December 12, 2025

Meta-analysis Finds Assisted Reproductive Techniques Associated with Offspring ADHD

Meta-analysis Finds Assisted Reproductive Techniques Associated with Offspring ADHD 

Background:

Recent progress in reproductive medicine has increased the number of children conceived via assisted reproductive techniques (ART). These include: 

  • In vitro fertilization (IVF), in which eggs are retrieved from the ovaries and fertilized with sperm in a laboratory; embryos are then transferred into the uterus.  
  • Intracytoplasmic sperm injection (ICSI), where a single sperm is injected directly into an egg. 
  • Intrauterine insemination (IUI), in which sperm is placed directly into the uterus around the time of ovulation. This is often combined with ovulation-inducing (OI) medications. 

Although ART helps with infertility, there are concerns about its long-term effects on offspring, especially regarding neurodevelopment. Factors such as hormonal treatments, gamete manipulation, altered embryonic environments, as well as parental age and infertility, may influence brain development and raise the risk of neurodevelopmental and mental health disorders. 

With previous studies finding conflicting results on a possible association between ART and increased risk of mental health disorders, an Indian research team has just published a new meta-analysis exploring this topic. 

The Study:

Studies were eligible if they were observational (cohort, case-control, or cross-sectional), reported confounder-adjusted effect sizes for ADHD, and were published in English in peer-reviewed journals. 

A meta-analysis of eight studies encompassing nearly twelve million individuals indicated a 7% higher prevalence of ADHD in offspring conceived via IVF/ICSI compared to those conceived naturally. The heterogeneity among studies was minimal, and no evidence of publication bias was observed. 

The study’s 95% confidence interval ranged from 4% to 10%. Further analysis of five studies comprising almost nine million participants that distinguished outcomes by sex revealed that the increase in ADHD risk among female offspring was not statistically significant. In contrast, the elevated risk in male offspring persisted, though it was marginally significant, with the lower bound of the confidence limit at only 1%. 

Results:

A meta-analysis of three studies (1.4 million participants) found a 13% higher rate of ADHD in children conceived via ovulation induction/intrauterine insemination (OI/IUI) compared to natural conception. The effect size, though doubled, remains small. Minimal heterogeneity and no publication bias were observed. 

The team concluded, “The review found a small but statistically significant moderate certainty evidence of an increased risk of ADHD in those conceived through ART, compared to spontaneous conception. The magnitude of observed risk is small and is reassuring for parents and clinicians.” 

Our Take-Away:

Overall, the meta-analysis points to a small, but measurable increase in ADHD diagnoses among children conceived through ART, but the effect sizes are modest and supported by moderate-certainty evidence. And we must always keep in mind that the researchers who wrote the original articles could not correct for all possible confounds.  These findings suggest that while reproductive technologies may introduce slight variation in neurodevelopmental outcomes, the effects are small and uncertain. For families and clinicians, the results are generally reassuring: ART remains a safe and effective avenue to parenthood, and the results of this study should not be viewed as a prohibitive concern. Thoughtful developmental monitoring and open, evidence-based counseling can help ensure that ART-conceived children receive support that caters to their individual needs.

 

Puneet Rana Arora, Ritu Sirohi, Priyadarshini Puri, Sakshi Rawat, and B. Shama Ansari, “Risk of ADHD in children born through assisted reproductive techniques: a systematic review and meta-analysis,” Journal of Tropical Pediatrics (2025) 71(6), fmaf047,  https://doi.org/10.1093/tropej/fmaf047

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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

Does Obesity Directly Contribute to Risk of ADHD in Offspring?

Does Acetaminophen use During Pregnancy Cause ADHD in Offspring?

Many media outlets have reported on a study suggesting that mothers who use acetaminophen during pregnancy may put their unborn child at risk for ADHD. Given that acetaminophen is used in many over-the-counter painkillers, correctly reporting such information is crucial. As usual, rather than relying on one study, looking at the big picture using all available studies is best. Because it is not possible to examine this issue with a randomized trial, we must rely on naturalistic studies.

One registry study (http://www.ncbi.nlm.nih.gov/pubmed/24566677)reported that fetal exposure to acetaminophen predicted an increased risk of ADHD with a risk ratio of 1.37. The risk was dose-dependent, in the sense that it increased with increased maternal use of acetaminophen. Of particular note, the authors made sure that their results were not accounted for by potential confounds (e.g., maternal fever, inflammation, and infection). Similar results were reported by another group (http://www.ncbi.nlm.nih.gov/pubmed/25251831), which also showed that the risk for ADHD was not predicted by maternal use of aspirin, antacids, or antibiotics. But that study only found an increased risk at age 7 (risk ratio = 2.0) not at age 11. In a Spanish study, (http://www.ncbi.nlm.nih.gov/pubmed/27353198), children exposed prenatally to acetaminophen were more likely to show symptoms of hyperactivity and impulsivity later in life. The risk ratio was small (1.1) but it increased with the frequency of prenatal acetaminophen use by their mothers.

We can draw a few conclusions from these studies. There does seem to be aweak, yet real, the association between maternal use of acetaminophen while pregnant and subsequent ADHD or ADHD symptoms in the exposed child. The association is weak in several ways: there are not many studies, they are all naturalistic, and the risk ratios are small. So mothers that have used acetaminophen during pregnancy and have an ADHD child should not conclude that their acetaminophen usecausedtheir child's ADHD. On the other hand, pregnant women who are considering the use of acetaminophen for fever or pain should discuss other options with their physician. As with many medical decisions, one must balance competing for risks to make an informed decision.

Find more evidence-based blogs at www.adhdinaduls.com.

March 14, 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