February 13, 2022

Nationwide cohort study finds association between miscarriage and ADHD

Spontaneous abortion is the medical term used for what is more commonly known as miscarriage. It means the unintended loss of an embryo or fetus before the 20th week of pregnancy. This must not be confused in any way with induced abortion, which is a deliberate and intentional act to terminate a pregnancy.

Most miscarriages occur when the fetus is not developing properly. Among the major causes of miscarriage are chromosomal abnormalities, birth defects, abnormal hormonal imbalances, infections, and exposure to toxins.

A team of Chinese researchers used the Danish national registers to explore a nationwide cohort for associations between previous miscarriage and ADHD in subsequent offspring. They included all 1.1 million births in Denmark over the 17 years from 1995 through 2012. They excluded all children with chromosomal abnormalities, those born either extremely early (after less than 22 weeks gestation) or extremely late (greater than 45 weeks), and those for whom this information was missing. That left over one million children in the study cohort.

The team classified children as having ADHD either based on a recorded hospital diagnosis or after receiving ADHD medication prescriptions at least twice after the age of 3 years. A total of 25,747 children were identified as ADHD individuals (554 mothers having at least two miscarriages, 3,087 mothers having one miscarriage, and 22,106 mothers without miscarriage). The average age of the first ADHD diagnosis was 10 years.

Just over 130,000 children (12.2%) were born to mothers who had at least one miscarriage. Of these, just under 113,000 (10.6%) were born to mothers with a single miscarriage before birth, and just over 17,000 to mothers with more than one prior miscarriage.

Based on previous research, the team identified potential confounders, including sex, preterm birth (less than 37 weeks), low birth weight, small for gestational age, low Agar score (performed right after birth to assess the risk of infant mortality), maternal and paternal ages at birth, maternal diabetes, maternal hypothyroidism, maternal smoking during pregnancy, maternal education level, maternal and paternal psychiatric disorders before birth.

After adjusting for these possible confounders, children of mothers with a single prior miscarriage were 9% more likely to develop ADHD than those of mothers without any miscarriage. Children of mothers with two or more prior miscarriages were 22% more likely to be diagnosed with ADHD. This upward exposure-response trend was statistically significant.

Preterm birth was found to be the strongest confounding mediator of this trend but accounted for under 4% of the association. The authors concluded, "the observed associations were independent of several factors, such as maternal socioeconomic status, type of spontaneous abortion, parental history of psychiatric disorders, pregnancy characteristics (maternal smoking status, infection, diabetes and hypothyroidism status during pregnancy)and birth outcomes (low birth weight, preterm birth, low Agar score, and small for gestational age)."

They also noted that given the frequency of miscarriages, affecting more than one in eight women, "a small increase of neurodevelopmental problems in offspring could have major public health implications."

Hui Wang, Fei Li, Maohua Miao, Yongfu Yu, Honglei Ji, HuiLiu, Rong Huang, Carsten Obel, Jun Zhang, and Jiong Li, "Maternal spontaneous abortion and the risk of attention-deficit/ hyperactivity disorder in offspring: a population-based cohort study", Human Reproduction(2020), vol. 35, no. 5, 1211-1221,https://doi.org/10.1093/humrep/deaa035.

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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.