Prenatal opioid use not tied to autism or ADHD risk

A large Swedish cohort study found that exposure to prescribed opioid analgesics during pregnancy was not causally associated with an increased risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children after accounting for genetic and environmental confounders. The findings were published September 16, 2025, in PLOS Medicine by Emma N. Cleary, PhD, of Indiana University Bloomington, and colleagues.^1,2

Prescribed opioids are commonly used for pain management during pregnancy, but their safety regarding long-term child neurodevelopmental outcomes has been uncertain. Previous studies suggested a potential link to increased rates of ASD and ADHD, though causality remained unclear.

Methods and population

The retrospective cohort study included 1,267,978 children born in Sweden between 2007 and 2018 for ASD analysis and 918,771 children born between 2007 and 2015 for ADHD analysis. Researchers linked national registers to examine opioid exposure during pregnancy, measured through prescription fills, and compared outcomes in exposed and unexposed children.

Children were followed until 2021 for diagnoses of ASD and ADHD, identified through inpatient or outpatient records or dispensed ADHD medications. Exposure was categorized by dose and duration, using oral morphine equivalents as a standardized measure.

Key findings

At age 10, 2.0% of unexposed children were diagnosed with ASD, compared with 2.9% of children exposed to low-dose opioids and 3.6% of those exposed to high doses. For ADHD, similar trends appeared, with higher unadjusted risks in exposed groups.

Initial analyses showed associations between cumulative dose or duration of opioid use and higher rates of ASD and ADHD. However, when researchers adjusted for measured covariates, parental health conditions, prescriptions before but not during pregnancy, and sibling comparisons, the increased risks largely disappeared. For example, in sibling comparisons, hazard ratios were near 1.0, indicating no significant difference in risk.

The authors noted that extremely high doses or prolonged opioid use were rare in Sweden and could not be fully evaluated. Nevertheless, the study concluded that typical prescription patterns did not appear to substantially increase risk for neurodevelopmental disorders.

Clinical perspective

Cleary explained the motivation for the research: “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.”²

She added, “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 2 common neurodevelopmental disorders, providing more data to support decision-making.”

Co-author Ayesha C. Sujan, PhD, emphasized the clinical implications: “Our findings suggest that the observed associations between prenatal exposure to opioid analgesics and 2 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.”

Implications for practice

The results provide reassurance that prescribed opioid use during pregnancy, at levels observed in Sweden, is unlikely to directly increase the risk of ASD or ADHD in children. For clinicians, this evidence may support a more balanced approach to pain management in pregnancy, focusing on individualized assessment and comprehensive counseling.

Still, the authors noted that higher exposures could not be fully studied and recommended continued research in populations with different prescribing practices. For now, the findings highlight the importance of considering confounding factors when evaluating risks of prenatal medication exposure.

References:

1. Cleary EN, Sujan AC, Rickert ME, et al. Prescribed opioid analgesic use in pregnancy and risk of neurodevelopmental disorders in children: A retrospective study in Sweden. PLoS Medicine. 2025;22(9):e1004721-e1004721. doi:https://doi.org/10.1371/journal.pmed.1004721
2. PLOS. Prescribed opioid pain medications during pregnancy likely aren’t associated with increased risk of autism, ADHD. Eurekalert. September 16, 2025. Accessed September 19, 2025. https://www.eurekalert.org/news-releases/1097557