September 5, 2024
A 2021 consensus statement by an international group of scientists and clinicians (Bauer et al.) recommended that pregnant individuals “forego [acetaminophen] unless its use is medically indicated,” due to the potential risk of developmental disorders such as autism and attention-deficit/hyperactivity disorder (ADHD).
A mostly Swedish research team, collaborating with a U.S. researcher, nevertheless noted that previous studies have been limited by:
Sweden has a single-payer health insurance system that includes virtually its entire population, and national registers that enable tracking the health history of mothers and their children, including their children’s siblings.
The team used the Swedish registers to identify the roughly two-and-a-half million children born in Sweden from mid-1995 through 2019. They were also able to identify all siblings to be able to control for otherwise unmeasured familial and genetic confounding.
Almost 186,000 of these children were exposed to acetaminophen during pregnancy.
After adjusting for available known confounders, including (but not limited to) child sex and birthdate, mother’s age and medical history, use of any other painkillers, use of any psychoactive medications, country of birth, residential region, smoking status, highest household education, and disposable income, children exposed to acetaminophen during pregnancy were 7% more likely to be diagnosed with ADHD subsequently than those who were not exposed.
However, roughly the same results were found for other painkillers, including aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and antimigraine medication. High doses of acetaminophen did not produce any stronger association with subsequent ADHD than low dosage.
Moreover, when confining results to siblings – 8,526 children who were exposed versus 87,679 who were unexposed – the association between acetaminophen use during pregnancy and subsequent offspring ADHD vanished altogether (and, again, at every dose level). The associations similarly vanished with every other painkiller medication.
The Swedish team concluded, “Acetaminophen use during pregnancy was not associated with children’s risk of autism, ADHD, or intellectual disability in sibling control analyses. This suggests that associations observed in models without sibling control may have been attributable to confounding.”
Viktor H. Ahlqvist, Hugo Sjöqvist, Christina Dalman, Håkan Karlsson, Olof Stephansson, Stefan Johansson, Cecilia Magnusson, Renee M. Gardner, and Brian K. Lee, “Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability,” JAMA (2024), 331(14):1205-1214, https://doi.org/10.1001/jama.2024.3172.
Ann Z. Bauer, Shanna H. Swan, David Kriebel, Zeyan Liew, Hugh S. Taylor, Carl-Gustaf Bornehag, Anderson M. Andrade, Jørn Olsen, Rigmor H. Jensen, Rod T. Mitchell, Niels E. Skakkebaek, Bernard Jégou, and David M. Kristensen, “Consensus Statement: Paracetamol use during pregnancy — a call for precautionary action,” Nature Reviews Endocrinology (2021), 17, 757-766, https://doi.org/10.1038/s41574-021-00553-7.
Brandlistuen, R. E., Ystrom, E., Nulman, I., Koren, G. & Nordeng, H. (2013). Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol 42, 1702-13.
Background:
Noting that “Previous research has demonstrated that attention significantly influences various domains such as language, literacy, and mathematics, making it a crucial determinant of academic achievement,” an international study team performed a comprehensive search of the peer-reviewed medical literature for studies evaluating effects of physical activity on attention.
The Study:
The team’s meta-analysis of ten studies with a combined total of 474 participants found moderate reductions in attention problems following physical activity. They found no significant evidence of publication bias, but there was considerable variation in outcomes between studies (heterogeneity).
To tease out the reasons for this variability, the team looked at specific attributes of the physical activity regimens used in the studies.
The seven studies with 168 participants that involved mentally engaging physical activity reported large reductions in attention problems, whereas the three studies with 306 persons that used aerobic exercise found no reduction whatsoever. Heterogeneity in the former was reduced, in the latter all but disappearing.
Comparing studies with other interventions as control groups (6 studies, 393 participants) with those with no intervention as control (4 studies, 81 participants), the former reported only small improvements in attention problems, while the latter reported large improvements.
Duration of physical activity made little difference. The four studies with physical activity of an hour or more reported better outcomes than the six with less than an hour, but the difference was not significant.
Greater frequency did make a difference, but in a counterintuitive way. The seven studies with one or two physical activity interventions per week (162 participants) reported large reductions in attention problems, whereas the three studies with three or more interventions per week (312 participants) showed no improvement.
Conclusion:
The authors concluded, “Our study suggests that cognitively engaging exercise is more effective in improving attention problems in school-aged children with ADHD.” Moreover, “the benefits of improved attention in school-age children with ADHD are not necessarily positively correlated with higher frequency and longer duration of physical activity.” Also keep in mind that exercise, while important for all children, should not replace medical and psychological treatments for the disorder.
The National Health Interview Survey (NHIS) is conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. The NHIS is done primarily through face-to-face computer-assisted interviews in the homes of respondents. But telephone interviews are substituted on request, or where travel distances make in-home visits impractical.
For each interviewed family, only one sample child is randomly selected by a computer program.
The total number of households with a child or adolescent aged 3-17 for the years 2018 through 2021 was 26,422.
Based on responses from family members, 9.5% of the children and adolescents randomly surveyed throughout the United States had ADHD.
This proportion varied significantly based on age, rising from 1.5% for ages 3-5 to 9.6% for ages 6-11 and to 13.4% for ages 12-17.
There was an almost two-to-one gap between the 12.4% prevalence among males and the 6.6% prevalence among females.
There was significant variation by race/ethnicity. While rates among non-Hispanic whites (11.1%) and non-Hispanic blacks (10.5%) did not differ significantly, these two groups differed significantly from Hispanics (7.2%) and Others (6.6%).
There were no significant variations in ADHD prevalence based on highest education level of family members.
But family income had a significant relationship with ADHD prevalence, especially at lower incomes. For family incomes under the poverty line, the prevalence was 12.7%. That dropped to 10.3% for family incomes above the poverty level but less than twice that level. For all others it dropped further to about 8.5%. Although that might seem like poverty causes ADHD, we cannot draw that conclusion. Other data indicate that adults with ADHD have lower incomes. That would lead to more ADHD in kids from lower income families.
There was also significant geographic variation in reported prevalence rates. It was highest in the South, at 11.3%, then the Midwest at 10%, the Northeast at 9.1%, with a jump down to 6.9% in the West.
Overall ADHD prevalence did not vary significantly by year over the four years covered by this study.
This study highlights a consistently high prevalence of developmental disabilities among U.S. children and adolescents, with notable increases in other developmental delays and co-occurring learning and intellectual disabilities from 2018 to 2021. While the overall prevalence remained stable, these findings emphasize the need for continued research into potential risk factors and targeted interventions to address developmental challenges in youth.
It is also important to note that this study assessed the prevalence of ADHD being diagnosed by healthcare professionals. Due to variations in healthcare accessibility across the country, the true prevalence of ADHD may differ still.
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Background:
An international research team used the nationally representative 2020–2021 U.S. Survey of Children’s Health to explore associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity.
"Sleep sufficiency" refers to the recommended amount of sleep for an individual. Sleep recommendations vary by age and other factors, such as health and lifestyle. For example, 7-9 hours is typically considered sufficient sleep for most adults, but an active teen may require closer to 10 hours of sleep per day.
Previous studies have shown that issues with both falling and staying asleep are common in individuals with ADHD.
The Study:
The team matched 7,671 children and adolescents with ADHD aged 3-17 to 51,572 controls.
Noting that “The few available population-based studies examining sleep in children with ADHD have focused on circumscribed age ranges, limiting generalizability across childhood, and have seldom included controls,” and “bedtime irregularity has received limited empirical attention in children with ADHD,” this study focused on these aspects of sleep impairment.
The study group excluded children and adolescents with ADHD with Down syndrome, current or lifetime cerebral palsy, and current or lifetime intellectual disability. In the control group, it excluded individuals with Down syndrome, cerebral palsy, intellectual disability, speech and language disorder, autism spectrum disorder, ADHD, anxiety, depression, behavioral or conduct problems, Tourette syndrome, and use of mental health services in the preceding 12 months. These groups were excluded to limit potential confounding factors.
After adjustment for covariates, parents of children and adolescents with ADHD reported weekday sleep insufficiency 65% more frequently than parents of controls.
However, when comparing matched controls with children and adolescents with ADHD who were being treated with ADHD medication, there was no significant difference.
Similarly, there was a small but significant effect size increase in bedtime irregularity among children and adolescents with ADHD relative to their matched controls.
Yet there was also a small but significant effect size decrease in bedtime irregularity among those taking medication for ADHD relative to those who were unmedicated.
The team noted, “Interestingly, here, ADHD medication use was linked to less bedtime irregularity across full and age-stratified samples, and not related to sleep insufficiency. However, research indicates the association between stimulant use and sleep problems is attenuated with longer duration of use, and also suggests the potential for stimulants to produce positive effects on sleep through reduced bedtime resistance. Further, ADHD medication type, not specified, may have influenced outcomes.”
The Take-Away:
The study concluded that ADHD in children was linked to insufficient sleep and irregular bedtimes in a nationally representative sample, reinforcing and expanding previous research. The findings emphasize the influence of various factors on sleep insufficiency and bedtime irregularity, including race, screen time, poverty, ADHD severity, and depression.
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