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.
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.”
Congenital cleft lip and palate (CCLP) are birth defects associated with genetic and environmental factors. The latter include heavy maternal consumption of alcohol and fetal exposure to retinoid drugs derived from vitamin A.
Methods:
Taiwan has an island-wide single-payer health insurance system that reaches over 99% of the population. To explore the relationship between CCLP and various psychiatric disorders including ADHD, a Taiwanese study team used the island’s National Health Insurance Research Database to identify all 1,158 children and adolescents with CCLP during a ten-year period. They matched them ten-to-one with 11,580 age and sex-paired controls without CCLP.
Summary of Results:
Further adjusting for demographic data (income, residence) and family history of major psychiatric disorders, children and adolescents with CCLP were more than seven times more likely to be diagnosed with ADHD during the follow-up period than controls. Patients with both cleft palate and cleft lip were more than nine times more likely to be subsequently diagnosed with ADHD than controls.
Patients with CCLP were also six times more likely to be diagnosed with autism spectrum disorder and more than seven times as likely to be diagnosed with schizophrenia as non-CCLP controls. They were also more likely to be diagnosed with bipolar disorder or major depressive disorder, but these results did not reach statistical significance.
Conclusion:
This study highlights a significant association between congenital cleft lip and palate (CCLP) and an increased risk of developing ADHD, with CCLP patients being more than seven times as likely to be diagnosed with the disorder. Additionally, CCLP was linked to a higher prevalence of other psychiatric conditions, including autism spectrum disorder and schizophrenia. These findings underscore the importance of monitoring mental health in individuals with CCLP and call for further research into the risk factors connecting these birth defects with psychiatric disorders.
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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