One Less Headache During Pregnancy

Scandi scientists report that children exposed to the widely used pain medicine acetaminophen/paracetamol in the womb, did not go on to develop autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) or intellectual disabilities at a higher rate than other youngsters1.

The study published in JAMA earlier this year, followed over two million kids born in Sweden between 1995 and 2019. Researchers found no causal link between the common over-the-counter pain pill and any of the three conditions. Paracetamol and acetaminophen are the same drug, well-known brands include Tylenol and Panadol. It’s also an active ingredient in cold and flu medicines such as LemSip and DayQuil.  

Troubling Reports

Previous research2 suggested a link between paracetamol use during pregnancy and giving birth to a child with a neurodevelopmental disorder. The Swedish scientists, however, argue that paracetamol does not interfere with brain development. Rather, they claim, the underlying illness that prompted the mum to pop the pill is more likely the culprit.

In 2014 doctors and scientists began to suspect a connection between prenatal paracetamol exposure and ADHD. Reports that ASD and intellectual disability might also be more common in children whose mothers used paracetamol soon followed. In response, the United States Food and Drug Administration issued a drug safety notice in 20153

Since then, over 25 research studies across the global North have suggested that paracetamol has adverse effects on neurodevelopment. As a result, endocrinologists have made calls for precautionary action4. With such a widely used medication under scrutiny, scientists were ready to dig into these findings to understand the relationship better.

A Nationwide Investigation

The Karolinska Institute based investigators undertook the mammoth task of reviewing medical more than 2.4 million records. The researchers examined the notes of nearly all kids born in Sweden over a 25-year period. The studies that initially linked paracetamol to ADHD or autism were too small and too general to pin down the relationship between the drug and brain development. Often the reported correlation was an incidental finding; the researchers took a bird’s-eye view of the kids’ health, and this was one of many patterns they spotted.

 In contrast, this vast dataset allowed the Swedish researchers to identify 185,909 youngsters exposed to paracetamol in the womb. They made more detailed comparisons between the children than in previous projects, creating a clearer picture. What’s more, they explicitly designed this study to probe the relationship between ASD, ADHD, intellectual disability and paracetamol, to gather all the relevant information.

Initially, the researchers compared two factors: “did the mother use paracetamol” and “did the child have ASD, ADHD, or an intellectual disability.” They found a tiny increase in the number of kids with a diagnosis—a 0.09% uptick in risk over ten years. However, when they accounted for other variables like premature birth, maternal illness or medication, and parental diagnoses, the difference disappeared.

In the Genes

The scientists speculated that the alleged link between over-the-counter painkillers and brain development might actually be due to the mother’s health or genes. If the mother endured a brain-related illness (for example chronic headaches or migraine), her underlying genes might also have contributed to her child’s neurodevelopmental disorder. The best way to test this is to compare children with very similar genes and upbringing. This meant comparing siblings. Were kids exposed to prenatal paracetamol more likely to have ASD, ADHD, or intellectual disabilities than their brother or sister who had not?
 
The results were clear: they found no difference in the likelihood that either set of children would go on to develop any of the neurodevelopmental disorders.

Siblings were similarly likely to develop the same neurodevelopmental problems regardless of whether their mother took paracetamol during her pregnancy. This indicated that genetics and maternal health were the biggest contributors to risk.

Get Your COVID-19 Shots

So if paracetamol wasn’t the culprit, why were other researchers spotting a link between neurodevelopmental disorders and the drug? It turns out that the most significant contributors to the risk of a child having ASD, ADHD or an intellectual disability were maternal health and a family’s socioeconomic background. Data gathered during the SARS-COV2 pandemic highlighted the effect of fever on unborn children1. If a mother has a fever during pregnancy, it can affect her baby’s developing brain5 6regardless of which medicine, if any, she used.  

Genetic studies suggest a link between migraines and neurodevelopmental disorders. Women experiencing painful headaches or migraines were more likely to take paracetamol, and more likely to have children with ASD, ADHD or intellectual disability. Paracetamol is associated with a higher risk, but it doesn’t cause it. It’s like saying people who ate ice cream outside were more likely to get sunburned—but did the sweet treat cause the burn? 

Lessons Learned

Parents concerned about acetaminophen/paracetamol and its effect on brain development should be reassured. There is little evidence of a causative link between this pain medication and ADHD, ASD or intellectual disability. What’s more, maternal health is the most important factor in the health outcomes of children. Maternal health encompasses genetic background, lifestyle, and even her ability to earn enough money to buy the best food and medicines. If we can learn anything from the original studies calling attention to maternal use of paracetamol, it’s that pregnant people need easy and consistent access to health care and social support.

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