Photography, rowing and the pursuit of data.....and Renee  

HEALTH CARE 

For anyone who is interested in the storm in a teacup associated with  Autism. Without understanding the medicine but just looking at statistics, this lay persons assessment is that their data shows around a 19% increase in Autism Syndrome Diagnosis (ASD) with Tylenol use. There was 17-46% increase in Autism Syndrome Diagnosis (ASD) for circumcised boys. These effects were similar or weaker than the effect of low birth weight, premature birth, low Apgar score (baby health after 5 mins) , C section, congenital malformations, old and very young mothers, or smokers. In particular, the authors conclusion that a 2x increase in early onset ASD is correlated with  circumcision is probably an artifact of a very small number of cases < 10 in a population of over 300,000, and the difference in response of Muslim and non-Muslim families to ASD symptoms.  ASD case rates in the USA were 3x higher than in Europe,  similar to the much poorer infant and maternal mortality in USA compared to Europe. ​

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The more interesting observation was the for boys in Denmark,  the ASD case rate was 0.9% for children, 1.5% for boys 0-9 and  0.3% for girls. ​For the US,  the case rate was 3x higher at  3.2% for children according to estimates from CDC's AD.

Autism and Tylenol 

The study of studies that started the RFK furor. 

Prada et al, "Evaluation of the evidence of acetominophen use and neurodevelopmental disorders"  They conclude   "evidence consistent with an association between exposure to acetomenophen during pregnancy and offspring with NDD's including ASD and ADHD, although observational limitations preclude definitive causation."

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They looked at 8 studies looking at ASD. The largest study showed a HR = 1.05 compromised by  limited drug information. The next largest based on Denmark National Registry had an HR = 1.19 in the middle of the range of the other studies. This is very similar to  the study on circumcision discussed below using the same data base.  The same  confounding variables of low birth weight etc. apply. 

Autism and circumcision 

The 2015  paper by Frisch and Simonsen https://journals.sagepub.com/doi/full/10.1177/0141076814565942

with critique by Morris and Wiswell https://journals.sagepub.com/doi/full/10.1177/0141076815590404

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The Frisch and Simonsen paper is an analysis of a data set from Denmark National Registry 1994-2003, looking for a connection between circumcision and autism. In a total of 342,877 boys, there were 4986 cases of ASD for a case rate of 1.5% for boys 0-9. The rate for girls was 0.3%.   

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For the US, about 3.2% children aged 8 years have been identified with ASD according to estimates from CDC's ADDM.  Network. 

https://www.cdc.gov/autism/data-research/index.html

​Circumcision is rare in Demark, only 1% of the boys in the study which limits the number of ASD cases. In the general population, Denmark has a circumcision rate of 5%, US a rate of 55%. Predominantly Muslim countries have rates as high as 99%. If circumcision was an important factor there would be huge country to country variation. There is no evidence of tracking, but ASD diagnosis is not standardized. Japan has the highest diagnosis rate and a 9% circumcision rate. 

https://worldpopulationreview.com/country-rankings/autism-rates-by-country

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In the  Frisch and Simonsen paper;

                                      ASD/Population       Hazard Ratio  

Intact                            4929/339,530                  1.0

Circumcised                    57/3347                        1.17

               muslim boys    50/2903                        1.19

               non muslim       7/444                           1.09

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In spite of the large analysis population of over 300,000 boys, there were only 57 Cases in the test population, less than the benchmark of at least 100 that is used to validate a vaccine based on Moderna press releases. The much smaller subset of circumcised boys in  non-Muslim families had a lower raw HR.  Of the possible confounding variables, similar or greater Hazard ratios were found for; low birth weight, premature, low Apgar score, C section, congenital malformations, old and very young mothers, smokers. 

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The authors used a multivariate Cox exponential analysis to adjust for these confounding variables, details were not provided. 

For circumcised boys the adjusted HR was more than doubled to HR = 1.46 and became statistically significant at 95% confidence. The higher HR is entirely dependent on the robustness of the multivariate analysis, no details were provided to allow independent assessment. 

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The authors emphasized that for early onset (diagnosed early)  ASD (< 4 years old), the adjusted Hazard Ratio for circumcised was much higher at HR= 1.8. They failed to note that for the majority who were Muslim boys, it was much lower with an adjusted HR = 1.54. The effect of onset time was almost entirely due to the small non-Muslim group that  contributed  7 ASD cases at a adjusted HR = 4.23. In contrast there  was only 1 ASD case in circumcised boys in  non -Muslim families diagnosed after 4 years.  These very small case numbers limit any conclusions. There is also no obvious medical reason to distinguish Muslim and non-Muslim populations, but a high probability of cultural differences in seeking diagnosis. In reality the data does not support any elevated risk of early onset ASD.  

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The authors conclusion that a 2x increase in early onset ASD is correlated with  circumcision is an probably an artifact of a very small number of cases < 10 in a population of over 300,000, and the difference in response of Muslim and non-Muslim families to ASD symptoms.

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​Folic Acid 

Double blind studies on maternal supplements has produced inconsistent results, some with concerning negative effects.

However, in a recent randomized controlled single-blind study of 67 children and adults with ASDs from Arizona vs. 50 non-sibling neurotypical controls of similar age and gender, it was confirmed a significant improvement in nonverbal intellectual ability in the treatment group (~600 μg FA) compared to the non-treatment group by using different tests, such as IQ (+6.7 ± 11 IQ points vs. −0.6 ± 11 IQ points, p = 0.009) and non-verbal intelligence index (+10% in treatment group vs.−1%, p value 0.01) based on a blinded clinical assessment. There is also a mechanistic rationale support for the role of folic acid. 

https://pmc.ncbi.nlm.nih.gov/articles/PMC8394938/​

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This seems to validate a number of strong anecdotal reports of remarkable improvements in some children with ASD after supplement.

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