Full article published in The Journal of Restorative Medicine Volume 2 Issue 1 October 2013, Dr. William Shaw 

One of the puzzling aspects of autism is the marked increase that began in the U.S. in the early 1980s and has increased continuously since. Increased autism due to more effective diagnosis was disproved in the study of Irva Hertz-Picciotto who showed that perhaps 12% of the increased autism diagnoses could be attributed to improved diagnosis. A wide range of environmental factors has been associated with increased autism incidence, including pesticides, chemicals, phthalates, polychlorinated biphenyls, solvents, heavy metals, or other pollutants. Although toxic chemicals are undoubtedly not beneficial for the health of any person, is there any information that indicates a toxic avalanche of chemicals inundated the U.S. in the early 1980s? Indeed a wealth of knowledge about environmental chemicals has led to marked reductions in exposure to chemicals such as lead and dichlorodiphenyltrichloroethane (DDT) in the U.S. over the past 50 years. For example, acceptable safe limits for levels of lead in the blood have decreased from 60 µg/dL in 1960 to <5 µg/dL in 2010. 

Making a connection between disease appearance and causative agent is important. Clinical studies, epidemiological studies, and post-market pharmacovigilence (Drug Safety) are of utmost importance in recognizing signals and drug-induced side effects. If there was a geographic region in the world in which the incidence of autism was much lower than that in the U.S., a comparison of medical or dietary differences might provide a significant clue to the major cause of autism. 

Such a country is Cuba. The population percentage with autism in the U.S. is 298 times higher than in Cuba. Cuba is much more economically challenged than the U.S., with the per capita income of Cuba approximately eight times lower than that in the U.S. Despite the economic challenges presented to the communist government of Cuba, basic healthcare is readily available and a large number of physicians are trained in 14 different medical schools. Unlike the U. S., where vaccines are optional in many states, vaccines are compulsory in Cuba, which has one of the most highly vaccinated populations in the world against a wide variety of infectious agents. For example, the vaccination rate for measles was reported to be 99.7%. 

However, a topic much less frequently addressed in association with autism is the therapies that are given in conjunction with vaccines. The practice of prescribing acetaminophen as a prophylactic fever preventative is widespread in the U.S. but very uncommon in Cuba. In the U.S., some physicians have started to advise parents to begin taking acetaminophen prophylactically daily five days prior to childhood vaccines; some children on such treatment had an autistic regression that began prior to vaccination. In Cuba, acetaminophen is not approved as an over-the-counter (OTC) product; however, it has been available as an OTC product since 1959 in the U.S. Furthermore, in Cuba, prophylactic use of antipyretic drugs is not the standard medical treatment for vaccine-related fever. If high fever continues after vaccination in Cuba for more than 2 days, the parents are advised to visit the physician's office where the drug metamizole is most commonly prescribed. Prescription of acetaminophen in such cases is rare. 

One study includes the survey results of parents who had given their child the combined measles, mumps, rubella (MMR) vaccine, which revealed that children with autism had more adverse reactions to the MMR vaccine and were more likely to have been given acetaminophen than ibuprofen for those reactions. Compared with controls, children aged 1–5 years with autism were eight times more likely to have become unwell after the MMR vaccine, and were six times more likely to have taken acetaminophen. Children with autism who regressed in development were four times more likely to have taken acetaminophen after the vaccine. Illnesses concurrent with the MMR vaccine were nine times more likely in autistic children when all cases were considered, and 17 times more likely after limiting cases to children who regressed. There was no increased incidence of autism associated with ibuprofen use. 

The incidence of attention deficit with hyperactivity (ADHD) over the last 50 years follows patterns similar to those of autism and asthma. Before 1970, the diagnosis of ADHD was relatively rare for schoolchildren and almost nonexistent for adolescents and adults. Between 1980 and 2007, there was an almost 8-fold increase of ADHD prevalence in the U.S. compared with rates of 40 years ago. Prevalence of ADHD in American schoolchildren was 1% in the 1970s, 3–5% in the 1980s, and 4–5% in the mid-to-late 1990s. A study of hospital discharge rates for ADHD between 1989 and 2000 found a 381% increase over the study period. 

It is interesting that Cuba, which has a lower autism rate than the U.S., allows the use of acetaminophen only by prescription; therefore, the use of acetaminophen in Cuba is only a minuscule fraction compared to the U.S. and many other countries throughout the world. When acetaminophen use was limited by a prescription requirement in the U.S., the rate of autism was a small fraction of current rates of autism. 

Acetaminophen toxicity is usually due to exceeding the recommended daily dosage, often occurring due to accidental combination use of multiple products containing acetaminophen or through changes in dosage amounts by manufacturers. Adding to this are reports that acetaminophen products have been contaminated at various times, potentially increasing health risks. These problems have been documented in FDA inspection reports and subsequent recalls. 

Within the last 10 years, the FDA has chronicled manufacturing problems including mislabeling of children's tablets, where packages of the product listed an incorrect amount of the ingredients per tablet, inadequate cleaning of equipment used for manufacturing, insufficient follow-up in investigating consumer complaints, product mix-ups, and contamination with metal fragments and bacteria. The latter resulted in a recall of 135 million bottles of children's medications containing acetaminophen. 

Other FDA-publicized inspection reports of acetaminophen include: 

• Recalls in 2009 and 2010 due to trace amounts of the chemical 2,4,6-tribromoanisole found in infant, children, and adult OTC products, prompted by 775 consumer reports of nausea, vomiting, stomach pains, and diarrhea received by FDA due to the contamination. 

• Acetaminophen-manufacturing facilities with inadequate quality controls, lack of safeguards to isolate "rejected" raw materials and other drugs, and several human errors resulting in product mix-ups; including several recalls due to failed FDA manufacturing inspections and contaminated products affecting >300 million bottles of adult and children's medicines. 

A large-scale, long-term study of both prenatal and postnatal effects of acetaminophen exposure on the incidence of autism, ADHD, and asthma should be conducted. However, such a study would probably take at least 5 years. If acetaminophen is indeed the cause of all of these illnesses, should acetaminophen use continue for such a long period of time while millions of additional children are further affected? 

Since all children may be at risk from asthma, Dr. McBride, Professor of Pediatrics at Department of Pediatrics, Northeast Ohio Medical University, urges people to take notice, “Until such evidence is forthcoming, I will recommend avoidance of acetaminophen by all children with asthma or those at risk for asthma and will work to make patients, parents, and primary care providers aware of the possibility that acetaminophen is detrimental to children with asthma." Dr. McBride is in effect saying that acetaminophen is contraindicated for the treatment of any children. The severe asthma risk combined with the risks of autism and ADHD are so severe that we as a society should maintain a degree of caution with acetaminophen given the proven overall toxicity due to accidental overdose of the drug, and the availability of ibuprofen or abstaining from treatment as alternatives. 

Given associations of acetaminophen with increased rates of cancer, increased testicular damage, increased rates of asthma, and allergy, plausible causation of autism, and in vitro evidence of brain damage associated with metabolites of acetaminophen, new assessments of the relative risk of aspirin causing Reye's syndrome versus the risks of acetaminophen in children should be undertaken. If a clear link between acetaminophen use pre- or post-natally and autism is established, medical practice guidelines may need to be adjusted and alternative analgesics or antipyretics, such as ibuprofen, recommended. 

In 2013, Bauer and Kriebel reported that prenatal use of acetaminophen was strongly correlated with Autism Spectrum Disorder (ASD) prevalence (r = 0.80) using all available country-level data (n = 8) for the period 1984 to 2005. In addition, the authors found that after acetaminophen became commonly used to treat circumcision pain after 1995, there was a strong correlation between countrylevel (n = 9) autism/ASD prevalence in males and a country's circumcision rate (r = 0.98). A very similar pattern was seen among US states and when comparing the three main racial/ethnic groups in the US. 

The full article and references are found at http://www.greatplainslaboratory.com/home/eng/Acetaminophen.asp