A recent study suggests that confounding may explain the increased risks of
Many obstetrician-gynecologists prescribe opioid analgesics to help manage their patients’ pregnancy pain. However, research has suggested a potential link between prenatal POA exposure and neurodevelopmental disorders.
It was not known if the association between prenatal POA exposure and neurodevelopmental disorders in children is causal or driven by confounding. In this retrospective study, investigators analyzed how the dose and duration of POA use during pregnancy were associated with autism and ADHD risk in children.
“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 lead investigator Emma N. Clearly, BA, from Indiana University Bloomington, and colleagues, in a statement.2 “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.”
Using national register data from Sweden, this study examined a population-based cohort, with nearly half female (48.6%).1 The ASD cohort included 1,267,978 children born between July 1, 2007, and December 31, 2018, with a follow-up through 2021. Since ADHD is typically diagnosed later, investigators applied a shorter eligibility window, including 918,771 children born through December 31, 2015.
The team used test-mining algorithms to calculate cumulative dose and duration of POA exposure during pregnancy from filled prescriptions and to identify those prescribed on an “as needed” basis.1 Outcomes included inpatient or outpatient clinical diagnoses of ASD and ADHD or dispensed ADHD medications.
To address unmeasured confounding, the analysis incorporated several comparison groups: children whose birthing parent had a diagnosed painful condition but did not receive POAs, children whose birthing parent received POAs in the year prior to but not during pregnancy, and unexposed siblings.
Among the 1,267,978 children, 4.4% were exposed to POAs when in their mother’s womb. At 10 years old, the cumulative incidence of ASD was 3.6% and 2.9% among children exposed to high and low POA doses, respectively, compared with 2% among children unexposed to POAs.1
Unadjusted models (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.63–1.87) and models adjusted for measured covariates (HR, 1.34; 95% CI, 1.24–1.44) showed that the cumulative maximum POA dose was associated with an increased risk of ASD. However, these associations were weak or nonexistent in alternative study designs, particularly when compared with children whose birthing parent had received POAs before, but not during, pregnancy (HR, 1.10; 95% CI, 1.00 – 1.21). The sibling comparison analysis showed no associations between ASD and POA exposure (HR, 0.99; 95% CI, 0.81 – 1.21).1
Investigators noted that they did not assess the impact of extremely high doses and long durations of opioids due to limited data in the Swedish cohort.2
“We are excited to share our findings because we believe that they have important clinical implications,” said investigator Ayesha C. Sujan, PhD, from Stanford University School of Medicine, in the statement.2 “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.”
References
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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 Med. 2025;22(9):e1004721. Published 2025 Sep 16. doi:10.1371/journal.pmed.1004721
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Prescribed opioid pain medications during pregnancy likely aren’t associated with increased risk of autism, ADHD. EurekAlert! Published September 16, 2025. Accessed September 17, 2025. https://www.eurekalert.org/news-releases/1097557