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September 25, 2023
There have been indications that infants who have difficulty sleeping are more likely to later develop ADHD in childhood. Would this hold up in a large nationwide cohort study?
Noting that "Norway has several national health registries with compulsory and automatically collected information," and "registries can be linked on an individual level, making it possible to conduct large cohort studies," a Norwegian team of researchers studied the association between sleep-inducing medications prescribed to infants under three years old and diagnoses of ADHD between the ages of five and eleven.
Norway has a national health insurance system that covers all residents, and pays in full for youths under 16 years old. Norwegian pharmacies must register all dispensed prescriptions into a national register as a prerequisite for reimbursement.
The study included all children born in Norway from 2004 through 2010, minus those who died or emigrated, leaving a total of 410,555 children.
In addition to traditional hypnotic and sedative drugs and melatonin, the study looked at antihistamines, which though intended for respiratory use, are frequently used for gentle sedation.
The two most frequently prescribed drugs were found to be dexchlorpheniramine (girls 7%, boys 8%) and trimeprazine(girls 3%, boys 4%), both of which are antihistamines.
After adjusting for parental education as an indicator of family socioeconomic status, and parental ADHD as indicated by prescription of ADHD medications, girls who had been prescribed sleeping medications on at least two occasions were twice as likely to subsequently develop ADHD, and boys about 60 percent more likely. For, dexchlorpheniramine equivalent associations were not statistically significant for either boys or girls. But girls prescribed trimeprazine on at least two occasions were almost three times as likely to subsequently develop ADHD, and boys were well over twice as likely.
A limitation of the study was that there was no direct data for sleep diagnosis. The authors noted, "The Norwegian prescription database does not contain diagnosis unless medications are reimbursed and hypnotics are not reimbursed for insomnia or sleep disturbances in general. Sleep diagnoses were also not available from the Norwegian Patient Registry, as there seems to be a clinical tradition for not using the ICD- 10G47 Sleep Disorders diagnosis for children."
The authors concluded, "It has previously been shown that infant regulation problems, including sleep problems, are associated with ADHD diagnosis. We replicate this finding in a large cohort, where continuous data collection ensures no recall bias and no loss to follow-up. We find that the use of hypnotic drugs before 3 years of age, signifying substantial sleeping problems, increases the risk of a later ADHD diagnosis. This was especially true for the antihistaminic drug, trimeprazine."
Ingvild Holdo¸, Jorgen G. Bramness, Marte Handal, Berit Hjelde Hansen, Vidar Hjellvik, Svetlana Skurtveit, "Association Between Prescribed Hypnotics in Infants and Toddlers and Later ADHD: A Large Cohort Study from Norway," Child Psychiatry & Human Development (2020), https://doi.org/10.1007/s10578-020-01039-9.
The Background:
Previous research has suggested that people with ADHD have higher rates of death than those without the condition. Until now, many of those studies lacked the detail needed to untangle why this might be the case. A recent meta-analysis of eight separate studies reported that ADHD roughly doubled the risk of death, and it hinted that factors like socioeconomic status and other mental illnesses might help explain the link.
The Study:
To explore this in more detail, researchers used the US National Health Interview Survey, a nationally representative prospective cohort of just over 52,000 adults. Survey records were linked with the National Death Index, and participants were followed from the date of interview until death or December 31, 2019, whichever came first. The main outcome was death from any cause. With a median follow-up of just under eight years, there were 6,024 deaths recorded.
When the team adjusted their analysis for age, sex, ethnicity, and the year of the survey, having ADHD was associated with a 58% higher risk of death. Controlling further for family income and educational level reduced that increased risk slightly, to 50%.
Controlling for health conditions (like high blood pressure, diabetes, stroke, heart disease, and cancer) and lifestyle factors (smoking, alcohol use, physical activity, and body weight) also reduced the association to about 46%.
By contrast, when the researchers adjusted for two psychiatric conditions (anxiety and depression) commonly found alongside ADHD, the link between ADHD and higher mortality disappeared statistically. In other words, once anxiety and depression were taken into account, ADHD itself was no longer associated with a clearly measurable increase in the risk of death.
What Does This Mean?
The authors conclude that the apparent effect of ADHD on mortality seems to operate largely through accompanying mental illness, and to a lesser extent through lifestyle and physical health problems. They suggest that treating and managing these co-occurring issues (through medications, therapy, and behavioral interventions) might help reduce the risk of premature death in people with ADHD, although they note that further evidence is needed.
The Background:
Dementia is a rapidly growing public health problem affecting more than 50 million people worldwide. Nearly 10 million new cases are diagnosed each year, and that number is expected to almost triple by 2050. The most common form is Alzheimer’s disease, accounting for roughly 60–70% of cases, followed by vascular dementia at around 20%. Other types include dementia with Lewy bodies, Parkinson’s disease dementia, and frontotemporal dementia. While no cure exists, managing modifiable risk factors (such as high blood pressure, smoking, physical inactivity, and poorly controlled diabetes) can delay or slow both the onset and progression of the condition.
Several studies have reported an elevated dementia risk among people with ADHD, and a number of mechanisms may explain this association. These include shared genetic or neurobiological vulnerabilities, reduced cognitive reserve (leaving the brain less resilient to age-related damage), and greater lifetime exposure to other established dementia risk factors.
Earlier reviews explored the possible link between ADHD and dementia, but tended toward a broader scope (incorporating other neurodegenerative disorders or mixing study designs), which introduced substantial variability and precluded quantitative synthesis. The relevant research literature has also expanded considerably since those reviews appeared.
The Study:
This meta-analysis restricted inclusion to case-control and cohort studies, yielding five that met the criteria. One was a case-control study with 400 participants; the other four were cohort studies collectively covering 3.7 million individuals, two retrospective and two prospective.
The Results:
Pooling the four cohort studies, individuals with ADHD showed approximately two-and-a-half times the dementia risk of those without the diagnosis. There was no indication of publication bias.
The Take-Away:
The authors concluded that ADHD is associated with a significantly increased risk of all-cause dementia in later life, while noting that its relationship to specific dementia subtypes remains less clear and warrants attention in future research.
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The Background:
Women with polycystic ovary syndrome (PCOS) themselves show higher rates of ADHD. Because ADHD is partly heritable (meaning genes contribute to the condition), some of the increased ADHD seen in children of mothers with PCOS could come from shared genetic factors. In other words, a mother’s and her child’s increased risk might sometimes reflect common genes rather than an effect of the pregnancy itself.
Beyond genetics, growing evidence points to maternal metabolic problems during pregnancy as another important risk factor for neurodevelopmental outcomes. PCOS is one of these conditions and is considered both potentially modifiable (treatable or manageable) and biologically plausible as a contributor to risk. PCOS affects an estimated 5–10% of women of reproductive age worldwide and is characterized by signs such as hyperandrogenism (higher-than-normal levels of “male” hormones), insulin resistance (poorer ability to use the hormone insulin, which can affect blood sugar and metabolism), and chronic low-grade inflammation.
However, studies to date have not all reached the same conclusions. Some research suggests the association between maternal PCOS and offspring ADHD is stronger for girls, while other studies did not analyze results by child sex. Methodological differences make it harder to draw clear conclusions.
The Study:
It’s important to note that the studies included in this meta-analysis were observational (cohort studies and case-control studies). Observational studies can identify associations (that two things occur together) but cannot prove that one causes the other. A cohort study follows people over time, and a case-control study compares people with a condition to similar people without it.
The pooled results came from six studies that together included almost 1.4 million mother–child pairs and that adjusted for confounders (other factors that might influence the result, such as maternal age or socioeconomic status). After statistical adjustment, children of mothers with PCOS had about 40% greater odds of ADHD than children of mothers without PCOS. The analysis reported no evidence of publication bias (no clear sign that only positive studies were published) and zero heterogeneity (the results were consistent across the studies).
There was no meaningful difference in results between cohort and case-control studies, and the meta-analysis did not find a significant difference in the association when comparing male and female offspring.
The Take-Away:
The research team concluded that this large-scale synthesis found an association between maternal PCOS and higher odds of ADHD and other neuropsychiatric conditions in children. They suggested that children born to mothers with PCOS may benefit from developmental monitoring to identify and address problems early, while emphasizing that causal relationships have not been established. They called for further studies to confirm these findings and to investigate the biological and environmental mechanisms that might explain the association. Indeed, because women with PCOS show higher rates of ADHD than other women, we need genetically informed research designs to see if the reported association is confounded.
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