2010年至2025年疫苗、硫柳汞和自闭症谱系障碍

Evidence review 2010 to 2025 Vaccines, thimerosal and autism spectrum disorder Evidence review 2010 to 2025 CONTENTS Acknowledgements EXECUTIVE SUMMARY BACKGROUNDOBJECTIVESSUMMARY OFMETHODS 16 OVERVIEW OF FINDINGS TOPIC 1: ASSOCIATION BETWEEN THIOMERSAL AND ASD REVIEWING THE EVIDENCE FOR AND AGAINST AN ASSOCIATION BETWEEN THIOMERSAL ANDASD17ASSESSMENT OF PRENATAL AND NEONATAL THIOMERSAL EXPOSURE ANDASDORNDD(N=2)17ASSESSMENT OF CHILDHOOD THIOMERSAL EXPOSURE ANDASDORNDD(N=5)18 TOPIC1CONCLUSION TOPIC 2: VACCINES AND AUTISM EVIDENCE REJECTING AN ASSOCIATION BETWEEN VACCINES(AND VACCINE-RELATED INTERVENTIONS) ASD PRENATALVACCINATIONS ANDASDORNDDIN CHILDREN(N=5)23CHILDHOOD VACCINATION ANDASD(N=5)23REPEATED VACCINE EXPOSURE,ANTIGEN EXPOSURE,ANTIBODY RESPONSE ANDASDIN CHILDREN(N=3)25 DISCUSSION REFERENCES APPENDICES: STUDY SUMMARIES TOPIC1:THIOMERSAL ANDASD APPENDIX1.1:ASSESSMENT OF PRENATAL THIOMERSAL EXPOSURE ANDASDORNDD(TABLE1)36APPENDIX1.2:ASSESSMENT OF CHILDHOOD THIOMERSAL EXPOSURE ANDASD/NDD(TABLE2)37APPENDIX1.3:REPORTED ASSOCIATION BETWEEN THIOMERSAL ANDASD/NDDS(TABLE3)40 TOPIC2:VACCINES ANDASD APPENDIX2.1:PRENATALVACCINATIONS ANDASDORNDDIN CHILDREN(TABLE5)46APPENDIX2.2:CHILDHOOD VACCINATION ANDASD(TABLE6)49APPENDIX2.3:REPEATED VACCINE EXPOSURE,ANTIGEN EXPOSURE,ANTIBODY RESPONSE ANDASD Acknowledement This report is the result of a review carried out by Daniels BA, Davis R, Ring E (Davis Pier Consulting) andDeeks S (Dalhousie University) on behalf of the Pharmacovigilance (PVG) Team, Department ofRegulation and Prequalification (RPQ), World Health Organization (WHO). The review was guided by thePVG Team: Shanthi Pal and Xinyu Weng shaped the research questions and coordinated the reviewprocess; Madhav Ram Balakrishnan, EunMi Kim, Smaragda Lamprianou, Sujeet Jain provided technical Acronyms ASD:Autism Spectrum DisorderNDD / NDDs:Neurodevelopmental Disorder(s)SoE:Strength of EvidenceRoB:Risk of BiasWHO:World Health OrganizationPRISMA:Preferred Reporting Items for Systematic Reviews and Meta-AnalysesPHAC:Public Health Agency of CanadaAEFI:Adverse Events Following ImmunizationADHD:Attention-Deficit/Hyperactivity DisorderSSRIs:Selective Serotonin Reuptake InhibitorsBCG:Bacille Calmette–Guérin vaccineDTaP:Diphtheria, Tetanus, acellular Pertussis vaccine VAR:Varicella vaccineOR:Odds Ratio Executive Summary Background Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental conditions characterized by varyingdegrees of difficulty with social interaction and communication, with onset typically occurring in early Concerns about a potential link between vaccines and ASD gained significant attention in the late 1990s,following the publication of a fraudulent study that proposed connections between natural or vaccine-derivedmeasles virus, inflammatory bowel disease, and ASD—particularly in relation to the measles–mumps–rubella(MMR) vaccine (Wakefield et al., 1998; see retraction notice, Editors of the Lancet, 2010). Additionally, vaccines Concerns about thiomersal-containing vaccines and MMR vaccines (which do not contain a preservative) havepersisted over time, despite no strong evidence to support a causal relationship. The Global Advisory Committee on Vaccine Safety has reviewed the evidence regarding a potential linkbetween vaccines and autism multiple times between 2002 and 2012, consistently concluding that theevidence does not support a causal relationship. This updated review was commissioned by the World Health Objectives To complete a systematic review that answers the following research questions. based on literature that has What is the relationship between thiomersal-containing vaccines, and ASD?More broadly, what is the relationship between vaccines and ASD? As a secondary objective, we explored the relationship between vaccines and broader NDDs by including andanalyzing studies returned by the search strategy that specified NDD outcomes (regardless if ASD was also Summary of Methods Briefly, systematic searches for scientific literature were conducted in PubMed, Ovid, MEDLINE, Embase, andPsychINFO during the month of August 2025, with search dates from 2010 to August 2025. Eligible studies werehuman studies that assessed any vaccine exposure and/or specific exposure to thiomersal, with outcomesrelated to ASD or NDDs. All studies were peer-reviewed; pre-prints were excluded. Data extraction was screened for validity by the senior review author. A qualitative assessment of the Strength of Evidence (SoE)and Risk of Bias (RoB) was performed by at least two reviewers for each article and if there was no consensus,the more conservative value was used. Studies were grouped by the two research questions, and sub-groupedbased on key themes (Ahmed et al., 2025) including study population (e.g., prenatal, childhood), and the Summary of Findings The search strategy yielded a total of 36 research articles, 31 primary research studies and 5 meta-analyses. Ofthose