September 25, 2023

A Norwegian nationwide cohort study finds link between prescribed drugs widely used as sleeping aids and subsequent ADHD

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.

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Higher Relative Fat Mass (RFM) Associated with Lower ADHD Risk in Boys but Higher ADHD Risk in Girls

Background: 

Traditional measures of obesity, like body mass index (BMI) and waist circumference, have been linked to ADHD risk — but they aren’t great at capturing where fat is actually stored in the body. A newer index called relative fat mass (RFM), which combines height and waist circumference, does a better job of estimating overall body fat and predicting metabolic risks like heart disease and metabolic syndrome. Because those conditions share some underlying biological mechanisms with ADHD, researchers wondered whether RFM might also help explain the relationship between obesity and ADHD — particularly in children. 

That question is complicated by the fact that ADHD doesn't look the same in boys and girls. Boys tend to display more hyperactive and impulsive behavior, making their ADHD easier to spot. Girls more often show inattention, which is quieter and frequently goes undiagnosed. 


The Study: 

A new study set out to test whether RFM is associated with ADHD in children, and whether that association differs between sexes. Using data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2004, the researchers narrowed a large initial pool of over 31,000 participants down to 5,089 children and adolescents aged 6 to 14 who had complete data on height, waist circumference, ADHD screening, and other relevant variables. 

After adjusting for age, race/ethnicity, Poverty-Income Ratio, maternal age at delivery, maternal smoking during pregnancy, health insurance coverage, and birth weight, the results revealed a striking split along sex lines.  

In boys, higher RFM was associated with lower odds of ADHD. Compared to boys in the lowest fat-mass quartile, those in the second quartile had about 10% lower odds of ADHD, rising to over 30% lower in the third quartile and nearly 40% lower in the highest. In girls, the pattern reversed entirely. While girls in the second quartile showed similar odds to those with the lowest RFM, girls in the third and fourth quartiles had 60% to 70% greater odds of ADHD. 

Conclusion & Why This Matters:  

In recent years, the relationship between obesity and ADHD has become an increasingly important focus in pediatric neurodevelopmental research. Studies have reported higher rates of ADHD symptoms among children and adolescents with obesity compared with their non-obese peers, and difficulties with peer relationships have also been linked to increased obesity risk (Sönmez et al., 2019). From a neurobiological standpoint, both conditions may involve shared underlying mechanisms, particularly dysfunction in dopaminergic pathways.

The authors concluded that higher body fat levels appear to lower ADHD risk in boys while raising it in girls. This finding highlights why sex-specific analysis matters in ADHD research. The underlying biological reasons for this divergence, however, remain an open question and open the door for future research. 

US Study Highlights the Social Roots of ADHD

While ADHD is a developmental disorder, shaped by biology and genetics, growing evidence shows that it is also influenced by the social and environmental conditions in which children grow up. Research on the social determinants of health emphasizes that development is shaped not only by biology but also by factors such as family income, access to healthcare, neighborhood safety, and material stability. These factors can affect both how developmental challenges appear and whether they are recognized and diagnosed. 

Children facing socioeconomic disadvantage consistently show higher risks of developmental and behavioral difficulties. Chronic stress linked to poverty – including financial strain, food insecurity, and limited access to resources – has been associated with problems in attention, emotional regulation, and daily functioning. Children from lower-income families also tend to experience more severe ADHD symptoms and face greater barriers to ongoing care. 

Neighborhood conditions matter as well. Unsafe environments can limit opportunities for play and social interaction while increasing caregiver stress, all of which may influence children’s behavior and development. Material hardships, such as food insecurity, can further undermine stability at home. 

The Study:

The study analyzed six years of data from the National Survey of Children’s Health (2018–2023), covering more than 205,000 U.S. children aged 3 to 17. After accounting for age, sex, race and ethnicity, region, family structure, survey year, and other social factors, the researchers found a strong income gradient in ADHD prevalence. Compared with children in households earning at least four times the federal poverty level, those in households earning two to four times that level had 28 percent higher odds of ADHD. Odds rose to 70 percent higher in households earning one to two times the poverty level, and more than doubled among children living below the poverty line. 

Parental education showed a similar pattern. Compared with children whose parents had completed college, ADHD odds were 20 percent higher among those whose parents had some college education, 40 percent higher among those whose parents had only a high school education, and 80 percent higher among those whose parents had not finished high school. 

Children living in unsafe neighborhoods had nearly twice the odds of ADHD compared with those in safe neighborhoods, and food insecurity was also linked to almost double the odds. 

By contrast, race and ethnicity alone were associated with much smaller differences. Compared with non-Hispanic White children, children in non-Hispanic Black households had an 18 percent higher likelihood of ADHD, while children in Hispanic households had a 25 percent lower likelihood. No substantial differences were observed for children from other or multiracial households. 

Conclusion and Takeaway:

The study team concluded, “Children living in lower-income households, experiencing food insecurity, and residing in unsafe neighborhoods consistently showed higher prevalence and higher adjusted odds of both conditions. … Overall, these findings reinforce the need to view neurodevelopmental disorders within a broader social and structural framework.” 

It should be noted that this study is not aiming to name social factors as direct causes of ADHD. Rather, it points to socioeconomic disparities as contributing to the way ADHD develops and how it is treated. This type of research, as well as acknowledging barriers to care, is crucial for clinicians, counselors, teachers, etc., to consider when working with youth with ADHD. 

 

 

Norwegian Nationwide Population Study: Single Umbilical Artery Shows Weak Link to ADHD

Counting umbilical cord vessels is standard in prenatal ultrasounds and confirmed at birth. Single umbilical artery (SUA) occurs in about 1 in 200 cases, with roughly 10% associated with anomalies, including central nervous system defects. Isolated SUA (iSUA) means one artery is missing without other structural issues. 

Research on SUA, especially isolated iSUA, and childhood neurodevelopmental disorders (NDD) is limited and inconclusive. iSUA is linked to preterm birth and small-for-gestational age (SGA), both of which are NDD risk factors.  

This Norwegian nationwide population study aimed to assess NDD risk in children with iSUA at birth, the influence of sex, and how preterm birth and SGA mediate this relationship. 

The nation’s universal single-payer health insurance and comprehensive population registries made it possible to analyze all 858,397 single births occurring from 1999 to 2013, with follow-up continuing through 2019. Among these cases, 3,532 involved iSUA. 

After adjusting for confounders such as parental age, education, and maternal health factors, no overall link was found between iSUA and later ADHD diagnosis. However, females with iSUA had about a 40% higher risk of subsequent ADHD compared to those without iSUA, even after adjustment. 

The authors concluded, “The present study indicates that iSUA is weakly associated with ID [intellectual disability] and ADHD, and these associations are influenced by sex. This association is mediated negligibly through preterm birth and SGA. The associations were not clinically significant, and the absence of associations of iSUA with other NDD is reassuring. This finding can be useful in the counseling of expectant parents of fetuses diagnosed with iSUA.”