Because the use of ADHD medications in reproductive-aged women appears to be increasingly common, additional research on the reproductive safety of ADHD medications is needed so that we can inform women and their health care providers about any potential risks associated with ADHD medication exposure during pregnancy. While we have a growing body of literature investigating the risk of major malformations in infants with prenatal exposure to commonly used stimulant medications, we have less information on the long-term effects of prenatal exposure to ADHD medications.
A recent population-based cohort study leveraged data from the Danish national registers to investigate neurodevelopmental outcomes and growth in children exposed to ADHD medication. This analysis included 1,068,073 liveborn singletons born between 1998 and 2015 who were followed until the diagnosis of any developmental disorder, death, emigration, or December 31, 2018.
The outcomes of 898 children born to mothers who continued ADHD medication treatment during pregnancy (with methylphenidate, amphetamine, dexamphetamine, lisdexamfetamine, modafinil, atomoxetine, or clonidine) were compared to the outcomes of 1,270 children born to mothers with ADHD who had discontinued ADHD medications prior to pregnancy. In addition, they included another reference group of women (n=1,065,905) with no exposure to ADHD medication either before or during pregnancy.
As is the case in most naturalistic studies, women with ADHD (whether they chose to continue or stop medication) differed from women with no ADHD. Specifically, in the discontinuation and exposed groups, a larger proportion of mothers were younger than 25 years of age at delivery (40.9% and 33.6%) versus 12.8% in the unexposed group. In addition, a larger proportion of children were born preterm (8.0% and 9.1%) in the discontinuation and exposed groups compared to the unexposed group (5.7%). Women in the discontinuation and exposed groups also had low birthweight (6.2% and 6.5%) compared to the unexposed group (3.6%). The discontinuation and exposed groups had lower proportions of mothers with more than a 9th grade education (41% and 39.8%, respectively) compared to the unexposed group (82.2%) and higher proportions of smokers during pregnancy (41.2% and 42.9%) compared to the unexposed group (15.4%).
Reassuring But Limited Information on the Risk of Neurodevelopmental Disorders
Outcomes in children exposed to ADHD medication were compared to outcomes in a control group of 1270 children whose mothers discontinued ADHD medication prior to pregnancy. After adjusting for potential confounding variables, the researchers observed no increased risk of any developmental disorders in the exposed compared to unexposed offspring (adjusted hazards ratio 0.97, 95% CI 0.81 to 1.17). Looking at specific subcategories of developmental disorder, the researchers observed no differences in rates of ADHD, autism spectrum disorder, cerebral visual or auditory impairments, seizure disorders, or growth restriction when comparing children who were prenatally exposed to ADHD medication with children whose mothers discontinued ADHD medication prior to pregnancy.
The number of childbearing women receiving treatment with ADHD medications is on the rise. While we have reassuring data on the risk of major malformations in women treated with stimulant medications, as well as atomoxetine, our data regarding the long-term effects of prenatal exposure to ADHD medications is sparse. These findings will undoubtedly be reassuring to women with ADHD who are considering the use of ADHD medications in pregnancy.
One of the shortcomings of this study, however, is that ADHD medications were considered as a group together. The majority of women (n=703) used methylphenidate during pregnancy; fewer women used amphetamines (n=20) or other medications, including atomoxetine (n=125), clonidine and modafinil (n=50). While these medications may share certain similarities, there are structural and chemical differences that may potentially affect outcomes. Thus, the data is more reassuring for methylphenidate but may not be generalizable to other ADHD medications. Future study will help to provide more information on the other ADHD medications.
Ruta Nonacs, MD PhD
Bang Madsen K, Robakis TK, Liu X, Momen N, Larsson H, Dreier JW, Kildegaard H, Groth JB, Newcorn JH, Hove Thomsen P, Munk-Olsen T, Bergink V. In utero exposure to ADHD medication and long-term offspring outcomes. Mol Psychiatry. 2023 Feb 9.