|ORIGINAL ARTICLE - PROSPECTIVE STUDY
|Year : 2022 | Volume
| Issue : 3 | Page : 122-125
Lactate dehydrogenase as marker for foetal outcome in pre-eclampsia
Seema-Gul Salman1, Maria Rafiq2
1 Department of Gynae, Category-D Hospital, Peshawar, Pakistan
2 Department of Gynae, DHQ Hospital, Upper Dir, KPK, Pakistan
|Date of Submission||17-Jan-2022|
|Date of Decision||07-Apr-2022|
|Date of Acceptance||08-May-2022|
|Date of Web Publication||21-Sep-2022|
House No. 5, Street H, Danish Abad, Peshawar, KPK
Source of Support: None, Conflict of Interest: None
Background: Studies have shown LDH is raised in Pre-eclampsia (PE) with levels increasing with increased severity of PE. Aims and Objectives: To study lactate dehydrogenase (LDH) as a marker for foetal outcome in mothers with pre-eclampsia (PE). Materials and Methods: A prospective cohort study was conducted at our facility from February 2019 to November 2021 on all admitted patients with PE. Two hundred and two patients were studied during this period. The inclusion criteria were mild and moderate PE. The exclusion criteria were severe PE, haemolysis, elevated liver enzymes and low platelets syndrome, eclampsia, any comorbid disease, and multiple gestations. Patients were divided into two groups. Group 0 had mothers with LDH <600 IU/L and Group 1 included mothers with LDH ≥ 600 IU/L. Both groups were documented and monitored until delivery to document foetal outcome as live birth or death in utero. Results: The mean maternal characteristics were as follows: age in years (26.45 ± 3.74), body mass index (30.04 ± 1.58), parity (2.39 ± 0.91), and age of gestation in weeks (33.27 ± 1.18). Group 1 had 61 (30.2%) previous history of PE, 84 (41.6%) live births, and 17 (8.4%) deaths in utero. Group 0 had 60 (29.7%) previous history of PE, 95 (47%) live births and 6 (3%) deaths in utero. The mean gestational age of Group 1 was shorter; 32.29 ± 1.17 weeks versus 33.23 ± 1.16 for Group 0. LDH as a marker for death in utero had a P = 0.01 which is significant. Conclusion: LDH can be used as a marker for foetal outcome in women with PE.
Keywords: Death in utero, lactate dehydrogenase, pre-eclampsia
|How to cite this article:|
Salman SG, Rafiq M. Lactate dehydrogenase as marker for foetal outcome in pre-eclampsia. Hamdan Med J 2022;15:122-5
| Introduction|| |
Pre-eclampsia (PE) is a relatively common condition usually appearing in first-time pregnancies. It is a combination of hypertension and urinary protein appearing after 20 weeks of completed gestation. It is an important cause of maternal and foetal morbidity and mortality. The incidence of PE is between 2%–5% globally and this is almost half of the global incidence of all hypertensive diseases during pregnancy i.e., 4%–10%. In Pakistan, the incidence of PE is 9.3%. From 1990 to 2019, there has been a 10.92% increase in the global incidence of hypertensive disorders of pregnancy. The exact aetiology of PE is unknown, but important contributors include placentation defects and dysfunction in the endothelium. It is a multisystem disorder which can commonly affect the nervous, hepatorenal and clotting systems. The main system affected, however, is the placenta. As a result, it can have a variety of features of which the most predictive for PE include pain, epigastric or right upper quadrant, nausea, vomiting, headache and visual changes. Good management requires timely diagnosis and multidisciplinary treatment.
Blood pressure rise can be predicted early whenever a combination of vasospasm, platelet aggregation and damaged endothelium result in elevated lactate dehydrogenase (LDH), a phenomenon also used for the diagnosis of haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. Serum levels of LDH are elevated whenever endothelial damage occurs as it is found in the intracellular environment and thus has high sensitivity but low specificity. Serum level ≥600 IU/L is considered elevated.
Mammalian LDH is coded by two genes giving rise to five tetramers, i.e., LDH types A4, B4, A3B, AB3 and A2B2. A4 catalyses pyruvate into lactate in skeletal muscles, whereas B4 catalyses lactate to pyruvate in aerobic cardiac tissue. In addition, LDH A4 is more specific to endothelial cells in utero placental vessels, and isozyme B is found in the syncytiotrophoblast. Patients with PE have 1.6 times increased levels of LDH-A, and isozyme LDH-A4 which is found in high concentration in the human placenta can be used for this. Elevated LDH (≥600 IU/L) has also been shown to be associated with fewer live births and higher deaths in utero.
This study was conducted to provide further data for the creation of a local Pakistani guideline for the management of PE to reduce adverse and preventable maternal and foetal outcomes for this common pregnancy-associated disease.
| Subjects and Methods|| |
A prospective cohort study was carried out at our health facility of all deliveries from February 2019 to November 2021 after the hospital's Ethical and Research Committee's Approval and in accordance with the ethical principles mentioned in the Helsinki Declaration 2013. Patients were counselled about fetomaternal outcomes and complications beforehand. Patient data related to the study were recorded in the ward's register for each patient. All patient data were reviewed from the register and they were grouped as Group 1: elevated LDH (≥600 IU/L) and Group 0: normal LDH (<600 IU/L), respectively.
Inclusion criteria were mild and moderate PE i.e., only pregnancy-induced hypertension (PIH) with proteinuria without any other complication. Mild PE was defined as PIH and Alb+1 (i.e., >300 mg) and moderate as PIH and Alb+2 (1000 mg) without any other symptoms. Patients with severe PE and HELLP syndrome were excluded due to a lack of required support set up in our hospital and were referred to the nearest tertiary care unit with available intensive care unit (ICU) resources.
The additional exclusion was done for eclampsia, any comorbid maternal disease and multiple gestations.
Patients were booked and followed regularly; twice monthly till 28 weeks and then weekly till delivery. They were diagnosed with PE using LDH at 28 weeks in the antenatal period. PE was diagnosed with a combination of hypertension (>140/90 mmHg, 4 h apart) and proteinuria (>0.3 g/dL in a 24-h urine collection).
Other data recorded for the study included maternal age (years), body mass index (BMI) (kg/m2), parity and gestational age (weeks) calculated by the first-trimester scan and previous history of PE. The age of gestation (weeks) was recorded until the delivery of the baby spontaneously. The foetal outcome was measured in terms of live birth or death in utero. Statistical analysis was performed with the Statistical analysis was completed with SPSS 23 (IBM Corporation, New York, USA). Results were considered statistically signiﬁcant at P ≤ 0.05.
| Results|| |
During the period from February 2019 to November 2021, there were a total of 463 cases of PE seen at the outpatient department and emergency. Of these 463 cases, 224 cases were excluded based on the exclusion criteria. Fourteen patients were excluded because they did not want to be included in the study group. Twenty-two patients were excluded due to incomplete data required for this study. One patient was not included to have an equal number of patients in both groups for symmetric comparison. As a result, a total of 202 PE pregnancies were included. The following results were obtained, as shown in [Table 1].
|Table 1: Lactate dehydrogenase as a marker for foetal outcome in pre-eclampsia|
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The mean maternal age (years) was: overall 26.45 ± 3.74, Group 1 26.44 ± 3.75 and Group 0 26.46 ± 3.75, respectively. The maternal age was not statistically significant. The mean BMI (kg/m2) was: overall 30.04 ± 1.58, Group 1 30.03 ± 1.57 and Group 0 30.05 ± 1.6, respectively. BMI was not statistically significant.
The mean parity was: overall 2.39 ± 0.91, Group 1 2.39 ± 0.89 and Group 0 2.38 ± 0.94, respectively. Parity was not statistically significant.
Age of gestation (weeks) until delivery of the baby spontaneously was calculated. The mean age of gestation (Weeks) was: overall 33.27 ± 1.18, Group 1 32.29 ± 1.17 and Group 0 33.23 ± 1.16, respectively. Age of gestation was statistically significant with a P = 0.01.
In Group 1, 61 (30.2%) patients had a previous history of PE compared to 60 (29.7%) patients in Group 0.
In Group 1, 84 (41.6%) patients had live births and 17 (8.4%) deaths in utero compared to 95 (47%) live births and 6 (3%) deaths in utero in Group 0, respectively. All necessary interventions were undertaken to avoid adverse fetomaternal outcomes, however, with shorter gestational age, these are higher, and patients were counselled beforehand for this reason. Foetal outcome was statistically significant between the groups with a P = 0.01.
| Discussion|| |
PE has been defined by The American College of Obstetricians and Gynaecologists as a combination of hypertension (>140/90 mmHg, 4 h apart) and proteinuria (>0.3 gm/dL/24-h urine collection). Alternatively, eclampsia is defined as new-onset grand mal seizures in a pre-eclamptic woman. Umasatyasri et al. have shown that elevated LDH (≥600 IU/L) is associated with fewer live births and higher deaths in utero.
In their study, Umasatyasri et al. showed that elevated LDH was associated with 51.43% live births and 14.29% deaths in utero compared to 56.52% and 4.3%, respectively, in the non-elevated group. Qublan et al. showed that elevated LDH is associated with increased perinatal mortality (P < 0.001) with 4.8% death in utero, 33.9% intrauterine growth restriction and 77.9% prematurity. Vinitha et al. also showed that elevated LDH is associated with a statistically significant elevation in perinatal mortality. Jaiswar et al. showed a similar increase in perinatal complications (P = 0.003), stillbirths (P < 0.01) and perinatal mortality (P = 0.003).
Regarding adverse foetal outcomes and PIH, Bera et al. showed that LDH can be used as a marker for predicting the severity of PIH and adverse foetal outcomes. Andrews and Patel showed that elevated LDH was associated with severe PE (854.05 ± 247.45), mild PE (609.91 ± 136.92) and eclampsia (P < 0.0001). They showed that 28 cases of perinatal mortality occurred in the LDH elevated group: 06 (21.5%) in LDH <600 IU/L, 8 (28.5%) in LDH 600–800 IU/L and 14 (50%) in LDH >800 IU/L. Hak et al. showed that elevated LDH was associated with lower gestational age and early labour induction with an Intra Uterine Device (IUD) of 11.4%.
Among local studies carried out in this regard, similar findings were shown by Mahmood et al. with an association between elevated LDH and reduced gestational age and adverse foetal outcome, i.e., death in utero; 22 (16.54%) versus 8 (6.08%) between the groups, respectively.
Finally, in addition to the absence of such studies i.e., LDH in relation to the adverse foetal outcome, locally, further studies on this subject and exploration of its association with maternal and perinatal morbidity need to be carried out. The present study was an initial step in this direction in our setup, and a follow-up on the above is planned for the future.
| Conclusion|| |
LDH can be a valuable and affordable tool for foetal outcomes in PE. Such patients are associated with a shorter age of gestation and the possibility of adverse foetal outcomes. This can alert the obstetrician to time management or referral for such patients. In the authors' recommendation, LDH should be measured weekly after 32 weeks in cases with elevated LDH. This can prevent adverse outcomes and help initiate active management including time delivery and neonatal ICU management.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The study was approved by the institutional Ethics Committee of Health Care Center, Peshawar, via approval No. 02/2019.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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