367 - Tylenol, pregnancy, and autism: What recent studies show and how to interpret the data

A blood pressure medication (Category C) that 'can't be ruled out' for risk during pregnancy, but benefits for the mother may justify its use.

A framework that replaced the FDA's letter categories about 10 years ago to provide more descriptive guidance on drug risks during pregnancy and lactation.

The journal where a systematic review of earlier research on acetaminophen and autism was published in late August, triggering recent alarms.

A very large prospective cohort study in Sweden (2.5 million children) that found a small correlation between prenatal acetaminophen use and autism in a general cohort, but this correlation was abolished in sibling-controlled analysis.

The individual who, in 1965, put forth the Bradford Hill criteria to assist epidemiologic researchers in examining data when randomized controlled trials (RCTs) are not available.

Mentioned in a meta-analysis showing a 5% higher increase in prostate cancer, an association deemed 'nonsensical' and highlighting the issue of trolling for signal in noisy data.

Author of the August review paper, who believes maternal acetaminophen use during any part of pregnancy increases fetal risk.

A revision of the Diagnostic and Statistical Manual of Mental Disorders that expanded the definition of autism from strict infantile autism to autistic disorder.

A common alternative to Tylenol, considered category B in the first two trimesters but category D in the third trimester due to risks like premature closure of a blood vessel in the fetus.

A researcher who believes prenatal acetaminophen exposure carries little risk if the mother has a healthy liver, arguing the greatest risk comes during the neonatal period or birth itself.

Molecules that contribute to pain and inflammatory response; acetaminophen's effects are mediated in part through their inhibition, and they also play a role in neurodevelopment, offering a handwavy biological plausibility for a link to autism.

A class of drugs (Category C) for which the host lacks sufficient data to advise on pregnancy use but outlines the nuanced thinking required, considering if it prevents gestational diabetes, for which metformin is typically first-line.

A medication (Category C) that 'can't be ruled out' for risk during pregnancy, but benefits for the mother may justify its use.

A class of drugs (Category C) used to treat depression, which 'can't be ruled out' for risk during pregnancy, but benefits for the mother may justify their use.

A statistical issue where if you look at enough variables, you are bound to find statistically significant associations by chance alone, leading to false hits.

Discussed as having a stronger statistical association with Type 2 Diabetes (1.10 relative risk increase) than acetaminophen with autism, yet likely confounded by 'healthy user bias' and not causal.

A website that demonstrates how easy it is to find significant correlations between unrelated variables, illustrating the multiple comparisons problem.

The latest edition of the Diagnostic and Statistical Manual of Mental Disorders, which collapsed all PDD subtypes into a single diagnosis called Autism Spectrum Disorder (ASD), significantly expanding its umbrella.

A drug (Category X) that women should simply not take during pregnancy due to definitive evidence of significant fetal harm.

Essential supplements that fall into FDA category A, with no demonstrated risk in controlled human studies during pregnancy.

A recent nationwide study in Japan (220,000 children) supporting the Swedish study's findings; found a modest 6% uptick in autism rates with prenatal acetaminophen exposure in the general cohort, which, like the Swedish study, was abolished with sibling analysis.

Mentor of the host, quoted for saying 'a thousand SARS makes not a pearl necklace' to emphasize that quantity of small, flawed studies does not equate to strong evidence.

Used to treat bipolar disorder (Category D), with positive human fetal risk data, but may be used when the benefit to the mother outweighs the risk.

The Diagnostic and Statistical Manual of Mental Disorders that, along with the ICD-10, created the 'pervasive developmental disorder' (PDD) family of diagnoses.

The International Classification of Diseases, which, along with the DSM-IV, created the 'pervasive developmental disorder' (PDD) family of diagnoses.

A seizure medication (Category D) with positive human fetal risk data, but may be used when the benefit to the mother outweighs the risk due to debilitating seizures.

Another prostaglandin inhibitor, shown to have modest protective effects against autism-like symptoms in animal studies and a 13% relative risk reduction in the Swedish cohort study, which argues against acetaminophen's causal link.

A type of fat in the blood. Although not mentioned by name, the host references APOB which is a component of triglyceride-rich lipoproteins.

A seizure medication (Category D) with positive human fetal risk data, but may be used when the benefit to the mother outweighs the risk due to debilitating seizures.

Nine principles laid out in the mid-1960s to help determine whether an observed observation in epidemiology is likely to be causal, not a checklist but a disciplined framework.

A small 2020 study that reported a strong association between acetaminophen and autism, but used a single cord blood sample and had potential participant bias, making its conclusions unreliable.

The senior author of the Swedish study, interviewed by JAMA, who confirmed that once genetics and home environmental exposures are controlled for, the risk of autism related to acetaminophen exposure is not causal.

Short-term use in Category C, but long-term use is in Category D due to positive human fetal risk data, potentially outweighed by maternal benefits.