Autism Spectrum Disorder and infant vaccines

Retrospective study of VAERS adverse events

Co-author: Dr. Jessica Rose , see: https://substack.com/@jessicar

Introduction

In a small case series in 1998, Wakefield et al. published a study in the Lancet that indicated a possible association of ASD with the triple MMR vaccination. This article was retracted in 2010.¹  Note that Thimerosal is not found in the MMR vaccine. In a retrospective study in Denmark, 263 of 440,655 vaccinated children (normalized frequency = 59.7)[1] developed ASD while 53 of 96,658 unvaccinated children (normalized frequency = 54.8) developed ASD.² A time trend analysis observed increasing risks of ASD from 1988 to 1993 while the MMR vaccination rate remained consistent at over 95% for United Kingdom boys aged 2 to 5.³ A similar retrospective time trend analysis from California also showed increasing rates of ASD that were not associated with MMR vaccination.⁴ Based on multiple studies including,^2–5 the current medical community consensus does not associate ASD onset with MMR immunization. In addition to exposure-associated AEs, individual genetics plays a role in ASD. A large number of genetic variants (copy number variations, duplications, deletions, translocations, inversions, and mutations) are associated with ASD^6–9 including mutations in the genes chromodomain helicase DNA binding protein 8 (CHD8),¹⁰ neuronal voltage-gated sodium channel, type 2, alpha Na_V1.2 (SCN2A),^11,12 katanin catalytic subunit A1 like 2 (KATNAL2)¹³ and other genes.

3.4. Autism spectrum disorder (ASD) AEs

The pattern of AEs for ASD is low from 1990 until 1997, increases from 1999 until 2010 and subsequently decreases after 2010 for multiple vaccines (Table S4). In the case of MMR, peaks in 2000 to 2003, 2007 and 2009 are observed. Altered reporting bias likely occurred after the 1998 Wakefield et al. Lancet article that associated ASD with MMR vaccination was published and since this article was retracted in 2010,¹ the reporting bias appears to be altered again (Table S4). Twenty-five individual vaccines have enriched normalized frequencies for ASD compared to Influenza (Figure 4) for ASD AEs reported from 2011 to 2023; 12 of these 25 normalized frequencies are greater than 10-fold higher than that of Influenza (Figure 4). An estimate of ASD onset is 559.4 per 100,000 per year¹⁴; this yields an estimate of b^ASD = 559.4 per year/(365 days/year) = 1.53 which is 6 times lower than the normalized frequency for Influenza (adjusting P for children with no Influenza symptoms – 18.5/2 vs. 1.53). Summing the normalized ASD frequencies for the seven recommended vaccines for infants aged 0 and 1 (Table 1) yields 15,368 for two years; adjusting population size (P) for children with no symptoms yields a population frequency estimate (e.g., P=250,000 reduces estimate to 6,147/2 years or 3,073/year = 1 in 32 children/year) that aligns with current reports of 1 in 36.¹⁵

(again) The annual population frequency for ASD is consistent with the sum of the normalized frequencies for recommended infant vaccines.

---

[1] Normalized frequency was calculated by dividing the total number of AEs by the number of vaccinated individuals and multiplying by 100,000 to obtain the rate of AE occurrence per 100,000 people vaccinated.

Figure 4. Autism Spectrum Disorder day 0 onset; VAERS data from 2011 to November 3, 2023 and 1990 to November 3, 2023. VAERS vaccine names: DTAP: Diphtheria and Tetanus toxoids and acellular Pertussis, DTP: Diphtheria and Tetanus toxoids and Pertussis, HEPB: Hepatitis B, HIB: Haemophilus B conjugate, IPV: Poliovirus, inactivated, and Pneumo: Pneumococcal.

Note that there is a differnece in Figure 4 for vaccines: Polio virus, MMR, and HIB. The yearly details for these three vaccines follow in Figure 5. Look at the differences between different vaccines in Figure 5.

Figure 5. Autism Spectrum Disorder (ASD) yearly normalized frequencies for (A) Polio virus, inactivated; (B) Measles, Mumps, and Rubella (MMR); and, (C) Haemophilus B conjugate vaccine (HIB).  VAERS data from 1990 to November 3, 2023.

Each bar in Figure 5 represents a different year. Major changes in formulations (or reduction of manufacturing contaminants, etc.) will show up as larger differences in the height of the bars.

Observations

While excipients may vary between different individual vaccines for the same target pathogens, and can be modified over time, the results (Figure 5) might also be consistent with possible manufacturing contaminant(s) [e.g., endotoxins¹⁶] (with possible overlaps between unrelated vaccines) associated with AEs. See Substack posts by Dr.GeoffPain (https://substack.com/@geoffpain) on endotoxins in vaccines.

Working Hypothesis: ASD associated with infant vaccines may be direct results of one or more manufacturing contaminants (e.g., endotoxins)!

Suggestion: Rather than attacking messengers, perhaps a better strategy should be examining the data closely and examining potential causes of adverse events.

Note: ASD also occurs independently of vaccine adverse events. This retrospective study only examines VAERS adverse event reports and normalizes them per 100,000 VAERS reports for each vaccine.

References

1.            Laura Eggertson. Lancet retracts 12-year-old article linking autism to MMR vaccines. CMAJ. 2010;182(4):E199. doi:10.1503/cmaj.109-3179

2.            Madsen KM, Hviid A, Vestergaard M, et al. A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism. N Engl J Med. 2002;347(19):1477-1482. doi:10.1056/NEJMoa021134

3.            James A Kaye, Maria del Mar Melero-Montes, Hershel Jick. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ. 2001;322(7284):460. doi:10.1136/bmj.322.7284.460

4.            Dales L, Hammer SJ, Smith NJ. Time Trends in Autism and in MMR Immunization Coverage in California. JAMA. 2001;285(9):1183-1185. doi:10.1001/jama.285.9.1183

5.            Hviid A, Hansen JV, Frisch M, Melbye M. Measles, Mumps, Rubella Vaccination and Autism. Ann Intern Med. 2019;170(8):513-520. doi:10.7326/M18-2101

6.            De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014;515(7526):209-215. doi:10.1038/nature13772

7.            Fernandez BA, Scherer SW. Syndromic autism spectrum disorders: moving from a clinically defined to a molecularly defined approach. Dialogues Clin Neurosci. 2017;19(4):353-371. doi:10.31887/DCNS.2017.19.4/sscherer

8.            Turner TN, Hormozdiari F, Duyzend MH, et al. Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA. Am J Hum Genet. 2016;98(1):58-74. doi:10.1016/j.ajhg.2015.11.023

9.            Zhou X, Feliciano P, Shu C, et al. Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. Nat Genet. 2022;54(9):1305-1319. doi:10.1038/s41588-022-01148-2

10.         Bernier R, Golzio C, Xiong B, et al. Disruptive CHD8 Mutations Define a Subtype of Autism Early in Development. Cell. 2014;158(2):263-276. doi:10.1016/j.cell.2014.06.017

11.         Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485(7397):237-241. doi:10.1038/nature10945

12.         Ben-Shalom R, Keeshen CM, Berrios KN, An JY, Sanders SJ, Bender KJ. Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures. Biol Psychiatry. 2017;82(3):224-232. doi:10.1016/j.biopsych.2017.01.009

13.         Neale BM, Kou Y, Liu L, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012;485(7397):242-245. doi:10.1038/nature11011

14.         Roman-Urrestarazu A, Yang JC, van Kessel R, et al. Autism incidence and spatial analysis in more than 7 million pupils in English schools: a retrospective, longitudinal, school registry study. Lancet Child & Adolesc Health. 2022;6(12):857-868. doi:10.1016/S2352-4642(22)00247-4

15.         NIMH. Autism Spectrum Disorder (ASD). Published 2024. Accessed January 12, 2024. https://www.nimh.nih.gov/health/statistics/autism-spectrum-disorder-asd

16.         Geier M R, Stanbro H, Merril C R. Endotoxins in commercial vaccines. Applied and Environmental Microbiology. 1978;36(3):445-449. doi:10.1128/aem.36.3.445-449.1978

Note: this is a free substack.