MMR & Autism - Madgen et al, NEJM 2002

MMR & Autism - Madgen et al, NEJM 2002

1. Research Question: MMR cause autism?

2. Funded: Danish Research Foundation, CDC, National Alliance for Autism Research

3. Year Study Began: Retrospective, 1991-1999

4. Published: 2002 NEJM

5. Study Location: Denmark

6. Who was studied? All children born in Denmark Jan 1991-Dec 1998

7. Who was excluded? Conditions associated with Autism: Tuberous sclerosis, Angelman syndrome, Fragile X, Congenital Rubella +emigration+death

8. How many patients? 537,303 (82% received MMR, and 18% didn't)

9. Outcome measured: which children received MMR, at what age vaccine administered

10. Denmark Vaccination Schedule MMR: 15 months, 12 years (booster)

11. Australia: 12 months MMR, 18 months MMRV (varicella)

12. Identification of Autism: Suspected --> child psychiatrist --> registry, Method: check registry, date when diagnosis made

13. Follow-up: monitored for autism to age 1 until end of study period (Dec 31, 1999, mean age at end of study 5 years)

14. End point: rates of autism and rates of autism-spectrum disorders

15. Results

    • 82% of chidlren in study received MMR vaccine
    • mean age of vaccination 17 months
    • mean age of diagnosis was 4 years and 3 months
    • prevalence of Autism among 8 year old's in study was 7.7/10,000 (0.08%)
    • no clustering of autism diagnosis at any time interval after vaccination
    • No association between age at which vaccine given and the subsequent development of autism

16. Limitations

    • Families with hx of Autism would not have vaccinated their kids due to published link between MMR and Autism
    • Dataset did not contain the date when the 1st symptoms were noted, it is possible clustering of first symptoms post vaccination but NOT diagnoses (due to delay)

17. Controversy

    • Autism signs and symptoms: 2nd and 3rd year of life, shortly after giving MMR vaccine
    • Wakefield et al, Lancet 1998, retracted 2010, stated series of children developed GI symptoms, and signs of Autism after MMR, FALSIFIED DATA
    • AAP undertook a systematic review of all research vaccine safety and review failed to link MMR to Autism (MAGLIONE et al, Paediatrics, 2014)