Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka s42

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA

Synopsis of Dissertation

ONE YEAR NEURODEVELOPMENTAL FOLLOW UP STUDY OF BABIES BORN TO MOTHERS HAVING PREGNANCY INDUCED HYPERTENSION

Submitted by: Dr. Debashish Roy, MBBS Post Graduate Student in Paediatrics

Department of Paediatrics Adichunchanagiri Institute of Medical Sciences, B.G. Nagar, Nagamangala Taluk, Mandya District -571 448 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.DEBASHISH ROY (IN BLOCK LETTERS) P.G.IN PAEDEDIATRICS DEPERTMENT OF PAEDIATRICS A.I.M.S., B.G.NAGARA, MANDYA (DIST.) -571 448.

2. NAME OF THE INSTITUTION ADICHUNCHANAGIRI INSTITUTE OF

MADICAL SCIENCES, B.G.NAGARA. 3. COURSE OF STUDY AND SUBJECT M.D. IN PAEDIATRICS

4. DATE OF ADDMISSION TO COURSE 31ST MAY 2007

5. TITLE OF THE DISSERTATION “ONE YEAR NEURODEVELOPMENTAL FOLLOW-UP STUDY OF BABIES BORN TO MOTHERS HAVING PREGNANCY INDUCED HYPERTENSION’’ 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. MATARIALS AND METHODS APPENDIX-II

7.1 SOURCE OF DATA APPENDIX-IIA

7.2 METHOD OF COLLECTION OF DATA : APPENDIX-IIB (INCLUDING SAMPLING PROCEDURE IF ANY)

7.3 DOES THE STUDY REQUIRED ANY INVESTIGATION OR INTERVENTIONS TO NO BE CONDUCTED ON PATIENTS OR OTHER APPENDIX-IIC ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY.

7.4 HAS ETHICAL CLEARENCE BEEN NA OBTAINED FROM YOUR INSTITUTION IN APPENDIX-IID CASE OF 7.3

8. LIST OF REFERENCES APPENDEX-III

9. SIGNATURE OF THE CANDIDATE

10. REMARKS OF THE GUIDE NAME AND DESIGNATION OF (IN BLOCK Dr. VENKATAMURTHY. M, (MBBS, MD) 11. LETTERS)-11.1 GUIDE PROFESSOR AND H.O.D. Dept .OF PEADIATRICS, AIMS. B.G.NAGARA.

11.2 SIGNATURE

11.3 CO-GUIDE (IF ANY) NO

11.4 SIGNATURE

Dr. VENKATAMURTHY M.,(MBBS, MD ) PROFESSOR AND H.O.D. 11.5 HEAD OF THE DEPARTMENT Dept OF PEADIATRICS, AIMS. B.G.NAGARA.

11.6 SIGNATURE

12. 12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL

12.2 SIGNATURE

APPENDIX-I 6. BRIEF RESUME OF THE INTENDED WORK:

APPENDIX-IA

6.1 NEED FOR THE STUDY

Hypertension is one of the most common medical complications of pregnancy. Pregnancy induced hypertension complicate 12-22% pregnancy. Hypertensive disorders of pregnancy are responsible for significant maternal and prenatal morbidity and mortality. Hypertensive disorders of pregnancy predispose women to acute or chronic uteroplacental insufficiency resulting in ante- or intrapartum anoxia that may leads to fetal death, intrauterine growth retardation and/or preterm delivery.

Prematurity is the most important factor responsible for increased perinatal morbidity and mortality.

Neonatal complications occurring in babies of pre-eclamptic mother closely relate to the severity of hypertension and proteinuria.

Babies born to hypertensive mothers are susceptible to illness (morbidity) or death (mortality), because of immaturity, dysmaturity, physical disorders or complications during or after birth.

Advances in neonatology have contributed to improved survival of high risk neonates. Hence motor and mental developments of these high risk neonates need to be closely monitored.

The spectrum of neurological problems in high risk neonates include: Cerebral palsy, seizure, hydrocephalus, microcephaly, visual handicaps, deafness, mental retardation, fine motor coordination difficulties, learning and language disabilities and behavior problems.

Developmental assessment provides vital information to the pediatrician. After a full developmental examination, he is able to make an early diagnosis of the defects of vision, hearing or other mental and physical handicaps which are treatable and for which early diagnosis is very important.

A large number of children are born each year with biological, socioeconomic or environmental factors that contribute to an increased risk of developmental disability. In most cases, however, resources for early intervention are limited and may be reserved for children with identified developmental delay. In that case, a system that would track the child and monitor his or her development would be a fairly efficient method for identification of developmental delay early and thereby allowing for timely referral for evaluation, or for early interventional programs.

Nutritional anthropometry has been recommended for measurement of physical dimension and gross composition of human body at different age levels for proper assessment of growth status.

Thus early identification of neurodevelopmental disorders is important for the prevention or mitigation of disability, helping the affected children and their families in finding medical and appropriate services, and helping the child to make the most his potential.

The proposed study will be conducted at Sri Adichunchanagiri Institute of Medical Sciences and Research centre. Since this institution is the only rural-based healthcare providing facility in this region, this study may provide vital data for proper healthcare planning and implementation.

APPENDIX -IB 6.2 REVIEW OF LITERATURE:

Disorders characterized by hypertension complicate pregnancy are important cause of perinatal mortality and morbidity 2. Depending on the severity and duration of maternal hypertension or presence of preeclampsia, fetal loss is increased 5-20 times as compared to uncomplicated pregnancies. They are responsible for approximately 12% of all perinatal deaths as a consequence of preterm deliveries that they cause 2.

Tiedemann in Germany (1787) was the first one to publish a detailed record of the development of a child; but Charles Darwin in 1877 published a detailed account of development of one of his own 10 children.

In 1931 Shirley wrote on extremely full account of 25 children in their first two years.

In one study conducted by J. Nakarni, J. Bhal and P. Parekh showed that out of 5402 mother delivered, 450 had hypertension (7.49%) and among the hypertensive pregnancies 50.4% were preeclamptic and 10.6% were eclamptic. 51.7% babies were low birth weight, 44.3% were preterm, Intrauterine growth retarded babies were 21.3 %, birth asphyxia 14%, neonatal hyperbilirubinemia 6% and perinatal morbidity was 159/1000 birth4.

One study conducted by Han et al showed 437 survivors at preterm infancy. 4.8% of all survivors subsequently developed cerebral palsy. The prevalence of cerebral palsy was 12% among infants that weighed <2000gm at birth, but it was only 0.4% among those that weighed >2000gms7.

Another study by Mindy E Kronenberg, Sarah Raz Craig and J Sander found that SOIUG (Suboptimal Intrauterine Growth) was associated with a significant reduction in cognitive and motor skills (P<0.05), were linearly associated with the extent of intrauterine growth deficit when the latter was taken as continuous variable8. APPENDIX-IC

6.3 OBJECTIVES OF THE STUDY

 To assess the physical growth and neurological development in babies born to pregnancy induced hypertensive mothers.

 The help in early identification of developmental delays so as enable early intervention with physical, occupational and psychosocial rehabilitative services.

 APPENDIX-II 7. MATERIALS AND METHODS: APPENDIX-II A:

7.1 SOURCE OF DATA Data will be collected from the pregnant women complicated by hypertension who will be delivering in SAH&RC over a period from December 2007 to June 2008, and one year neurodevelopmental follow up study of these babies (from birth up to 1 year of age).

Inclusion criteria:  Babies born to pregnant women with diagnosed PIH (i.e. blood pressure more than or equal to 140/90 mm of Hg on two occasions at least 6 hours apart).

Exclusion criteria:  Babies born to mothers where pregnancy is complicated by any other risk factors for increased maternal and/or fetal morbidity and mortality such as:- 1. Rh incompatibility, 2. Diabetes mellitus, 3. Any other medical diseases such as heart disease, severe anemia, renal diseases and endocrinal disorders.

 Babies born with severe congenital anomalies. APPENDIX-II B

7.2 METHOD OF COLLECTION OF DATA  In this study the babies born to hypertensive mother above mentioned time will be taken for one year follow up (from birth up to one year of age).  The subjects for this study will be followed up at 1, 3, 6 and 12 months of age.  Neurological assessment will be done under 1) Neurodevelopmental assessment. 2) Neurosensory assessment.

 Neurodevelopmental assessment: Will be done at the time of each follow up by the following parameters: a) DAS II: Development assessment scales for Indian infants, Revised Baroda norms 1997, Based on Bayley’s scales of infant development (BSID). b) Vineland Social maturity scale (VSMS). c) Clinico-neurological examination.

 Neuro sensory examination: Will be done by clinical assessment of hearing and ophthalmologic examination at 6 and 12 months of age.

 APPENDIX-II C

7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CODUCTED ON PATIENTS OR OTHER ANIMALS; IF SO PLEASE DESCRIBE BRIEFLY.

NO. (This is not an interventional study. Routine and special investigations will be done as per regular treatment protocol, and not for the sake of the study. Conducting this study will not affect the management of the mothers and the babies.)

 APPENDIX-II D 7.4 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?

NOT APPLICABLE. LIST OF REFERE NCES

(1) Sanjivani Khanna: A new look at preeclampsia and eclamsia principles and practice of obstratrics and gynecology-for post graduates; 1st edition Komal Buckshee Vasant B Patwardhan. Rustom P. Soonawala, Jaypee Brothers Medical Publishers (P). Limited New Delhi; 1997-Pp 35-49. (2) Reports of WHO Study group: The hypertensive disorder of pregnancy. WHO TECH Rep. Ser .758, 1987- 758. (3) Chesley L C; Hypertensive disorder in pregnancy; inGleicher (Ed): principles of medical therapy in pregnancy, Newyork, plenum publishing crop.1985, pp, 751-775. (4) J.Nadkarni, J.Bhal, P.parekh; Prenatal out come in pregnancy Associated Hypertension, Indian Pediatrics 2001, 38,174-178. (5) Illingworth R.S, The development of the infant and young child: Normal and Abnormal, Edinburg, Churchill Livingstone, 1991, 1-16. (6) Udani P.M., Text Book of Pediatrics. Vol.1; 1998:126-163. (7) Han T.R.Bang MS, Lim JY, Yoon.BN, KimIO, Risk factor of cerebral palsy in preterm infants American Journal of physical Medicine and Rehabilitation.81 (4); 297-303; April (8) Mindy E.Kronenbarg, Sarah Raz and Cavig J Sandar; Neurodevelopmental out come in children born to mother with hypertension in pregnancy: the significance of suboptimal intrauterine growth (Available at www.journals.ovid.com/readarticle/126735368hpq/ Neuro677989224.pdf ; last accessed September 2007) (9) D.C.Dutta hypertension disorder in pregnancy .Text Book of obstetrics, 6th edition, Hiralal Konar; New central book agency (P) limited India, 2006, pp-221-242. (10)American college of obstetrician and Gynecologist: Diagnosis and management of preeclampsia and eclamsia: ACGO Practice Bulletin No.33. Oyster Gynecol 2002; 99: 159-167. (11) Meharban Singh, Care of the Newborn, New Delhi:Sagar publications; 6e:2004: pp 315-335 (12) Marilee C A; The Child with developmental disabilities, The High Risk Infants: Paed. Clin. North. Am.; 1993: 40:479-489

APPENDIX-IID PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL

SECTION A A. Title of the study “ONE YEAR NEURODEVELOPMENTAL FOLLOW UP STUDY OF BABIES BORN TO MOTHERS HAVING PREGNANCY INDUCED HYPERTENSION” B. Principal investigator DR. DEBASHISH ROY (Name and Designation) P.G IN PAEDIATRICS, AIMS, BG NAGARA C. Dr. VENKATAMURTHY.M (MBBS,MD) Co-investigator PROFESSOR AND H.O.D. (Name and Designation) Dept .OF PAEDIATRICS, AIMS. B.G.NAGARA

D. Name of the collaborator DEPT. OF OBSTETRICS AND GYNECOLOGY; A.I.M.S; B.G NAGARA. Department / institute

E. Whether permission has been obtained from the head of the collaborating YES department and institution SECTION-B APPENDIX-II Summary of the project SECTION-C APPENDIX-IC Objective of the study SECTION –D APPENDIX-IIB Methodology A. Where the proposed study will be SAH & RC, B.G.NAGARA. Undertaken B. Duration of the project 18 MONTHS

C. Nature of the subject :

Does the study involve adult patients? NO Does the study involve children? YES Does the study involve normal volunteers? NO Does the study involves psychiatric NO Patients? Does the study involve pregnant women? NO D. If the study involves healthy volunteers NA 1. Will they be institute students? NO 2. Will they be institute employees? NO 3. Will they be paid? NA 4. If they are to be paid, how much per person? NA

E. Is the study multi central trial? NO

F. If yes, who is the coordinator? (name and designation) NA

Has the trial been approved by the ethical NA committee of other centers?

If the study involves the usage of drugs: NA Please indicate whether,

1. the drug is marketed in India for the indication in which it will be used in the study.

2. the drug is marketed in India but not for the indication in which it will be used in the study.

3. the drug is only used for experimental use in humans.

4.clearance of the drug controller of India has been obtained for :

-Use of the drug in the healthy volunteers

-Use of drug in-patients for a new indication. -phase one and two clinical trials.

-experimental use in-patients and healthy volunteers.

G. How do you propose to obtain the drug to be used NA in the study? -Gift from a drug company -hospital supplies -patients will be asked to purchase -other sources (Explain) H. Funding (if any) for the project. Please state. NONE -None -Amount -Source -To whom payable I. Does any agency have a vested interest in NO The outcome of the project?

J. Will data relating to subjects/controls be NO Stored in a computer? K. Will the data analysis be done by

-The researcher? YES

-The funding agency NO

L. Will technical / nursing help be required YES for the staff of hospital, if yes,

Will it interfere with their duties? NO

Will you recruit other staff for the duration of the NO study? If yes give details of I Designation NA II Qualification NA III Number NA IV Duration of employment NA M. Will informed consent be taken? YES If yes, Will it be written informed consent? YES Will it be oral consent? NO Will it be taken from the subjects themselves? NO Will it be from the legal guardian? YES If no, give reason: NA N. Describe design, Methodology and APPENDIX-II Techniques

Ethical clearance has been accorded.

Date: 12.11.07 Place: B.G. NAGARA

Chairman PG Training-cum research committee A.I.M.S., B.G.Nagar

Abbreviations used: NA: Not Applicable PIH Pregnancy Induced Hypertension