Clinical Research Report
Relationship between
newborn leptin levels and
selected growth parameters
Journal of International Medical Research
2019, Vol. 47(6) 2591–2597
! The Author(s) 2019
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/0300060519848613
journals.sagepub.com/home/imr
Amer Mahmoud Sindiani , Rawan Obeidat,
Omar Jbarah and Ethar Hazaimeh
Abstract
Objectives: This study aimed to determine leptin levels in term newborns who were born in the
north of Jordan. We also aimed to investigate the relationships of leptin levels with fetal growth
parameters, and to assess the difference in leptin levels according to sex and gestational age.
Methods: A cross-sectional descriptive study that involved 170 term newborns was conducted.
A working sheet for data collection was created for each newborn and included sex, weight,
length, head circumference, gestational age, and Apgar score. Blood samples were obtained from
the umbilical cord vein of newborns after delivery to measure serum leptin levels. Data are
shown as frequency, percentages, means, and standard deviations.
Results: We found that the mean leptin level was 1.17 0.48 ng/mL. The independent t-test
showed that the mean leptin level in boys (0.93 0. 34 ng/mL) was significantly lower than that in
girls (1.38 0.47 ng/mL). Pearson’s correlations showed that leptin levels of newborns were
positively and significantly correlated with weight, length, and head circumference.
Conclusion: In Jordanian healthy term newborns, leptin levels correlate with sex and intrauterine growth parameters.
Keywords
Leptin, newborn, weight, length, Apgar score, head circumference
Date received: 2 October 2018; accepted: 15 April 2019
Introduction
Leptin is considered an anorexigenic hormone that has an important function in regulating energy by lowering food intake and
increasing consumption of energy.1–4
Department of Obstetrics and Gynecology, Faculty of
Medicine, Jordan University of Science and Technology,
Irbid, Jordan
Corresponding author:
Amer Mahmoud Sindiani, Department of Obstetrics and
Gynecology, Faculty of Medicine, Jordan University of
Science and University, P.O. box 3030, Jordan Street, Irbid,
22110 Jordan.
Email: amsindiani0@just.edu.jo
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative
Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which
permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is
attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
2592
Adipose tissue is the main site of leptin production and to some extent it is produced
by the placenta, stomach, and mammary
epithelium.5–7 Leptin plays an important
role in development of a neonate’s hypothalamic pathways and is involved in controlling energy and appetite.8 Evidence from
animal studies has suggested that leptin
can act on the brain to improve formation
of the neural circuits regulating future food
intake and adiposity.9 Many studies have
focused on adult leptin levels and their correlation with body mass index, but limited
studies have investigated newborn leptin
levels and their correlation with intrauterine
growth.10
In a cross-sectional study10 on cord
blood samples that were taken from 50 newborns, cord blood leptin levels were corre€
lated with fetal growth. Recently, Okdemir
11
et al. conducted a study on 84 mothers
and their newborns to examine the relationships between leptin levels and maternal
weight gain and newborn anthropometric
measurements. These authors showed that
in newborns, leptin levels significantly
varied
according
to
birth
weight
(P ¼ 0.013). Furthermore, leptin levels
were associated with fetal adiposity.
Schuster et al.12 conducted a prospective,
longitudinal study to evaluate leptin levels
in the blood of 23 healthy lactating mothers
and in their breast milk, as well as in their
neonates. These authors showed that serum
leptin levels were much higher than those in
breast milk.
A review of the relevant literature in
Jordan showed some studies on leptin
among adults, but no studies on leptin in
newborns. Abu-Samak et al.13 conducted
a study to analyze the effect of hyperleptinemia on fasting lipid and hematological
parameters in healthy young men in
Jordan. These authors found that mean
serum leptin levels were higher in those
with hyperlipidemia than in those without
hyperlipidemia.
Journal of International Medical Research 47(6)
The current study aimed to determine
newborn leptin levels in the north of
Jordan, to investigate the relationships
between newborn leptin levels and selected
growth parameters, such as weight, length,
and head circumference, and to assess the
differences in leptin levels according to sex
and gestational age.
Methods
Study design
A descriptive-cross-sectional design was
used to assess the relationship between newborn leptin levels and selected growth
parameters, and to assess the differences
in leptin levels according to sex and gestational age.
Samples and sampling technique
A convenient sampling technique was used
to recruit a convenience sample of 170 term
newborns whose mothers agreed to participate in this study. Using a convenience
sample may affect the external validity of
the results because it is unlikely to be representative of the population under study.
The eligibility criteria for the participants
were as follows: term newborns of mothers
who had no medical illnesses during their
pregnancies, and mothers were aged older
than 18 years old and agreed to include
their newborns in the current study.
Newborns of mothers with medical illness
or those who were delivered preterm
were excluded.
The sample size was calculated on the
basis of parameters of G* power software
(free software).14 The sample size required
was 138 participants on the basis of the following statistical factors for Pearson’s r: an
alpha level of 0.05, a power level 0.95, and
an effect size of 0.30. To overcome the
problem of attrition or missing data, an
extra 32 term newborns were included in
2593
Sindiani et al.
the final sample size to have at least 170
participants.
Site and setting of the study
This study was conducted in the University
Educational Hospital in Irbid Province,
which has the second largest metropolitan
population in Jordan after Amman. The
total capacity of this hospital is more than
650 beds with an impressive occupancy rate
of close to 99%. This hospital includes different specialties, such as internal medicine,
cardiology, orthopedics, pediatric neurology, maternity, and dermatology.
Study procedure
The study method and protocol were
approved by the Institutional Review
Board of the University Hospital. Written
informed consent was obtained from the
newborns’ mothers, who agreed to include
their newborns in the study. The confidentiality of the participants was protected by
providing a code number for each participant during the data collection and analysis
phases of the study. No physical, psychological, social, or economic harm or risk
affected the newborn. There were no complications in the blood sample collection
process for the newborns. No blood loss,
infections, or complications developed
during or after the procedure. A qualified
competent staff nurse was responsible for
obtaining blood samples from the umbilical
cord of the newborns. This procedure was
performed under a hospital policy of withdrawing blood under an aseptic technique.
A blood sample was taken as a routine
check for each newborn in the period immediately after delivery.
Files of the newborns and mothers were
carefully checked to ensure their eligibility
to participate in the study. The primary
researcher collected data regarding sex,
weight, length, gestational age, head
circumference, and Apgar score. To measure serum leptin levels, blood samples
were obtained from the umbilical cord
vein of the newborn after delivery.
Serum leptin measurement
Approximately 5 mL of venous blood was
collected from each newborn in a serum
separator tube. The samples were allowed
to clot for 2 hours at room temperature or
overnight at 4 C before being centrifuged
for 15 minutes at 1000 g. The serum was
then removed and assayed immediately or
divided into aliquots, and the samples were
stored at 80 C.
Quantitative measurement of serum
leptin levels was performed using a leptin
enzyme immunoassay or Human Leptin
ELISA kit (MBS700713; MyBioSource,
San Diego, CA, USA) according to the
manufacturer’s instructions. This assay
uses the quantitative sandwich enzyme
immunoassay technique. Antibody specific
for leptin was pre-coated onto a microplate.
Standards and samples were then pipetted
into the wells and any leptin present was
bound by the immobilized antibody. After
removing any unbound substances,
a biotin-conjugated antibody, specific
for leptin, was added to the wells. After
washing, avidin-conjugated horseradish
peroxidase was added to the wells.
Following a wash to remove any unbound
avidin–enzyme reagent, a substrate solution
was added to the wells and color developed
in proportion to the amount of leptin that
was bound in the initial step. Color development was stopped and the intensity of the
color was then measured.
Statistical analysis
Descriptive statistics, including frequency,
percentage, mean, and standard deviation,
are used to describe the data. The relationships between leptin levels and newborns’
2594
Journal of International Medical Research 47(6)
growth parameters (weight, length, and
head circumference) were tested using
Pearson’s product-moment correlations.
The independent t-test was also used to
examine differences in leptin levels according to sex and gestational weeks.
Significance was considered at P < 0.05.
Results
General characteristics of newborns
The newborns’ characteristics are shown in
Table 1. The mean leptin level was 1.17
0.48 ng/mL, the mean birth weight was
3.11 0.52 kg., and the mean length was
49.71 2.20 cm. The mean gestational age
was 38.28 1.36 weeks, and it ranged
from 37 to 42 weeks. More than half of
the newborns were girls (n ¼ 92).
Effect of sex and gestational age on
newborn leptin levels
newborns delivered at >38 to 42 weeks’
gestational age was not significant
(t[168] ¼ 0.39).
Relationship between newborn leptin
levels and growth parameters
There was a significant, but weak, positive
correlation between leptin levels and newborn weight (r[168] ¼ 0.16, P ¼ 0.044).
Furthermore, Pearson’s correlation also
showed that there was a significant, but
weak, positive correlation between leptin
levels and newborn length (r[168] ¼ 0.15,
P ¼ 0.049). Moreover, there was a significant, but weak, positive correlation between
Table 2. Effect of sex and gestational age on
newborn leptin levels (n ¼ 170).
Standard
Mean deviation t(168) P value
Variable
The mean leptin level in boys was significantly lower than that in girls (t[168] ¼
2.62, P ¼ 0.010, Table 2). Furthermore, the
difference between the mean leptin level in
newborns delivered at 37 to 38 weeks’ gestational age and the second group of
Boys
Girls
37–38 gestational
weeks
>38–42 gestational
weeks
0.93 0.34
1.38 0.47
1.15 0.48
2.62 0.010
0.39 0.69
1.22 0.52
P was determined by the independent t-test
Table 1. Sample characteristics of the newborns (n ¼ 170).
Variable
Mean (SD)
Leptin levels (ng/mL)
Birth weight (kg)
Length (cm)
Head circumference (cm)
Apgar score at 1 minute
Apgar score at 5 minutes
Sex
Boys
Girls
Gestational age categories
37–38 gestational weeks
>38–42 gestational weeks
1.17
3.11
49.71
35.15
8.34
9.53
SD standard deviation.
(0.48)
(0.52)
(2.20)
(1.99)
(1.00)
(0.74)
Range
n (%)
0–4
2–4
36–55
29–53
4–10
8–10
78 (45.9)
92 (54.1)
110 (64.7)
60 (35.3)
2595
Sindiani et al.
Table 3. Pearson’s correlations between newborn leptin levels and their growth
parameters (n ¼ 170).
Variable
Weight
Length
Head
circumference
Leptin
0.16 *
0.15*
0.16*
Apgar score
at 1 minute
0.02
Apgar score
at 5 minutes
0.07
Values are shown as Pearson r. *P < 0.05.
leptin levels and newborn head circumference (r[168] ¼ 0.16, P ¼ 0.032). However,
there were no significant correlations
between the Apgar score at 1 minute (r
[168] ¼ 0.02) and the Apgar score at 5
minutes (r[168] ¼ 0.07) and leptin levels
(Table 3).
Discussion
The present study showed that the mean
leptin level in Jordanian newborns was
1.17 0.48 ng/mL. In Ohkawa et al.’s
study,15 serum leptin levels of newborns
were less (approximately 0.8 ng/mL) than
those in our study. Our study showed that
female newborns had higher leptin levels
compared with male newborns. This finding
is generally consistent with the results
obtained by Torgerson et al.,16 who
reported that women had significantly
higher levels of leptin than did men
(P < 0.05). Some studies reported differences in leptin levels between males and
females that were attributed to differences
in body composition, to variations in hormones, and to genes responsible for sex
specifications.17 Other studies have reported
that sex hormones have different effects on
leptin levels; testosterone has an inhibitory
effect on leptin, whereas estrogen has a
stimulatory effect.18However, a prospective
cohort study19 of 100 women who had full
term newborns showed no significant difference in leptin levels between male and
female newborns.
Our study showed positive correlations
between newborn leptin levels and weight,
length, and head circumference. These findings are consistent with the results of other
studies as follows. Koistinen et al.10
reported a positive correlation between
leptin levels and fetal growth. Mantzoros
et al.20 found that leptin was a predictor
of weight gain. Savino et al.21 reported a
relationship between serum leptin levels
and body mass index (P ¼ 0.042).
However, Karakosta et al.22 found a negative association of blood leptin levels with
growth in early childhood. Additionally,
another study conducted by Tung et al.
(2009)23 assessed the relationship between
venous umbilical cord leptin levels and
anthropometric measurements in term
healthy Taiwanese newborns. These
authors found that birth weight was the
only predictor of leptin levels.
There was no association between newborn leptin levels and their Apgar scores in
our study. This finding is not in agreement
with that of Taghreed et al.24 who reported
a positive correlation between the Apgar
score and leptin levels. However, these
authors found growth-restricted fetuses
had lower blood leptin levels compared
with controls.
Conclusions
We conclude that leptin is present in utero
and it correlates with intrauterine growth
parameters in newborns in Jordan. This
finding confirms the results of other studies
2596
about the possible role of leptin in
fetal growth.
Study recommendations and implications
A larger, randomly selected, and heterogeneous sample of participants from north,
central, and south Jordan is required in the
future to make our findings more widespread and applicable. This research can be
considered a baseline for conducting other
research projects that aim to assess changes
in leptin levels in patients with comorbid
diseases, such as diabetes and obesity.
Furthermore, longitudinal research studies
need to be conducted to assess the changes
in leptin levels over time and their relationship with different physiological parameters.
This study provides better understanding
of fetal growth and different factors that
participate in growth. Future studies may
implement multiple factors to predict newborns that are growth restricted rather than
being small for gestational age.
Study limitations
This study has some limitations. Restriction
of the study to the north of Jordan and use
of a convenience sample of newborns could
pose a problem for its generalizability, and
affect the external validity of the results.
Therefore, we recommend that further studies be conducted, using a larger more heterogeneous sample, thereby enhancing the
generalizability of the findings.
Acknowledgements
The authors would like to thank the study participants and Jordan University of Science
and Technology.
Declaration of conflicting interest
The authors declare that there is no conflict
of interest.
Journal of International Medical Research 47(6)
Funding
This research received no specific grant from any
funding agency in the public, commercial, or
not-for-profit sectors.
ORCID iD
Amer Mahmoud Sindiani
0000-0001-5115-7372
https://orcid.org/
References
1. Olga M, Juana S, Andreu P, et al. A physiological role of breast milk leptin in body
weight control in developing infants.
Obesity 2006; 14: 1371–1377.
2. Perianes-Cachero A, Burgos-Ramos E,
Puebla-Jiménez L, et al. Leptin-induced
downregulation of the rat hippocampal
somatostatinergic system may potentiate its
anorexigenic effects. Neurochem Int 2012;
61: 1385–1396.
3. Sobrino Crespo C, Perianes Cachero A,
Puebla Jiménez L, et al. Peptides and food
intake. Front Endocrinol (Lausanne) 2014;
5: 58.
4. Deck CA, Honeycutt JL, Cheung E, et al.
Assessing the functional role of leptin in
energy homeostasis and the stress response
in vertebrates. Front Endocrinol (Lausanne)
2017; 8: 63.
5. Galic S, Oakhill JS and Steinberg GR.
Adipose tissue as an endocrine organ. Mol
Cell Endocrinol 2010; 316: 129–139.
6. Itoh M, Suganami T, Hachiya R, et al.
Adipose tissue remodeling as homeostatic
inflammation.
Int
J
Inflam
2011;
2011: 720926.
7. Coelho M, Oliveira T and Fernandes R.
Biochemistry of adipose tissue: an endocrine
organ. Arch Med Sci 2013; 9: 191–200.
8. Woods SC and D’Alessio DA. Central control of body weight and appetite. J Clin
Endocrinol Metab 2008; 93: S37–S50.
9. Bouret SG and Simerly RB. Developmental
programming of hypothalamic feeding circuits. Clin Genet 2006; 70: 295–301.
10. Koistinen HA, Koivisto VA, Andersson S,
et al. Leptin concentration in cord blood
correlates with intrauterine growth. J Clin
Endocrinol Metab 1997; 82: 3328–3330.
2597
Sindiani et al.
11. Okdemir D, Hatipoglu N, Kurtoglu S, et al.
The role of irisin, insulin and leptin in maternal and fetal interaction. J Clin Res Pediatr
Endocrinol 2018; 10: 307–315.
12. Schuster S, Hechler C, Gebauer C, et al.
Leptin in maternal serum and breast milk:
association with infants’ body weight gain in
a longitudinal study over 6 months of lactation. Pediatr Res 2011; 70: 633.
13. Abu-Samak M, Yousef AM, Al-Jarie A,
et al. Lipid and hematological parameters
in hyperleptinemic healthy Arab male
youth in Jordan. Pak J Biol Sci 2011;
14: 344–350.
14. Faul F, Erdfelder E, Lang AG, et al.
G*Power 3: a flexible statistical power analysis program for the social, behavioral, and
biomedical sciences. Behav Res Methods
2007; 39: 175–191.
15. Ohkawa N, Shoji H, Ikeda N, et al.
Relationship between insulin-like growth
factor 1, leptin and ghrelin levels and
catch-up growth in small for gestational
age infants of 27–31 weeks during neonatal
intensive care unit admission. J Paediatr
Child Health 2017; 53: 62–67.
16. Torgerson JS, Carlsson B, Stenl€
of K, et al. A
low serum leptin level at baseline and a large
early decline in leptin predict a large 1-year
weight reduction in energy-restricted obese
humans. J Clin Endocrinol Metab 1999;
84: 4197–4203.
17. Wilkin TJ and Murphy MJ. The gender
insulin hypothesis: why girls are born lighter
18.
19.
20.
21.
22.
23.
24.
than boys, and the implications for insulin
resistance. Int J Obes (Lond) 2006; 30: 1056.
Vázquez MJ, Romero-Ruiz A and TenaSempere M. Roles of leptin in reproduction,
pregnancy and polycystic ovary syndrome:
consensus knowledge and recent developments. Metabolism 2015; 64: 79–91.
Ali MA, Salman DA and Hallab HS.
Neonatal and placental birth weight and its
correlation with leptin level in maternal and
cord blood. Iraqi Med J 2017; 63: 97–104.
Mantzoros CS, Rifas-Shiman SL, Williams
CJ, et al. Cord blood leptin and adiponectin
as predictors of adiposity in children at 3
years of age: a prospective cohort study.
Pediatrics 2009; 123: 682–689.
Savino F, Liguori SA, Fissore MF, et al.
Looking for a relation between serum
leptin concentration and body composition
parameters in healthy term infants in the
first 6 months of life. J Pediatr
Gastroenterol Nutr 2008; 46: 348–351.
Karakosta P, Roumeliotaki T, Chalkiadaki
G, et al. Cord blood leptin levels in relation
to child growth trajectories. Metabolism
2016; 65: 874–882.
Tung WK, Lin SJ, Hwang YS, et al.
Association of cord plasma leptin with
birth size in term newborns. Pediatr
Neonatol 2009; 150: 255–260.
ALhaidari TK, Tuma WE and Jassim TK.
The effect of leptin level in pregnancy complicated by intrauterine growth restriction
on neonatal outcome, in an Iraqi center.
Al-Kindy Col Med J 2012; 8: 1–13.