EVALUATION OF MATERNAL SERUM

LEPTIN LEVEL AS A MARKER OF

PREECLAMPSIA
Protocol of Thesis
Submitted for
Partial Fulfillment of the Master Degree in
Obstetrics and Gynecology

Presented by
Nasser Hassan Said Mohamed
M.B.B.CH.

Al Azhar University (Asuit)

(1999)
Resident at Edfu General Hospital
Ministry of Health

Under Supervision of
Prof. Hazem Fadel El shahawy
Assist. Prof. of Obstetrics and Gynecology
Faculty of Medicine Ain Shams University

Dr. Rany Mohamed Mahmoud Harara

Lecturer of Obstetrics and Gynecology
Faculty of Medicine Ain Shams University

Faculty of Medicine
Ain Shams University
Cairo
2008
 Introduction
Preeclampsia is common pregnancy specific syndrome in 3-5% of
pregnancies which is one of major causes of antenatal and prenatal
morbidity and mortality worldwide. The onset and clinical course
unpredictable. The etiology is unknown but the placenta is essential for
the disease process and the only treatment is a delivery (Roberts and
Lain2002).
The minimal criteria for diagnosis of preeclampsia are proteinuria
defined as 300 mg or more of urinary protein per 24h, and hypertention of
140/90 mmHg or higher and first diagnosed after 20 wk of gestation
(National High Blood Pressure Education Program 2000).
Preeclampsia can be considered as two stages disease. (Roberts and Lain
2003)
The first stage is a reduction in fetal placental perfusion, the second
stage is the maternal syndrome. (Khong et al, 1986) (Arias et al, 1993)
A reliable early marker of preeclamesia would permit identification of
patient who might benefit from prophylaxis, when it becomes available.
A huge number of tests have been proposed to predict preeclampsia,
beginning from asking the simple question of how the patient is feeling
and standard methods of antenatal care such as blood pressure
measurement and proteinuria by dip stik, to blood and urine biochemical
test, markers, ultrasonic and doppler evaluation. (Dalton K 1992)
Recent observation suggest that preeclampsia originate from an
abnormally shallow endovasculer cytotrophoblast invasion in spiral
arteries which lead to relative placental ischemia and increase inflamatory
response. (Campbell et al 1996)
 Also in preeclampsia the invasive trophoplast reach the vicinity of
spiral arteries but fail to pentrat them precluding the conversion of the
spiral arteries into low resistance channels and inducing placenta to
secrete hypertensive substances. (Kliman H J 2000).
Some placental hormones change in the maternal circulation indicating
the derangement of placental function the levels of several placental
hormones are elevated in maternal serum long before overt peeclampsia
is diagnosed and these may be considered preclinical manifestation of the
earlier stages of the disease. Therefore, such hormones have been
proposed as early predictive markers of preeclampsia. Patients with overt
preeclamesia in the third trimester have increased maternal serum HCGs
level. (Lieppman R E et al 2003).
Maternal serum activin A and inhibin A levels are substantially
increased in the presence of hypertensive disorders (D'Antona D et al
2000).
Direct or indirect measurements of the activity of the renin
angiotensin system have been proposed to predict preeclampsia. (Russen
SS et al 1998).
Increased maternal serum Corticotrophen Releasing Hormone
(CRH) levels are frequent feature of pregnancies complicated by
preeclampsia. (Ahmed 1 et al 2000).
Leptin, a 167 – amino acid peptide is recently discovered
antiobesty hormone and plays a key role in the hypothalamic regulation
of body weight. Leptin, a product of the obese gene is a protein that is
almost secreted in fat cells (Zhany et al 1994).
Leptin, an adipocyte – derived hormone that is also produced by
number of other tissues including the stomach, intestine and the placenta,
in humans, acts on hypothalamic receptors to decrease food intake and
increase energy expandure (Masuzaki H et al 1997).
 Weight loss, fasting and starvation are known to induce reduction
in leptin concentrations, whereas concentrations are increased with
weight gain and hyperinsulinemeia (Havel P J et al 1996).
Changes in circulating leptin concentration in pregnant women are
generally consistent with changes in maternal fat stores and glucose
metabolism. Maternal leptin concentration are known to increase 2-to 3-
fold above non pregnant women, with the peak occurring around 28
weeks of gestation (Schubring C T et al 1998).
Elevated maternal leptin levels have been described in women in
the third trimester (Anim – Nyame N et al 2000). but not at delivery
(Laml T, et al 2001).
The most probable mechanism of leptin increase in preeclampsia is
increased production (Mise H et al 1998), And this explains why
preeclampsia subverts the physiological relationship between adiposity
and leptin levels in pregnant women (Williams M A et al 1999).
A longitudinal study showed increase leptin levels beginning at 20
gestational weeks in women disitned to developing preeclampsia,
suggesting that leptin might be an early marker of the disease (Williams
M A et al 1999).
Both leptin and uric acid concentrations are increased in
preeclamsia. In nondiabetics, leptin is closely related to urate
concentration independent of blood pressure. This relationship may have
several explanations as both leptin and urate may be markers of
preeclamsia . (Fruehwold-Schultes et al. 2004)
Leptin may contribute to the increased uric acid concentration as
plasma uric acid concentrations are increased by oxidative stress.
(Davidge 2003).
 Leptin has been reported to induce oxidative stress in cultured
human endothelial cells. So there are several possible explanations for the
higher leptin concentration in preeclampsia. (Bouloumie et al 2005).
Some studies have shown that leptin may influence autonomic and
cardiovascular functions. (Hayness et al, 2005)
Chronic infusion of leptin in animals modules causes an increase in
heart rate and development of hypertension and similar findings have
been observed in essential hypertension. (Nakiewicz et al, 2004).
 Aim of the work

The aim of the work is to evaluate the serum leptin levels in the
third trimester of pregnancy as a marker of preeclamesia.
 Patients and Methods

This case – control study will be done in Ain Shams University

Maternity Hospital including 80 ladies in the third trimester of pregnancy
subdivided into two groups.
• Group 1 (control group) will include 40 pregnant ladies between 26
– 40 week gestational age, single viable fetus with no
preeclampsia.
• Group 2 (study group) 40 preeclamptic patients between 26 – 40
week subdivided into two groups :-
- Group 2a including 20 case of mild preeclampsia which
blood pressure 140/190 mm Hg but less than 160/1110 mm
Hg and albumin in urine (+) or (++).
- Group 2b including 20 cases if sever preeclampsia which
blood pressure 160/110 mm Hg or more and albumin in
urine (+++) or more.
The following patients will be excluded:
1- Patients in labour.
2- Obese patients
3- Patients with any known medical diseases as essential hypertension,
Diabetes Mellitus (D M), hepatic patients, renal patients, cardiac
patients, SLE and any patients with any medical disease affecting
the results.
4- Patients with multiple pregnancy.
- All patients will be subjected to full history, full clinical, vaginal
examination as well as urine analysis.
- Blood samples will be taken from the patients between 26 – 40
week gestational age and the serum will be separated and thin
examined by ELISA test for serum letpin level.
- Patients will be followed up till delivery to detect maternal and
neonatal outcome.
 Results

The results of this study will be subjected to statistical analysis

using computerized-based program comparing between the results from
preeclapmptic and non preeclamptic patients using paired t-test and
unpaired t-test (if SD > 50%) for quantitative data and chi-square test (x2)
for qualitative data
Then Rank Spearman correlation coefficient test will be done to
test correlation between variables.
- Receiver operator characteristic (ROC) carve will be performed to find
out the best cut-off value of serum leptin to screen for preclamesia and
detect its prognosis.
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