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Vol. 5/2006 Nr 4(17)
Endokrynologia Pediatryczna
Pediatric Endocrinology
Serum leptin levels in breast-fed and formula-fed neonates
Stężenie leptyny w surowicy krwi noworodków karmionych naturalnie
i sztucznie
Danuta Chlebna-Sokół, Iwona Ligenza, Katarzyna Haładaj, Wiktor Sabanty
Klinika Propedeutyki Pediatrii i Chorób Metabolicznych Kości
I Katedry Pediatrii Uniwersytetu Medycznego w Łodzi
Adres do korespondencji:
prof. dr hab. n. med. Danuta Chlebna-Sokół, Klinika Propedeutyki Pediatrii i Chorób Metabolicznych Kości I Katedry Pediatrii
Uniwersytetu Medycznego w Łodzi, 91-738 Łódź, ul. Sporna 36/50, tel./fax 0 42 61 77 715,
e-mail: [email protected]
Key words: leptin, newborns, kind of feeding
Słowa kluczowe: leptyna, noworodki, sposób karmienia
ABSTRACT/STRESZCZENIE
Leptin is the product of the ob gene and is produced by adipocytes. It has been proved that it is produced by
a placenta and plays an important role in the growth of a featus and an infant. Results of some studies prove that
breast-fed infants present a different growth pattern Reasons for differences in the growth and body composition
between breast and formula-fed children are not very clear. They may depend on different endocrine reaction to
feeding. Supposedly, the concentration of leptin might have an influence on this reaction. The aim of the studywas
the assessment of the concentration of leptin in infants; the attempt to find out whether the concentrations depend on
the kind of feeding. Patients and methods. The research was carried out on 114 eutrofic infants (54 girls and 60 boys),
51 mature, 63 premature infants. The infants under research were divided into 4 groups depending on the kind of
feeding. The concentration of leptin in serum was determined by a radioimmunological method. Results. We proved
statistically significant differences of concentrations of leptin in separated groups of mature and premature babies.
There were no such differences in the concentrations of serum leptin in breast and formula fed children, both in the
group of premature and mature babies. Pediatr. Endocrinol., 5/2006;4(17):9-14
Leptyna jest wytwarzanym przez adipocyty białkowym produktem genu ob, uczestniczy w wielu procesach
metabolicznych organizmu; udokumentowano również, iż jest ona produkowana przez łożysko i odgrywa ważną rolę
w rozwoju płodu i noworodka. Jednocześnie wyniki niektórych badań dowodzą, iż niemowlęta karmione naturalnie
prezentują inny aniżeli karmione sztucznie wzorzec wzrastania. Przyczyny różnic we wzrastaniu i składzie ciała
między niemowlętami karmionymi sztucznie i naturalnie nie do końca są jasne. Być może, zależą one od różnej
endokrynnej odpowiedzi na karmienie; na odpowiedź tę mogłoby mieć wpływ np. stężenie leptyny. Celem pracy
była ocena stężeń leptyny u dzieci w okresie noworodkowym; próba uzyskania odpowiedzi na pytanie, czy stężenia
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te mogą zależeć od sposobu karmienia. Pacjenci i metody. Badaniami objęto 114 eutroficznych noworodków (54
dziewczynki i 60 chłopców), w tym 51 donoszonych i 63 dzieci przedwcześnie urodzonych. Noworodki objęte
badaniem podzielono na grupy w zależności od sposobu karmienia. U wszystkich dzieci oznaczono stężenie leptyny
w surowicy krwi (ng/ml) metodą radioimmunologiczną. Wyniki. Stwierdzono istotne statystycznie różnice stężeń
leptyny w poszczególnych grupach dzieci donoszonych i przedwcześnie urodzonych. Różnic takich nie stwierdzono
w zakresie stężeń leptyny w surowicy między dziećmi karmionymi naturalnie i sztucznie, zarówno w grupie
wcześniaków, jak i dzieci donoszonych. Endokrynol. Ped., 5/2006;4(17):9-14
Introduction
The aim of study
Leptin is the product of the ob gene and is
produced by adipocytes. In humans, the increment
of the subcutaneous fat tissue is linked with the
higher concentration of leptin and leads to higher
level of metabolism and the reduction of food
intake [2]. Leptin is present in many metabolic
processes in a human body. It has been proved that
it is produced by a placenta and plays an important
role in the growth of a featus and an infant. In 1997
Casabiell and associates as well as Houseknech
and associates discovered leptin in breast milk
[5, 6]. Smith-Kirwin and associates point out that
leptin in human milk seem to be connected with fat
particles, thus the concentration of the hormone is
higher in whole rather than in skimmed milk [7].
Recent research proves that that pasteurization of
breast milk reduces the amount of detectable leptin;
the authors of the research imply that formula does
not contain any leptin because bovine milk proteins,
of which it is composed, are isolated from skimmed
milk and leptin connected with fat particles is
removed in the skimming process [8].
R esults of some studies prove that breast-fed
infants present a different growth pattern [9, 10].
Italian researchers point to the inhibition of the
pace of growth in breast-fed infants between 6th
and 12th month, whereas constant growth of body
weight is observed in formula-fed babies [9]. The
DARLING study presents significantly higher
Z-score values for weight-growth indicators for
formula-fed children in comparison to breast-fed
ones. Breast-fed babies of 7-18 months are slimmer
than formula-fed children.
Reasons for differences in the growth and
body composition between breast and formula-fed
children are not very clear. They may depend on
different endocrine reaction to feeding. Supposedly,
the concentration of leptin might have an influence
on this reaction. Factors regulating the level of
leptin in infants, especially in the ones presenting
deviations in health condition have not been
completely found out.
The aim of the study was the assessment of the
concentration of leptin in infants; the attempt to find
out whether the concentrations depend on the kind
of feeding.
Patients and methods
The research was carried out on 114 eutrofic
infants (54 girls and 60 boys), 51 mature, 63
premature infants. The average foetal age of
premature babies was 31.3 weeks (24–34), the
average weight 1480 g (600–2100 g) (Chart 1).
Mature infants were admitted for treatment at the
Infant Pathology Unit from infant units of the city
mainly because of delivery infections. The average
hospitalization period for the group was 14 days
(8–42). All the premature babies were hospitalized
long-term at the Intensive Care Ward for life threat
conditions and next at the Infant Pathology Unit,
Clinic of Paedriatrics Introduction and Metabollic
Diseases of Bones. The hospitalization period
in both wards was from 24 to 102 days (average
29 days).
The concentration of leptin in serum was
determined by radioimmunological method with
the use of the set Biosource Leptin Easia produced
by BioSource Europe S.A. The leptin assessment
was made 1-2 days before babies’ dismissal from
hospital, thus in children in a relatively good health
condition. The infants under research were divided
into 4 groups depending on the kind of feeding.
Group A were 38 mature, breast-fed babies, (breast
feeding ‘on request’). Group B were 13 babies
fed on formulas (Bebiko 1, Nan1, Bebilon1) or
a preliminary formula of type Bebilon Pepti 1 (2
children). Group D were premature infants, the
majority formula-fed on formulas for pre-mature
babies: Bebilon, Nenatal, Alprem, or therapeutic
formulas (Humana with MCT, Bebilon Pepti 1).
Group C – were 7 premature patients fed on breast
milk from a bottle or breast, nonetheless they were
formula – or mixed-fed earlier.
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Chlebna-Sokół D. et all – Serum leptin levels in breast-fed and formula-fed neonates
The assessment of somatic development was
made on the basis of anthropometric measurements
of weight and length of the body and a circumference
of a head, chest and arm, according to the binding
technique (the measurements were made on the
day of taking blood samples from the babies) [11].
In order to assess the condition of nourishment, a
body-weight indicator was calculated which is a
quotient of body weight in kgs and squared length
in metres as well as an arm-head indicator, which is
the proportion of arm and head circumference (in
centimeters). The results of the measurements were
compared to the norms for mature and premature
infants, accordingly to their sex and age [11, 12].
Foetal and calendar ages of babies at the time of
examination are presented in Tab. 1
Results of the research
The results of the anthropometric measurements
as well as the indicators calculated are presented in
Tab. 2. The concentrations of leptin in separated
groups of mature and premature babies are shown
in Tab. 3 and 4. They are statistically significant.
There were no such differences in the
concentrations of serum leptin in breast and formula
fed children, both in the group of premature and
mature babies. Tab. 5 presents the concentrations of
leptin.
Discussion
The excessive body weight in childhood leads to
obesity in adulthood, which in turn might result in
serious health disorders. As it is commonly known,
breast-fed babies are slimmer, thus protected against
obesity in adulthood [13]. Vast research indicates
that bioactive substances in breast milk might
modify the reaction of newborns to the energy
intake as well as influence their metabolism. Leptin,
present in breast milk which, after placenta, is
another source of this hormone, is a potential growth
factor and an integral part of the energy regulatory
system. It has been proved that the concentration
of leptin in umbilical cord blood is significantly
Table I. Foetal and calendar age at the time of examination of babies under research
Tabela I. Wiek płodowy i wiek w chwili badania oraz masa urodzeniowa badanych dzieci
Premature neonates (n=63)
mature neonates (n=51)
Foetal age (weeks)
31.3 + 3.8
40.2 + 2.8
Calendar age (weeks)
37.5 +5.4
42.6 + 3.1
Birth body weight (g)
1480.1 + 753.2
229.5 +703.2
Table II. Anthropometric measurements and indicators of nourishment of babies under research
Tabela II. Pomiary antropometryczne i wskaźniki stanu odżywienia badanych dzieci
mature neonates (n=51)
natural delivery
(n=38)
Caesarian delivery
(n=13)
Premature neonates (n=63)
Natural delivery
(n=7)
Caesarian delivery
(n=56)
Arithmetic means and deviations from standards
Body weight (g)
3444.2 + 821.3
3640 + 1100.2
2150.3 + 978.1
2410.5 + 857
Length (cms)
53.4 + 2.7
54.1 + 3.6
44.9 + 3.8
46.6 + 2.7
Head circumference (cms)
34.9 + 1.9
34.6 + 2.2
32.2 + 2.8
32.9 + 3.1
Chest circumference (cms)
33.8 + 2.4
34.0 + 2.1
29.8 + 2.4
30.9 + 2.0
Arm circumference (cms)
11.2 + 1.6
10.9 + 1.2
9.7 + 1.9
10.00 + 1.6
Indicator. BMI (kgs/m2)
12.3 + 1.8
12.9 + 2.3
10.7 + 2.8
11.2 + 1.9
Arm – head indicator. (cms/
cms)
0.32 + 0.02
0.32 + 0.04
0.30 + 0.12
0.30 + 0.08
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Table III. Serum leptin concentration in babies under research depending on the duration of gestation
Tabela III. Stężenie leptyny w surowicy krwi badanych dzieci w zależności od czasu trwania ciąży
Premature neonates (n=63)
mature neonates (n=51)
2.8 +1.0
(0.15-14.2)*
4.3 + 0.9
(2.3-22.5)*
Leptin (ng/ml)
* p<0.0.5
Leptin (ng/ml)
f (n=28) 3.0
m (n=35) 2.6
f (n=26) 3.9
m (n=25) 4.7
Table IV. Serum leptin concentration in babies under research depending on the kind of feeding
Tabela IV. Stężenie leptyny w surowicy krwi badanych dzieci w zależności od sposobu karmienia
mature neonates (n=51)
Leptin (ng/ml)
Premature neonates (n=63)
natural delivery
(n=38)
Caesarian delivery
(n=13)
natural delivery
(n=7)
Caesarian delivery
(n=5)
5,7 + 5,2
4,8+6,2
3,5+6,7
2,7+4,2
Table V. Leptin concentrations in pre-mature babies depending on the body weight
Tabela V. Stężenia leptyny u dzieci przedwcześnie urodzonych w zależności od masy ciała
Body weight at the time of examination
(ng/ml)
Number of babies
Average leptin concentration
1501 - 2000 g
8
2.4
2001 - 2500 g
32
2.1
2501 - 3000 g
17
3.1
3001 - 3500 g
6
3.5
lower than in mother’s serum and correlates with
a birth body weight [16]. The premature newborns
under research demonstrated significantly lower
concentration of leptin in comparison with the
mature ones, which corresponds to the findings
of other authors [17, 18]. In the research no
statistically significant differences have been found
between the leptine concentration in breast-fed
and formula-fed newborns, both in premature and
mature babies. The findings correspond with the
results of American authors, Lonenerdal and Havel,
who proved the lack of differences in the leptin
concentration and leptine/BMI factor in the first
and the fourth month of life between breast-fed and
formula-fed neonates [19]. Savino and associates
report higher plasma leptine concentration at all
breast-fed patients, both male and female, however
their research has been carried on older neonates of
one to twelve months [19]. The above mentioned
authors emphasize that the differences in the leptin
concentration might depend on reagents even if
used in one type of method – radioimmunological
method. It is also possible that these differences are
caused by dissimilarities of populations. It should be
also pointed out that the infants under research were
hospitalized for health disorders; they were mainly
pneumonia in mature babies, and complications
related to early delivery in premature infants:
breathing disorders, infections, intravetricular
haemorrhage. Although the assessment of leptin
concentration was cerried out just before dismissal
from hospital, thus in a relatively good health
condition, earlier disorders could have influenced
the concentration of serum leptin, by the weakening
of the efficiency of metabolic processes.
The role of leptin has been emphasized in the foetal
growth and in the first year of life [20–22]. The
relation of the amount of leptin to fat tissue implies
that serum leptin concentration should be lower
in breast-fed children than in formula-fed ones.
The fact that it is not most often true suggests that
serum leptin in these babies may come from other
sources, such as breast milk. This thesis is based on
the finding that breast milk contains leptin whereas
formulas do not, as the pasteurization process
destroys this hormone [7]. It is also emphasized that
the concentration of leptin correlates with the serum
leptin concentration both in a baby and a mother
[7]. The group of premature babies, especially the
ones with an extremely low birth body weight is a
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unique paedriatric group of patients. Both early and
late complications of prematurity have a significant
influence on the development of an organism in the
first years of life. They are affected by the activity
of endogenic factors e.g. leptin. Its influence on
angiogenesis, bone metabolism, immunological
growth, brain development, thus all the processes
of growth and maturity is really significant but can
be modified by environmental factors [17, 23]. The
production of this hormone by fat tissue depends on
the amount of it, and body weight together with the
subcutaneous fat tissue is significantly connected
with the course of an early-infant period. It is
admitted that there is a critical ‘body weight’ above
which the relation of leptin concentration is directly
proportional to the body weight and weight-growth
indicators. The levels of leptin below this weight
are different. Spear and associates pointed to a
reverse relation between the concentration of leptin
and anthropometric measurements. Although in
their research the increment of body weight and,
at the same time, ot fat tissue was observed in
premature babies, there was a slight, but statistically
significant decrease/ fall in leptin concentration.
Other authors’ observations related to the processes
of growth revealed the rise of the leptin level.
Low values of this hormone were connected
with undernourishment [2, 8, 21]. For the proper
development of a child it is crucial to sustain the
level of leptin on the right level. Egzogenic delivery
of leptin e.g. with breast milk is a protective factor
for a premature baby. The number of premature
breast-fed babies under research was low and they
caused objective difficulties – prematurity, the lack
of sucking reflex, diseases, the lack of lactation,
separation from a mother. Although ther were
no higher levels of leptin in this group of babies
(breast-fed ones), individual analysis revealed a
far more advantageous course of treatment. Recent
research points out that the addition of leptin to
formulas for premature babies is possible, which
may become a supporting factor in the processes of
growth and development of formula-fed babies [8].
Summing up, in the group of children under
research the higher level of leptin in serum of breastfed children was not observed in their first month of
life, which does not confirm observations of other
researchers. The lack of differences may result from
the fact that both the mature and premature infants
in our research were in the period of weakening
of metabolic processes after their infections or
complications of prematurity. The research was
carried out at the beginning of convalescence.
Conclusions
1. On the basis of the research, the relation between
the concentration of serum leptin and the kind of
feeding in infancy and early babyhood was not
confirmed.
2. The concentration of leptin in pre-mature babies
was lower than in the mature ones.
3. A slight tendency of the growth of the
concentration of leptin was observed with higher
body weight of an infant.
4. The lack of observation of the higher level of
serum leptin in breast-fed infants, observed by other
researchers may be explained by the weakening of
the efficiency of metabolic changes connected with
health disorders.
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