RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA
SYNOPSIS OF DISSERTATION
TO STUDY THE EFFECTIVENESS OF CORD BLOOD ALBUMIN AS A PREDICTOR OF NEONATAL JAUNDICE
Submitted by Dr. MURALI. S.M. M.B.B.S. POST GRADUATE STUDENT IN PAEDIATRICS (M.D)
DEPARTMENT OF PAEDIATRICS ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES, B.G.NAGARA-571448 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA ANNEXURE II PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 NAME OF THE CANDIDATE Dr. MURALI. S.M. AND ADDRESS POST GRADUATE STUDENT (in block letters) DEPARTMENT OF PAEDIATRICS, ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES, B.G. NAGARA, MANDYA DISTRICT -571448 ADICHUNCHANAGIRI INSTITUTE OF 2. NAME OF THE INSTITUTION MEDICAL SCIENCES, B.G.NAGARA.
3. COURSE OF STUDY AND SUBJECT M.D. IN PAEDIATRICS
4. DATE OF ADMISSION TO COURSE 30TH MAY 2011
TO STUDY THE EFFECTIVENESS OF 5. TITLE OF THE TOPIC CORD BLOOD ALBUMIN AS A PREDICTOR OF NEONATAL JAUNDICE 6. BRIEF RESUME OF INTENDED WORK APPENDIX-I 6.1 NEED FOR THE STUDY APPENDIX-IA 6.2 REVIEW OF LITERATURE APPENDIX-IB 6.3 OBJECTIVES OF THE STUDY APPENDIX-IC 7 MATERIALS AND METHODS APPENDIX-II
7.1 SOURCE OF DATA APPENDIX-IIA
7.2 METHOD OF COLLECTION OF DATA : (INCLUDING SAMPLING APPENDIX-IIB PROCEDURE IF ANY)
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS YES TO BE CONDUCTED ON PATIENTS OR APPENDIX-IIC OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY.
7.4 HAS ETHICAL CLEARENCE BEEN YES OBTAINED FROM YOUR INSTITUTION APPENDIX-IID IN CASE OF 7.3 8. LIST OF REFERENCES APPENDIX – III
9. SIGNATURE OF THE CANDIDATE
2 Early prediction of significant neonatal 10. REMARKS OF THE GUIDE jaundice helps in better management of hyperbilirubinemia, thus prevents the complications like kernicterus. NAME AND DESIGNATION 11 (in Block Letters)
11.1 GUIDE Dr. VENKATAMURTHY M. M.B.B.S., M.D. Professor, Department of Paediatrics, AIMS, B.G. Nagara-571448
11.2 SIGNATURE OF THE GUIDE
11.3 CO-GUIDE (IF ANY) -
11.4 SIGNATURE -
11.5 HEAD OF DEPARTMENT Dr. SHIVAPRAKASH. N.C M.B.B.S., M.D. Professor & H.O.D Department of Paediatrics, AIMS, B.G. Nagara-571448
11.6 SIGNATURE
12 12.1 REMARKS OF THE CHAIRMAN The facilities required for the investigation will AND PRINCIPAL be made available by the college
Dr. M.G. SHIVARAMU M.B.B.S., MD PRINCIPAL, AIMS, B.G. NAGARA.
12.2 SIGNATURE
APPENDIX-I
3 6.BRIEF RESUME OF THE INTENDED WORK:
APPENDIX –I A
6.1 NEED FOR THE STUDY:
Neonatal jaundice is commonest abnormal physical finding during the first week of life.
Over two third of newborn babies develop clinical jaundice.12
Early discharge of healthy term newborns after normal vaginal delivery has become a common practice, because of medical reasons like prevention of nosocomial infections, social reasons like in early naming ceremony as practiced in Muslim community, and also due to economical constrains.
American Academic of pediatrics recommends that newborn discharged with in 48 hours should have a follow-up visit after 48 to 72 hours for any significant jaundice and other problems.2
This recommendation is not appropriate for our country due to limited follow-up facilities in the community. These babies may develop jaundice which may be over looked or delay in recognition unless the baby is closely monitored.
Concern of pediatrician regarding the early discharge are reports of bilirubin induced brain damage occurred in healthy term infants even without hemolysis.14,15
By predicting the newborns developing significant neonatal jaundice early at birth, we can design and implement the follow-up programme in high risk groups effectively.
The present study is conducted to find out critical value of cord blood albumin in predicting the subsequent development of significant neonatal jaundice requiring interventions like phototherapy or exchange transfusion.
APPENDIX –I B
4 6.2 REVIEW OF LITERATURE
Neonatal jaundice in term new born is when total bilirubin level in serum is >7mg/dl.
Nearly 25 to 50% of all healthy term newborn develops clinical jaundice. A significant serum bilirubin >15mg/dl is found in 3% of normal term neonates.1
Catabolism of 1 mol of hemoglobin produces 1 mol of Carbon monoxide and 1 mol of bilirubin. Bilirubin is non-polar, insoluble in water and is transported to liver bound to serum albumin. Bilirubin bound to albumin does not usually enter the center nervous system and is thought to be non-toxic.1
In term babies physiological jaundice is seen to appear between 36 to 72 hours of age, maximum intensity of jaundice is seen on 4th day of life. Serum bilirubin doesn’t exceed
15mg/dl and jaundice disappear by 10th day of life. And physiological jaundice never appears before 24hours of life.12
Originally described by Kramer, dermal staining of bilirubin may be used as a clinical guide to the level of jaundice. Dermal staining in newborn progresses in a cephalo-caudal direction. The newborn should be examined in good daylight. The skin should be blanched with digital pressure and the underlying color of skin and subcutaneous tissue should be noted.
A rough guide for level of dermal staining with level of bilirubin is included in table 1.
Table 1
Area of body Level of bilirubin
Face 4-6 mg/ dl Chest, upper abdomen 8-10 mg/dl Lower abdomen, thighs 12-14 mg/dl Arms, lower legs 15-18 mg/dl Palms, soles 15-20 mg/dl
5 Newborns detected to have yellow discoloration of the skin beyond the thighs should have an urgent laboratory confirmation for levels of bilirubin. Clinical assessment is unreliable if a newborn has been receiving phototherapy and if the baby has dark skin.13
Management of hyperbilirubinemia in the healthy term newborn2
Consider Exchange transfusion if Phototherapy, if Age (Hours) Phototherapy, if intensive phototherapy SB.mg/dl SB. mg/dl Fails, if SB.mg/dl
25 – 48 ≥12 ≥15 ≥20
49 – 72 ≥15 ≥18 ≥ 25
>72 ≥17 ≥20 ≥25 SB=Serum bilirubin.
In order to reduce hospital cost, most healthy term babies delivered by vaginal route without any complication are discharged from hospital within 48 hours or less. These babies may develop neonatal jaundice which may be missed or delay in recognition if the follow up is not done.
A study done by Thomas B Newman et al, combing clinical risk factors with serum bilirubin levels to predict neonatal jaundice course in new born, showed significant improved prediction of neonatal jaundice when clinical risk factors are combined with early total serum bilirubin compared with early total serum bilirubin alone.3
Study done by Zakia Nahar et al, estimating umbilical cord bilirubin level in predicting significant hyperbilirubinemia, showed critical value of cord blood bilirubin >2.5mg/dl had high sensitivity (77%) and specificity (98.6%).4
Similar study done by Sao Paulo et al, showed cord blood bilirubin level of 2.0mg/dl indicates there is 53% probability of phototherapy required in that baby and as the cord blood bilirubin level increased the probability of phototherapy requirement in baby increased.5
6 A study done by David K Stevenson, et al, to predict hyerbilirubinemia, by measuring
End Tidal Carbon monoxide (ETCO), failed to improve the predictive ability of an hour- specific bilirubin normogram. But the combination of measuring serum total bilirubin with
ETCO as early as around 30 hours of life, helps in identifiying increase bilirubin production
(eg: hemolysis) or decrease elimination of bilirubin (eg: conjugation defect) hence helps in determining early follow-up for problems like pathological jaundice or late anemia.6
A study conducted by K L Tan et al, showed that by estimating cord blood alpha- fetoprotein as a screening procedure to detect infants at high risk for hyperbilirubinemia. At cord blood level of alpha-fetoprotein 130mg/L, incidence of significant jaundice with a false positive and false negative values were 25.5% and 11.8% respectively.7
A study by Vinod K Bhutani et al, regarding predictive ability of predischage serum bilirubin for subsequent development of significant jaundice after plotting on hour-specific bilirubin normogram. Low risk zone (<40th percentile), there was no measurable risk for significant hyperbilirubinemia and vise versa. Universal policy of measuring predischage serum bilirubin would facilitates targeted intervention, follow-up and also helps to reduce the potential risk for kernicterus development.8
A similar study done by measuring predischage bilirubin, but by transcutaneous bilirubinometer (bilicheck) and plotting its value on hour-specific bilirubin normogram.
Bilicheck values above 75th percentile on hour-specific bilirubin normogram may be considered to be at high risk for subsequent excessive hyperbilirubinemia.9
A study done by M.Granat et al, showed no statistical significant correlation between maximal serum bilirubin level in the neonatal versus total protein level in the cord blood.10
7 A study done by Suchanda Sahu et al, showed the predicton of significant hyperbilirubinemia by measuring cord blood albumin. 82% of neonate who had cord blood albumin level <2.8g/dl developed hyperbilirubinemia requiring phototherapy and 12% need exchange transfusion. Neonates with cord blood albumin level>3.3g/dl did not need any intervention for hyperbilirubinemia or didn’t develop significant hyperbilirubinemia.11
APPENDIX –IC
6.3 AIMS AND OBJECTIVES OF STUDY
1. To study the association between various levels of cord blood albumin and significant
neonatal jaundice requiring interventions like phototherapy or exchange transfusion.
2. To predict the proportion of new born requiring intervention for neonatal jaundice
(phototherapy or exchange transfusion) based on cord blood albumin level at birth.
8 APPENDIX-II
7.0 MATERIALS AND METHODS
APPENDIX-II A
7.1 SOURCE OF DATA
120 single live term born normal neonates delivered at Adichunchanagiri hospital and research center from December 2011 – May 2012 will form cohort of this prospective study.
Sample size is determined my Altman’s monogram standardized difference.
APPENDIX-II B
7.2 METHOD OF COLLECTION OF DATA
Cord blood 2ml in plain sample bottle at birth is collected by the investigator. Under aseptic precaution 1ml of venous blood is drawn from all the babies enrolled in study on after
72 hours of life, for estimation of serum total bilirubin.
INCLUSION CRITERIA Term babies both genders
Mode of delivery ( normal and c-section)
Birth weight >2.5kg.
APGAR = or> 7/10 at 1 min.
EXCLUSION CRITERIA Preterm
Rh incompatibility.
Neonatal sepsis.
Instrumental delivery (forceps and vaccum)
Birth asphyxia.
9 Respiratory distress.
Meconium stained amniotic fluid.
Neonatal jaundice within 24 Hours of life.
PROCEDURE:
Cord blood albumin collected at birth will be analyzed by auto analyzer method.
All enrolled baby is followed up for 3 days and clinical assessment for jaundice is done
according to Kramer dermal scale.
Under aseptic precaution 1ml of venous blood is drawn from all the babies enrolled in
study on after 72 hours of life, for estimation of serum total bilirubin.
DATA ANALYSIS:
Data will be analyzed by test parameters (proportions, sensitivity, specificity, positive and negative predictive value) and Statistical significance test that can be applied are chi square test or Analysis of variance (ANOVA) test.
APPENDIX-II C
7.3 Does the study require any investigation or intervention to be conducted on the patients or animals, if so please describe briefly
YES
APPENDIX-II D
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
YES
10 APPENDIX-IID
PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL
SECTION A TO STUDY THE EFFECTIVENESS OF a Title of the study CORD BLOOD ALBUMIN AS A PREDICTOR OF NEONATAL JAUNDICE
Dr. MURALI. S.M. POST GRADUATE STUDENT Principle investigator b DEPARTMENT OF PAEDIATRICS, (Name and Designation) ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES, B.G. NAGARA, MANDYA DISTRICT -571448
Dr. VENKATAMURTHY M. Co-investigator M.B.B.S., M.D. c Professor, (Name and Designation) Department of Paediatrics, AIMS, B.G. Nagara-571448 Name of the Collaborating d NIL Department/Institutions
Whether permission has been obtained from e the heads of the collaborating departments & NA Institution Section – B APPENDIX – II Summary of the Project Section – C APPENDIX – IC Objectives of the study Section – D APPENDIX - IIB Methodology A Where the proposed study will be undertaken S.A.H. & R.C., B.G.NAGARA
B Duration of the Project 18 MONTHS C Nature of the subjects: Does the study involve adult patients? NO Does the study involve Children? YES Does the study involve normal volunteers? NO Does the study involve Psychiatric patients? NO Does the study involve pregnant women? NO
11 D If the study involves health volunteers I. Will they be institute students? NO II. Will they be institute employees? NO III. Will they be Paid? NA IV. If they are to be paid, how much per NA session?
E Is the study a part of multi central trial? NO
F If yes, who is the coordinator? (Name and Designation) NA
Has the trail been approved by the ethics NA Committee of the other centers?
If the study involves the use of drugs please NA indicate whether.
I. The drug is marketed in India for the NA indication in which it will be used in the study.
II. The drug is marketed in India but not for the indication in which it will be used in the NA study
III. The drug is only used for experimental use in humans. NA
IV. Clearance of the drugs controller of India NA has been obtained for:
Use of the drug in healthy volunteers Use of the drug in-patients for a new indication. NA Phase one and two clinical trials Experimental use in-patients and healthy volunteers.
12 G How do you propose to obtain the drug to be used in the study? - Gift from a drug company NA - Hospital supplies - Patients will be asked to purchase - Other sources (Explain) H Funding (If any) for the project please state - None - Amount NONE - Source - To whom payable
Does any agency have a vested interest in the I NO out come of the Project?
Will data relating to subjects /controls be stored J YES in a computer? Will the data analysis be done by K - The researcher YES - The funding agent NO L Will technical / nursing help be required form NO the staff of hospital.
If yes, will it interfere with their duties? NO
Will you recruit other staff for the duration of NO the study?
If Yes give details of I. Designation NA II. Qualification III. Number IV. Duration of Employment
13 M Will informed consent be taken? If yes YES Will it be written informed consent: YES Will it be oral consent? NO Will it be taken from the subject themselves? NO Will it be from the legal guardian? If no, give YES reason:
N Describe design, Methodology and techniques APPENDIX II
Ethical clearance has been accorded.
Chairman, P.G Training Cum-Research Institute, A.I.M.S., B.G.Nagara. Date :
PS : NA – Not Applicable
14 APPENDIX-III 8. LIST OF REFERENCES
1. John P. Cloherty, Eric C. Eichenwald, Ann R. Stark, Chapter 18: Neonatal
Hyperbilirubinemia, Manual of neonatal care 6th edition, New Delhi: Lippincot
Williams & Wilkins, a Wolters Kluwer business, 2010:180-211.
2. American Academy Of Pediatrics, Clinical Practice Guideline; Management of
Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation, Pediatrics
2004;114(1):297-316
3. Thomas B.Newman et al Combining Clinical Risk Factors With Serum Bilirubin Levels
to Predict Hyperbilirubinemia in Newborns, Archpediatrics 2005;159:113-119.
4. Zakia Nahar et al, The Value of Umbilical Cord Blood Bilirubin Measurement in
Predicting the Development of Significant Hyperbilirubinemia in Healthy Newborn,
Bangladesh J Child health 2009;33(1):50-54.
5. Sao Paulo et al, Bilirubin dosage in cord blood: could it predict neonatal
hyperbilirubinemia? Sao Paulo medical journal 2004;122(3):99-103.
6. David K.Stevenson et al, Prediction of Hyperbilirubinemia in Near-Term and Term
Infants, Pediatrics 2001;108(1):31-39.
7. K L Tan et al, Cord Plasma α-Fetoprotein Values and Neonatal Jaundice, pediatrics
1984;74(6)1065-1068.
8. Vinod K Bhutani et al, Predictive Ability of a Predischarge Hour-specific Serum
Bilirubin for Subsequent Significant Hyperbilirubinemia in Healthy Term and Near-
term Newborns, Pediatrics 199;103(1):6-14.
9. Vinod K Bhutani et al, Noninvasive Measurement of Total Serum Bilirubin in a
Multiracial Predischarge Newborn Population to Assess the Risk of Severe
Hyperbilirubinemia, Pediatrics 2000;104(2):1-9
15 10. M.Garant et al, Bilirubin and protein concentration in cord blood after spontaneous
versus induced labor. Correlation to neonatal hyperbilirubinemia, J.Perinat.med
1981;1:27-34.
11. Suchanda Sahu et al, Cord blood albumin as a predictor of neonatal jaundice,
Internation J.Biological and medical research 2011;2(1):436-438.
12. Meharban singh, Care of the newborn, 7th edition, chapter 18, 2010: 254-274.
13. Kramer LI et al, Advancement of dermal icterus in jaundiced newborn, Am J Dis Child
1969;118:454-458.
14. Penn AA, et al. Kernicterus in a full term infant. Pediatrics 1994;93:1003-1006.
15. Maisels MJ, et al. Kernicterus in otherwise healthy breast-fed term newborns, Pediatrics
1995;96:730-733.
16 PROFORMA
Serial No: I.P.No.:
Mother’s Name:
Father’s Name:
Address:
Family Income:
Date & Time of birth:
Place of birth:
Birth Order:
Delivery Type: Normal Vaginal:
Instrumental:
Caesarian Section:
Amniotic fluid: Clear/ Meconium.
Period of Gestational age:
Mothers blood group:
Baby’s blood group:
Cord blood albumin level.
Serum bilirubin level after 72 hours.
Phototherapy given: Yes/ No.
Nicu admission:
17 ADICHUNCHANAGIRI INSTITUE OF MEDICAL SCIENCES B.G.NAGARA, NAGAMANGALA TALUK, MANDYA DISTRICT-571448. KARNATAKA. PH: 08234-287433, FAX: 08234-287242.
Ref No AIMS/PRI/ /2011-2012
TO, The Registrar, R.G.U.H.S., Jayanagar, 4th block, Bangalore-560011, KARNATAKA.
Respected Sir,
SUB: Institutional Ethical Clearance
With regard to subject mentioned above the dissertation subject titled “To study the effectiveness of cord blood albumin as a predictor of neonatal jaundice.” is justifiable & has taken ethical clearance from the institution.
Thanking you,
Yours Faithfully,
Principal, AIMS, B.G. Nagara. Mandya
18 ADICHUNCHANAGIRI INSTITUE OF MEDICAL SCIENCES B.G.NAGARA, NAGAMANGALA TALUK, MANDYA DISTRICT-571448. KARNATAKA. PH: 08234-287433, FAX: 08234-287242.
Ref No AIMS/PRI/ /2011-2012
To, The Chairman, Ethical clearance committee, Sri Adichunchanagiri Hospital and Research Centre, B.G. Nagara, Mandya District-571448
Respected Sir,
SUB: Institutional Ethical Clearance
With regard to subject mentioned above the dissertation subject titled “To study the effectiveness of cord blood albumin as a predictor of neonatal jaundice.” I request you to kindly issue an ethical clearance certificate for the same.
Thanking you,
Yours Faithfully,
Dr. MURALI. S.M. P.G. IN Pediatrics, AIMS, B.G. Nagara. Mandya
19 ADICHUNCHANAGIRI INSTITUE OF MEDICAL SCIENCES B.G.NAGARA, NAGAMANGALA TALUK, MANDYA DISTRICT-571448. KARNATAKA. PH: 08234-287433, FAX: 08234-287242.
INFORMED CONSENT FORM
Title of the study: “To study the effectiveness of cord blood albumin as a predictor of neonatal jaundice.”
Name of the participant:______
Name of the principal investigator: Dr. MURALI S M Name of the institution: Sri Adichunchanagiri Hospital and Research Centre, B.G. Nagara
I, mother/father of ______aged ______hrs/days delivered at Sri Adichunchanagiri Hospital and Research Centre, B.G. Nagara, I have been explained in my own language the need for the study and the investigation of cord blood albumin and serum total bilirubin of the baby by using cord blood and venous blood.
Hereby give my consent to include my child as a participant in the study : “To study the effectiveness of cord blood albumin as a predictor of neonatal jaundice.” The doctor has explained the proposed procedure in my own language and I understand the procedure. I understand that a doctor other than the Consultant may conduct the procedure. I understand this could be a doctor undergoing further training.
I REQUEST TO HAVE THE PROCEDURE Name ______Signature of the parent______Date ______Time ______Name ______Signature of the impartial witness ______Date ______Time ______Name ______Signature of the Investigator ______Date ______Time ______
20