Rajiv Gandhi University of Health Sciences s111

SYNOPSIS

Rajiv Gandhi University of Health Sciences,

Bangalore, Karnataka.

TOPIC:

“SERUM LACTATE DEHYROGENASE (LDH) AS A BIOCHEMICAL MARKER

FOR MATERNAL & PERINATAL OUTCOME IN PREECLAMPSIA AT RRMCH”

NAME OF THE CANDIDATE: Dr. Aishwarya B

GUIDE: Dr. Nagarathnamma

COURSE AND SUBJECT: M.S.OBG

DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY,

RAJARAJESWARI MEDICAL COLLEGE AND HOSPITAL,

BANGALORE – 560074 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION.

1. NAME : AISHWARYA B

2. ADDRESS : POST GRADUATE

DEPARTMENT OF OBSTETRICS AND

GYNAECOLOGY

RAJESWARI MEDICAL

COLLEGE

AND HOSPITAL, BANGALORE

3. NAME OF THE INSTITUTION : RAJA RAJESWARI MEDICAL

COLLEGE

AND HOSPITAL

4. COURSE OF STUDY AND SUBJECT : MS OBSTETRICS AND GYNAECOLOGY

5. DATE OF ADMISSION TO COURSE : 29th May 2013

6. TITLE OF THE THESIS:

SERUM LACTATE DEHYROGENASE (LDH) AS A BIOCHEMICAL MARKER

FOR MATERNAL & PERINATAL OUTCOME IN PREECLAMPSIA AT RRMCH 6. BRIEF RESUME OF INTENDED WORK:

6.1 NEED FOR THE STUDY

Hypertensive disorders of pregnancy and their complications rank as one of the major cause of maternal mortality and morbidity in the world. It accounts for approximately a quarter of all antenatal admissions. In addition, as it is strongly associated with fetal growth retardation and prematurity, it also contributes largely to perinatal mortality and morbidity.(1)

Pre-eclampsia is a multi-system disorder of unknown etiology, unique to pregnancy, with onset after 20 weeks of gestation.(2)

Preeclampsia complicates 2-8% of pregnancies and is a major cause of maternal morbidity, perinatal mortality & morbidity and premature delivery.(3) FOGSI and other studies show the incidence of pre eclampsia in India ranges between 11-13%.

Lactate Dehydrogenase (LDH) is mainly an intracellular enzyme. It is responsible for interconversion of pyruvate and lactate in the cells. Its levels are several times greater inside the cells than in the plasma. So its levels are increased in the scenario of increased cell leakiness, hemolysis and cell death .Preeclampsia is a multisystem disorder and leads to a lot of cellular death. So, serum LDH levels can be used to assess the extent of cellular death and thereby the severity of disease.(4)

Hence Serum LDH Levels can be further used as help in making decision, regarding the management strategies to improve the maternal and fetal outcome.

This study aims to compare serum LDH levels in normal pregnant women and women with preeclampsia & also to correlate the maternal and perinatal outcome & severity of the disease with serum LDH levels. 6.2 REVIEW OF LITERATURE

1) A prospective study conducted Between January and December 2002, by Qublan et al At King

Hussein Medical Centre Jordan. 111 preeclampsia women (29 with mild and 62 with severe

preeclampsia) and 60 normotensive controls were studied. The symptoms and complications of

preeclampsia along with foetal outcome were analyzed according to the levels of LDH ;

They demonstrated a significant association of serum LDH levels with severe preeclampsia. Increase

in the incidence of perinatal deaths was observed in patients with increasing levels of serum LDH

levels. Intrauterine fetal death was seen in 4.8% of cases, intrauterine growth restriction in 33.9% and

prematurity in 77.9%. Neonatal deaths were reported in 95.2% in severe preeclampsia group.

Severely pre-eclamptic women with LDH levels of < 800 IU/l showed a significant increase in

complications in terms of eclampsia, abruption placenta and various other complications compared to

women who had lower serum LDH levels.

The Qublan et al Study concluded that Pre-eclampsia is a pregnancy-specific disease, and in its severe

form, serious multisystem complications may occur & Elevated levels of lactic dehydrogenase,

indicative the cellular damage and dysfunction, can be used as a biochemical Marker because it

reflects the severity of the disease, the occurrence of complications, and fetal outcome. (5)

2) A study done in 2008 by Rubin Aziz & Tabassum Mahboob et at Holy Family Hospital and Godhra

Muslim Medical Centre, Karachi ; 100 pregnant women with 50 as normal pregnant women as

control and 50 preeclampsia women as study group , Demonstrated that mean serum LDH was

significantly higher in preeclampsia patients & concluded that preeclampsia is a multisystem disorder,

characterized by vascular endothelial dysfunction & Higher levels Serum LDH can be a useful marker

to identify the occurrence of complications of preeclampsia in early pregnancy which may reduce the

risk of occurrence of disease. (6) 3) A prospective comparative study conducted in 2008-09 & published in 2011 by Jaiswar S.P et al in the

department of Obstetrics and Gynecology in collaboration with the department of Pathology CSM

Medical University, Lucknow for 1 year. Total 146 patients were studied, out of which 39 (26.7%)

were normal pregnant women which served as control group; remaining 107 (73.3%) cases included

pregnancy with eclampsia and preeclampsia. Out of these 107 cases 35 (32.7%) were mild

preeclampsia, 36 (33.6%) were severe preeclampsia and 36 (33.6%) cases were of eclampsia clearly

observed that there is significant rise in the LDH levels with increasing severity of the disease. The

occurrence of neonatal complications, stillbirths and perinatal deaths were significantly higher in

mothers who had increased serum levels of LDH.

The study concluded that LDH levels were significantly elevated in women with preeclampsia and

eclampsia & Higher LDH levels had significant correlation with severity of the disease as well as

poor maternal and perinatal outcome. (7)

4) In A cross sectional study published in 2012 by Amit D.Sonagra; study cases were selected from

Bapuji Hospital and Chigateri Hospital, Davangere (J.J.M. Medical College, Davangere).Case control

study was done taking 30 women with preeclampsia (group I), 30 with gestational hypertension

(group II), 30 with normal pregnancy (group III) and 30 age matched healthy non-pregnant women

(controls). A serum level of LDH was measured using commercially available kits. Statistical analysis

was done using SPSS 17.0. It was seen that the mean serum LDH was 26% higher in group I when

compared with group II & 135% higher when compared with group III. The mean serum LDH was

86% higher in group II when compared with group III.

The study concluded that Serum LDH gradually increase as the disease severity increases. Regular

monitoring of its serum level in women with Hypertension in Pregnancy may give a clue of disease

severity. (8)

6.3 OBJECTIVES OF THE STUDY

 To compare serum LDH levels in normal pregnant women and in women with preeclampsia & to

correlate the maternal and perinatal outcomes and severity of the disease with serum LDH levels

7. MATERIALS AND METHODS:

7.1 SOURCE OF DATA

All Antenatal cases with gestational age ≥20weeks between 18yrs and 35yrs of age as per the inclusion and exclusion criterias attending the OPD or admitted under OBG department, Rajarajeshwari medical college,

Bangalore

PERIOD – November 2013 to March 2015.

An informed consent will be taken from all the patients for inclusion in the study

INCLUSION CRITERIA

All Pregnant women ≥20weeks of gestation will be enrolled in this study and divided into following

groups:

 Group 1—Healthy normotensive (Normal) pregnant women (Controls)

 Group-2—Patients of preeclampsia and eclampsia (Subjects).

Subjects will be further subdivided into following subgroups

 Sub group A- Mild Preeclampsia

 Sub group B- Severe Preeclampsia

Sub group A- Mild preeclampsia(9) Defined as Pregnant female of ≥20 weeks of gestation with blood pressure ≥140/90 mm of Hg & <160/110 mm of Hg noted first time during pregnancy on ≥2 occasions at least 6 hours apart with proteinuria of ≥1+

(≥30mg/dl) by dipstick method in a random urine sample would be considered as having mild preeclampsia after excluding urinary tract infection .

Sub group B- Severe preeclampsia(9)

Defined as the presence of 1 of the following symptoms or signs:

 SBP of 160 mm Hg or higher or DBP of 110 mm Hg or higher on 2 occasions at least 6 hours apart

while the patient is in bed rest

 Proteinuria of 5g or higher in a 24-hour urine specimen or 3+ or greater on two random urine samples

collected atleast 4 hours apart 3+ on 2 random urine samples collected at least 4 hours apart

 Oliguria of less than 500ml in 24 hours

 Cerebral or visual disturbances

 Pulmonary oedema or cyanosis

 Epigastric or right upper quadrant pain

 Impaired Liver function

 Thrombocytopenia ( platelets <100000/-)

 Intrauterine growth restriction

(From ACOG Practice Bulletin No.33, January 2002)

 The two groups & Sub groups would be matched according to age, gravidity, parity, maternal weight,

trimester, and maternal and perinatal outcomes.

 All women would be followed until delivery and early postpartum period and babies till early

neonatal period.

Subjects would also be divided according to the serum LDH levels into following groups(6)

 (a) < 600 IU/l  (b) 600–800 IU/l  (c) > 800 IU/l

NORMAL SERUM LDH VALUES (10)

Non pregnant women 115 to 211 IU/L First Trimester 78 to 433 IU/L Second Trimester 80 to 447 IU/L Third Trimester 82 to 524 IU/L

Serum LDH value above the reference range is taken as raised.

Exclusion Criteria

These included pregnant women with essential hypertension or hypertension <20 weeks gestation;

Preexisting diabetes mellitus, renal disease, liver disorder, thyroid disorder, epilepsy & with urinary tract infection.

DESIGN OF STUDY: Prospective comparative Study.

SAMPLE SIZE: This is a Hospital based study, all Antenatal cases as per the inclusion and exclusion criterias attending the OPD or admitted under OBG department, RRMCH Bangalore from November 2013 to

March 2015

TARGET NUMBER: Minimum 100

(Which includes the number of patients with Preeclampsia as subject group and equal number of normotensive patients as control group)

7.2 METHOD OF COLLECTION OF DATA

 SAMPLE COLLECTION: Blood samples will be collected Plain blood sample on empty stomach will be collected for analysis of LDH which will be done in fully automated biochemistry analyzer.

Investigations to be done:

 HAEMATOLOGIC:

 Complete Haemogram

 Blood grouping and typing

 HIV,HBsAg,VDRL

 Platelet count, clotting time, bleeding time,

 Lactate dehydrogenase (LDH).

 Renal function tests(RFT)-blood urea, serum creatinine, serum uric acid

 Liver function tests(LFT)-serum bilirubin(direct and indirect),ALT and AST,Total

Protien,Albumin,A/G ratio

 URINE ANALYSIS:

 Urine routine-albumin ,sugar and microscopy

 RADIOLOGIC: ultrasonic assessment for the fetal weight, AFI, BPP, placental location and

maturity & Colour Doppler study

 NON STRESS TEST

 FUNDOSCOPY

 OTHER SPECIAL INVESTIGATIONS:

In suspected coagulation disorder-Prothrombin time, aPTT and serum fibrinogen.

STATISTICAL ANAYSIS: The statistical analysis would be done by Chi-square test (for proportional data) analysis of variance and sample ‘‘t’’ test (for parametric data).

7.4 DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR INTERVENTIONS TO BE

CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS? IF SO, PLEASE DESCRIBE

BRIEFLY.

Yes, this study involves human population; informed consent will be obtained as per the proforma.

Appropriate investigations (Serum LDH along with other Antenatal routine investigations)

7.5 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF

7.4 - YES

8 LIST OF REFERENCES

1. Park K.Textbook of preventive and social medicine.21st edn. M/s Banarasidas Bhanot

publishers;2011.Chapter: Preventative medicine in obstetrics, pediatrics & geriatrics:514-517.

2. Ian Donald.Renu Misra MS,editor.Ian Donald’s Practical Obstetric Problem.6th Edition.New Delhi.BI

Publications Pvt Ltd;2012.Chapter:Hypertensive Disorders in Pregnancy:281-309

3. Duley L.Pre-eclampsia and the Hypertensive disorders of pregnancy.Br Med J

2003;67:161

4. Vasudevan D, Sreekumari S, Vaidyanathan K.Textbook of biochemistry,6th edition. New Delhi

Jaypee Brothers, 2011. .Clinical enzymology and biomarkers :146-159

5. Qublan H, 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(8): CR393-397.

6. Rubina Aziz, Tabassum Mahboob .Relation between Preeclmapsia and cardiac enzymes.ARYA

Atherosclerosis Journal 2008,4(1):29-32

7. Jaiswar S.P.,Gupta Amrit,Sachan Rekha,Natu S.N,Shaili Mohan. Lactic Dehydrogenase:A

biochemical AMrker for preeclampsia-eclampsia. JOGI, Nov-Dec 2011, 61(6):645-648 8. Amit D. Sonagra, Dattatreya. K, Jayaprakash Murthy D.S. Serum LDH,ALP and Uric Acid in

Hypertensive Disorders of Pregnancy.IJPBS ,Volume 2,Issue 3 ,July-Sept ,2012:201-209

9. Fernando Arias, Shirish N Daftary,Amarnath G Bhinde “High risk pregnancy & delivery”3rd

edition ,Reed Elsevier India Pvt.Ltd. 2013,Chapter 16,P.417

10.Gary Cunningham F,Kenneth J Leveno,steven l Bloom,John C Hauth,Dwight J Rouse, Catherine Y

Sponge,editors.Wlliams Obstetrics.23rd Edition.The McGraw Hill Company;2010:1261

9. SIGNATURE OF CANDIDATE

10. REMARKS OF THE GUIDE:

Being a tertiary care centre, we are getting good number of High Risk Pregnancy cases specially

Preeclampsia. This study will be great help to the clinicians to make decision at right time and plan for delivery at the earliest so that major maternal & perinatal mortality and morbidity can be prevented.

11. NAME AND DESIGNATION OF

11.1 GUIDE: Dr. NAGARATNAMMA

PROFESSOR AND HOD

DEPARTMENT OF OBSTETRICS

GYNAECOLOGY

RAJA RAJESHWARI MEDICAL

COLLEGE,

BANGALORE

11.2 SIGNATURE: 11.3 HEAD OF DEPARTMENT: Dr.NAGARATNAMMA

PROFESSOR AND HOD

GYNAECOLOGY

RAJA RAJESHWARI MEDICAL

COLLEGE,

BANGALORE

11.4 SIGNATURE

12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL

12.2 SIGNATURE: ETHICALCOMMITTEE CLEAREANCE

1. TITLE OF DISSERTATION : “SERUM LACTATE DEHYROGENASE (LDH) AS A BIOCHEMICAL MARKER FOR MATERNAL & PERINATAL OUTCOME IN PREECLAMPSIA AT RRMCH”

2. NAME OF THE CANDIDATE : Dr.AISHWARYA B

3. NAME OF THE GUIDE : Dr. Dr. NAGARATNAMMA

PROFESSOR AND HOD

AND GYNAECOLOGY

RAJA RAJESWARI MEDICAL COLLEGE

AND HOSPITAL,BANGALORE

4. APPROVED/NOT APPROVED : YES

SUPERINTENDENT

Rajarajeswari medical college and hospital

Bangalore

PROFESSOR & HOD

Department of OBG Rajarajeswari Medical College and Hospital Bangalore

DEAN AND DIRECTOR

Rajarajeswari medical college and hospital

Dr.Aishwarya B

Post-Graduate in Obstetrics and Gynaecology

Department of Obstetrics and Gynaecology

Rajarajeswari medical college and hospital,Bangalore

Registrar (Evaluation)

Rajiv Gandhi University of Health Sciences,Bangalore

THROUGH PROPER CHANNEL

Respected Sir,

Subject: Submission of Synopsis titled

FOR MATERNAL & PERINATAL OUTCOME IN PREECLAMPSIA AT RRMCH

I am hereby submitting the above titled synopsis (4 copies)as mentioned above, so kindly accept my application and do the needful

Thanking you

Yours faithfully

(Dr. Aishwarya B)

Forwarded to Dean and Director, Raja rajeswari medical college and hospital for further needful action

PROFESSOR AND HEAD

Date : Department of Obstetrics and Gynaecology

Raja rajeswari medical college and

Place: Bangalore hospital, Bangalore CONSENT FORM

PATIENT NAME:

IP/OP NO.

STUDY TITLE

FOR MATERNAL & PERINATAL OUTCOME IN PREECLAMPSIA AT RRMCH

1. I have been explained and have understood the procedures involved in the study

2. I confirm that I have read and understand the information sheet for the above study.

3. I have had the opportunity to consider the information, ask questions and have had these answered

satisfactorily.

4. I understand that my participation is voluntary and that I am free to withdraw at any time, without giving

any reason, without my medical care or legal rights being affected.

5. I understand that relevant sections of any of my medical notes and data collected during the study may be

looked at by responsible individuals from [Raja rajeshwari Medical College], where it is relevant to my

taking part in this study. I give permission for these individuals to have access to my records.

6. I agree to take part in the above study.

Name and signature of interviewer Signature of subject

Date: Date