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.
There has been consistent evidence of an association between ADHD and subjectively reported sleep problems even in patients not medicated for the disorder. There have also been studies using wrist-worn actigraphy (a wrist watch-like device that measures gross motor activity) and sleep lab-based polysomnography that measure objective sleep parameters.
What has been missing are large population-based cohort studies to explore the prevalence rates of different sleep disorders and medical prescriptions in ADHD.
Methods Used:
Sweden has a single-payer health insurance system and a series of national population registers that track virtually its entire population. Using the Swedish Total Population Register, a local research team created a cohort of all 6,470,658 persons born between 1945 and 2008. They linked this to the Swedish National Patient Register, which includes inpatient hospitalizations from 1975 to 2013, and outpatient specialist diagnoses from 2001 to 2013, to identify diagnoses of sleep disorders. They also linked to the Prescribed Drug Register, covering 2005 to 2013, to identify prescriptions for sleep medications.
Summary of Findings:
Overall, persons with ADHD were eight times more likely to be diagnosed with any sleep disorder relative to normally developing peers. Broken down by age, adolescents with ADHD were 16 times more likely to receive such diagnoses, young adults (18-30) twelve times more likely, children and mid-age adults (31-45) eight times more likely, and older adults six times more likely.
Broken down by specific sleep disorder diagnoses, relative to normally developing peers, persons with ADHD were:
As for sleep medication, relative to normally developing peers, persons with ADHD were:
Conclusion:
The team concluded, “Our findings also suggest that greater clinical attention should be directed towards addressing sleep problems in individuals with ADHD. This entails implementing proactive measures through sleep education programmes and providing both pharmacological and non-pharmacological approaches such as cognitive behavioural therapy and parental sleep training.”
Attention is a critical determinant of academic achievement, influencing domains such as language, literacy, and mathematics. To explore whether physical activity can improve attention in children with ADHD, an international team conducted a meta-analysis of peer-reviewed studies. The goal was to evaluate the impact of various physical activity regimens on attention-related outcomes in this population.
The researchers performed a comprehensive search of the medical literature to identify studies examining the effects of physical activity on attention in schoolchildren with ADHD. They included 10 studies with a total of 474 participants in their meta-analysis. The studies evaluated two main types of physical activity:
Additionally, they examined variations based on the frequency, duration, and type of control groups used in the studies. To assess consistency, they also analyzed heterogeneity (variability of outcomes) and checked for potential publication bias.
Key findings from the meta-analysis include:
The authors concluded that mentally engaging exercise is more effective than aerobic exercise in improving attention problems in schoolchildren with ADHD. Furthermore, higher frequency and longer duration of physical activity do not necessarily yield better outcomes.
This research underscores the importance of tailoring physical activity interventions to emphasize cognitive engagement over intensity or duration. By refining strategies, educators and parents can better support children with ADHD in achieving academic success. But take note: given the results from controlled studies, it seems clear that if there is a positive effect of exercise, it is very small so should not replace standard treatments for ADHD.
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Previous studies have examined how stimulant medications affect the brain in controlled settings, but less is known about their impact in real-world conditions, where children may not always take their medication consistently or may combine it with other treatments. A new study leverages data from the Adolescent Brain Cognitive Development (ABCD) study to explore how real-world stimulant use impacts brain connectivity and ADHD symptoms over two years.
Changes in Brain Connectivity Researchers used brain imaging data from the ABCD study to examine the functional connectivity—communication between brain areas—of six regions within the striatum, a brain area involved in motivation and movement control. They focused on how stimulant use influenced connectivity between the striatum and other networks involved in executive functioning and visual-motor control.
The study found that stimulant exposure was linked to reduced connectivity between key striatal areas (such as the caudate and putamen) and large brain networks, including the frontoparietal and visual networks. These changes were more pronounced in children taking stimulants compared to those who were not medicated, as well as compared to typically developing children. Importantly, this reduction in connectivity seemed to regulate certain brain networks that are typically altered in children with ADHD.
Symptom Improvement In addition to brain changes, 14% of children taking stimulants experienced a significant reduction in ADHD symptoms over the two-year period. These children showed the strongest connectivity reductions between the right putamen and the visual network, suggesting that stimulant-induced connectivity changes may contribute to improvements in visual attentional control, which is a common challenge for children with ADHD.
Why This Matters This study is one of the first to examine how stimulant use in real-world conditions affects brain networks in children with ADHD over time. The findings suggest that stimulants may help normalize certain connectivity patterns associated with ADHD, particularly in networks related to attention and control. These insights could help clinicians better understand the potential long-term effects of stimulant treatment and guide personalized approaches to ADHD management.
Conclusion Stimulant medications appear to alter striatal-cortical connectivity in children with ADHD, with some changes linked to symptom improvement. This research highlights the potential for stimulant medications to impact brain networks in ways that support attention and control, highlighting the importance of understanding how real-world medication use influences ADHD treatment outcomes.
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