December 8, 2023

Is there an association between maternal thyroid dysfunction during pregnancy and ADHD in offspring?

Hyperthyroidism, an overactive thyroid gland, occurs in about one in five hundred women. It has been tied to adverse effects in both mother and fetus, including pre-eclampsia (a condition in pregnancy characterized by high blood pressure, sometimes with fluid retention and excessive protein in the urine, which can indicate kidney damage), preterm delivery, heart failure, and in uteri retardation of growth.

In hypothyroidism, on the other hand, thyroid activity is abnormally low, which retards growth and mental development. It is particularly common in regions with widespread iodine deficiency. Depending on the region, it affects one in three hundred to one in thirty women. Maternal hypothyroidism is associated with an increased risk of pre-eclampsia, premature separation of the placenta from the wall of the uterus, miscarriage, in uteri growth retardation, and fetal death.

The fetus relies on maternal thyroid hormones until its own thyroid function initiates halfway through pregnancy. As we have just seen, this direct link in the early stages of pregnancy has serious consequences described above. Does it also affect the risk of developing ADHD in offspring?

A team of researchers based in Hong Kong reformed a comprehensive search of the peer-reviewed medical literature on this subject. It then conducted two meta-analyses, one examining maternal hyperthyroidism during pregnancy, the other on maternal hypothyroidism.

The meta-analysis for maternal hyperthyroidism during pregnancy combined two nationwide cohort studies with a total of over 3.1 million persons, using the Danish and Norwegian medical registries. It found a slight but significant association with ADHD in offspring.

The meta-analysis for maternal hypothyroidism during pregnancy included the same two nationwide cohort studies, plus an Israeli nationwide cohort study (along with a tiny U.S. cohort study), with a total of over 3.4 million persons. It likewise found a slight but significant association with ADHD in offspring.

Though the component studies did some assessment of confounders, the authors of the meta-analyses noted, "By including a more comprehensive range of confounding factors and biologically relevant covariate (e.g. thyroxine treatment), future studies are warranted to re-visit the association between maternal thyroid dysfunction and various health outcomes in offspring."

Grace Mengqin Ge, Miriam T. Y. Leung, Kenneth K. C. Man, Wing Cheong Leung, Patrick Ip, GloriaH.Y. Li, Ian C. K. Wong, Annie W.C. Kung, Ching-Lung Cheung, "Maternal thyroid dysfunction during pregnancy and the risk of adverse outcomes in the offspring: a systematic review and meta-analysis," The Journal of Clinical Endocrinology& Metabolism (2020), https://doi.org/10.1210/clinem/dgaa555.

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Probiotics and ADHD Symptoms: Meta-Analysis

Meta-analysis Finds Probiotics Have No Discernable Effect on ADHD Symptoms in Children and Adolescents

Background: 

Noting that “the results of previous investigations into the therapeutic benefits of probiotics in the treatment of ADHD symptoms remain inconsistent,” a Taiwanese study team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis. 

The Study:

The team identified seven randomized controlled trials (RCTs) that met criteria for inclusion: focusing on children and adolescents under 18, with ADHD diagnoses, comparing probiotic interventions with placebo, and using standardized behavioral rating scales to assess ADHD symptoms. 

Meta-analysis of these seven RCTs with a combined total of 342 participants found no significant improvement in ADHD symptoms. In fact, six of the seven RCTs clustered tightly around zero effect, while the seventh – a small sample (38) outlier – reported a very large effect size improvement.  

Meta-analysis of the three RCTs with a combined 154 individuals that used probiotics with single strains of microorganisms showed absolutely no improvement in ADHD symptoms with no between-study variation (heterogeneity). 

Meta-analysis of the four RCTs with a total of 188 participants that used multiple strains pointed to a medium – but statistically nonsignificant – effect size improvement, with high heterogeneity. Removing the previously mentioned outlier RCT collapsed the effect size to zero. 

Two of the RCTs (with 72 total individuals), including the outlier, offered probiotics in conjunction with methylphenidate treatment. Meta-analysis of the other five RCTs with 270 persons that were structured around pure supplementation yielded absolutely no improvement in ADHD symptoms with no heterogeneity. 

Meta-analyses of the four RCTs with a combined total of 238 participants that examined ADHD subtypes reported no effect on either inattention symptoms or hyperactivity/impulsivity symptoms. 

Trivially, given the lack of efficacy, probiotic regimens were tolerated as well as placebo. 

The Take-Away: 

Ultimately, this meta-analysis found no evidence that probiotics improve ADHD symptoms in children and adolescents. Across seven randomized controlled trials, results consistently showed no significant benefit compared to a placebo. While probiotics were well-tolerated, they did not meaningfully impact inattention, hyperactivity, or impulsivity. These findings suggest that probiotics, whether single or multi-strain, are not an effective treatment for ADHD.

March 17, 2025

Meta-analysis Suggests Physical Activity Improves Attention in Schoolchildren with ADHD

Background: 

Noting that “Previous research has demonstrated that attention significantly influences various domains such as language, literacy, and mathematics, making it a crucial determinant of academic achievement,” an international study team performed a comprehensive search of the peer-reviewed medical literature for studies evaluating effects of physical activity on attention. 

The Study:

The team’s meta-analysis of ten studies with a combined total of 474 participants found moderate reductions in attention problems following physical activity. They found no significant evidence of publication bias, but there was considerable variation in outcomes between studies (heterogeneity). 

To tease out the reasons for this variability, the team looked at specific attributes of the physical activity regimens used in the studies. 

The seven studies with 168 participants that involved mentally engaging physical activity reported large reductions in attention problems, whereas the three studies with 306 persons that used aerobic exercise found no reduction whatsoever. Heterogeneity in the former was reduced, in the latter all but disappearing. 

Comparing studies with other interventions as control groups (6 studies, 393 participants) with those with no intervention as control (4 studies, 81 participants), the former reported only small improvements in attention problems, while the latter reported large improvements. 

Duration of physical activity made little difference. The four studies with physical activity of an hour or more reported better outcomes than the six with less than an hour, but the difference was not significant. 

Greater frequency did make a difference, but in a counterintuitive way. The seven studies with one or two physical activity interventions per week (162 participants) reported large reductions in attention problems, whereas the three studies with three or more interventions per week (312 participants) showed no improvement. 

Conclusion:

The authors concluded, “Our study suggests that cognitively engaging exercise is more effective in improving attention problems in school-aged children with ADHD.” Moreover, “the benefits of improved attention in school-age children with ADHD are not necessarily positively correlated with higher frequency and longer duration of physical activity.”  Also keep in mind that exercise, while important for all children, should not replace medical and psychological treatments for the disorder.

March 10, 2025

Updated Analysis of ADHD Prevalence in The United States

The National Health Interview Survey (NHIS) is conducted annually by the National Center for Health Statistics at the Centers for Disease Control and Prevention. The NHIS is done primarily through face-to-face computer-assisted interviews in the homes of respondents. But telephone interviews are substituted on request, or where travel distances make in-home visits impractical.  

For each interviewed family, only one sample child is randomly selected by a computer program.  

The total number of households with a child or adolescent aged 3-17 for the years 2018 through 2021 was 26,422. 

Based on responses from family members, 9.5% of the children and adolescents randomly surveyed throughout the United States had ADHD.  

This proportion varied significantly based on age, rising from 1.5% for ages 3-5 to 9.6% for ages 6-11 and to 13.4% for ages 12-17. 

There was an almost two-to-one gap between the 12.4% prevalence among males and the 6.6% prevalence among females. 

There was significant variation by race/ethnicity. While rates among non-Hispanic whites (11.1%) and non-Hispanic blacks (10.5%) did not differ significantly, these two groups differed significantly from Hispanics (7.2%) and Others (6.6%). 

There were no significant variations in ADHD prevalence based on highest education level of family members. 

But family income had a significant relationship with ADHD prevalence, especially at lower incomes. For family incomes under the poverty line, the prevalence was 12.7%. That dropped to 10.3% for family incomes above the poverty level but less than twice that level. For all others it dropped further to about 8.5%. Although that might seem like poverty causes ADHD, we cannot draw that conclusion.  Other data indicate that adults with ADHD have lower incomes.  That would lead to more ADHD in kids from lower income families.

There was also significant geographic variation in reported prevalence rates. It was highest in the South, at 11.3%, then the Midwest at 10%, the Northeast at 9.1%, with a jump down to 6.9% in the West. 

Overall ADHD prevalence did not vary significantly by year over the four years covered by this study. 

Study Conclusion:

This study highlights a consistently high prevalence of developmental disabilities among U.S. children and adolescents, with notable increases in other developmental delays and co-occurring learning and intellectual disabilities from 2018 to 2021. While the overall prevalence remained stable, these findings emphasize the need for continued research into potential risk factors and targeted interventions to address developmental challenges in youth.

It is also important to note that this study assessed the prevalence of ADHD being diagnosed by healthcare professionals.  Due to variations in healthcare accessibility across the country, the true prevalence of ADHD may differ still.

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March 7, 2025