Arch Gynecol Obstet
DOI 10.1007/s00404-013-2915-8
GENERAL GYNECOLOGY
Maternal serum leptin as a marker of preeclampsia
Amal Mohamed El shahat • Abeer Bahaa Ahmed
Magdy Refaat Ahmed • Heba Saber Mohamed
Received: 1 February 2013 / Accepted: 3 June 2013
Ó Springer-Verlag Berlin Heidelberg 2013
Abstract
Purpose To assess maternal leptin levels as a marker for
preeclampsia (PE) and to explore the possibility of leptin
being a marker of severity of preeclampsia.
Participants and methods Comparative prospective study
was conducted among a total of 72 pregnant women at
28–38 weeks of gestation. They were divided into two
groups (control and study) according to the absence or
presence of clinical parameters of preeclampsia. Leptin
was measured for both groups at the time of presentation,
once weekly and at the termination of pregnancy.
Results Leptin levels were found to be significantly
higher among all preeclampsia patients when compared to
the control group; whether at admission or at the time of
delivery. Mean serum leptin level at admission in control
group was 9.8 ng/ml versus 10.9 ng/ml in mild cases and
17.6 ng/ml in severe cases. At the time of delivery, mean
serum leptin in control group decreased to 4.7 ng/ml while
in preeclampsia patients it increased up to 22 ng/ml in mild
cases and 42.6 ng/ml in severe cases. ROC curve analysis
has shown that a cut off value [13.7 ng/ml can be used to
detect presence of preeclampsia with a sensitivity of 91 %
and specificity 100 % while a cut off value [22.5 ng/ml
can be used to detect severity of preeclampsia with a
sensitivity of 85 % and specificity 100 % .
Conclusion Maternal serum leptin is significantly ele-
vated in preeclampsia, also it can be used as a marker for
the presence of preeclampsia and to differentiate patients
with mild preeclampsia from those with severe disease.
A. M. El shahat
A. B. Ahmed
M. R. Ahmed (&)

H. S. Mohamed
Department of Obstetrics and Gynecology, Faculty of Medicine,
Suez Canal University, Round Road, Ismailia 41111, Egypt
e-mail: dr_magdygyn@yahoo.com
•
Keywords Preeclampsia
Serum leptin
Marker
Introduction
Preeclampsia (PE) is one of the most important compli-
cations for pregnancy. It complicates 5–7 % of all pregnant
women and about 10–12 % of all primigravida. It is the
most common cause of maternal and fetal morbidity and
mortality [1, 2].
Leptin is a 16 kDa protein hormone that plays a key role
in energy intake and energy expenditure. It is produced by
a specific gene found in fat cells called the obese (ob) gene
[3]. Leptin is expressed predominantly by adiposities.
Smaller amounts of leptin are also secreted by cells in the
epithelium of the stomach and in the placenta. Leptin
receptors are highly expressed in areas of the hypothalamus
known to be important in regulating body weight, as well
as in T lymphocytes and vascular endothelial cells [4].
Leptin levels are elevated under normal pregnancy espe-
cially during the second trimester, which rapidly decrease and
return to normal at delivery indicating the role of leptin as
gestational hormone for energy balance [5]. The significant
increase in maternal circulating leptin during the first and
second trimesters of normal pregnancy is suggested to be in
response to the marked changes in maternal weight, energy
expenditure and hormonal status. However, recent data show
that the increase occurs in early pregnancy before any change
in body fat or resting metabolic rate, supporting the idea that
hormonal factors may be responsible [6]. Leptin produced by
placental or fetal tissues acts through specific leptin receptors
to regulate fetal growth and development [7].
Placenta may be both a source of leptin and a target for
its action, as leptin [8] and leptin receptor mRNA have
been detected in placental trophoblasts [9]. It was reported
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that leptin secretion by first-trimester placental villous
tissue is approximately 50-fold greater than that by tissue
collected at term [10]. The expression of leptin by human
trophoblast cell line was also significantly increased when
cultured under hypoxic conditions compared with standard
conditions.
Placental ischemia could therefore explain the rapid
increase in leptin concentrations during late third trimester
in preeclampsia. Alternatively, the increase may represent
an adaptive response by the fetoplacental unit to impaired
placental perfusion mounted in an attempt to meet the
energy requirements of the fetus [11].
Increase of placental leptin production reflects placental
hypo perfusion and/or hypoxia. Hypoxia increases pla-
cental leptin production inducing a group of placental
genes in trophoblastic cells. Thus, it is deduced that ele-
vated leptin level is a general response of trophoblastic
cells to hypoxia [12].
There is abundant evidence for increased leptin pro-
duction with regard to endothelial dysfunction in women
with preeclampsia, which could be produced by oxidative
stress in human endothelial cells through the accumulation
of reactive oxygen species [13]. Thus, there are several
possible explanations for the higher leptin concentrations
in pregnancies destined to develop preeclampsia [14], and
so this study was done to compare the serum leptin levels
in normal pregnancies with those pregnancies which are
complicated by preeclampsia and to investigate the possi-
bility of leptin being as a marker for the detection of
occurrence and severity of preeclampsia.
Participants and methods
After approval of the Ethics Committee of Faculty of Med-
icine, Suez Canal University, this prospective comparative
study was conducted among 72 pregnant women with sin-
gleton pregnancy, 28–38 weeks of gestation, presented to
emergency ward and/or outpatient clinic of Obstetrics and
Gynecology Department, Suez Canal University Hospital
during the period from July 2010 to September 2011.
Women with preexisting chronic hypertension, preexisting
diabetes mellitus, gestational diabetes, any chronic illness
which may affect the results (renal disease, cardiac diseases
or hepatic diseases), known history of peripheral vascular
disease or obese patients (BMI C 30) were excluded from
the study. The required sample size for each group was
estimated depending on the previously reported correlation
between serum leptin and diastolic blood pressure (as indi-
cator for diagnosis and severity of preeclampsia) [15] using
an a error of 0.05 and power of study 80 % [16].
Studied women were divided into two groups: control
and study group. Control group included 36 pregnant
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Arch Gynecol Obstet
women with blood pressure \140/90 mmHg and protein-
uria \300 mg/l in 24 h urine collection while the study
group included 36 pregnant women with high systolic and
diastolic blood pressure (C140/90 mmHg), and proteinuria
C300 mg/l in 24 h urine collection.
An informed written consent was obtained from all
studied patients. Thorough obstetric history, complete
general and obstetric examination were done. Ultrasound
was performed in all patients to document fetal viability,
evaluate gestational age, and to assess fetal weight, bio-
physical profile and fetal Doppler to measure S/D ratio and
resistive index. Dipstick urine test and 24 h urine collection
were done to detect proteinuria in association with full
laboratory investigations (CBC, ALT, AST, PT, PTT,
creatinine and uric acid).
Leptin assay was done by obtaining 5 ml of peripheral
venous blood from both groups under strict aseptic mea-
sures. Each sample was labeled with patient’s name and
identification number. Blood samples were transferred
immediately to chilled siliconized glass tubes containing
Na2EDTA (1 mg/ml) which was centrifuged and then
stored at -20 °C until assayed. Total circulating leptin
concentration was measured by radioimmunoassay (RIA).
In control group, leptin was measured at 32 weeks of
gestation and then followed up weekly till termination of
pregnancy while in study group serum leptin was measured
with diagnosis of disease and then weekly till time of ter-
mination of pregnancy.
Statistical analysis
Gathered data were processed using SPSS version 15
(SPSS Inc., Chicago, IL, USA). Quantitative data were
expressed as mean ± SD while qualitative data were
expressed as numbers and percentages (%). Student t test
was used to test significance of difference for quantitative
variables and Chi Square was used to test significance of
difference for qualitative variables; analysis of variance
(ANOVA) test was used to compare quantitative variables
among the three groups. Receiver operating characteristic
(ROC) curve was used to identify a cut-off value for serum
leptin levels to detect presence and severity of pre-
eclampsia. A probability value (p value) \0.05 was con-
sidered statistically significant. Data were analyzed and
appropriately presented in tables and figures.
Results
Both groups were matched as regarding age (26.4
and 27.8 years), gestational age at presentation (32 and
32.4 weeks), BMI (27.6 and 27.5 kg/m2) in control
and study preeclampsia groups, respectively. Systolic and
Arch Gynecol Obstet

diastolic blood pressure were (151.3 and 98.4 mmHg, Table 2 Neonatal outcome among both groups
respectively) significantly higher in preeclampsia group Control group Preeclampsia p value
while in control group systolic and diastolic blood pressure (n = 36) group (n = 36)
were within normal ranges (Table 1).
GA at termination 37.6 ± 0.6 35.5 ± 8.8 0.2
Concerning neonatal outcome at both groups, it was
(weeks) (NS)
found that neonates of preeclampsia groups have signifi-
Birth weight (g) 3,622.2 ± 271.6 2,911.7 ± 707.1 0.001*
cantly lower birth weight, lower Apgar score at 1 and
Apgar score (1 min) 8.8 ± 0.1 7 ± 0.2 0.001*
5 min, with higher incidence of fetal growth restriction and
Apgar score (5 min) 9.8 ± 0.07 6.8 ± 0.4 0.001*
neonatal ICU admission. Mean birth weight was 3,622.2 g
Fetal growth 0 (0 %) 8 (22.2 %) 0.01*
within control group versus 2,911.7 g at preeclampsia restriction
group (p value \ 0.01). Also mean Apgar score at 1 min NICU admission 0 (0 %) 16 (44.4 %) 0.001*
was 8.8 versus 7 in control and preeclampsia group,
respectively, and at 5 min was 9.8 versus 6.8 in control and NS no statistically significant difference
preeclampsia group, respectively. None of the neonates of * Statistically significant difference
control group showed fetal growth restriction while 22.2 %
of neonates of preeclamptic mothers have fetal growth
restriction (p value \0.05). Rate of NICU admission was
44.4 % among newborn of preeclamptic mothers versus
none of control group (p value \ 0.01) (Table 2). predictive value (NPV) of 95 % while a cut off level
Serum leptin levels were found to be significantly higher [22.5 ng/ml can be used to detect severity of preeclampsia
among all preeclampsia patients when compared to control with sensitivity of 85 %, specificity 100 %, PPV 100 %
group values whether at admission or at time of delivery. and NPV of 99 % (Figs. 1, 2).
Mean serum leptin level at admission in control group was
9.8 versus 10.9 ng/ml in mild cases and 17.6 ng/ml in
severe cases. At the time of delivery mean serum leptin in Discussion
control group decreased to 4.7 ng/ml while in preeclampsia
patients it increased up to 22 ng/ml in mild cases and According to the International Society for the Study of
42.6 ng/ml in severe cases, hence patients with severe Hypertension, preeclampsia is defined as blood pressure
disease have significantly higher serum leptin levels com- C140/90 mmHg on two separate occasions 4 h apart or a
pared to patients with mild diseases (Table 3). single recording of a diastolic blood pressure of
ROC curve analysis has shown that a cut-off value 110 mmHg, in association with proteinuria C1? on dip-
[13.7 ng/ml can be used to detect the presence of pre- stick testing. The clinical course of the disease is pro-
eclampsia with sensitivity of 91 %, specificity 100 %, gressive and is characterized by continuous deterioration
positive predictive value (PPV) 100 % and negative that is ultimately stopped only after delivery [17].
In the current study, we found that patients with
preeclampsia had higher serum leptin than normal con-
Table 1 Patients baseline characteristics trol group with mean 24.42 ng/ml in preeclamptic group
while 7.28 ng/ml in control group; also serum leptin is
Control group Preeclampsia p value
(n = 36) group (n = 36) elevated more in severe preeclampsia than in mild pre-
eclampsia with mean 30.11 ng/ml in severe preeclamp-
Maternal age (years) 26.4 ± 4.3 27.8 ± 5.6 0.2 (NS) sia, 16.45 ng/ml in mild preeclampsia, which indicates
Gestational age at 32 ± 0.01 32.4 ± 2.4 0.4 (NS) that serum leptin increases with the severity of
presentation (weeks)
preeclampsia.
Residence
Increase of placental leptin production reflects placental
Urban 27 (75 %) 18 (50 %) 0.05 (NS)
hypo perfusion and/or hypoxia. Hypoxia increases pla-
Rural 9 (25 %) 18 (50 %)
cental leptin production inducing a group of placental
Primigravida 10 (27.7 %) 21 (41.6 %) 0.2 (NS)
genes in trophoblastic cells. Thus, it is deduced that ele-
Multigravida 26 (72.2 %) 15 (58.3 %)
vated leptin level is a general response of trophoblastic
Systolic BP (mmHg) 110.3 ± 5.2 151.3 ± 7.9 0.001* cells to hypoxia. Leptin is a marker of severe preeclampsia,
Diastolic BP (mmHg) 72.9 ± 4.4 98.4 ± 4.9 0.001* reflecting placental hypoxia [12].
BMI (kg/m2) 27.6 ± 1.1 27.5 ± 1.2 0.2 (NS) Our results agreed with Iftikhar et al. [15], and Sucak
NS no statistically significant difference et al. [18] who found that maternal serum leptin levels were
* Statistically significant difference significantly higher in preeclamptic group than in control

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Table 3 Comparison in serum leptin levels among both groups

Serum leptin levels (ng/ml) Control group (n = 36) Preeclampsia group (n = 36)
Mild cases Severe cases All patients

At admission (first visit) 9.8 ± 3.4 10.9 ± 4.9# 17.6 ± 5.8* 13.3 ± 6.1*
à
At time of delivery 4.7 ± 1.6 22 ± 4.4*,#,à 42.6 ± 10.1*,à 31.2 ± 9.7*,à
Mean level 7.28 ± 2.4 16.45 ± 3.8*,# 30.1 ± 6.6* 24.4 ± 8.8*
* Statistically significant difference versus control group
#
Statistically significant difference versus severe preeclampsia group
à
Statistically significant difference versus value at admission

Fig. 1 ROC curve analysis for

serum leptin as a marker of
preeclampsia

Area under the curve: 90%, 95% confidence interval: 0.85 – 0.93, P-value = 0.0001
(Statistically significant)

Opitimum cut off value >13.7 ng/mL

Sensitivity 91%
Specificity 100%
PPV 100%
NPV 100%

group. According to the severity of PE, the serum leptin
levels were found to be statistically higher in severe group
than in mild group and control group as well as what we
have found in the present study.
Therefore, leptin may serve as a marker of preeclampsia,
indicating the associated placental hypoxia [19, 20]. On the
other hand, elevated leptin levels may represent the adap-
tation mechanism of the foeto-placental system, which
attempts to compensate for the impaired placental perfu-
sion and to provide the metabolic needs of the fetus.
Preeclampsia induces inflammatory mediators, such as
tumor necrosis factor-a and interleukin-6, which may in
turn trigger leptin release [21].
Our findings were also consistent with other previous
studies that have shown significant increase in serum leptin
levels in preeclampsia women compared to control group
[18, 22–24]. However, some studies have shown incon-
sistent results and have reported that serum leptin levels
were similar in preeclampsia and control pregnant women
[25–27].

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Fig. 2 ROC curve analysis for

serum leptin as a marker of
severity of preeclampsia

Area under the curve: 90%, 95% confidence interval: 0.89 – 0.96, P-value = 0.0001
(Statistically significant)

Optimum cut off value >22.5 ng/mL

Sensitivity 85%
Specificity 100%
PPV 100%
NPV 99%

We have found that serum leptin value of 13.7 and
22.5 ng/ml can be used to detect preeclampsia presence
and severity, respectively, with high sensitivity and speci-
ficity. Previous reports have also confirmed the role of
serum leptin in detecting presence and severity of pre-
eclampsia with similar values [15, 18, 20, 21, 23, 25–27].
In conclusion, maternal serum leptin is significantly
elevated in preeclamptic patients at onset of disease and
continues to rise till termination of pregnancy and it can be
used as a marker of presence of preeclampsia and also to
differentiate patients with mild preeclampsia from those
with severe disease.
preeclampsia with marker of 13.7 and 22.5 ng/ml,
respectively.
Recommendations
Serum leptin can be used as a marker for preeclampsia and
also as a marker of severity of preeclampsia so that the risk
of imminent eclampsia can be reduced. Large-scale, multi-
center studies are required to refine the cut-off value of
serum leptin that can be used as marker for occurrence and
severity of preeclampsia.
Conflict of interest The authors report no declaration of interest.

Conclusion
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