Now that ADHD pharmaceuticals are among the most widely prescribed medications during pregnancy, we need to be aware of any long-term harms to offspring from in-utero exposure.
Denmark has a single-payer public health care system that encompasses virtually its entire population. Combined with national registers that track demographic as well as health data for the whole population, this makes it easy to do population-wide studies.
Availing itself of these registers, an international study team looked at all 1,068,073 single births from 1998 to 2015. It then followed all these individuals through the end of 2018, or until any developmental diagnosis, death, or emigration, whichever came first.
The team compared children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy with children of mothers who discontinued ADHD medication before pregnancy. There were 898 of the former and 1,270 of the latter in the cohort.
To reduce the influence of potential confounding variables, the team adjusted for maternal age, parity, maternal psychiatric history, in- or outpatient admission to psychiatric ward within two years prior to pregnancy and until delivery, use of other psychotropic medications during pregnancy, number of hospitalizations during pregnancy not related to psychiatry, smoking during pregnancy, living alone, education, birthyear, and psychiatric history of the father.
Children exposed in utero to ADHD medication were found to be at no greater risk of any developmental impairment.
The timing of the exposure by trimester of pregnancy made no difference. Neither did the duration of exposure.
Neither children exposed to stimulant medications (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil) nor to non-stimulants (atomoxetine, clonidine) were at greater risk of any developmental impairment.
Focusing more narrowly on specific impairments, children exposed in utero to ADHD medication were no more likely to be autistic. They were more likely to have ADHD, but the association did not reach statistical significance.
Children exposed in utero to ADHD medication were also no more likely to develop hearing or cerebral vision impairment or febrile seizures or a growth impairment. Surprisingly, they were 40% less likely to become epileptic, the only statistically significant association found in the study.
The authors concluded, “Our results are important because stimulant medications are critical for many adults, including women of childbearing age, to perform their essential functions at work, home, and school. Pregnant women who depend on stimulants for daily functioning must weigh the potential of exposing their fetus to unknown developmental risks against potential medical, financial, and other consequences to both mother and child that are associated with exacerbation of ADHD symptoms when stopping the medication, such as inability to maintain employment and unsafe driving. The present study provides reassurance that several essential categories of child outcomes that could reasonably be suspected to be affected by stimulants, including body growth, neurodevelopment, and seizure risk, do not differ based on antenatal stimulant exposure. Future studies would benefit from larger sample sizes making it possible to conduct stratified analyses on ADHD medication type.”
Kathrine Bang Madsen, Thalia K. Robakis, Xiaoqin Liu, Natalie Momen, Henrik Larsson, Julie Werenberg Dreier, Helene Kildegaard, Jane Bjerg Groth, Jeffrey H. Newcorn, Per Hove Thomsen, Trine Munk-Olsen, and Veerle Bergink, “In utero exposure to ADHD medication and long-term offspring outcomes,” Molecular Psychiatry (2023), https://doi.org/10.1038/s41380-023-01992-6.
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