In a massive study looking at more than two million individuals, scientists have failed to find any meaningful link between the use of opioid painkillers and the prevalence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), challenging earlier research suggesting otherwise.
Researchers from Indiana University Bloomington investigated dose and duration of opioid use during pregnancy and the child’s risk of later being diagnosed with either or both of these neurodevelopmental conditions. They examined the health records of more than 1.2 million children born in Sweden between 2007 and 2018 to assess rates of ASD among mothers who used painkillers during pregnancy, and an additional 900,000 kids born between 2007 and 2015 and rates of ADHD in this cohort.
What they found was that 2% of kids born to mothers who had no opioid use had received an autism diagnosis by the age of 10, versus 2.9% in kids exposed to a low dose of prescribed painkillers while in the womb. Children who were exposed to higher doses had a 3.9% rate of autism by age 10. For ADHD, there was a similar trend.
While the study didn't examine how extremely high doses and long durations of pain medication impacted developing brains, the findings provide little evidence that exposure during pregnancy significantly increases a child’s risk for autism and ADHD.
Of course, given such a large study pool, and what we know of autism and ADHD, there are a suite of genetic and environmental factors that the researchers say are more likely to influence these conditions than painkillers themselves. When the team applied statistical methods and factored in those other influences, the perceived increased risk in the data disappeared.
"We wanted to conduct this study to help provide more information for pregnant individuals and their physicians who are trying to make complex decisions about how to best manage pain during pregnancy," said Emma N. Cleary, a researcher at Indiana University Bloomington. “These decisions are made even more difficult due to insufficient data on the safety of these medications during pregnancy.
"While this study is not able to rule out small increased risks with high amounts of exposure, the results suggest that there is not a causal effect of prescribed opioid analgesics on risk for two common neurodevelopmental disorders, providing more data to support decision-making," Cleary added.
Earlier research has tied prenatal opioid-based painkiller use to a higher risk of ADHD in children, yet scientists caution that more research is needed to clarify the relationship between biological, environmental, social risk and ADHD symptoms.
In a 2019 study, the first to suggest such an association, researchers found that mothers prescribed opioid painkillers were 2.43 times more likely to have children diagnosed with autism. However, the researchers also noted that this was not enough to conclude that the medications alone were responsible in the increased risk.
"While our analyses adjusted for several factors known to be associated with both ASD risk and opioid prescription, such as maternal age, smoking, and maternal psychiatric conditions, our estimates could be biased due to unmeasured confounders such as yet to be discovered risk factors for both ASD and opioid prescription," the researchers noted.
Meanwhile, over-the-counter (OTC) pain medication acetaminophen has been implicated in contributing to an increased risk of autism and/or ADHD if used during pregnancy. At the same time, comprehensive studies have countered this, finding no credible link between neurodevelopmental issues and OTC medications.
“Our findings suggest that the observed associations between prenatal exposure to opioid analgesics and two major neurodevelopmental disorders – autism and ADHD – are largely driven by factors leading up to opioid analgesic use rather than the opioid exposure itself," said co-author Ayesha C. Sujan. "Our results, therefore, elucidate the critical need to provide pregnant individuals experiencing pain with psychosocial support and evidence-based pain management tools. These can include both pharmaceutical and non-pharmaceutical approaches.”
Perhaps the only conclusion we can draw is that neither autism nor ADHD exists in a vacuum with a single contributing factor that can "cause" the conditions. In fact, what we do know is that ADHD and ASD are highly heritable, with studies suggesting they have a 60-93% genetic basis. Beyond this, social and environmental influences remain poorly understood.
"Pregnant individuals and their physicians must weigh the importance of managing painful conditions with concerns about potential consequences of fetal exposure to prescribed opioid pain medications," Cleary added. "These concerns include potential impacts on child neurodevelopment."
The research was published in the journal PLOS Medicine.
Source: Indiana University Bloomington via EurekAlert!
