RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE – II
Proforma for Registration of Subjects for Dissertation
1. / NAME OF THE CANDIDATE AND ADDRESS / : / DR. DEEPTHI. R,M.D. IN PEDIATRICS
#5, 5 TH CROSS, J. M. LANE, BALEPET,
BANGALORE - 560053
2. / NAME OF THE INSTITUTION / : / BANGALORE MEDICAL COLLEGE AND RESEARCH INSTITUTE, BANGALORE.
3. / COURSE OF STUDY AND SUBJECT / : / M.D. IN PEDIATRICS.
4. / DATE OF ADMISSION TO THE COURSE / : / 02-05-2009
5. / TITLE OF THE TOPIC / : / A STUDY OF HEPATIC ENZYMES AND LACTATE DEHYDROGENASE ACTIVITY FOLLOWING PERINATAL ASPHYXIA IN FULL TERM NEONATES.
6. BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY:
Birth Asphyxia is the commonest primary cause of neonatal death (54.9%). In India, 8.4% of inborn babies have a 1 minute Apgar score less than 7 and 1.4% suffer from hypoxic ischemic encephalopathy (HIE). 1
Apgar scoring is used as a predictor of survival in asphyxiated neonates, but it can also be decreased in depression from maternal drugs, anamalous babies, trauma, metabolic or infectious insults. The predictive value of Apgar score for detection of hypoxic ischemic encephalopathy is insufficient during first hour of life.2 A biochemical parameter that correlates with hypoxic ischemic encephalopathy is of interest since ventilator treatment, sedative drugs and anticonvulsant therapy could make evaluation of severity of hypoxic ischemic encephalopathy difficult.
The defense mechanisms when a fetus is exposed to hypoxia-ischemia is based on ability to centralize cardiac output to prioritized organs such as the brain, heart and the adrenals at the expense of less important organs such as the liver, lungs, skin and muscles. Multi organ dysfunction is a natural consequence of this defense mechanism3. The most frequently affected organs are lungs (86%) and liver (85%).
Injured cells leak intracellular enzymes like lactate dehydrogenase, glutamic oxaloacetic transaminase, glutamic pyruvate transaminase.These enzymes may be used as potential predictors of timing and grade of hypoxic ischemic injury in both perinatal period and in infants with antepartum asphyxia. [2, 3, 4, 5]
This study intends to analyse the occurrence of hypoxic hepatitis in full-term neonates after perinatal asphyxia and correlation between rise in enzymes and severity of the asphyxia and CNS symptomatology and hence, to know whether it can be used as a prognostic tool for assessment of degree of hypoxic ischemic encephalopathy during first hours of life and hence the study is undertaken.
6.2 REVIEW OF LITERATURE:
KarlssonMathias et al in their study at Sweden,found that in 12 of the 26(46.1%) asphyxiated infants, serum alanine aminotransferase (S-ALAT) pattern compatible with hypoxic hepatitis was found.Similar patterns were seen in serum aspartate aminotransferase (S-ASAT). S-ALAT and ASAT concentrations 0-72 h after birth correlated significantly with severity of hypoxic-ischaemic encephalopathy .4
Saili et al in their study at Kalawati Saran Children's Hospital, New Delhi, found that two-thirds of the neonates(64.52%) with perinatal asphyxia had a deranged hepatic function reflected through rise in serum aminotransferases and alkaline phosphatase. Out of this group with elevated enzymes 60% expired, and in the other group with normal levels of enzymes 9.1% expired, the difference was statistically significant(P<0.01). Alkaline phosphatase was raised in 58% of the subjects.5
Aylin Tarcan et al in their study at Turkey, found that 22 of the 56 newborns withperinatal asphyxia which was diagnosed based on elevated serum alanine transaminase level (>100U/L, twice upper normal). Fetal distress, thrombocytopenia, convulsions, pathologic findings on imaging of the central nervous system, and a high rate of intrauterine growth retardation were the factors significantly associated with hepatocyte injury. This damage was also associated with high mortality .6
Esque Ruiz et al in their study at Spain, found that the newborn infants with HIE presented higher levels of transaminases, especially of AST (p= 0.000001). No relation was found between values of blood ammonia and transaminases. 7
Sanath Reddy et al in their study at Postgraduate Institute of Medical Education and Research, India found that LDH at 72 hours of life was the most accurate test for discriminating asphyxia from other illnesses among neonates who presented with non-specific signs of illness. LDH could be used at 3 days of age to diagnose asphyxia retrospectively in such cases. Raised LDH had 100% sensitivity, while CK-MB had 100% specificity for asphyxia .8
Lackmann et al in their study at University of Marburg, found that the asphyxiated newborns had significantly increased serum activities of lactate dehydrogenase and hydroxybutyrate dehydrogenase up to 72 h postpartum, whereas healthy newborns showed higher creatine kinase and lactate dehydrogenase activities. Only the activities of glutamic pyruvate transaminase, lactate dehydrogenase, and hydroxybutyrate dehydrogenase seemed to depend on the oxygen supply of the fetus or newborn. If other causes of increased serum enzyme activities are excluded, elevated serum activities should draw one's attention to a perinatal hypoxic-ischaemic insult of the newborn. 9
6.3 OBJECTIVES OF THE STUDY:
· To know the occurrence of hypoxic hepatitis in full-term neonates after birth asphyxia.
· To know whether the degree of hypoxic hepatitis correlates with the severity of the asphyxia and CNS symptomatology.
· To assess whether elevated enzyme levels can be used a prognostic indicator for assessment of degree of hypoxic ischemic encephalopathy during first few hours of life for aid in counselling.
7 MATERIALS AND METHODS:
Study Design:- Hospital based prospective study.
7.1 SOURCE OF DATA:-
A sample of 50 consecutive term neonates with perinatal asphyxia admitted to Neonatal Intensive care unit of Vanivilas Children Hospital and Bowring and Lady Curzon hospital attached to Bangalore Medical College & Research Institute during 2010 & 2011.
7.2 METHOD OF COLLECTION OF DATA:-
Blood sample is collected at less than 12 hours of birth and at 72 hours after the birth for estimation of serum lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT) , serum glutamic pyruvate transaminase (SGPT) and alkaline phosphate after taking informed written consent from parents. Serum LDH value above 580 U/L is considered abnormal. Values of SGOT above 140 U/L, SGPT above 50 U/L and alkaline phosphatase above 225 I U/L are considered abnormal .10
Sample size: Subjects will be 50 term neonates with perinatal asphyxia.
7.3 INCLUSION CRITERIA: -
· Apgar score less than or equal to 3 at 1 minute or less than 7 at 5 minutes of birth.
· Full term neonates [gestational age between 37 to 42 weeks].
· Resuscitation with more than 3 min of positive ventilation before stable spontaneous respiration.
7.4 EXCLUSION CRITERIA:-
· Preterm neonates [gestational age < 36 weeks].
· Neonates with bacterial sepsis.
· Neonates on potentially hepatotoxic drugs therapy.
· Neonates born to mothers with viral hepatitis.
A predesigned, prestructured proforma will be used for collection of neonatal and maternal data. Pretest and post test counselling will be given to parents / guardian.
7.5 STATISTICAL ANALYSIS
The data will be analyzed using Student t test, ANOVA and Pearson’s correlation analysis.
7.6 Does the study require any investigation or interventions to be conducted on patients or other human beings or animals? If so please describe briefly?
INVESTIGATIONS- YES
2 ml of clotted blood for serum lactate dehydrogenase, glutamic oxaloacetic transaminase, glutamic pyruvate transaminase and alkaline phosphatase enzymes levels.
INTERVENTIONS-Nil
7.7 Has the ethical committee clearance been obtained for this study from your institution? yes.
8 LIST OF REFERENCES:
1. NNPD network. National Neonatal Perinatal Database–report for the year 2002-2003. NNF NNPD network. New Delhi: 2005.
2. Groenendaal F S, De vries L S. Selection of babies for intervention after birth asphyxia. Seminars in neonatology 2000;5:17-32.
3. Jensen A, Garnier Y, Berger R. Dynamics of fetal circulatory responses to hypoxia and asphyxia. European journal of Obstetrics, Gynaecology and Reproductive Biology 1999;84:155-172.
4. KarlssonMathias, BlennowMats, Nemeth Antal, WinbladhBirger Dynamics of hepatic enzyme activity following birth asphyxia. Acta Paediatrica.2006 Nov; 95(11):1405-11.
5. Aylin Tarcan, Filiz Tiker, Hakan Guvenir, Berkan Gurakan. Hepatic involvement in perinatal asphyxia. The Journal of Maternal-Fetal & Neonatal Medicine 2007;20(5):407–410.
6. Saili, Sarna, Gathwala, Kumari, Dutta. Liver dysfunction in severebirthasphyxia. Indian Pediatrics 1990 December 1;27(12):1291-1294.
7. Esque Ruiz, Figueras Aloy, Salvia Roiges, Carbonell Estrany. Blood ammonia and transaminases in full term infants suffering from perinatal asphyxia. Revista de neurologia 2003 May 1-15;36 (9):801-805.
8. Sanath Reddy, Sourabh Dutta, Anil Narang. Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among sick neonates. Indian Pediatrics 2008 February 17;45:144-147.
9. Lackmann GM, Tollner U, Mader R .Serum enzyme activities in full-term asphyxiated and healthy newborns: enzyme kinetics during the first 144 hours of life. Enzyme Protein. 1993;47(3):160-72.
10. Nicholson JF, Perce MA. Reference ranges for laboratory tests and procedures. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of Pediatrics. 17th ed. Philadelphia: Saunders;2004:2396-2427.
9. / SIGNATURE OF THE CANDIDATE / : /DR.DEEPTHI R
10. / REMARKS OF THE GUIDE / Very few studies have been done to know the prognostic value of enzymes in perinatal asphyxia and its use in the counselling regarding neurological outcome and mortality of neonates within the first few days of life, hence this study is undertaken.
11. / NAME & DESIGNATION OF GUIDE
11.1 / GUIDE / : / DR. SARALA SABAPATHY,
PROFESSOR,
DEPARTMENT OF PEDIATRICS,
BOWRING AND LADY CURZON HOSPITAL,
BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE
11.2 / SIGNATURE / :
11.3 / HEAD OF THE DEPARTMENT / : / DR. GANGADHAR B. BELAVADI,
PROFESSOR AND HOD,
DEPARTMENT OF PEDIATRICS,
VANIVILAS CHILDREN HOSPITAL,
BANGALORE MEDICAL COLLEGE & RESEARCH INSTITUTE, BANGALORE
11.4 / SIGNATURE / :
12.1 / REMARKS OF THE DEAN & DIRECTOR / :
12.2 /
SIGNATURE
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