Prenatal exposure to opioid analgesics not linked to increased risk of autism or ADHD

Previous studies have suggested that children exposed to opioid pain medications while in the womb have higher rates of autism spectrum disorder (ASD) and attention- deficit/hyperactivity disorder (ADHD), but a new study finds that any increased risk could be explained by other factors. Emma N. Cleary of Indiana University Bloomington, USA, and colleagues published these findings on September 16^th in the open-access journal PLOS Medicine.

Opioids are commonly prescribed to help manage pain during pregnancy, but it is unclear whether opioid exposure in utero increases a child’s risk of neurodevelopmental disorders like ASD and ADHD. In the new study, researchers looked for connections between the dose and duration of opioid exposure during pregnancy, and the child’s risk of later being diagnosed with these two conditions.

Researchers looked at rates of ASD in more than 1.2 million children born in Sweden between 2007 and 2018, and rates of ADHD in more than 900,000 children born between 2007 and 2015, along with their level of exposure to opioid pain medications during pregnancy. They saw that while 2.0% of the unexposed children had ASD by age 10, 2.9% of children exposed to a low dose of opioids and 3.6% of children exposed to a high dose were diagnosed with the condition. Rates of ADHD followed a similar trend. However, when the researchers used statistical methods and different comparisons to consider confounding by genetic and environmental factors that might be obscuring the relationship between opioids and neurodevelopmental disorders, the increased risk disappeared.

The researchers cautioned that their study did not look at the impact of extremely high doses and long durations of opioids, since their dataset did not include such information due to Swedish opioid prescription practices. However, overall, the findings provide little evidence that exposure to prescribed opioid pain medications during pregnancy substantially increases a child’s risk for autism and ADHD at the levels they studied.

Emma N. Cleary says, “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. 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. These concerns include potential impacts on child neurodevelopment. 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.”

We are excited to share our findings because we believe that they have important clinical implications. 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. 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.”

Ayesha C. Sujan, Co-author