BIRTH WEIGHT: ETHNIC DIFFERENCES AND HEALTH OUTCOMES IN CHILDHOOD JEANNETTE LEE MBBS, BMed Sci, FRACGP A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF MEDICINE DEPARTMENT OF COMMUNITY, OCCUPATIONAL AND FAMILY MEDICINE, YONG LOO LIN SCHOOL OF MEDICINE NATIONAL UNIVERSITY OF SINGAPORE 2005 ACKNOWLEDGEMENTS My deepest appreciation to my supervisor, Professor David Koh who provided ongoing encouragement, support and advice for this thesis His motivation and support has not only encouraged me to complete this thesis but to venture into the world of academia I am also grateful for the support of Associate Professors Chia Kee Seng and Chew Suok Kai and Drs Derrick Heng and Stefan Ma for their collaboration in this research project Many thanks also to the Singapore National Registry of Births and Deaths, the Central Claims Processing System and the Singapore Cancer Registry This thesis would certainly not exist without their kind assistance and permission to use the data Also many thanks to Mr Cheung Kwok Hang, who so very kindly and patiently assisted in the preparation of the data, and Doris for your editing help My friends and colleagues of COFM, who have provided much support, encouragement and a wonderful work environment throughout the years My dear husband Kit Min for his loving, kind and steadfast support, and our children Shu-Wen and Wei-Sheng for being the mostly wonderful children they are My dear parents, brothers and sister for their never ending love and support My precious Lucky dog, who has always given me his unconditional love And finally to my daughter, Lauren Chye Shu-Lin, you are the one who inspired and spurred me to finish this thesis before your arrival into this world i TABLE OF CONTENTS ACKNOWLEDGEMENTS i TABLE OF CONTENTS ii SUMMARY x LIST OF TABLES xiii LIST OF FIGURES xv LIST OF APPENDICES xvi LIST OF MANUSCRIPTS, PUBLICATION AND PRESENTATIONS xvii CHAPTER INTRODUCTION AND GENERAL OBJECTIVE CHAPTER GENERAL BACKGROUND 2.1 FACTORS THAT AFFECT BIRTH WEIGHT 2.2 EPIDEMIOLOGICAL RESEARCH USING RECORD LINKAGE OF NATIONAL REGISTERS 2.2.1 Introduction 2.2.2 Advantages of register-based data 2.2.3 Limitations of register-based data 2.2.4 Summary ii 2.3 DATA LINKAGE IN SINGAPORE 2.3.1 Introduction 2.3.2 Birth certificate/National Registration Identity Card Number (NRIC) 2.3.3 National Registers 2.3.4 Linkage of national registers 13 2.3.5 Data privacy and confidentiality 13 CHAPTER ETHNIC DIFFERENCES IN BIRTH WEIGHT AND INFANT MORTALITY 14 3.1 BACKGROUND 14 3.1.1 Introduction 14 3.1.2 Asian Indians and low birth weight 14 3.1.3 Differences in infant mortality between ethnic groups and the “low birth weight paradox” 17 3.2 OBJECTIVES 19 3.3 METHODS 20 3.3.1 Data linkage 20 3.3.2 Cohort selection 20 3.3.3 Variables 20 iii 3.3.4 Outcome 21 3.3.5 Data analysis 21 3.4 RESULTS 23 3.4.1 Characteristics of the three ethnic groups 23 3.4.2 Variables associated with moderately low birth weight 26 3.4.3 Infant Mortality 29 3.5 DISCUSSION 33 3.5.1 Summary 33 3.5.2 Birth weight and infant mortality of the ethnic groups 33 3.5.3 “Fetal origins” hypothesis and further research 35 3.5.4 Strengths and limitations 36 CHAPTER EFFECT OF LOW BIRTH WEIGHT AND PREMATURITY ON SUBSEQUENT HOSPITAL ADMISSIONS IN CHILDREN 37 4.1 BACKGROUND 37 4.1.1 Introduction 37 4.1.2 Prospective short-term studies 37 4.1.3 Prospective long-term studies 38 4.2 OBJECTIVES 42 iv 4.3 METHODS 43 4.3.1 Data linkage 43 4.3.2 Cohort selection 43 4.3.3 Variables 43 4.3.4 Outcomes 44 4.3.5 Data analysis 45 4.4 RESULTS 46 4.4.1 Hospitalization by preterm status and birth weight groups 46 4.4.2 Factors associated with hospital admission 48 4.4.3 Common admissions 50 4.5 DISCUSSION 53 4.5.1 Summary 53 4.5.2 Comparison of incidence rate of preterm births 53 4.5.3 Hospital admissions 54 4.5.4 Further areas for research: Non-hospital associated morbidity and socio-economic and psychological impact 55 4.5.5 Possible preventive measures 56 4.5.6 Specific strengths and limitations 56 v CHAPTER THE EFFECT OF BIRTH, MATERNAL FACTORS AND PRIOR HOSPITAL ADMISSIONS FOR RESPIRATORY TRACT INFECTIONS ON INCIDENT ASTHMA ADMISSION 58 5.1 BACKGROUND 58 5.1.1 Introduction 58 5.1.2 Birth weight and gestational age and risk of asthma 58 5.1.3 Infectious diseases and risk of asthma 62 5.1.4 Other risk factors for asthma that can be studied using data from the registries in Singapore 64 5.2 OBJECTIVES 66 5.3 METHODS 67 5.3.1 Data linkage 67 5.3.2 Cohort selection 67 5.3.3 Variables 68 5.3.4 Outcome 68 5.3.5 Data analysis 69 5.4 RESULTS 70 5.4.1 Asthma admissions 70 vi 5.4.2 Univariate analysis of variables 70 5.4.3 Multivariate analysis of variables 71 5.5 DISCUSSION 74 5.5.1 Summary 74 5.5.2 Birth weight was not associated with IAA but gestational age is 74 5.5.3 Other factors associated with IAA 74 5.5.4 Areas for further research 76 5.5.5 Specific strengths and limitations 77 CHAPTER BIRTH WEIGHT AND THE RISK OF EARLY CHILDHOOD CANCER 79 6.1 BACKGROUND 79 6.1.1 Introduction 79 6.1.2 Birth weight and all cancers combined 79 6.1.3 Birth weight and leukaemia 80 6.1.4 Birth weight and other childhood cancers 80 6.1.5 Biological relationship between birth weight and childhood cancer 83 6.1.6 Studies of birth weight and childhood cancer in Asian populations 84 6.2 OBJECTIVE 85 vii 6.3 METHODS 85 6.3.1 Data linkage 85 6.3.2 Cohort selection 85 6.3.3 Variables 85 6.3.4 Outcomes 86 6.3.5 Data analysis 86 6.4 RESULTS 87 6.4.1 Childhood cancer in Chinese, Malays and Asian Indians 87 6.4.2 Types of childhood cancer 90 6.4.3 Factors associated with childhood cancer in Chinese children 91 6.4.4 Birth weight and specific cancers for Chinese children 93 6.5 DISCUSSION 96 6.5.1 Summary 96 6.5.2 Higher birth weight and risk of childhood cancer 96 6.5.3 Higher birth weight and risk of childhood leukaemia 96 6.5.4 Birth weight and the risk of other childhood cancers 98 6.5.5 Further research 98 viii 6.5.6 Specific strengths and limitations 99 CHAPTER CONCLUSION 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available in the Singapore National Registry of Births and Deaths (i) For Births Field Name Description Format idno dob sex brthtype prst bw brthorde brthpl hrbrth gestatn system id number Date of birth Gender Birth Type PR Status Birth Weight Birth Order Birth Place Birth Hour Gestation System id Number of mother Mother Date of Birth Mother Date of Birth Mother Race Mother Education Mother Occupation System id Number of father Father Date of Birth Father Date of Birth Father Race Father Education Father Occupation Numeric Date Character Character Character Character Character Character Character Character m_idno m_dob m_dob_d m_race m_edn m_occup f_idno f_dob f_dob_d f_race f_edn f_occup Numeric Character Date Character Character Character Character Character Date Character Character Character 135 (ii) For Deaths Field Name Description idno sex dob ethnic bplace occup dth_date dth_pl dth_addr dth_caus cod certifier dialect citz sex_c race citz_c bplace_c Format System id Gender Date of Birth Ethnic Group Place of Birth Occupation Death Date Death Place Death Address Cause of Death Numeric Character Character Character Character Character Character Character Character Character Character Certifier Character Dialect Group Character Citizenship Character Cancer Indicator Character Cancer Registration Indicator Character Citizenship in Code Character Birth Place in Code Character 136 Appendix Variables available in the Singapore Cancer Register Field Name Type length Description idno acc_no addr_1 addr_2 d_o_b sex mstatus race citz bplace reside arr_yrs occup hospital surgeon prisite ageatdx dxdate dursym histol stage lymph remote status_not source_not necrop_no biopsy_no biopsy_lb dth_date dth_code dth_cause dth_source survival multiple dxbasis 21 15 1 1 20 1 1 10 28 28 1 1 Numeric Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character Character System ID Number System Generated account number Address line Address line Date of Birth Gender Marital Status Race Citizenship Place of Birth Country of Residence Year of Arrival Occupation Hospital Surgeon primary site age at dianosis Date of Diagnosis Duration of Symptoms Histological Diagnosis Stage of Disease Lymph Node Involvement Remote Metastases Status Notification Source Notification Necropsy Number Biopsy Number Biopsy Lab Date of Death Death Code Cause of Death Source of Death Date of Diagnosis to Date of Death Mulitiple Site Indicator Basis of Diagnosis 137 ... interesting to see if ethnic differences still remain in the current setting of a developed nation 15 Table 3.1 Studies of ethnic differences in birth weight between Asian Indians and other ethnic. .. Indians and Caucasians in Norway for perinatal mortality It would be interesting to determine if both currently exist in Singapore 3.1.2 Asian Indians and low birth weight Compared to other ethnic. .. Indians still have the lowest birth weight babies in a developed nation such as Singapore To determine if the “low birth weight paradox” exists for birth weight and infant mortality in the Singaporean