There is no link between prescription opioid use during pregnancy and an increased risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring, new research shows.

Instead, investigators suggest that other factors may account for the higher prevalence of ADHD and ASD among children exposed to opioids in utero.

“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 [POAs] on risk for two common neurodevelopmental disorders, providing more data to support decision-making,” study investigator, Emma N. Cleary, a graduate student in the Department of Psychological and Brain Sciences at Indiana University Bloomington, said in a press release.

The study was published on September 16 in PLOS Medicine.

Other Factors at Play

The researchers noted that the extent to which the documented association between prenatal POA exposure and neurodevelopmental disorders in children is causal or due to confounding is unknown.

To evaluate associations between dose and duration of POA exposure during pregnancy and ASD or ADHD in children while minimizing bias due to confounding and other sources.

Investigators noted that POAs are commonly prescribed to help manage pain during pregnancy. However, it’s unclear whether POA exposure increases the risk for neurodevelopmental disorders, including two of the most common — ADHD and ASD.

To examine the extent to which POA use during pregnancy increases these conditions, the investigators conducted a retrospective cohort study. Data of 1,267,978 children from Sweden born between July 2007 and December 2018 who were and were not exposed to POA were assessed for ASD. Similarly, another cohort of 918,771 children born between July 2007 and December 2015 who were and were not exposed to POA were evaluated for ADHD.

Researchers assessed prenatal POA exposure by using data on prescriptions filled 1 year before conception through birth. ASD and ADHD were identified from clinical diagnoses and ADHD medication use.

Researchers created several models to adjust for confounders, including unexposed siblings within the cohort, parents who filled opioid prescriptions before but not during pregnancy, and children whose parents had painful conditions but did not receive opioid medications.

Overall, 4.4% of children were exposed to POAs during pregnancy, and a majority of parents (72.3%) filled a single prescription for an opioid medication during pregnancy.

By age 10, the risk for ASD was 2.0% in children unexposed to opioids, 2.9% in those exposed to a low dose, and 3.6% in those exposed to a high dose during pregnancy.

Models estimating cumulative maximum dose showed an increased ASD risk in the unadjusted analysis (hazard ratio [HR], 1.74) and after adjusting for covariates (HR, 1.34). However, the association weakened or disappeared in models accounting for parental painful conditions (HR, 1.25), opioid exposure prior to pregnancy (HR, 1.10), and differentially exposed siblings (HR, 0.99).

‘Important Clinical Implications’

Decisions around how to manage pain during pregnancy can be complicated, Cleary noted.

“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,” she said.

The study findings have “important clinical implications,” study co-author Ayesha C. Sujan, postdoctoral fellow at Stanford University School of Medicine, Stanford, California, said in the release.

She noted that the associations between prenatal POA exposure and ASD or ADHD appear to be explained more by underlying factors preceding opioid use than by the 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.”

This study was supported by the National Institute on Drug Abuse of the National Institutes of Health. Cleary and Sujan reported no relevant financial relationships.