|Year : 2019 | Volume
| Issue : 2 | Page : 163-166
Lactate dehydrogenase and maternal and perinatal outcome in preeclamptic women
Simmi Kharb, N Bhandari, A Singh, A Gupta
Department of Biochemistry, Obstetrics and Gynecology, Pt BDS PGIMS, Rohtak, Haryana, India
|Date of Submission||23-Aug-2019|
|Date of Decision||08-Oct-2019|
|Date of Acceptance||10-Oct-2019|
|Date of Web Publication||16-Dec-2019|
Dr. Simmi Kharb
#1396, Sector-1, Urban Estate, Rohtak, Haryana
Source of Support: None, Conflict of Interest: None
Background: Preeclampsia is a condition that is characterized by hypertension and proteinuria occurring after 28 weeks of gestation. It complicates 5%–8% of all pregnancies. Lactate dehydrogenase (LDH) is an intracellular enzyme and its level is increased in preeclamptic women due to cellular death. Preeclampsia is a multisystem disorder and leads to a lot of cellular death. It carries substantial risks for both fetus and mother with a subsequent increase in the perinatal and maternal morbidity and mortality. Aim: The present study was planned to estimate and compare the serum LDH levels in women with preeclampsia and normal pregnant women and to correlate LDH levels with maternal and perinatal outcome in preeclampsia. Materials and Methods: This observational prospective study was conducted on 200 antenatal women. Women were divided into two groups, namely Group I (n = 100) comprised of women with preeclampsia (study group) and it was further subdivided into three categories on the basis of LDH levels: A (n = 53): <600 IU, B (n = 27): 600–800 IU, and C (n = 20): >800 IU and Group II (n = 100, control) comprised of normotensive pregnant women. LDH levels of both the groups were compared, and association of maternal and perinatal outcome was assessed in relation to LDH levels. Results: With increased severity of preeclampsia, rise in the LDH levels was observed. Severely preeclamptic women with LDH levels >800 IU/l showed a significant increase in incidence of eclampsia, abruption, hemolysis, elevated liver enzymes, and low platelet count syndrome, disseminated intravascular coagulation, and intensive care unit (ICU)/respiratory ICU transfer as compared to women who had lower levels <600 IU/l. A significant difference was observed among sepsis, mortality, and neonatal deaths between subgroups of preeclampsia according to the levels of LDH. Conclusion: LDH levels are associated with severity of preeclampsia and occurrence of maternal and fetal complications.
Keywords: Lactate dehydrogenase, preeclampsia, pregnancy
|How to cite this article:|
Kharb S, Bhandari N, Singh A, Gupta A. Lactate dehydrogenase and maternal and perinatal outcome in preeclamptic women. Arch Med Health Sci 2019;7:163-6
|How to cite this URL:|
Kharb S, Bhandari N, Singh A, Gupta A. Lactate dehydrogenase and maternal and perinatal outcome in preeclamptic women. Arch Med Health Sci [serial online] 2019 [cited 2020 Jan 29];7:163-6. Available from: http://www.amhsjournal.org/text.asp?2019/7/2/163/273043
| Introduction|| |
Preeclampsia is characterized by hypertension and proteinuria occurring after 28 weeks of gestation. It complicates 5%–8% of all pregnancies. Few studies suggest that there may be several underlying causes leading to endothelial dysfunction and causing the signs of hypertension, proteinuria, and edema., Preeclampsia is a multisystem disorder and carries substantial risks for both fetus and mother with a subsequent increase in the perinatal and maternal morbidity and mortality.
Lactate dehydrogenase (LDH) is an intracellular enzyme. Glycolysis is the major energy pathway in the placenta. Hypoxia in preeclampsia further enhances glycolysis and increases LDH activity. Studies have shown that LDH activity and gene expression are higher in placentas of preeclampsia than normal pregnancy., Hypoxia induces LDH isoenzyme activity in trophoblasts resulting in higher lactate production. LDH levels had been known to upregulate vascular endothelial growth factor A and indirectly induce basic fibroblast growth factor, a critical component of embryonic stem cell.,, LDH has five isoforms, and among all, LDHA4 seen in placentae with preeclampsia is most responsive to hypoxia.,,, Elevated levels of LDH are indicative of cellular damage and dysfunction, so it can be used as a biochemical marker since it reflects the severity of the disease, occurrence of complications, and fetal outcome. The levels of LDH in serum are increased in clinical situations associated with cell damage, leak, hemolysis, and cell death. Hence, serum LDH levels can be used to assess the extent of cellular death and thereby the severity of disease and can be of help in making decisions regarding the management strategies to improve the maternal and fetal outcome.,,,
Thus, the present study was designed to estimate and compare the serum LDH levels in women with preeclampsia and normal pregnant women and to correlate LDH levels with maternal and perinatal outcome in preeclampsia.
| Materials and Methods|| |
This observational prospective study was conducted on 200 antenatal women admitted labor room emergency in the Department of Obstetrics and Gynaecology in collaboration with the Department of Biochemistry at Pt. B. D. Sharma, PGIMS, Rohtak. Antenatal women with singleton pregnancy and 28 weeks onward were enrolled in the study randomly by computer-related randomization. The study was approved by the Ethical Committee of the institute. Women were divided into two groups: Group I (n = 100) comprised of pregnant women with preeclampsia (study group). Group I women were further subdivided into three categories on the basis of LDH levels: A (n = 53): <600 IU, B (n = 27): 600–800 IU, and C (n = 20): >800 IU; Group II (n = 100) comprised of normotensive pregnant women (control group). Women with chronic hypertension, medical disorders, and taking hepatotoxic drugs were excluded from the study.
After obtaining informed and written consent, the detailed history and thorough clinical examination of all participants were done. All women were subjected to routine antenatal investigations. Serum LDH levels were estimated by enzymatic method on the autoanalyzer. Participants were followed till delivery, and feral and maternal outcomes were assessed in terms of spontaneous or induced labor, gestational age at delivery, and mode of delivery. LDH levels of both the groups were compared, and association of maternal and perinatal outcome was assessed in relation to LDH levels. Data thus collected were analyzed by Statistical Package for the Social Sciences version 2.4 (SPSS)/analysis. IBM SPSS Statistics: free trial version was used.
| Results|| |
[Table 1] depicts LDH levels in the study group and distribution of patients according to LDH levels in the study group. Most of the patients (66%) in the mild preeclampsia group had LDH levels <600 IU/l. Only 30.8% of patients had LDH levels >600 IU and out of 49, patients with severe preeclampsia, 62 patients had LDH >600 IU/l. On analyzing the above data, rise in the LDH levels was observed with increasing severity of preeclampsia.
|Table 1: Distribution according to lactate dehydrogenase levels in the study group|
Click here to view
[Table 2] shows maternal complications according to LDH levels in the study group. Severely preeclamptic women with LDH levels >800 IU/l showed a significant increase in terms of eclampsia, abruption, hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, disseminated intravascular coagulation, and intensive care unit/respiratory ICU (ICU/RICU) transfer compared with women who had lower levels <600 IU/l. Preterm labor and intrauterine growth restriction (IUGR) had no significant increase with high LDH level. One mortality was found in women with LDH levels >800 IU/l.
|Table 2: Maternal outcome according to lactate dehydrogenase levels in the study group|
Click here to view
There was no significant difference between subgroups of preeclampsia according to the levels of LDH in terms of Apgar at 1 min, birth asphyxia, rate of NICU admission, and stillbirth, but overall, it was observed that there was a significant difference among sepsis, mortality, and neonatal deaths (P< 0.01, <0.001, and <0.05, respectively).
| Discussion|| |
On analyzing the data in the present study, it was found that there is a significant risk in the LDH levels in preeclampsia patients as compared to the control group and that there is an increase in LDH value with increasing severity of preeclampsia (P< 0.01).
Qublan et al. done demonstrated that a significant association of LDH levels with severe preeclampsia. Moreover, increase in the incidence of perinatal deaths was also observed in patients with increasing levels of serum LDH levels, with intrauterine fetal death in 4.8% cases, IUGR in 33.9%, prematurity in 77.9%, and neonatal deaths in 95.2% in the severe preeclampsia group. Similar results were observed in studies conducted by Jaiswar et al., Hazari et al., and Gandhi et al.,, The findings of the present study are in agreement with these studies.
Multiorgan dysfunction in severe preeclampsia caused by vascular endothelial damage leads to excessive LDH leakage and elevated levels in serum. Severely preeclamptic women with LDH levels >800 IU/l in the present study showed a significant increase in maternal complications such as eclampsia, abruption, HELLP syndrome, disseminated intravascular coagulation, and ICU/RICU transfer compared with women who had lower levels <600 IU/l. Preterm labor and IUGR showed no significant increase with high LDH levels.
Catanzarite et al. reported a subgroup of patients who had elevated levels of LDH manifested with HELLP syndrome and at a risk for developing maternal mortality. Similarly, Demir et al. concluded that there was a statistically significant relation between maternal complications and high LDH levels. Schwartz et al. concluded that brain edema in patients with preeclampsia–eclampsia syndrome was primarily associated with laboratory-based evidence of endothelial damage (red blood cell morphology and LDH levels). Blood pressures, although elevated in all patients, were not significantly different in those with or without brain edema. An another study conducted by Jharia et al. assessed the role of serum LDH in prediction of adverse outcomes of preeclampsia. In this study, they found that poor perinatal outcome (in the form of sick/IUD) in majority of preeclampsia patients. The incidence of poor perinatal outcomes was significantly higher in preeclampsia patients with a higher level of serum LDH (>600 IU/L).
In the present study, it was illustrated that there was a significant difference among sepsis, mortality, and neonatal deaths (P< 0.01, <0.001, and <0.05, respectively) in the subgroups of preeclampsia according to the levels of LDH. However, in terms of Apgar at 1 min, birth asphyxia, rate of NICU admission, and stillbirth, no significant difference was observed.
He et al. found that preeclamptic women with small-for-gestational-age infants had significantly higher LDH concentrations than those in the appropriate-for-gestational-age group, but alanine transaminase and aspartate aminotransferase concentrations did not increase significantly. Munagavalasa et al. conducted a case–control study to know the levels of serum LDH in preeclampsia patients and the association between LDH levels and fetal outcome and found higher serum LDH levels in preeclampsia patients as compared to controls. The fetal outcome was poor in the group having high LDH levels, and they concluded that serum levels of LDH can be used as a biochemical predictor for the prognosis of preeclampsia.
LDH levels were found significantly increased in patients of preeclampsia as compared to normotensive women. It was observed that maternal complications such as eclampsia, disseminated impending coagulopathy, abruption, and HELLP syndrome and perinatal complications such as low birth weight and preterm delivery were associated with higher LDH levels in preeclampsia patients. Since LDH levels are associated with severity of preeclampsia and occurrence of complications of preeclampsia, these women with higher LDH levels require vigilant monitoring and prompt management to prevent/decrease the maternal and perinatal complications.
| Conclusion|| |
LDH levels are associated with severity of preeclampsia and occurrence of maternal and fetal complications. vigilant monitoring of these women might be of help in decreasing maternal and perinatal complications.
We would like to thank postgraduates, nursing staff, laboratory technicians, and women participating in the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lain KY, Roberts JM. Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA 2002;287:3183-6.
Noris M, Perico N, Remuzzi G. Mechanisms of disease: Pre-eclampsia. Nat Clin Pract Nephrol 2005;1:98-114.
Mustafa R, Ahmed S, Gupta A, Venuto RC. A comprehensive review of hypertension in pregnancy. J Pregnancy 2012;2012:105918.
Norwitz ER, Hsu CD, Repke JT. Acute complications of preeclampsia. Clin Obstet Gynecol 2002;45:308-29.
Tsoi SC, Zheng J, Xu F, Kay HH. Differential expression of lactate dehydrogenase isozymes (LDH) in human placenta with high expression of LDH-A(4) isozyme in the endothelial cells of pre-eclampsia villi. Placenta 2001;22:317-22.
Burd LI, Jones MD Jr., Simmons MA, Makowski EL, Meschia G, Battaglia FC, et al.
Placental production and foetal utilisation of lactate and pyruvate. Nature 1975;254:710-1.
Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3:721-32.
Semenza GL. HIF-1: Upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010;20:51-6.
Pepper MS, Belin D, Montesano R, Orci L, Vassalli JD. Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro
. J Cell Biol 1990;111:743-55.
Bougnères PF, Rocchiccioli F, Nurjhan N, Zeller J. Stable isotope determination of plasma lactate conversion into glucose in fasting infants. Am J Physiol 1995;268:E652-9.
Markert CL, Shaklee JB, Whitt GS. Evolution of a gene. Multiple genes for LDH isozymes provide a model of the evolution of gene structure, function and regulation. Science 1975;189:102-14.
Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 1994;269:23757-63.
Hofmeyr GJ, Belfort M. Proteinuria as a predictor of complications of pre-eclampsia. BMC Med 2009;7:11.
Munde SM, Hazari NR, Thorat AP, Gaikwad SB, Hatolkar VS. Gamma glutamyl transferase and lactate dehydrogenase as biochemical markers of severity of preeclampsia. Int J Med Health Pharm Biomed Eng 2014;8:50-3.
Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 2004;103:981-91.
Vasudevan D, Sreekumari S, Vaidyanathan K, editors. Clinical enzymology and biomarkers. In: Textbook of Biochemistry. 6th
ed. New Delhi: Jaypee Brothers; 2011. p. 146-59.
Umasatyasri Y, Vani I, Shamita. P. Role of LDH (Lactate dehydrogenase) in preeclampsia marker: An observational study. Int Arch Integr Med 2015;2:88-93.
Qublan HS, Ammarin V, Bataineh O, Al-Shraideh Z, Tahat Y, Awamleh I, et al.
Lactic dehydrogenase as a biochemical marker of adverse pregnancy outcome in severe pre-eclampsia. Med Sci Monit 2005;11:CR393-7.
Jaiswar SP, Gupta A, Sachan R, Natu SN, Shaili M. Lactic dehydrogenase: A biochemical marker for preeclampsia-eclampsia. J Obstet Gynaecol India 2011;61:645-8.
Hazari NR, Hatolkar VS, Munde SM. Study of serum hepatic enzymes in preeclampsia. Int J Curr Med Appl Sci 2014;2:1-8.
Gandhi M, Chavda R, Saini HB. Comparative study of serum LDH and uric acid in hypertensive versus normotensive pregnant woman. Int J Biomed Res 2015;6:25-8.
Catanzarite VA, Steinberg SM, Mosley CA, Landers CF, Cousins LM, Schneider JM, et al.
Severe preeclampsia with fulminant and extreme elevation of aspartate aminotransferase and lactate dehydrogenase levels: High risk for maternal death. Am J Perinatol 1995;12:310-3.
Demir SC, Evruke C, Ozgunen FT, Urunsak IF, Candan E, Kadayifci O, et al.
Factors that influence morbidity and mortality in severe preeclampsia, eclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Saudi Med J 2006;27:1015-8.
Schwartz RB, Feske SK, Polak JF, DeGirolami U, Iaia A, Beckner KM, et al.
Preeclampsia-eclampsia: Clinical and neuroradiographic correlates and insights into the pathogenesis of hypertensive encephalopathy. Radiology 2000;217:371-6.
Jharia J, Mathur P, Dave A, Mathur P. A prospective study to assess role of serum lactate dehydrogenase in prediction of adverse outcomes of pre-eclampsia and eclampsia. Int J Reprod Contracept Obstet Gynecol 2016;5:2522-9.
He S, Bremme K, Kallner A, Blombäck M. Increased concentrations of lactate dehydrogenase in pregnancy with preeclampsia: A predictor for the birth of small-for-gestational-age infants. Gynecol Obstet Invest 1995;39:234-8.
Munagavalasa S, Vaitla P, Vani N. Role of serum lactate. Dehydrogenase in preeclampsia in assessing the maternal and fetal outcome. IOSR J Biotechnol Biochem 2017;6:36-8.
[Table 1], [Table 2]