02. In Utero Exposure to ADHD Medication and Long-Term Offspring Outcomes

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Hi! David Rosenberg here from the Psychopharmacology Institute. In this CAP Smart Take, we will closely examine the long-term impact on children of mothers who continue using ADHD medication during pregnancy compared with children of mothers who discontinue ADHD medication during pregnancy. It is especially relevant clinically because ADHD medication is increasingly being used during pregnancy. Therefore, understanding the risks and benefits related to the impact on neurodevelopment and growth is imperative.

In a significant study from the Danish National Registry, over 1 million live-born infants from 1998–2015 were observed until they were diagnosed with any developmental disorder or until death, emigration, or December 31, 2018. The study compared 900 children of mothers who continued ADHD medication during pregnancy with 1,270 children of mothers who ceased these medications. The ADHD medication under consideration were methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, modafinil, atomoxetine, and clonidine. What were the results?

The findings were encouraging for women with ADHD who deemed their medication crucial during pregnancy. Specifically, no increased risk of developmental disorders, such as ADHD or autism spectrum disorder, was identified in children of mothers who continued vs those who stopped ADHD medication. Moreover, the neurodevelopment and growth of children whose mothers continued ADHD medication did not differ from those whose mothers stopped. Recognizing that side effects, like decreased appetite, insomnia, and growth impairment, are associated with stimulant medication in ADHD patients, it is assuring that their use during pregnancy did not have a prolonged negative impact. Stimulant toxicity, sometimes linked to seizures—though usually not at therapeutic doses—prompted questions about potential risks to the developing brain. However, concerns regarding seizures or other neurotoxicity were unfounded.

The study also revealed that mothers with ADHD, irrespective of their medication status during pregnancy, were younger at childbirth, more prone to smoking during pregnancy, and more likely to have premature or low birth weight children. This aligns with broader ADHD patterns, not limited to pregnancy. Smoking rates in ADHD patients surpass those in the general populace. Intriguingly, some data suggest nicotinic agents might alleviate ADHD symptoms.

In conclusion, although this is a robust study, its findings shouldn’t be misconstrued to advocate that all pregnant women continue ADHD medication without risks. The data cannot pinpoint the risk for individual patients, and more research is warranted—especially concerning comorbidities, medication dosages, and combinations. In a group analysis, there seems to be no augmented risk for pregnant women who maintain their ADHD medication. Still, this doesn’t translate to zero risk at the individual level. Pregnancy is a pivotal time, so medical decisions must be approached with caution. Given the repercussions of untreated ADHD—like impaired work and social functioning, substance abuse, and impulsive behavior—the findings indicate that continuing ADHD medication during pregnancy is generally safe and effective for most patients.

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

Reference

Madsen, K. B., Robakis, T. K., Liu, X., Momen, N., Larsson, H., Dreier, J. W., Kildegaard, H., Groth, J. B., Newcorn, J. H., Hove Thomsen, P., Munk-Olsen, T., & Bergink, V. (2023).

In utero exposure to ADHD medication and long-term offspring outcomes.

Molecular Psychiatry, 28

(4), 1739–1746