Meta-analysis suggests Covid-19 pandemic may lead to small increase in ADHD diagnoses, but high unexplained variability and signs of publication bias undercut the finding

During the COVID-19 pandemic, there were concerns about its disproportionate impact on children with ADHD. Canadian researchers decided to investigate whether symptoms of ADHD—such as inattention, hyperactivity, and impulsivity—had changed over the past three years due to the pandemic.

Research Approach

To explore this question, the researchers conducted a systematic review of peer-reviewed medical literature. They looked for studies that included children and adolescents aged three to eighteen and met the following criteria:

  1. Reported ADHD symptoms at least once before the pandemic started (before March 2020) or provided a retroactive report of pre-pandemic symptoms.
  2. Reported ADHD symptoms at least once after the pandemic began.

They found 18 studies with a total of 6,491 participants that could be combined for a meta-analysis. These studies were from four continents (North and South America, Asia, Europe) and ten countries (China, Japan, United States, Canada, Brazil, U.K., Germany, Spain, Italy, Lithuania).

Study Quality and Criteria

The researchers assessed the quality of the studies based on three criteria:

  1. Clear description of the research setting.
  2. Detailed description of data collection procedures.
  3. Statistical assessment of the reliability and validity of measurement tools.

Ten studies met all three criteria, and the remaining eight met two out of three.

Findings

The meta-analysis revealed a small but statistically significant increase in ADHD symptoms after the onset of the pandemic. However, there was a high degree of variability (heterogeneity) in the results between studies. The researchers couldn't identify any reasons for this variability. Factors such as gender, age, study design (prospective vs. retrospective), and the identity of the symptom evaluator (self or caregiver) didn't significantly affect the results. Additionally, the researchers did not report any specific outcomes based on the ten higher-quality studies alone.

Moreover, there was strong evidence of publication bias. The researchers did not perform a trim-and-fill analysis, which could have shown how publication bias might have influenced the effect size. Given the small effect size initially reported, this leaves the overall findings uncertain.

Conclusion

While the study found a slight increase in ADHD symptoms among children during the pandemic, the high variability in results and the evidence of publication bias make it difficult to draw definitive conclusions. More research is needed to understand the true impact of the pandemic on ADHD symptoms in children and adolescents.

Maria A. Rogers and Gordon MacLean, “ADHD Symptoms Increased During the Covid-19 Pandemic: A Meta-Analysis,” Journal of Attention Disorders (2023), 1-12, https://doi.org/10.1177/10870547231158750.

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No Association Found Between Acetominophen Use During Pregnancy, Subsequent ADHD

Swedish Nationwide Population Study Finds No Association Between Acetaminophen Use During Pregnancy and Offspring ADHD

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: 

  • Confounding by indication, because acetaminophen is taken for infection, fever, and pain (including pain from autoimmune disease), which are themselves risk factors for neurodevelopmental disorders such as ADHD. 
  • Confounding by parental health and genetics, because neurodevelopmental disorders are highly heritable. 
  • Small sample sizes. 

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.” 

September 5, 2024

No Link Found Between In Utero Antipsychotic Exposure and ADHD

Meta-analysis with Millions of Participants Finds No Link Between Antipsychotic Use in Pregnancy and ADHD in Offspring

Antipsychotic medications are used to treat a variety of psychiatric disorders, including schizophrenia, bipolar disorder, sleeping problems, major depression, and severe anxiety. 

Untreated maternal mental illness is associated with poor health outcomes for both mothers and their offspring. On the other hand, one must guard against any potential direct harms of medications on development – including neurological development – of the fetus.  

Because prenatal use of antipsychotics is infrequent, previous observational studies have suffered from small sample sizes that have not enabled precise and reliable assessment of risk. The clinical decision about whether to continue antipsychotic treatment in patients who become pregnant has therefore remained inconclusive. 

In search of more reliable guidance, an international study team conducted a systematic search of the peer-reviewed medical literature to perform the first meta-analysis on this topic.  

They evaluated study quality and only included studies rated “good” or better. 

Identification of ADHD was determined by clinical diagnosis. 

Meta-analysis of four studies encompassing over eight million participants found a slight association. Children exposed to maternal antipsychotics during pregnancy were 11% more likely to be diagnosed with ADHD subsequently.  

But even in observational studies with millions of participants, such associations – especially when slight to begin with – could be due to unmeasured confounders. 

The team therefore compared children with gestational exposure to siblings from the same mother who were not exposed, to address shared genetic and social factors at the family level. 

Meta-analysis of two population-based sibling-matched studies with a combined total of over 4.6 million participants in Denmark, Norway, Sweden, Finland, Iceland, and Hong Kong found no significant association between gestational exposure to antipsychotic medications and subsequent diagnosis of ADHD

The team concluded, “Our systematic review and meta-analysis of observational studies indicates that the heightened risks of ADHD and ASD observed in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relation to the antipsychotic itself.” 

 

August 28, 2024

Australian Survey Reveals 10x Higher Suicidality Risk in Kids with ADHD

Australian Nationwide Survey Finds More Than Tenfold Greater Odds of Suicidality or Self-harm Among Children with ADHD

Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time. 

An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107  children who have been followed up every two years since birth. 

The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.  

Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year. 

The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ). 

Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10. 

With a diagnosis of ADHD at age 10 and all other factors held constant: 

  • The odds of suicidal thoughts, plans, or attempts at age 14 increased elevenfold. This was twice as pronounced among boys as among girls. 
  • The odds of self-harm at age 14 increased 25-fold. This was more than three times as pronounced among boys as among girls. 

Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect. 

Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes. 

The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.” 

August 26, 2024