ms-2008-obst-nasser hassan

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EVALUATION OF MATERNAL SERUM

LEPTIN LEVEL AS A MARKER OF

PREECLAMPSIA

Protocol of Thesis

Submitted forPartial Fulfillment of the Master Degree in

Obstetrics and Gynecology

Presented by

Nasser Hassan Said MohamedM.B.B.CH.

Al Azhar University (Asuit)(1999)

Resident at Edfu General Hospital

Ministry of Health

Under Supervision of

Prof. Hazem Fadel El shahawyAssist. Prof. of Obstetrics and Gynecology

Faculty of Medicine Ain Shams University

Dr. Rany Mohamed Mahmoud HararaLecturer of Obstetrics and Gynecology

Faculty of Medicine Ain Shams University

Faculty of Medicine

Ain Shams University

Cairo

2008


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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 Program2000).

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 anabnormally shallow endovasculer cytotrophoblast invasion in spiral

arteries which lead to relative placental ischemia and increase inflamatory

response. (Campbell et al 1996)


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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).


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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).


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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).


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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.


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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 40week subdivided into two groups :-

- Group 2a including 20 case of mild preeclampsia whichblood 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 whichblood 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 patients3- 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 andneonatal outcome.


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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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