Maternal opioid use during breastfeeding and the risk of adverse infant outcomes : a nationwide cohort study

목차 (Table of Contents)

• Chapter I. Introduction 10
• 1. Overview 10
• 2. Breastfeeding (Lactation) 12
• A. Importance of breastfeeding 12
• B. Medication use during breastfeeding 14
• 3. Opioid treatment 16
• A. Global and local concerns regarding opioid crisis 16
• B. Maternal opioid treatment after delivery 18
• C. Concerns regarding Maternal opioid treatment after delivery 19
• D. Information regarding opioid during breastfeeding 20
• 4. Study Objectives 22
• Chapter II. Literature Review 23
• 1. Case reports and case series 23
• A. Early case reports and case series including "Toronto Case" 23
• B. Rebuttal of the Toronto case 28
• 2. Observational Studies on maternal opioid use during breastfeeding 30
• 3. Remaining Evidence Gaps and Statement of Originality 33
• Chapter III. Methods 35
• 1. Data Source 35
• 2. Study Design 39
• 3. Study Population 42
• 4. Exposure Definition 45
• 5. Study Outcomes and Follow-Up 48
• A. Primary and Secondary Outcomes 48
• B. Definition of Follow Period 49
• 6. Potential Confounders 50
• 7. Propensity Score Methods 55
• 8. Statistical Analyses 58
• 9. Subgroup and Stratified Analyses 60
• 10. Sensitivity Analyses 63
• 11. Sample Size Calculation 65
• 12. Supplementary Analysis with Re-definition of Exposure of Interest 66
• 13. Ethic approval 68
• Chapter IV. Results 69
• 1. Identification of Study Cohort 69
• 2. Prevalence of opioid prescription 72
• 3. Baseline Characteristics of Study Cohort 73
• 4. Main Analyses 82
• A. Incidence and Hazard of primary outcome 82
• B. Incidence and Hazard of secondary outcome 84
• 5. Subgroup Analyses 86
• A. Stratified by Characteristics of Maternal Opioid Prescriptions 86
• B. Stratified by Characteristics of Neonates 87
• C. Stratified by Opioid Classes 91
• D. Stratified results of secondary outcomes 94
• 6. Sensitivity Analysis 97
• A. Restriction to Fully Breastfed Neonates 97
• B. Modifying the Follow-up Periods 98
• C. Alternative Propensity Score Weighting Approaches 99
• D. Re-definition of Primary Outcome Only to Inpatient Setting 100
• 7. E-value calculation 105
• 8. Supplementary analysis 107
• Chapter V. Discussion 109
• 1. Main Findings 109
• 2. Interpretation and Implications 111
• A. Implications with the Results of Neonatal Death 111
• B. Implications with the Results of Emergency Department Visit 112
• C. Pharmacokinetics of different opioid classes 114
• D. Discussion of Subgroup Analyses 115
• 3. Significance of the Study 117
• 4. Strengths and Limitations 119
• A. Strengths 119
• B. Limitations 119
• Chapter VI. Conclusion 121
• List of Abbreviations 122