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

0
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

1
9. SIGNATURE OF THE CANDIDATE

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

2
 APPENDIX-I

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.

3
 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

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

4
 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

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 SB. intensive phototherapy
SB.mg/dl
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

5
 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

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

6
 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

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.

7
 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.

8
  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

9
 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 DEPARTMENT OF PAEDIATRICS,
b
(Name and Designation)
ADICHUNCHANAGIRI INSTITUTE OF
MEDICAL SCIENCES, B.G. NAGARA,
MANDYA DISTRICT -571448

Dr. VENKATAMURTHY M. M.B.B.S., M.D.

Co-investigator
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

10
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.

11
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

12
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

13
 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

14
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.

15
 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:

16
 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

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 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

18
 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 _____________________
Date ______________
Name _____________________
Date ______________
Name _____________________
Date ______________
Signature of the parent_____________
Time ____________
Signature of the impartial witness _________
Time ____________
Signature of the Investigator _____________
Time ____________

19