November 6, 2023

Nationwide population study: threatened spontaneous abortions not a risk factor for ADHD

Threatened spontaneous abortion is defined as vaginal bleeding without cervix dilation within 20 weeks of the onset of pregnancy.

Risk factors include advanced age, obesity, lifestyle (e.g., caffeine intake, lack of physical exercise, stress, cigarette smoking, and alcohol intake), socioeconomic variables, and low serum progesterone. Progesterone is a female hormone that plays a key role in the implantation of the fertilized egg, formation of the placenta, and sustaining a pregnancy.

Threatened spontaneous abortion affects roughly a fifth of pregnancies in the first trimester (first three months). Up to 11 weeks into pregnancy, it seldom leads to spontaneous abortion, but after 11 weeks the likelihood shoots up to as high as half of the affected pregnancies.

Denmark has universal single-payer health insurance. A team of researchers at Aarhus University used their country's comprehensive administrative and healthcare registries to explore any possible association between threatened spontaneous abortion and subsequent ADHD.

That enabled them to analyze a nationwide population of 1,864,221 singletons (as opposed to multiple births such as twins or triplets) live-born from 1979 to 2010. Of these children,59,134 (3.2%) experienced threatened spontaneous abortion within 20 weeks of gestation.

The team adjusted for a series of covariants that could confound outcomes: characteristics of mothers [age at childbirth, pre-pregnancy co-morbidities (somatic, neurologic, psychiatric), healthcare use, medication use, income, education, and employment]; fathers (age on the date of the child's birth, psychiatric co-morbidities a history of epilepsy, cerebral palsy, and ADHD); and children (birth year, birth order).

With these adjustments, they found that children who had experienced threatened spontaneous abortion were a fifth (21%) more likely to have ADHD. But it's exceedingly difficult to account for all confounding variables.

Because of the enormous size of the sample, however, the team was also able to compare 15,875 individuals who experienced threatened spontaneous abortions with an equal number of their paired full siblings who did not, to examine the effect of residual confounding variables. This time, they found no significant differences in the likelihood of ADHD between full siblings.

The authors observed that "controlling for family-shared factors, including genetic makeup and other factors remaining constant between pregnancies and in children's early environments, removed family-shared confounding." They concluded, "After removal, by the sibling design, of time-invariant family-shared confounding, there was no evidence of an increased risk of epilepsy or ADHD among TAB [Threatened Abortion]-affected children."

Elena Dudukina, Erzsébet Horváth-Puhó, HenrikToft Sørensen, and Vera Ehrenstein, “Long-term risk of epilepsy, cerebral palsy and attention-deficit/hyperactivity disorder in children affected by threatened abortion in utero,” International Journal of Epidemiology (2021)dyab069, published online, https://doi.org/10.1093/ije/dyab069.

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Meta-analysis Finds Little Evidence in Support of Game-based Digital Interventions for ADHD

ADHD treatment usually involves a combination of medication and behavioral therapy. However, medication can cause side effects, adherence problems, and resistance from patients or caregivers. 

Numerous systematic reviews and meta-analyses have evaluated the effects of non-pharmacological interventions on ADHD. With little research specifically examining game-based interventions for children and adolescents with ADHD or conducting meta-analyses to quantify their treatment effectiveness, a Korean study team performed a systematic search of the peer-reviewed medical literature to do just that.  

The Study: 

To be included, studies had to be randomized controlled trials (RCTs) that involved children and adolescents diagnosed with ADHD. The team excluded RCTs that included participants with psychiatric conditions other than ADHD.  

Eight studies met these standards. Four had a high risk of bias.  

Meta-analysis of four RCTs with a combined total of 481 participants reported no significant improvements in either working memory or inhibition from game-based digital interventions relative to controls. 

Likewise, meta-analysis of three RCTs encompassing 160 children and adolescents found no significant improvement in shifting tasks relative to controls. 

And meta-analysis of two RCTs combining 131 participants reported no significant gains in initiating, planning, organizing, and monitoring abilities, nor in emotional control

The only positive results were from two RCTs with only 90 total participants that indicated some improvement in visuospatial short-term memory and visuospatial working memory.  

There was no indication of effect size, because the team used mean differences instead of standardized mean differences.  

Conclusion:

The team concluded, “The meta-analysis revealed that game-based interventions significantly improved cognitive functions: (a) visuospatial short-term memory … and (b) visuospatial working memory … However, effects on behavioral aspects such as inhibition and monitoring … were not statistically significant, suggesting limited behavioral improvement following the interventions.” 

Simply put, the current evidence does not support the effectiveness of game-based interventions in improving behavioral symptoms of ADHD in children and adolescents. The only positive results were from two studies with a small combined sample size, which does not qualify as a genuine meta-analysis. All the other meta-analyses performed with larger sample sizes reported no benefits. 

Understanding Teen Health and Well-being in ADHD: A Fresh Perspective from the CDC

Recent research from the Centers for Disease Control and Prevention (CDC) highlights distinct health and social-emotional challenges faced by teens diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). This study, published in the Journal of Developmental and Behavioral Pediatrics, offers critical insights directly from the teens themselves, providing a unique view often missed when relying solely on parent or clinical reports. 

Researchers analyzed nationally representative data from July 2021 through December 2022, comparing self-reported experiences of teens aged 12 to 17 with and without ADHD. Approximately 10% of teenagers had an ADHD diagnosis, and the findings reveal specific areas where teens with ADHD face notable difficulties. 

Teenagers with ADHD reported significantly higher rates of bullying victimization and struggles in making friends compared to their peers. Surprisingly, they were less likely to report a lack of peer support, suggesting complexities in how they perceive friendships and social networks. The study underscores the importance of directly engaging teens in assessing their social relationships, rather than solely relying on parental perspectives. 

Sleep difficulties emerged as another critical issue for teens with ADHD. About 80% reported problems like difficulty waking up and irregular wake times, markedly higher than their non-ADHD counterparts. Such disruptions can exacerbate attention difficulties and emotional regulation issues, further complicating daily life for these teens. 

Excessive screen time also stood out, with nearly two-thirds of teens with ADHD spending over four hours daily on screens, excluding schoolwork. This high screen usage is concerning, given its potential negative impact on physical and mental health, including sleep quality and social interactions. 

Notably, the study found no significant differences in physical activity levels or concerns about weight between teens with and without ADHD. This finding contrasts with previous studies that have highlighted lower physical activity among children with ADHD, suggesting the need for continued research on how physical activity is measured and encouraged in this population. 

The study’s authors emphasize the importance of health promotion interventions tailored specifically for teens with ADHD. By directly engaging teens and considering their unique perspectives, interventions can better address social-emotional well-being and healthy lifestyle behaviors, ultimately improving long-term outcomes for this vulnerable group. 

Overall, this research provides compelling evidence for healthcare providers, educators, and families to focus on supporting teens with ADHD in areas of social skills, sleep hygiene, and healthy screen time habits. Such targeted support can significantly enhance the quality of life and health outcomes for adolescents navigating the challenges of ADHD. 

Meta-analysis Reports No Significant Evidence for Efficacy of Neuromechanistic Treatments for Adult ADHD

The Background on ADHD Treatments, rTMS and tDCS:

Methylphenidate is known as the gold-standard treatment for ADHD, increasing dopamine concentrations and helping to focus. However, these psychostimulants may be less well-tolerated in adults. Adverse effects include decreased appetite, nausea, racing heartbeat, restlessness, nervousness, and insomnia. 

Neurofeedback is a non-pharmaceutical treatment that combines cognitive behavioral therapy techniques like conditioning and positive reinforcement with electroencephalography (EEG) feedback. Electrodes are placed on specific brain areas, guiding patients to regulate their brainwave activity. 

Repetitive transcranial magnetic stimulation (rTMS) uses electromagnetism to induce an electric field by passing a magnetic field through the scalp. Transcranial direct current stimulation (tDCS), on the other hand, directly applies an electric current through the scalp. Both repetitive transcranial magnetic stimulation (rTMS) and tDCS primarily target the outermost layers of neurons, as they are non-invasive methods. Nevertheless, both techniques are believed to affect deeper layers through interconnected neuronal networks.  

The Study:

A French research team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis to explore the efficacy of these experimental treatment techniques. 

Eight studies – four using rTMS and another four using tDCS – met the inclusion criteria. Studies had to be randomized controlled trials (RCTs), and had to involve multiple sessions of treatment. Participants had to be adults previously diagnosed with ADHD.  

Outcomes were measured through self-rated scales, neuropsychological tests, and electrophysiological pre-post evaluations. 

Separate meta-analyses of the four tDCS RCTs combining 154 participants and of the four rTMS RCTs encompassing 149 participants likewise reported no significant improvements. In all cases variation in outcomes between studies was moderate, and there were no signs of publication bias. 

The Conclusion on Neuromechanistic Treatments for ADHD:

Meta-analysis of all eight studies with a combined total of 421 participants reported no significant improvements over controls. Narrowing down to studies that used sham controls likewise produced no significant improvements. So, despite the title of this study, these neuromechanistic treatments do not appear to be the future of treatment for adult ADHD.