Drevon CA. Leptin levels in pregnant women and newborn infants: gender differences and reduction during the neonatal period. Pediatrics 101(3): E12 (1998).
• Matsuda J, Yokota I, Iida M, Murakami T, Naito E, Ito M, Shima K, Kuroda Y. Serum leptin concentration in cord blood: relationship to birth weight and gender. J Clin Endocrinol Metab 82(5): 1642-4 (1997).
• Wolf HJ, Ebenbichler CF, Huter O, Bodner J, Lechleitner M, Foger B, Patsch JR, Desoye G.Fetal leptin and insulin levels only correlate inlarge-for-gestational age infants. Eur J Endocrinol 142(6): 623-9 (2000).
• Cinaz P, Sen E, Bideci A, Ezgu FS, Atalay Y, Koca E. Plasma leptin levels of large for gestational age and small for gestational age infants. Acta Paediatr 88(7): 753-6 (1999).
• Albertsson-Wikland K, Boguszewski M, Karlberg J. Children born small-for-gestational age: postnatal growth and hormonal status. Horm Res 49 Suppl 2: 7-13 (1998).
• Boguszewski M, Dahlgren J, Bjarnason R, Rosberg S, Carlsson LM, Carlsson B, Albertsson-Wikland K. Serum leptin in short children born small for gestational age: relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment. Eur J Endocrinol 137(4): 387-95 (1997)
• Clapp JF 3rd, Kiess W. Cord blood leptin reflects fetal fat mass. : J Soc Gynecol Investig 5(6): 300-3 (1998).
• Wiznitzer A, Furman B, Zuili I, Shany S, Reece EA, Mazor M.Cord leptin level and fetal macrosomia. Obstet Gynecol 96(5Pt1): 707-13 (2000).
• Koistinen HA, Koivisto VA, Andersson S, Karonen SL, Kontula K, Oksanen L, Teramo KA. Leptin concentration in cord blood correlates with intrauterine growth. J Clin Endocrinol Metab 82(10): 3328-30 (1997).