Prenatal analgesic opioid exposure associated with elevated risk of ADHD in children


A study in JAMA Network Open has found that prenatal analgesic opioid exposure of 5 or more weeks is associated with a slightly elevated risk of attention-deficit/hyperactivity disorder (ADHD) in children compared to exposure of 4 weeks or less.

“The study is part of a Norwegian project called DrugsInPregnancy, which aims to understand the long-term effects of medications on neurodevelopment,” said lead author Johanne Tronnes, MScPharm, a pharmacist at the University of Oslo in Norway. She is also a PhD candidate in the Pharmacoepidemiology and Drug Safety Research group at the university, where she is investigating long-term outcomes in children after prenatal exposure to analgesics.

Johanne Tronnes, MScPharm

Johanne Tronnes, MScPharm

“I think this is an interesting and important topic, given the ongoing opioid epidemic and its potential consequences for the pregnant population,” Tronnes told Contemporary OB/GYNÒ. “At the same time, pregnant women with moderate to severe pains need adequate treatment, so it is crucial to generate the necessary knowledge that can inform clinical decisions.”

Tronnes noted that roughly 3% of children in Scandinavia and about 20% of children in the United States are exposed to opioids during fetal life.

“Concerns have been raised about the potential long-term effects of opioids on the developing fetal brain,” she said. “Currently, there are very few studies examining the long-term effects in children after prenatal opioid analgesic exposure, making this knowledge urgently needed.”

The study used data from the Norwegian Mother, Father and Child Cohort Study linked to other national health registries and had a mean follow-up of 10.8 years.

The analyses of ADHD diagnosis comprised 73,480 children, of whom 49% were girls. Analysis of ADHD symptoms consisted of 31,270 children, of whom 49.2% were girls.

Overall, 2.3% of children in the ADHD diagnosis sample and 2.1% in the ADHD symptom sample were exposed to an analgesic opioid at least once during gestation.

Yet no connections between timing of prenatal analgesic opioid exposure and ADHD diagnosis or symptoms were found.

However, exposure of 5 or more weeks was linked to a slightly elevated risk of ADHD diagnosis versus exposure of 4 weeks or less: hazard ratio (HR) = 1.60; 95% confidence interval (CI): 1.04 to 2.47.

But there was no such association for the risk of ADHD symptoms.

“I did not know what to expect because there was so little evidence about the long-term effects of prenatal analgesic opioid exposure,” Tronnes said. “Prior studies have mainly focused on immediate birth outcomes and/or been conducted among women using illicit opioids or women using opioids in the context of opioid maintenance therapy.”

Tronnes said it is reassuring that the study failed to find any association between the timing of analgesic opioid exposure and ADHD. “However, the slightly increased risk of ADHD diagnosis following longer duration of exposure needs to be replicated in other studies,” she said.

In light of the ongoing opioid epidemic, coupled with the study results, “long-term use of opioids during pregnancy should be avoided,” Tronnes said. “One should also be cautious of usage in the third trimester, due to increased risk of neonatal withdrawal syndrome.”

Nonetheless, pregnant women in need of pain medication should not be deprived of appropriate treatment, according to Tronnes. “Pain management should be discussed on an individual patient level, bearing in mind the benefits and risks of different analgesic therapies,” she said.

ADHD is only one important domain of child development. “Examining the association of prenatal exposure to opioid analgesics and other childhood outcomes is also warranted,” Tronnes said.



Tronnes reports no relevant financial disclosures.


Tronnes JN, Lupattelli A, Handal M, et al. Association of timing and duration of prenatal analgesic opioid exposure with attention-deficit/hyperactivity disorder in children. JAMA NetwOpen. 2021;4(9):e2124324. doi:10.1001/jamanetworkopen.2021.24324

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