EVALUATION OF HEPATIC BIOMARKERS IN PREGNANT WOMEN WITH PREECLAMPSIA
HTML Full TextEVALUATION OF HEPATIC BIOMARKERS IN PREGNANT WOMEN WITH PREECLAMPSIA
Seyyed Hossein Hassanpour * 1 and Seyyed Zeinab Karami 2
Department of Toxicology 1, Faculty of Pharmacy, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.
Department of Biology 2, Faculty of Basic Sciences, Yasouj University, Yasouj, Iran.
ABSTRACT: Preeclampsia is a pregnancy-related disorder and considered as one of the major reasons for infants and mothers death in developed nations. HELLP disorder is a problem related to child birth that usually happens in women with intense preeclampsia and associated with different features, including hemolysis, elevated liver enzymes, and low platelet count. Due to normal hepatic markers during pregnancy, our purpose is to examine these factors in pregnant women and their association with disorders such as preeclampsia and HELLP syndrome. This case-control study included 99 Iranian pregnant women that divided two groups including preeclamptic and normotensive pregnant women. Samples were collected from Ahvaz city. We measured liver enzymes activity (ALT, AST, and ALP), total bilirubin and direct bilirubin and blood platelets by calorimetry methods in both groups. The results showed that there was no significant difference in the platelet level in both groups. However, we found a significant difference in the serum level of ALT, AST, ALP and total bilirubin between two groups (p<0.05), while the result related to direct bilirubin was not significant at the end of the study. The outcomes related to this study show that hepatic biomarkers in pregnant women with preeclampsia higher than normal pregnant women; therefore, we can predict more likely to develop HELLP syndrome in pregnant women with preeclampsia.
Keywords: Preeclampsia, HELLP, ALT, AST, Bilirubin
INTRODUCTION: Preeclampsia is a pregnancy-related disorder and considered as one of major reasons for infants and mothers death in developed nations 1. Some of the risk factors for the development of preeclampsia are diabetes mellitus, hypertension, obesity, and anti-phospholipid antibody syndrome 2.
Each year, 585,000 women die due to complications related to pregnancy that is 95% of them in developing countries, and among them, 30% of cases are due to problems of hypertension during pregnancy and particularly preeclampsia 3. In the USA, 18% of mortality among women is related to pregnancy period and especially hypertension disorders during this period 4.
Generally, the definition of preeclampsia is complicated due to differences in its diagnosis, but persistence in blood pressure that occurs in 12 - 22% of pregnancies and is dependent on the type of population can be one of its reasons 5.
Also, vascular endothelial dysfunction is the final common pathway that causes the mother's system response 1. For the example, one study was showed that in women with preeclampsia, increase in the level of soluble forms-like tyrosine kinase 1 (sFlt-1), and a decrease in PlGF levels is higher than the control group, as these changes occur several weeks before the first onset, their measurement can be a good predictor 6. Researchers have been found that men and women, whose mothers during pregnancy have preeclampsia, likely their children develop preeclampsia later that shows the effect of genetic factors in this disorder, although not too much information in this field 7.
Also, a study was conducted in Iran, winter and urinary tract infection were considered as risk factors for preeclampsia 8. It has been reported that slightly changes occur in biomarkers of the liver during pregnancy, indeed in this period, the level of AST, ALT, GGT, serum bilirubin, and bile acids usually remain within the normal range; therefore any change in their level may indicate a problem 9. HELLP disorder is a problem related to childbirth that usually happens in women with intense preeclampsia 10. This syndrome occurs mainly in preterm and sometimes in during late gestation and after childbirth 11.
HELLP is expressed as the following three features: hemolysis elevated liver enzymes, and low platelet count 12. This syndrome is a very dangerous situation and leads to serious problems such as hemolysis, epigastria pain, a decrease of liver enzymes and thrombocytopenia in during this syndrome 10. In Iran, a study conducted on preeclampsia was showed that there is a relationship between preeclampsia and Vitamin D 13.
Also, Shahbazian et al., 2014 examined the relationship between preeclampsia and hypertension and microalbuminuria 14. As the women health is important during pregnancy and there are few studies on pregnancy and liver problems in Iran, we studied liver markers in pregnant women and their association with disorders such as preeclampsia and HELLP syndrome.
Also, this study was in line with our recent studies on women health, including cell cycle arrest in ovarian cancer 15, the effect of purslane extract on antioxidant balance in women with type 2 diabetes 16, changes in the level of AGEs and β2-microglobulin and imbalance of trace elements in type 2 diabetes 17, 18.
MATERIAL AND METHODS:
Subjects: This case-control study was performed on 99 Iranian pregnant females, who divided two groups, including preeclampsia and normotensive pregnant women.
Measurements: We measured enzyme activity of liver biomarkers (ALT, AST, and ALP), total bilirubin and direct bilirubin by calorimetry method and blood platelets by Hematology Analyzer - Sysmex KX-21 in pregnant women with preeclampsia (n=50) and normotensive (n=49). HELLP syndrome among woman with preeclampsia by the following criteria: total bilirubin ≥ 0.6 mg/dl for detection of hemolysis, AST ≥ 20 IU /L, ALT ≥ 15 IU /L for the diagnosis of liver damage and blood platelet count less than 50,000 cells/µL.
Statistical Analysis: The data were expressed as mean ± standard deviation. For comparison of groups was used independent t-test and Mann-Whitney test for platelet count and serum ALT, AST, ALP, total bilirubin, direct bilirubin, respectively. The different level was set at P<0.05.
RESULTS: The outcomes of the present study was reported for 99 pregnant women, including preeclampsia (n=50) and normotensive (n=49) case. The summary of these results is presented in Table 1. The current data show that there was no significant difference in the platelet levels between normotensive pregnant and preeclampsia pregnant women.
However, we obtained the significant difference in the ALT serum level between normotensive pregnant women and preeclamptic pregnant women at the end of study (P<0.05) also it was found a significant difference in the AST level between two groups (P<0.05).
The evaluation of serum ALP serum level was also indicated that its level in preeclamptic pregnant women was significantly higher than normotensive pregnant women (about 2-fold) (P<0.05). About bilirubin level (either direct or total), the result was confirmed that direct bilirubin level in preeclamptic pregnant women had not obvious difference compared to normotensive pregnant women, while the level of total bilirubin in preeclamptic pregnant women was higher than normotensive pregnant women so that it was significant (P<0.05).
TABLE 1: COMPARISON FACTORS RELATED TO PREECLAMPSIA IN BOTH GROUPS
Factor | Group | |
Preeclampsia (n=50) | Normotensive (n=49) | |
Blood platelet (cell/µL) | 223.80 ± 72.63 | 216.45 ± 47.48 |
ALT (IU/L) | 34.34 ± 12.77* | 14.51 ± 3.93 |
AST (IU/L) | 41.10 ± 10.61* | 20.55 ± 6.82 |
ALP (IU/L) | 397.20 ± 174.49* | 180.02 ± 46.72 |
Direct bilirubin (mg/dl) | 0.23 ± 0.08 | 0.15 ± 0.4 |
Total bilirubin (mg/dl) | 0.99 ± 0.91* | 0.42 ± 0.13 |
Values are expressed as mean ± SD; comparisons were made using independent t-test and Mann-Whitney test for platelet count and serum ALT, AST, ALP, total bilirubin, direct bilirubin, respectively. * Significant different with Normotensive group (P < 0.05).
DISCUSSION: Liver function tests are abnormal in 20% to 30% of pregnancies that are associated with preeclampsia 19, 20, and are related poor motherhood and embryonic result 21, 22. Preeclampsia is a disorder with three features: proteinuria, hypertension, and edema that occur during the last trimester of 5% - 10% of pregnancies. Although the liver problem is infrequent in this disorder, nevertheless intense preeclampsia is related to perinatal illness and death. It is the most common reason of hepatic sensitivity and liver impairment in gestation period and 2% - 12% of cases will suffer from HELLP syndrome that this syndrome is expressed as the following three features: hemolysis, elevated liver enzymes, and low platelet count.
Liver involvement of preeclampsia is required no specific therapy, although the involvement is an indicator to prevent more serious disorders such as eclampsia, hepatic rupture, or necrosis 22.
We studied hepatic markers and liver damage in pregnant women in both normotensive and preeclamptic group. In agreement with studies conducted by Weinstein et al., 1982 12 and Shukla et al., 1978 23 our data showed that there was a significant difference in the serum ALT level between normotensive pregnant women and preeclampsia pregnant women (P<0.05).
Also, line with Cerutti et al., 1976 24, Weinstein et al., 1982 12 and Shukla et al., 1978 23 our data indicated that there was a noticeable difference in the AST level between two groups (P<0.05). Surprisingly, the current data showed that there was no significant difference in the platelet level between normotensive pregnant and preeclampsia pregnant women. But there was a significant difference in the serum ALP level and total bilirubin level between the two groups (P<0.05).
The various investigations have been examined the evaluation of liver function tests and liver damage in pregnant women with preeclampsia and normal pregnant women, so that obtained different results. For example; in a study by Girling et al., 1997 stated that the rate of liver function tests are less in normal gestation than the scope of reference presently used 25. The results of our project also revealed that more hepatic markers such as total bilirubin, ALT, and ALP in pregnant women with preeclampsia were higher than normal pregnant women. In another study on the HELLP syndrome was indicated that AST, ALT, and bilirubin were abnormal 12. We as well as found that total bilirubin and ALT level were more in pregnant women with preeclampsia, but direct bilirubin level had not a significant difference compared to normal group. It has been reported AST level abnormality more than 18 U/L 26, 30 U/L 52 to 57 U/L (20) 70 U/L 24, 27.
In normal gestation, ALT and AST are lower than non-pregnant age-matched women; however, AST changes to lesser amount 23. Based on the study of Cerutti et al., 1976 AST, ALT and GGT significantly increase during the sixth month of pregnancy; however it is not obvious whether this is compared with early gestation 24. The primary fluctuations in liver function evaluation may be due to red cell demolition and ultimately happens liver injury 28. The results showed that liver damaged in pregnant women with preeclampsia. Although platelet count was nearly equal in both group, other biomarkers were higher in pregnant women with preeclampsia compared with normal pregnant women.
CONCLUSION: At the end of the study, we conclude that pregnancy with preeclampsia likely results in HELLP syndrome. We suggest further studies to understand the exact mechanism of the problem.
ACKNOWLEDGEMENT: Nil
CONFLICTS OF INTEREST: Nil
REFERENCES:
- Leung TN, Zhang J, Lau TK, Chan LY and Lo YD: Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem 2001; 47(1): 137-9.
- Powe CE, Levine RJ and Karumanchi SA: Preeclampsia, a disease of the maternal endothelium the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation 2011; 123(24): 2856-69.
- Conde‐Agudelo A and Belizan JM: Risk factors for pre‐eclampsia in a large cohort of Latin American and Caribbean women. BJOG 2000; 107(1): 75-83.
- Leeman L and Fontaine P: Hypertensive disorders of pregnancy. Am Fam Physician 2008; 78(1): 93-00.
- Sibai B, Dekker G and Kupferminc M: Preeclampsia. The Lancet 2005; 365(9461): 785-99.
- Levine RJ, Maynard SE, Qian C, Lim KH, England LJ and Yu KF: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004; 350(7): 672-83
- Esplin MS, Fausett MB, Fraser A, Kerber R, Mineau G and Carrillo J: Paternal and maternal components of the predisposition to preeclampsia. N Engl J Med 2001; 344(12): 867-72.
- Kashanian M, Baradaran HR, Bahasadri S and Alimohammadi R: Risk factors for pre-eclampsia: a study in Tehran, Iran. Arch Iran Med 2011; 14(6): 412-5.
- Riely CA: Liver disease in the pregnant patient. Am J Gastroenterol 1999; 94(7): 1728-32.
- Haram K, Svendsen E and Abildgaard U: The HELLP syndrome: clinical issues and management. A Review. BMC pregnancy and childbirth 2009; 9:8.
- Arulkumaran N and Lightstone L: Severe pre-eclampsia and hypertensive crises. Best Pract Res Clin Obstet Gynaecol 2013; 27(6): 877-84.
- Weinstein L: Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy. Am J Obstet Gynecol 1982; 142(2): 159-67.
- Abedi P, Mohaghegh Z, Afshary P and Latifi M: The relationship of serum Vitamin D with pre‐eclampsia in the Iranian women. Matern Child Nutr 2014;10(2): 206-12.
- Shahbazian N, Shahbazian H, Ehsanpour A, Aref A and Gharibzadeh S: Hypertension and microalbuminuria 5 years after pregnancies complicated by pre-eclampsia. Iran J Kidney Dis 2011; 5(5): 324-7.
- Shirali S, Aghaei M, Shabani M, Fathi M, Sohrabi M and Moeinifard M: Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3. Tumour Biol 2013; 34(2): 1085-95.
- Barari A, Fakori Joybari M, Shirali S, Shojaee M and Khandandel A: Effect of eight-week consumption of purslane extract on peroxidane/antioxidant balance in women with type 2 diabetes. MLJ 2014; 8(2): 1-7.
- Sharifat M, Shirali S and Ebadi P: Investigation of changes in levels of AGEs and β2-microglobulin in patients with type 2 diabetes. JAAS 2014; 4(9): 1-10.
- Mahdizadeh R, Shirali S and Ebadi P: Investigation of imbalance of trace elements in patients with type 2 diabetes mellitus. JAAS 2014;4(9): 11-21.
- Borglin N: Serum transaminase activity in uncomplicated and complicated pregnancy and newborns. J Clin Endocrinol Metab 1958; 18(8): 872-7.
- Romero R, Vizoso J, Emamian M, Duffy T, Riely C and Halford T: Clinical Significance of Liver Dysfunction in Pregnancy-Induced Hypertension. Obstetric Anesthesia Digest 1989; 8(4): 162.
- Verhaeghe J, Anthony J and Davey D: Platelet count and liver function tests in proteinuric and chronic hypertension in pregnancy. S Afr Med J 1991; 79(10): 590-4.
- Hay JE: Liver disease in pregnancy. Hepatology 2008; 47(3): 1067-76.
- Shukla P, Sharma D and Mandal R: Serum lactate dehydrogenase in detecting liver damage associated with pre‐ Br J Obstet Gynaecol 1978; 85(1): 40-2.
- Cerutti R, Ferrari S, Grella P, Castelli G and Rizzotti P: Behaviour of serum enzymes in pregnancy. Clin Exp Obstet Gynecol 1976; 3: 22-4.
- Girling J, Dow E and Smith J: Liver function tests in pre‐eclampsia: the importance of comparison with a reference range derived for a normal pregnancy. Br J Obstet Gynaecol 1997; 104(2): 246-50.
- Van DP, Renier M, Baekeland M, Buytaert P and Uyttenbroeck F: Disseminated intravascular coagulation and the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia. Obstet Gynecol 1989; 73(1): 97-02.
- Goodlin R: Beware the great imitator-severe preeclampsia. Contemp Ob Gyn 1982; 20: 215.
- McMahon L, O'Coigligh S and Redman C: Hepatic enzymes and the HELLP syndrome: a long‐standing error? Br J Obstet Gynaecol 1993; 100(7): 693.
How to cite this article:
Hassanpour SH and Karami SZ: Evaluation of hepatic biomarkers in pregnant women with preeclampsia. Int J Life Sci & Rev 2017; 3(6): 67-70. doi: 10.13040/IJPSR.0975-8232.IJLSR.3(6).67-70.
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Article Information
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English
IJLSR
S. H. Hassanpour * and S. Z. Karami
Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.
Dr.hossein1366@yahoo.com
05 May 2017
15 June 2017
19 June 2017
DOI: 10.13040/IJPSR.0975-8232.IJLSR.3(6).67-70
30 June 2017