February 6, 2026

South Korean Nationwide Population Study: Prenatal Exposure to Acid-suppressive Medications Not Linked to Subsequent ADHD

Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, are often prescribed during pregnancy to treat heartburn and gastroesophageal reflux disease. 

Research shows changes in the gut microbiome can negatively affect neurodevelopment. Since acid-suppressive medications alter gut microbiota, maternal use during pregnancy may impact offspring’s neurodevelopment. Because PPIs and H2 receptor antagonists readily cross the placental barrier, they could potentially influence fetal neurodevelopment.  

The link between prenatal exposure to acid-suppressive medications and major neuropsychiatric disorders is not well understood. With the use of these medications during pregnancy rising, it is important to assess their impact on children's long-term neurodevelopment. This study examined whether maternal use of acid-suppressive drugs is associated with increased risk of neuropsychiatric disorders in children, using a large, nationwide birth cohort from South Korea. 

South Korea operates a single-payer health insurance system, providing coverage for over 97% of its citizens. The National Health Insurance Service (NHIS) maintains a comprehensive database with sociodemographic details, medical diagnoses, procedures, prescriptions, health examinations, and vital statistics for all insured individuals. 

A Korean research team analyzed data from over three million mother-child pairs (2010–2017) to assess the risks of prenatal exposure to acid-suppressing medications. They applied propensity scoring to adjust for maternal age, number of children, medical history, and outpatient visits before pregnancy, to minimize confounding factors. That narrowed the cohort to just over 800,000 pairs, with half in the exposed group. 

With these adjustments, prenatal exposure to acid-suppressing medications was associated with 14% greater likelihood of being subsequently diagnosed with ADHD. 

Yet, when 151,737 exposed births were compared to the same number of sibling controls, no association was found between prenatal exposure and subsequent ADHD, which suggests unaccounted familial and genetic factors influenced the preceding results. 

The Take-Away:

Evidence of these medications negatively affecting pregnancies is mixed, mostly observational, and generally reassuring when these medications are used appropriately. Untreated GERD and gastritis, however, have known risks and associations with the development of various cancers. With no evidence of an association with ADHD (or for that matter any other neuropsychiatric disorder), there is no current evidence-based reason for expectant mothers to discontinue use of acid-suppressing medications.  

Acid-Suppressive Medications and Risk of Neuropsychiatric Disorders in Children,” JAMA (2026), https://doi.org/10.1001/jama.2025.23956

Xu YS, Chen ZR, Bian Y, Gao Y, Xin L, Wang LW. Association Between Gastroesophageal Reflux Disease and Extraesophageal Malignancies: A Systematic Review and Meta-Analysis. Cancers (Basel). 2025 Dec 4;17(23):3881. doi: 10.3390/cancers17233881. PMID: 41375082; PMCID: PMC12691378.

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What is Evidenced-Based Medicine?

What is Evidenced-Based Medicine?

With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling "facts" about the disorder.  But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual. 

My blog has several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:

Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. "Peer-reviewed" means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say "nearly all" because in some cases I've used books or other information published by colleagues who have a reputation for high-quality science.

When expressing certainty about putative facts, I am guided by the principles of evidence-based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements, such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies.  One study gives drug X to 10 ADHD patients and reported that 7 improved.  Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug-treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;http://www.cebm.net/).


The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:

  1. Mechanism-based reasoning.  For example, some data suggest that oxidative stress leads to ADHD, and we know that omega-3 fatty acids reduce oxidative stress. So there is a reasonable mechanism whereby omega-3 therapy might help ADHD people.
  2. Studies of one or a few people without a control group, or studies that compare treated patients to those that were not treated in the past.

Non-randomized, controlled studies.    In these studies, the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.  

  1. Non-randomized means that the comparison might be confounded by having placed different types of patients in the treatment and control groups.
  2. A single randomized trial.  This type of study is not confounded.
  3. Systematic review and meta-analysis of randomized trials. This means that many randomized trials have been completed and someone has combined them to reach a more accurate conclusion.

It is possible to have high-quality evidence proving that a treatment works but the treatment might not work very well. So it is important to consider the magnitude of the treatment effect, also called the "effect size" by statisticians. For ADHD, it is easiest to think about ranking treatments on a ten-point scale. The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.Omega-3 fatty acid supplementation 'works' with a quality rating of 5, but the score for the magnitude of the effect is only 2, so it doesn't work very well. We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment, and other issues when choosing a treatment for a specific patient, but we can only use an evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.

April 23, 2021

ADHD and Acetaminophen use During Pregnancy

ADHD and Acetaminophen use During Pregnancy

A recent CNN report, http://tinyurl.com/yannlfd6, highlighted a paper published in Pediatrics, which reported that pregnant women who use acetaminophen during pregnancy put their unborn child at two-fold increased risk for attention deficit hyperactivity disorder (ADHD).    In that study, acetaminophen use during pregnancy was common;  nearly half of women surveyed used the painkiller during pregnancy.   Other studies have reported similar associations of acetaminophen, also known as paracetamol with ADHD or with other problems in childhood (e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300094/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177119/ https://www.ncbi.nlm.nih.gov/pubmed/24566677https://www.ncbi.nlm.nih.gov/pubmed/24163279). Given these prior findings, it seems unlikely that the new report is a chance finding.  But does it make any biological sense?   One answer to that question came from an epigenetic study.  Such studies figure out if assaults from the environment change the genetic code.  One epigenetic study found that prenatal exposure changes the fetal genome via a process called methylation.  Such genomic changes could increase the risk for ADHD (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540511/). Because all of these studies are observational studies, one cannot assert with certainty that there is a causal link between acetaminophen use during pregnancy. 

The observed association could be due to some unmeasured third factor.  Although the researchers did a respectable job ruling out some third factors, we must acknowledge some uncertainty in the finding.  That said, what should pregnant women do if they need acetaminophen.   I suggest you bring this information to your physician and ask if there is a suitable alternative.

March 16, 2021

No Link Found Between In Utero Antipsychotic Exposure and ADHD

Meta-analysis with Millions of Participants Finds No Link Between Antipsychotic Use in Pregnancy and ADHD in Offspring

Antipsychotic medications are used to treat a variety of psychiatric disorders, including schizophrenia, bipolar disorder, sleeping problems, major depression, and severe anxiety. 

Untreated maternal mental illness is associated with poor health outcomes for both mothers and their offspring. On the other hand, one must guard against any potential direct harms of medications on development – including neurological development – of the fetus.  

Because prenatal use of antipsychotics is infrequent, previous observational studies have suffered from small sample sizes that have not enabled precise and reliable assessment of risk. The clinical decision about whether to continue antipsychotic treatment in patients who become pregnant has therefore remained inconclusive. 

In search of more reliable guidance, an international study team conducted a systematic search of the peer-reviewed medical literature to perform the first meta-analysis on this topic.  

They evaluated study quality and only included studies rated “good” or better. 

Identification of ADHD was determined by clinical diagnosis. 

Meta-analysis of four studies encompassing over eight million participants found a slight association. Children exposed to maternal antipsychotics during pregnancy were 11% more likely to be diagnosed with ADHD subsequently.  

But even in observational studies with millions of participants, such associations – especially when slight to begin with – could be due to unmeasured confounders. 

The team therefore compared children with gestational exposure to siblings from the same mother who were not exposed, to address shared genetic and social factors at the family level. 

Meta-analysis of two population-based sibling-matched studies with a combined total of over 4.6 million participants in Denmark, Norway, Sweden, Finland, Iceland, and Hong Kong found no significant association between gestational exposure to antipsychotic medications and subsequent diagnosis of ADHD

The team concluded, “Our systematic review and meta-analysis of observational studies indicates that the heightened risks of ADHD and ASD observed in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relation to the antipsychotic itself.” 

 

August 28, 2024

Meta-analysis: Cognitive Behavioral Therapy for Adult ADHD

A recent meta-analysis examined how well cognitive behavioral therapy (CBT) improves not just symptoms, but everyday functioning and quality of life in adults with ADHD. 

The Background:

ADHD in adults affects far more than attention or impulsivity. It often disrupts key areas of life: 

  • Education: Adults with ADHD tend to have lower GPAs, use fewer effective study strategies, achieve less academically, and are more likely to drop out.  
  • Work: They are more likely to experience job instability, including underperformance, unemployment, being fired, or frequent job changes.  
  • Social life: They often report smaller social networks, fewer close relationships, greater loneliness, and difficulty maintaining friendships or intimacy. Importantly, stronger social networks can help buffer (reduce) the impact of ADHD symptoms on daily life.  
  • Quality of life: Overall well-being is typically lower, affecting not only individuals but also their families and close relationships.

These broad impacts highlight a key issue: reducing symptoms does not automatically translate into better day-to-day functioning. 

CBT is a structured, skills-based therapy that helps people: 

  • Identify and challenge unhelpful thought patterns  
  • Reduce avoidance behaviors  
  • Build practical strategies for managing time, organization, and other executive functions (the mental skills used to plan, focus, and follow through)  

While both medication (especially stimulants) and CBT improve core ADHD symptoms, CBT is particularly aimed at improving real-world functioning. 

The Study:

The researchers analyzed studies involving adults diagnosed with ADHD (or showing clinically significant symptoms). They included: 

  • Randomized controlled trials (RCTs): studies comparing CBT to another treatment or to no treatment  
  • Within-subject studies: studies measuring change in the same individuals before and after CBT  

They focused specifically on outcomes beyond symptoms: 

  • Occupational functioning (work performance)  
  • Global functional impairment (overall daily functioning)  
  • Social relationships  
  • Academic functioning  
  • Quality of life  

The Results:

1.  Strongest Effects: Occupational functioning
CBT showed consistently strong improvements in work-related functioning compared to control groups, both immediately after treatment and at follow-up. This was the most robust finding across domains. 

2. Moderate Improvement: Global Functional Impairment
CBT led to moderate improvements in overall daily functioning, with some evidence that gains persist over time. In studies tracking individuals over time, improvements were even stronger at follow-up. 

3. Modest Gains: Social Relationships
CBT produced small to moderate improvements in social functioning. Benefits were present both after treatment and at follow-up, but were less pronounced than in work-related outcomes. 

4. Limited Effects: Academic Functioning
There were moderate short-term gains when CBT was compared to control groups, but these did not persist at follow-up. Within-subject studies showed only small improvements overall. 

5. Modest and Inconsistent Effects: Quality of Life
Improvements in quality of life were small when compared to control groups and often did not last. However, studies tracking individuals over time showed moderate improvements, suggesting some benefit that may not always show up clearly in between-group comparisons. 

Overall, the findings suggest: 

  • CBT does improve real-world functioning, not just symptoms  
  • The strongest and most consistent benefits are in occupational (work) functioning  
  • Gains in social life, academics, and overall quality of life are more modest and variable  
  • Improvements in functioning do not always track directly with symptom reduction  

One notable nuance: CBT did not always outperform other active treatments (like medication or other therapies). This suggests that while CBT is effective, its benefits may partly overlap with broader therapeutic or support effects rather than relying on a single, unique mechanism. 

The Take-Away: 

CBT is a valuable, evidence-based treatment for adults with ADHD, especially for improving work functioning and overall daily life management. However, its impact on relationships, academic outcomes, and quality of life is more limited and less consistent, pointing to the need for more targeted or combined approaches in those areas. 

 

June 9, 2026

When ADHD and Epilepsy Overlap, Cognitive Impacts Add Up

The Background:

ADHD and epilepsy are the two most common neurological disorders in children and adolescents. Additionally, they appear as co-diagnoses more often than chance would predict. Roughly a quarter of children with epilepsy also have ADHD, and children with ADHD face a 2.5-times greater risk of developing epilepsy than their peers. 

Clinicians have long suspected that carrying both diagnoses compounds cognitive difficulties, but no rigorous quantitative review has mapped out exactly how much, or in what ways. This new meta-analysis now fills that gap. 

The Study:

The team pooled data from peer-reviewed studies that included children and adolescents diagnosed with both conditions alongside at least one comparison group: children with neither condition, children with epilepsy alone, or children with ADHD alone. To capture the breadth of thinking skills, they constructed a general intelligence factor drawing on six cognitive domains: 

  • Crystallized intelligence — accumulated knowledge and its application 
  • Fluid reasoning — tackling novel problems through logical thinking 
  • Working memory — holding and mentally manipulating information in the short term 
  • Processing speed — executing simple or well-practiced mental tasks quickly 
  • Reaction time — responding rapidly to basic stimuli 
  • Long-term memory and fluency — efficiently storing and later retrieving new information 

The Results:

Across eleven studies (995 participants), children and adolescents with both conditions scored moderately lower on general intelligence than those with epilepsy alone. The same pattern held across all six cognitive domains. Seven studies (785 participants) comparing the dual-diagnosis group with those who had ADHD alone found an equally consistent moderate deficit, replicated in every domain. 

The clearest signal emerged when researchers compared children and adolescents carrying both diagnoses to typically-developing peers. Seven studies covering 427 individuals revealed a substantially larger gap in general intelligence, with the effects of the two conditions appearing to be roughly additive, meaning the combined burden was approximately equal to the sum of each condition's individual impact. This pattern held across five of the six domains. 

The Interpretation:

The results come with meaningful caveats. Variability across individual studies was moderate in the first two comparisons and high in the third, reflecting real differences in how studies were designed, which populations they sampled, and how they measured cognition. While there was no sign of publication bias in the first group, it was not assessed in two of the three analyses. 

The authors describe “a widespread profile of cognitive dysfunction” in children and adolescents with both epilepsy and ADHD, while underscoring that the substantial variability between studies warrants caution in drawing overly precise conclusions. The findings nonetheless carry practical weight: children managing both conditions may need more intensive cognitive screening and support than current clinical practice routinely provides. 

June 3, 2026

Exercise May Ease Social Difficulties in Young People with ADHD, New Meta-Analysis Suggests

The focus on children and adolescents with ADHD often revolves around behavioral issues and academic difficulties, but the social struggles are real. Around 60% of youth with ADHD experience meaningful difficulties in social skills, reading social cues, and forming reciprocal relationships with peers. Over time, these struggles can raise the risk of anxiety and depression. 

Medication remains the primary treatment for ADHD, with stimulants like methylphenidate (Ritalin) being the most commonly prescribed. While effective at reducing core symptoms such as inattention and impulsivity, medication has not been shown to improve social behavior or peer relationships.

The Background: 

Exercise has recently emerged as a promising adjunctive therapy. A newly published meta-analysis examined whether structured physical activity can specifically improve social functioning in young people with ADHD. It builds on a previous review from 2015, addressing gaps that earlier work left open: social outcomes were rarely treated as a primary focus, and no prior analysis had systematically compared exercise types or asked how much exercise is actually needed to see benefits. 

The Study: 

The analysis included 13 randomized controlled trials involving 703 participants aged 6 to 18, all clinically diagnosed with ADHD. Only exercise programs lasting at least four weeks were considered. Studies that combined exercise with other therapies, such as psychotherapy, were excluded to isolate exercise's specific effects. 

The researchers used a technique called network meta-analysis, which allows different interventions to be compared against one another even when they haven't been tested head-to-head, alongside dose-response modeling to identify how much exercise produces the greatest benefit. 

  • Closed-skill exercise: takes place in stable, predictable environments where movements can be planned in advance  (such as in gymnastics, track and field, or strength training). 
  • Open-skill exercise: unfolds in dynamic settings that demand constant adaptation  (team sports such as basketball or soccer, and those requiring specific hand-eye coordination such as table tennis). 
  • Multicomponent exercise blends both: a session might begin with a structured, self-directed drill (closed-skill) before transitioning into reactive, opponent-driven play (open-skill). 
  • Mind-body exercise integrates movement, mental focus, and controlled breathing (includes practices like yoga, tai chi, and qigong). 

Results: 

The most striking results came from closed-skill exercise: across four studies involving 92 participants, it was associated with a very large reduction in social dysfunction. Open-skill exercise, by contrast, showed no measurable improvement across four studies with 91 participants. Multicomponent exercise (the group combining elements of both open- and closed-skill) reported large gains in two smaller studies with 33 participants.  

Mind-body exercise showed a moderate benefit across three studies involving 44 participants. 

The dose-response analysis offered a practically useful finding: 30 to 60 minutes of moderate-intensity exercise per day appeared to produce the best outcomes, with a minimum of roughly 15 to 30 minutes daily needed to achieve any meaningful benefit. 

The Take-Away: 

The results are encouraging but should be interpreted carefully. The number of studies in each category was small (two to three studies each), and sample sizes were modest, meaning the findings may not hold up as more evidence accumulates. The absence of publication bias is reassuring, as is the use of rigorous methodology, but this remains an early-stage evidence base. Larger, well-designed trials are needed before firm clinical recommendations can be made. 

For now, the findings position structured physical activity  (particularly closed-skill and multicomponent exercise) as a plausible complement to existing ADHD treatment, specifically targeting the social difficulties that medication tends not to address. The practical dose guidance is a useful starting point: around half an hour of moderate daily exercise as a minimum, with an hour as the apparent sweet spot. As low-risk additions to a treatment plan go, that’s a relatively accessible bar for most families to consider alongside professional guidance. 

May 24, 2026