Meta-analysis Finds Strong Placebo Response in Treatment of ADHD, Mid-range Among Nine Neurological Disorders

The Spanish National Health Survey tracks health care outcomes through representative samples of the Spanish population. 

A Spanish research team used survey data to explore the relationship between ADHD symptoms and dental and gum health in a representative sample of 3,402 Spanish children aged 6 to 14.

While previous studies have found associations between ADHD and poor dental health, they have not fully accounted for such important determinants of poor oral health as socioeconomic status, dental hygiene, or diet. 

The team therefore adjusted for sociodemographic factors, lifestyle variables, and oral hygiene behaviors. More specifically, they adjusted for sex, age, social class, parental education, exposure to tobacco smoke, consumption of sweets, consumption of sugary drinks, use of asthma or allergy medication, adequate oral hygiene behavior of children, adherence to regular dental visits, parental adequate oral hygiene behavior, and parental adherence to regular dental visits.

With those adjustments, children with ADHD symptoms had over twice the incidence of dental caries (cavities) as their counterparts without ADHD symptoms.

Tooth extractions and dental restorations also occurred with over 40% greater frequency in children with ADHD symptoms.

Gum bleeding, a sign of gum disease, was more than 60% more common among children with ADHD symptoms than among their non-ADHD peers.

Importantly, excluding children with daily sugar consumption, which left 1,693 children in the sample, made no difference in the outcome for cavities.

Excluding children with poor oral hygiene habits, which left 1,657 children in the sample, those with ADHD had 2.5-fold more caries than their non-ADHD counterparts.

Excluding children of low social class, which left 1,827 children in the sample, those with ADHD had 2.6-fold more caries than their non-ADHD counterparts.

Turning to a different method to address potential confounding factors, the team used nearest-neighbor propensity score matching to create virtual controls. This compared 461 children with ADHD to 461 carefully matched children without ADHD.

This time, children with ADHD symptoms had just under twice the incidence of cavities as their counterparts without ADHD symptoms, but 60% more tooth extractions and about 75% more dental restorations. The difference in gum bleeding became nonsignificant.

Noting that “The increased risk of caries was maintained when the analyses were restricted to middle/high social class families and children with low sugar intake, good oral hygiene behaviors and regular dental visits,” the team concluded, “Children with ADHD symptoms in Spain had worse oral health indicators than those without ADHD symptoms. Our results suggest that the association of ADHD symptoms with caries was independent of socioeconomic level, cariogenic diet, frequency of toothbrushing, and dental visits.”

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This new meta-analysis confirms what other meta-analysis have already shown, i.e, that there exists in the population an association between maternal smoking during pregnancy and ADHD in their offspring.  But reader beware, association does not mean causation.

The team identified 55 studies with quantitative data suitable for meta-analysis, including 11 case-control, 13 cross-sectional, and 31 retrospective/prospective cohort studies. 

Altogether they combined more than four million persons in countries spanning six continents, including the United States, Finland, Sweden, Brazil, the Netherlands, Japan, the UK, Spain, China, Australia, New Zealand, Norway, Canada, France, Sweden, South Korea, Turkey, Romania, Bulgaria, Lithuania, Germany, Denmark, Egypt, and India.

Meta-analysis of all 55 studies found that offspring of mothers who smoked tobacco during pregnancy were about 70% more likely to develop ADHD than offspring of mothers who did not smoke during pregnancy.

Because variation in outcomes across studies was very high, the team performed subgroup analyses to explore potential sources of this heterogeneity. 

Comparing study designs, cohort studies reported roughly 50% greater odds of ADHD among children of mothers who smoked during pregnancy, whereas case-control studies reported roughly 70% greater odds and cross-sectional studies 2.3-fold greater odds.

Studies using the most reliable method of determining ADHD – clinical interview/professional diagnosis – reported 90% greater odds, contrasting with 66% through medical records/databases and 58% through self-report by child/parent or through teacher report.

Good quality studies reported roughly 75% greater odds. 

Studies with sample sizes above two thousand similarly found 70% greater odds.

There was no sign of publication bias using the more commonly used Egger’s test, but a marginal indication of publication bias using Begg’s test. Performing a standard correction reduced the effect size, indicating that the offspring of mothers who smoked tobacco during pregnancy were over 50% more likely to develop ADHD than the offspring of mothers who did not smoke during pregnancy.

The team concluded, “This systematic review and meta-analysis of 55 studies, encompassing over four million participants, provides compelling evidence that maternal tobacco smoking during pregnancy significantly increases the odds of ADHD in children … These findings underscore the critical need for public health interventions aimed at reducing tobacco smoking during pregnancy.”

However, we disagree with this conclusion; The authors ignore substantial evidence showing that maternal smoking during pregnancy is confounded by maternal ADHD. These mothers transmit ADHD via genetics, not via their smoking. This study should be seen not as "...[further evidence that smoking during pregnancy causes ADHD.] ", but as a lesson in how easy it can be to see correlation as causation.

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Study Background:

Animal-assisted interventions (AAIs) involve structured interactions with animals, designed and carried out by mental health teams assisted by trained human–animal professionals, to achieve specific therapeutic or educational goals. While a wide variety of animals may be used, horses and dogs tend to predominate. These interventions often involve physical contact, imitation, and play aimed at reducing stress and generating affection. Previous research has suggested that AAI to those with a range of developmental and mental health conditions.

Just how effective are they for treating ADHD in children and adolescents? Recent years have seen an increase in studies into AAIs for children with ADHD, but previous systematic reviews have not included quantitative meta-analysis to evaluate efficacy.

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The Study:

A Chinese study team based in Nanjing set out to remedy that with a systematic search of the peer-reviewed published medical literature aimed at performing meta-analyses of efficacy.

The team limited its search to randomized controlled trials (RCTs) and pre–post single-group studies involving children and adolescents diagnosed with ADHD.

Meta-analysis of five studies with a combined total of 95 participants reported no significant effect of AAIs on ADHD symptom severity. There was negligible variation (heterogeneity) in outcomes among the studies.

Similarly, meta-analysis of the six studies encompassing 323 individuals found no significant improvements in social behavior. There was no heterogeneity and no sign of publication bias. Breaking that down into subcategories of social interaction (4 studies, 190 persons), social skill (3 studies, 53 persons), and problem behavior (4 studies, 80 participants) made no difference.

Likewise, meta-analysis of the three studies encompassing 61 individuals found no significant improvements in emotional control. Again, there was no heterogeneity and no sign of publication bias.

Three studies combining 56 participants reported no significant reductions in anxiety and depression, again with no heterogeneity and no sign of publication bias.

However, meta-analyses of five studies encompassing 194 individuals found a medium effect size association between AAIs and declines in attention problems, and a medium-to-large effect size improvement in learning and cognition. Heterogeneity was negligible to low.

Finally, meta-analysis of three studies combining 95 participants reported a large effect size improvement in motor proficiency, with moderate heterogeneity.

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The Conclusion:

The team concluded, “As an ADHD management strategy complementary to gold-standard approaches, such as medication or multimodal interventions, AAIs did not appear to be more effective in improving the majority of core ADHD outcomes in children. Future studies should incorporate rigorous study designs with large sample sizes and a standard protocol to achieve more valid and reliable conclusions.”

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