|Year : 2019 | Volume
| Issue : 2 | Page : 470-475
Role of serum leptin as a marker of severity of pre-eclampsia
Ahmed N Eissa1, Tarek M Sayyed1, Amr S El-Bagoury2
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia Governorate, Egypt
2 Department of Obstetrics and Gynecology, Shebin El-Kom Teaching Hospital, Shebin El-Kom, Menoufia Governorate, Egypt
|Date of Submission||28-Feb-2018|
|Date of Acceptance||21-Apr-2018|
|Date of Web Publication||25-Jun-2019|
Amr S El-Bagoury
Gamal Abd El-Nasr Street, Shebin El-Kom, Menoufia Governorate
Source of Support: None, Conflict of Interest: None
The objective of this study was to evaluate the role of serum leptin level as a marker of severity of pre-eclampsia (PE).
PE is a hypertensive disorder in pregnancy that is associated with high blood pressure and proteinuria and develops after 20 weeks of gestation. PE is a major contributor to maternal mortality, complicating 2–8% of pregnancies.
Patients and methods
This study was conducted at the outpatient clinic and obstetric departments of Shebin El-Kom Teaching Hospital from February 2016 to January 2017. This study included 95 pregnant women, among which 20 were diagnosed as having mild PE (group A) and 45 had severe PE (group B), according to American College of Obstetricians and Gynecologists criteria, and 30 participants with normal pregnancy were taken as a control group (group C). Full history was taken; physical examination and obstetric ultrasound were done; and single blood sample was taken from all groups. The serum leptin level was measured using enzyme-linked immunosorbent assay kits.
There were no statistical significant differences between the studied groups with respect to the maternal age, parity, and the gestational age. Maternal serum leptin levels were statistically significantly higher (P < 0.001) in the PE groups (43.51±15.49 ng/ml) than in the control group (13.87±4.24 ng/ml). The serum leptin levels were found to be statistically significant higher (P < 0.001) in the severe group (49.37±14.4 ng/ml) than in the mild group (30.32±7.8 ng/ml).
Maternal serum leptin level is increased in PE. It can be taken independently or along with other parameters as a marker for severity of PE.
Keywords: hypertension, leptin, pre-eclampsia, pregnancy, severe
|How to cite this article:|
Eissa AN, Sayyed TM, El-Bagoury AS. Role of serum leptin as a marker of severity of pre-eclampsia. Menoufia Med J 2019;32:470-5
| Introduction|| |
Pre-eclampsia (PE) is a hypertensive disorder in pregnancy that is associated with high blood pressure and proteinuria and develops during the second half of pregnancy. PE affects 2–8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Although the exact cause of PE remains unknown, the origin of the condition is recognized as lying in the placenta. This is because PE occurs only during pregnancy, resolves after delivery of the placenta, and can occur in the absence of a viable fetus, like in molar pregnancy. The pathophysiology of PE has been proposed to occur in two stages: stage 1, reduced placental perfusion, and stage 2, the maternal clinical syndrome. Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors such as cytokines including tumor necrosis factor-α and interleukin-6, activated circulating immune cells and autoantibodies that have profound effects on blood flow and regulation of arterial pressure. Leptin is a protein hormone that has important effects in body weight regulation, metabolism, and reproductive functions. The protein has 167 amino acid sequences containing one disulfide bond; its molecular weight is ∼16 kDa and has four-helix bundle with one very short strand segment and two relative intermitting loops. Leptin is a product of ob/ob (obesity) gene produced by adipose tissue and synthesized during pregnancy by placenta resulting in increased serum leptin level with increasing gestational age particularly in PE and level decreases during postpartum period. In pregnant women, leptin is synthesized in and secreted from placental trophoblast into maternal circulation at a significant amount compared with that in nonpregnant woman. Leptin is a major placental protein that exhibits metabolic and physiological functions in a normal pregnancy. However, clinical and experimental trials have not clarified the definite role of leptin in pathogenesis of high-risk pregnancies. Leptin is secreted by the white adipose tissue mainly and synthesized in several nonadipose tissue organs including the placenta. Leptin plays important roles not only in satiety modulation and energy homeostasis but also in reproduction, ranging from paracrine effect on the placenta to regulation of fetus development and growth. Increased placental production of leptin might be a response to placental hypoxia caused by severe PE. This supports the idea that augmented plasma leptin levels reflect placental hypoperfusion and/or hypoxia in severe PE. Therefore, leptin may be a marker of PE, indicating the associated placental hypoxia.
| Patients and Methods|| |
This cross-sectional study had been conducted at the outpatient clinic and obstetric departments of Shebin El-Kom Teaching Hospital from February 2016 to January 2017, after obtaining an approval from hospital local medical ethics committee. The study was conducted on 95 pregnant women at 20–40 weeks of gestation. A total of 65 women were diagnosed as having PE, and 30 participants with normal pregnancy were taken as a control group (group C). Of the 65 PE, 20 were diagnosed as having mild PE (group A) and 45 as severe PE (group B). Diagnostic criteria for PE according to American College of Obstetricians and Gynecologists criteria were as follows: systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg, measured on two occasions at least 4 h apart, and proteinuria of more than 0.3 g per 24 h or at least 1+ proteinuria, detected by urine dipstick after 20 weeks of pregnancy. Severe PE is confirmed when any of the following criteria is present: systolic blood pressure of at least 160 mmHg, diastolic blood pressure of at least 110 mmHg, thrombocytopenia (platelet count <100 000/μl), renal insufficiency (serum creatinine concentration >1.1 mg/dl or a doubling of the serum creatinine concentration in the absence of other renal disease), impaired liver function (raised concentrations of liver transaminases to twice normal concentrations), pulmonary edema, or cerebral or visual problems.
Patients with chronic renal disease, chronic hepatic disease, multiple pregnancies, and diabetes mellitus were excluded from the study.
An informed written consent was obtained from all studied patients. Obstetric history, complete general examination, and obstetric examination were done followed by obstetrical ultrasound. Dipstick urine test was done to detect proteinuria in association with full laboratory investigations (complete blood count, alanine aminotransferase, aspartate aminotransferase, prothrombin time, partial thromboplastin time, creatinine clearance, and uric acid). A single venous blood sample of 5 ml was taken from all groups under strict aseptic measures. The sample was left to stand at room temperature for at least 30 min to allow the blood to clot, then centrifuged for 5 min, and frozen at (−20°C). Each sample was labeled with patient's name and identification number and kept without thawing till the day of testing. The serum leptin level was measured using ELISA kits (SPI-Bio, Montigny le Bretonneaux, France). After delivery, the following variables were derived for each case: Apgar scores at 1 and 5 min, neonatal weight, and the need for admission to neonatal ICU.
Mild PE and control groups were followed-up regularly every 2 weeks till 36 weeks and then weekly till delivery, including clinical examination and laboratory investigations to diagnose the development of PE. Antihypertensive drugs were given to mild group. Patients with severe PE were given MgSO4 (loading then maintenance dose), and then pregnancy was terminated.
Sample size was calculated by using PASS, version 11 (NCSS LLC, Kaysville, Utah, USA), according to Salimi et al.. At α error of 0.05 and study power of 80%, a total sample size of 95 women was required: 65 having PE and 30 with normal pregnancy as a control group.
Results were collected, tabulated, and statistically analyzed by an IBM compatible personal computer with SPSS statistical package version 20 (SPSS Inc., released 2011, IBM SPSS statistics for Windows, version 20.0; IBM Corp., Armonk, New York, USA). Quantitative data were expressed as mean±SD, whereas qualitative data were expressed as numbers and percentages. Student's t-test was used to test significance of difference for quantitative variables, and χ2 test was used to test significance of difference for qualitative variables. For expected values less than 5, Fisher's exact test was used. Kruskal–Wallis test was used for comparison of quantitative variables between more than two groups with nonparametric data. A P value of less than 0.05 was considered statistically significant. Data were analyzed and appropriately presented in tables and figures.
| Results|| |
Demographical, clinical, and biochemical data of the three studied groups are shown in [Table 1]. There were no significant statistical differences between the three studied groups with respect to the maternal age, parity, and the gestational age (P > 0.05). As expected, mean arterial pressure (MAP), proteinuria, and BMI values were higher in the PE groups (groups A and B) compared with the control group (group C). The mean of MAP of groups A, B, and C was 113.03±3.78, 133.78±6.18, and 83.19±8.32 mmHg, respectively, with highly significant statistical differences among the studied groups (P <0.001). The mean BMI of groups A, B, and C at the time of sampling was 31.30±1.48, 33.49±1.96, and 31.15±1.47 kg/m2, respectively, with highly significant statistical differences between groups B and A and between groups B and C (P <0.001). The results also showed that regarding mean serum uric acid, serum glutamic oxaloacetic transaminase, and serum glutamate pyruvate transaminase, there were highly significant statistical differences in severe PE group (P < 0.001) compared with mild PE and control groups. In contrast, there were no statistically significant differences among the three groups regarding urea level, creatinine level, prothrombin time, and platelet count. Concerning neonatal outcome of the three studied groups [Table 2], it was found that the duration of gestation was shorter among the PE groups, and neonates of PE groups (groups A and B) have statistically significant lower birth weight, lower Apgar score at 1 and 5 min, and higher incidence of neonatal ICU admission owing to lower birth weight, preterm labor and lower Apgar score. Moreover, there were no statistically significant differences regarding mode of delivery; cesarean birth was done owing to obstetric causes (previous uterine scar, cephalopelvic disproportion, malpresentations, etc.). [Table 3] shows that the mean serum leptin level of groups A, B, and C was 30.32 ± 7.8, 49.37 ± 14.4, and 13.87 ± 4.24 ng/ml, respectively, with highly statistical significant differences between groups A and C (P <0.001), between groups B and C (P < 0.001), and between groups A and B (P < 0.001). [Table 4] shows the correlation between leptin level and other parameters. There is a highly significant statistical positive correlation between leptin level and BMI, systolic blood pressure, diastolic blood pressure, MAP, proteinuria, and uric acid among PE groups by using correlation coefficient test (r-test). On the contrary, there was no significant statistical correlation between leptin level and maternal age, gestational age, urea, and creatinine among PE groups.
|Table 1: Demographical, clinical, and biochemical data of the studied groups|
Click here to view
| Discussion|| |
PE is a pregnancy-specific syndrome observed from 20 weeks of gestation up to 6 weeks of postpartum with systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg accompanied by significant proteinuria and is considered early onset before 34 weeks of gestation.
In this study, maternal serum leptin levels were significantly higher (P < 0.001) in the PE groups (43.51±15.49 ng/ml) than the control group (13.87±4.24 ng/ml). According to the severity of PE, the serum leptin levels were found to be statistically significant higher (P < 0.001) in severe group (49.37±14.4 ng/ml) than in mild group (30.32±7.8 ng/ml). Our results are in agreement with the study done by Song et al., which was conducted on 74 pregnant women with PE and 79 normal pregnant women who were matched in maternal and gestational age. Leptin levels were statistically significantly increased in the PE group (34.23±22.48 ng/dl) compared with the normal group (15.84±8.98 ng/dl). This result also is in agreement with the study done by Kharb et al. that included 25 pregnant women with PE and 25 normal pregnant women who were matched in maternal and gestational age, and leptin levels were significantly increased in the PE group (57.48 ± 18.67 ng/dl) compared with the normal group (21.77 ± 6.30 ng/dl). Moreover, the results are also consistent with the study done by Taylor et al., which was conducted on 562 pregnant women with PE and 377 normal pregnant women who were matched in maternal and gestational age and BMI, and leptin levels were significantly increased in the PE group (30.5±24.6 ng/ml; P = 0.0117) compared with the normal group (20.9±28.3 ng/ml). Furthermore, the results of this study are in agreement with the study done by Al-Ghazali. This study included 21 pregnant women having no hypertension (control group), 26 pregnant ladies with hypertension without proteinuria, 20 pregnant women with mild PE, and 33 pregnant women with severe PE. Serum leptin levels were higher in PE group than the control group (10.719±13.757), and there was significant elevation in severe PE (38.609±28.933) than mild PE (14.885±14.786).
There could be several possible causes for elevated leptin levels. Impaired renal function is a pathophysiological component of PE, and increased plasma leptin concentration may reflect the reduction of renal clearance. It has been suggested that BMI was responsible for the increase in maternal levels of leptin in PE women in several studies, as adipose tissue is the leptin source,. In pregnancy, however, the BMI does not accurately reflect fat accrual because the fetus, the placenta, the amniotic fluid, increase plasma volume and available degree of extravascular fluid accumulation all increase maternal weight. Finally, there is evidence that inflammatory mediators increase plasma leptin concentration and there is an increase in concentration of the inflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in PE. This study had some limitations such as single estimation of serum leptin level at whole pregnancy period, all participants were at third trimester, and the small sample size. Hence, the findings still need more future interpretation.
| Conclusion|| |
Maternal serum leptin is significantly increased in patients with PE compared with the normal pregnant women. According to severity, maternal serum leptin is significantly higher in severe PE than in mild PE. It has been concluded that serum leptin level can be taken independently or along with other parameters as a marker for severity of PE, hence, avoiding risk effects of PE to the mother and the fetus.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]