Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Users Online: 112
 
About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Advertise Login 
     


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 4  |  Issue : 4  |  Page : 256-259

Influences of birth weight, gender, and pregnancy induced hypertension on cord blood leptin in growth restricted and normal neonates


1 Department of Pediatrics, K. S. Hegde Medical Academy, NITTE University, Mangalore, Karnataka, India
2 Department of Biochemistry, K. S. Hegde Medical Academy, NITTE University, Mangalore, Karnataka, India

Date of Web Publication16-Oct-2015

Correspondence Address:
Rathika Damodar Shenoy
Department of Pediatrics, K. S. Hegde Medical Academy, NITTE University, Derlakatte, Mangalore - 575 018, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.165690

Rights and Permissions
  Abstract 

Leptin synthesized by adipose tissue has significant association with birth weight, body mass index and insulin-glucose ratio. Fetuses with growth restriction (FGR) have substantial reduction in adipose tissue; hence lower levels of leptin in cord blood. Hyperleptinemia has been observed in pregnancy induced hypertension (PIH). Objectives: To estimate leptin levels in cord blood of growth restricted and normal neonates and study the factors influencing the same. Methods: In this prospective study, a sample size of 40 each of growth restricted and appropriate for gestational age neonates were included. Data included maternal illnesses, anthropometry, maturity and ponderal index (PI). Cord leptin assay was done using commercial solid phase competitive ELISA and was expressed in ng/ml. Statistical analysis was done using t test and Pearson correlation co-efficient using recommended software. Results: Maternal PIH was the major etiological factor contributing to FGR (12, 30%, P =0.000). Mean cord leptin in ng/ml was 2.80±0.4 in growth restricted group and 3.53±0.5 in normal neonates with P value of 0.074. There was no correlation between cord leptin and birth weight (r=0.08; p=0.61) and PI (r=0.03; p=0.89). In female neonates and those born to mothers with PIH, mean leptin levels were 3.16±0.6 and 3.13±0.7 ng/ml respectively, higher in comparison with males and those born to mothers without hypertension. Conclusion: Mean cord leptin levels were lower in the growth restricted and higher in female gender and those born to maternal PIH. Cord leptin may be influenced by various maternal and fetal factors.

Keywords: Fetal growth restriction, fetal programing, hyperleptinemia, ponderal index


How to cite this article:
Maveli TM, Sindgikar SP, Shenoy RD, Kathyayani P, Shetty S. Influences of birth weight, gender, and pregnancy induced hypertension on cord blood leptin in growth restricted and normal neonates. J Clin Neonatol 2015;4:256-9

How to cite this URL:
Maveli TM, Sindgikar SP, Shenoy RD, Kathyayani P, Shetty S. Influences of birth weight, gender, and pregnancy induced hypertension on cord blood leptin in growth restricted and normal neonates. J Clin Neonatol [serial online] 2015 [cited 2019 Sep 19];4:256-9. Available from: http://www.jcnonweb.com/text.asp?2015/4/4/256/165690


  Introduction Top


Leptin a product of the obese gene is a 16-kD plasma protein synthesized by adipose tissue normally. The rate of leptin production is directly related to adiposity and afferent signals from peripheral adipose tissue to hypothalamus stimulate energy expenditure and suppress appetite. Thus, leptin plays a key role in the regulation of adiposity, body weight, and energy balance.[1],[2] Studies in term infants indicate significant association of leptin with birth weight, body mass index, and insulin with the insulin-glucose ratio, leading to the conclusion that adipoinsular pathway is already active during the fetal and neonatal period.[3] The fetal-programing paradigm has generated much interest ever since Barker et al., postulated the relationship between fetal growth restriction (FGR) and later manifestation of diseases such as diabetes mellitus, hypertension, and coronary heart disease in adulthood. Alterations in leptin level in utero prompt substantive hypothalamic changes in fetuses that eventually result in the altered nutritional intake, energy metabolism, and adiposity later as children and adults.[4],[5]

Prenatal growth and gestational age (GA) play crucial roles in adipose tissue maturation and accumulation, modifying leptin and adiponectin secretions, endocrine, and metabolic functions.[6] The third trimester of gestation is of considerable importance for the fetal development of adipose tissue and growth with an exponential accumulation of fat mass. However, this is dramatically reduced in fetuses and newborns with growth restriction. At birth, body fat mass is <3% of total weight in newborns with FGR as compared to 15% in those with normal growth.[7],[8] Umbilical cord blood concentrations of leptin are shown to correlate with neonates' birth weight, and the inadequately developed fat tissue in preterm and FGR neonates leads to lower fetal leptin.[9],[10] Similarly, studies show maternal hyperleptinemia in pregnancy induced hypertension (PIH) and sexual dimorphism.[9],[11],[12],[13],[14] This study is designed to estimate the cord leptin concentrations in growth restricted and neonates with normal growth and the influence of birth weight, gender and maternal PIH and anemia on leptin levels.


  Methods Top


This study was designed to be prospective over a calendar year in the neonatal unit of a teaching hospital with a sample size of 40 each of growth restricted and appropriate for GA neonates. Institutional Ethical Committee clearance and an individual informed consent were obtained. FGR was diagnosed when two serial antenatal ultra-sonograms showed fetal growth percentiles <10th centile for GA based on fetal biometry. Term and late preterm (34–36 weeks) neonates with FGR were included. Unbooked pregnancy, prematurity <34 weeks, infant of diabetic mothers, severe birth asphyxia, major congenital malformations, and identifiable syndromes were excluded. The two groups were matched for maternal age, parity, and socioeconomic class.

The maternal data included information on maternal nutrition, pregnancy specific illnesses including anemia, infection, and PIH which could influence the fetal growth. The ultra-sonogram records were analyzed for fetal biometry and umbilical artery blood flow indices. Neonatal data at delivery included Apgar scoring, maturity, and growth parameters. Birth weights were recorded to the nearest 0.001 kg in calibrated electronic weighing scale, length in cm in an infantometer, and head circumference (HC) in cm with a nonstretchable measuring tape. All neonates with FGR were classified into symmetric and asymmetric based on ponderal index (PI). At the time of delivery, 3 ml of cord blood was collected and centrifuged and stored at −20° centigrade. Leptin assay was done by commercial solid phase competitive ELISA according to manufacturer's instructions. Leptin concentrations were expressed in ng/ml.

Statistical analysis were performed using software packages Statistical package for social studies (SPSS) version 16.0. The relationship in serum leptin concentrations between the growth restricted and normal groups was calculated by independent sample t-test. Values are expressed as 95% confidence interval derived from the standard error of the mean. A P < 0.05 has been considered significant. Similar statistical significances were also derived for gender and pregnancy related issues after merging the two groups. Leptin concentration was also correlated against the birth weight and PI in the growth restricted using Pearson correlation co-efficient.


  Results Top


Maternal and neonatal demography is given in [Table 1]. The mean maternal age was 26.683 ± 0.5 years and the majority were primigravidae (48.60%). Maternal PIH was the major etiological factor contributing to FGR in our study (12.30%, P = 0.000). The proportion of maternal anemia was comparable in both groups (P = 0.61), but mean maternal hemoglobin was lower in the FGR group (10.73 ± 0.2 vs. 11.04 ± 0.3) with statistical significance (P = 0.046). In addition to FGR, oligohydramnios was seen in five, and abnormal Doppler in the form of absent or reversal of umbilical blood flow was seen in two of the antenatal ultra-sonograms. In the growth restricted group, 16 (40%) were born preterm. The mean birth weights were 2055 ± 53.7 and 3055 ± 61.3 g in the two groups with no statistical significance. However, the other anthropometry data including length, HC, and PI were statistically significant between the two groups.
Table 1: Demography of the study group and comparison of neonatal measurements

Click here to view


The comparison of levels against the growth restriction, gender, and maternal complications is given in [Table 2]. The mean cord leptin in ng/ml was lower in the growth restricted group (2.80 ± 0.4) in comparison with neonates who had appropriate growth (3.53 ± 0.5). The correlations between cord blood leptin and birth weight and PI in the growth restricted neonates are given in [Figure 1] and [Figure 2]. There was no correlation between cord blood leptin and birth weight (r = 0.08; P = 0.61) or PI (r = 0.03; P = 0.89). Though not statistically significant, higher levels of leptin were seen with female neonates and those born to mothers with PIH. Leptin levels were comparable in late preterm and term babies.
Table 2: Comparison of cord leptin levels against growth restriction, gender and maternal complications

Click here to view
Figure 1: Correlation of cord leptin with birth weight in growth restricted neonates

Click here to view
Figure 2: Correlation of cord leptin with ponderal index in growth restricted neonates

Click here to view



  Discussion Top


Leptin in pregnancy facilitates implantation, placental endocrine function, and fetal development is produced by maternal and fetal adipose tissues and placental trophoblasts.[12],[15] During pregnancy, maternal serum leptin level peaks in the second trimester until delivery when it declines rapidly. Umbilical venous blood leptin levels largely reflect fetal plasma leptin which is independent of placental leptin production. About 95% of placental leptin is released into maternal circulation with a minor contribution to fetal levels.[10],[16] There is a decline in the level in the newborn as well after birth which stimulates the feeding behavior.

Studies show the possible role of leptin on pregnancy related issues including PIH, birth weight, and FGR. In our study, though none of the relations were statistically significant several observations were made suggesting that leptin levels may be influenced by pregnancy related issues. Maternal anemia and maturity did not contribute to changes in fetal leptin levels. Maternal hyperleptinemia in PIH is placental in origin and is attributed to relative placental hypoxia and peripheral insulin resistance. This provides increased maternal free fatty acids and glucose for the fetus.[10],[12] The elevated fetal leptin seen in those born to mothers with PIH may be due to increased contribution from the placenta. Sexual dimorphism with higher leptin levels in female gender have been demonstrated by several authors.[9],[11],[13] This has been attributed to gender parse than a difference in fat distribution.[9]

The lower mean cord leptin levels in growth restricted neonates noted in our study though not statistically significant was similar to several others.[6],[9] In the largest study by Weyermann et al., the mean cord leptin in small (n = 103) and appropriate for GA neonates (n = 568) were 6.3 and 11.6 ng/ml, respectively, with a very high statistical significance. Their study also showed a significant correlation between cord leptin and birth weight. The mean cord leptin in Jaquet et al., study were 2.3 and 5.7 ng/ml in growth restricted and normal neonates with statistical significance. In the only published Indian study on cord leptin, Yajnik et al., noted the mean levels of 6.2 in 94 Pune born ethnic and 6.4 ng/ml in 60 London born Caucasian neonates with no statistical significance. Their mean birth weights were 2805 and 3475 g, respectively.[11] However, when matched for birth weight, cord leptin levels were significantly higher in the Indian babies suggesting a higher fat percentage. The lower level noted in growth restricted neonates reflects the relative body fat accumulation and may also play a role in catch-up growth until 24 months of age.


  Conclusion Top


Various factors including maternal illnesses such as PIH, the gender of the baby, and FGR may influence leptin levels and therefore, the statistical significance of studies based on the cord leptin. Longitudinal studies of various specific cohorts of newborn may be important to understand the role of leptin in growth and insulin resistance.

Indian Council of Medical Research, Government of India funded postgraduate dissertation project.

Financial support and sponsorship

Indian Council of Medical Research, Government of India funded postgraduate dissertation project.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-9.  Back to cited text no. 1
    
2.
Seeley RJ, Schwartz MW. Neuroendocrine regulation of food intake. Acta Paediatr Suppl 1999;88:58-61.  Back to cited text no. 2
    
3.
Marchini G, Fried G, Ostlund E, Hagenäs L. Plasma leptin in infants: Relations to birth weight and weight loss. Pediatrics 1998;101:429-32.  Back to cited text no. 3
    
4.
Barker DJ, Eriksson JG, Forsén T, Osmond C. Fetal origins of adult disease: Strength of effects and biological basis. Int J Epidemiol 2002;31:1235-9.  Back to cited text no. 4
    
5.
Barker DJ. In utero programming of chronic disease. Clin Sci (Lond) 1998;95:115-28.  Back to cited text no. 5
    
6.
Weyermann M, Beermann C, Brenner H, Rothenbacher D. Adiponectin and leptin in maternal serum, cord blood, and breast milk. Clin Chem 2006;52:2095-102.  Back to cited text no. 6
    
7.
Petersen S, Gotfredsen A, Knudsen FU. Lean body mass in small for gestational age and appropriate for gestational age infants. J Pediatr 1988;113:886-9.  Back to cited text no. 7
    
8.
Catalano PM, Drago NM, Amini SB. Factors affecting fetal growth and body composition. Am J Obstet Gynecol 1995;172:1459-63.  Back to cited text no. 8
    
9.
Jaquet D, Leger J, Levy-Marchal C, Oury JF, Czernichow P. Ontogeny of leptin in human fetuses and newborns: Effect of intrauterine growth retardation on serum leptin concentrations. J Clin Endocrinol Metab 1998;83:1243-6.  Back to cited text no. 9
    
10.
Lepercq J, Challier JC, Guerre-Millo M, Cauzac M, Vidal H, Hauguel-de Mouzon S. Prenatal leptin production: Evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab 2001;86:2409-13.  Back to cited text no. 10
    
11.
Yajnik CS, Lubree HG, Rege SS, Naik SS, Deshpande JA, Deshpande SS, et al. Adiposity and hyperinsulinemia in Indians are present at birth. J Clin Endocrinol Metab 2002;87:5575-80.  Back to cited text no. 11
    
12.
Henson MC, Castracane VD. Leptin in pregnancy: An update. Biol Reprod 2006;74:218-29.  Back to cited text no. 12
    
13.
Matsuda J, Yokota I, Iida M, Murakami T, Naito E, Ito M, et al. Serum leptin concentration in cord blood: Relationship to birth weight and gender. J Clin Endocrinol Metab 1997;82:1642-4.  Back to cited text no. 13
    
14.
Laivuori H, Gallaher MJ, Collura L, Crombleholme WR, Markovic N, Rajakumar A, et al. Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia. Mol Hum Reprod 2006;12:551-6.  Back to cited text no. 14
    
15.
Henson MC, Castracane VD. Leptin in pregnancy. Biol Reprod 2000;63:1219-28.  Back to cited text no. 15
    
16.
Linnemann K, Malek A, Sager R, Blum WF, Schneider H, Fusch C. Leptin production and release in the dually in vitro perfused human placenta. J Clin Endocrinol Metab 2000;85:4298-301.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
  Search Pubmed for
  Search in Google Scholar for
Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1367    
    Printed31    
    Emailed0    
    PDF Downloaded161    
    Comments [Add]    

Recommend this journal