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 of Exercise Interventions for Children and Adolescents Reports Medium-to-Large Improvements in Inhibitory Control, with Caveats

ADHD affects both individuals and society in many ways. Children and adolescents with ADHD often struggle with focusing, controlling impulses, and staying organized, which leads to problems with schoolwork, learning, and taking tests. These challenges can cause academic failure and make it harder for them to stay in school. 

ADHD symptoms often continue into adulthood, affecting jobs, relationships, and increasing risks for substance abuse and legal problems. 

Families of children and adolescents with ADHD face extra stress, with parents more likely to experience depression, anxiety, and relationship difficulties. The economic impact is also large, with billions spent each year on medical care, special education, lost productivity, and other related costs. 

Current treatments for ADHD mostly include medication, behavioral therapy, and educational support. While medications like stimulants can help control ADHD symptoms in the short term, they often cause side effects such as loss of appetite, trouble sleeping, slowed growth, cardiovascular risks, and potential substance dependence. These issues can make it hard for children and adolescents to stay on their medication, and about a third either don’t respond well or can’t tolerate the side effects. Once medication is stopped, the benefits fade quickly and do not lead to lasting improvements in executive functions (thinking skills). 

Behavioral therapy and parent training can help with behavior problems, but have limited effects on core mental skills like planning and self-control. These approaches also tend to be expensive, require a lot of support from parents and teachers, and are hard to use widely in schools and communities that lack resources.

Recently, exercise interventions have attracted growing interest as a non-pharmacological option. They provide several benefits: no drug-related side effects, easy accessibility, low cost, simple implementation in schools and communities, and enhanced physical and mental health. 

Previous meta-analyses examining how exercise interventions affect children and adolescents with ADHD have used traditional univariate models, which treat each study as if it only offers one independent effect size. In contrast, this study used multilevel meta-analysis — a more advanced statistical method modelling both between-study and within-study effects. This approach results in more accurate estimates and more dependable conclusions. 

Eligible studies were randomized controlled trials (RCTs) with usual care, no intervention, or waitlist controls, involving children and adolescents aged 5–18 diagnosed with ADHD by internationally recognized diagnostic criteria, and reporting inhibitory control outcomes. 

Eleven studies combining 512 children and adolescents met these inclusion standards. 

The analysis between experimental and control groups indicated that the exercise intervention group had significantly improved inhibitory control performance compared to the control group, with a medium-to-large effect size. There was very little variation (heterogeneity) in outcome between the studies, and no sign of publication bias.  

Within-group analyses showed that experimental groups had significant improvements after the intervention compared to baseline, with large effect sizes and moderate heterogeneity. 

By comparison, analyzing control groups over the same period revealed no significant differences, indicating that inhibitory control abilities in these groups remained largely unchanged throughout the observation period. There was little heterogeneity.  

Nevertheless, only one of the studies was rated low risk of bias, nine had some concerns, and two were rated high risk of bias. The greatest shortcomings were a lack of blinding and preregistration. 

The study authors therefore concluded that the overall evidence quality of this meta-analysis is low, limiting confidence in the results. While exercise interventions seem to improve inhibitory control abilities in children and adolescents with ADHD, significant methodological limitations create uncertainty about the effect size. These require more rigorous future studies to clarify these effects. Despite these caveats, they noted that all included studies reported statistically significant, consistent benefits from exercise interventions, offering preliminary support for their use as an adjunctive approach. 

Takeaway

This study lands in the same conversation as the adult ADHD exercise meta-analysis, and together they start to form a coherent picture: exercise appears to support attention and impulse control across the lifespan for people with ADHD, not just in one age group. The honest caveat is that the research quality in this field is still catching up to the enthusiasm — most studies have design weaknesses that limit confidence in the exact size of the effect. But the consistency of findings across studies, age groups, and now two separate meta-analyses is hard to dismiss.  

 

March 23, 2026

Global Data Indicates Gentle Quarter-century Decline in ADHD in Adolescents and Young Adults

A new study in the respected journal PLOS One analyzes data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to examine trends in the incidence, prevalence, and disability-adjusted life-years associated with ADHD among adolescents and young adults aged 10 to 24 years between 1990 and 2021.  

The GBD 2021, released by the Institute for Health Metrics and Evaluation (U.S.), is a comprehensive global analysis of 371 diseases, injuries, and risk factors – such as ADHD – across 204 countries from 1990 to 2021. Its open-source data are publicly available. 

First, a distinction. Incidence measures the number of new cases of a disease that develop in a specific population each year. Prevalence measures the total number of existing cases – both new and pre-existing – in a population each year.   

The estimated global incidence of ADHD declined marginally from 12.61 per 100,000 population in 1990 to 11.89 per 100,000 population in 2021, representing an average annual decrease of 0.6% in age-standardized incidence. The rates observed were comparable between males and females. 

Regional trends varied: Western Europe had the highest rise in ADHD incidence (0.5% annually), while North Africa and the Middle East saw the largest drop (0.7% annually). Overall, a higher Socio-Demographic Index (SDI) is linked to a greater incidence, although it is far from a perfect fit. Nationally, showed the highest increase in ADHD incidence (1.15% annually), while Qatar showed the largest decrease with an annualized reduction of 1.77%. 

The estimated global prevalence of ADHD declined marginally from 2.38% in 1990 to 2.17% in 2021. Again, the decline was similar for males and females, and across all age groups (10-14, 15-19, 20-24). Higher SDI was associated with higher prevalence, but inconsistently. 

Disability-adjusted life-years (DALYs) combine years lost from early death and years lived with disability to measure disease burden. Globally, the age-standardized DALYs rate for ADHD decreased slightly from 30.3 per 100,000 population to 26.6 per 100,000 population, for an average annual decline of 0.6%. The decline occurred across age groups and was similar between males and females.  

The authors concluded that ADHD rates and related health burdens have generally declined over the past quarter century, though recent patterns are less consistent due to factors like socioeconomic changes and evolving diagnostic standards. Continued research is needed to improve the accuracy and accessibility of ADHD diagnosis and treatment to further reduce its global impact. 

 Take-Away:

The broader takeaway is one of cautious reassurance. Despite rising public awareness and diagnosis rates in many Western countries, the global picture over 25 years shows a gentle decline in ADHD burden among young people as opposed to a crisis of escalating proportions as social media may make one think. That said, the variation between regions suggests that access to diagnosis, cultural factors, and reporting standards are shaping the numbers as much as underlying biology. Progress is real but uneven, and the work of improving equitable access to diagnosis and care is far from finished.

March 20, 2026

Swedish Nationwide Population Study: Newborn Seizures Double Risk of ADHD

The first few weeks of life are the time when babies are most vulnerable to seizures (known as neonatal seizures). This is partly because of events that can occur during birth, and partly because the newborn brain is naturally in a more excitable state than a mature brain, making it more prone to seizure activity. 

Seizures affect roughly 1 to 3 in every 1,000 full-term babies born, and the rate is considerably higher in premature babies, at around 11 to 14 per 1,000. In most cases, seizures at this age are triggered by a specific event or injury affecting the brain. In full-term newborns, the most common cause is a condition called hypoxic-ischemic encephalopathy (HIE), which occurs when the brain is deprived of adequate oxygen and blood flow around the time of birth. Other causes include genetic or metabolic conditions, stroke, bleeding in the brain, and structural abnormalities in how the brain developed. In very premature babies, bleeding into the fluid-filled spaces of the brain (known as intraventricular hemorrhage) is the leading culprit. 

Diagnosing seizures in newborns is tricky because many normal or abnormal movements and behaviors in this age group can look like seizures without actually being them. For this reason, monitoring the baby’s brain activity using an electroencephalogram (EEG) – a test that records electrical signals in the brain – is essential to confirm whether a seizure is truly occurring. 

Sweden’s single-payer health system provides universal coverage, with national registers linking healthcare and population data. Researchers tracked infants with EEG/aEEG-confirmed seizures born between 2009 and 2020 and compared them to controls without neonatal seizures. 

Altogether, 1062 infants with neonatal seizures were matched with 5310 controls. 

The team adjusted for birth, mode of delivery, sex, birth weight, and Apgar scores – quick, standardized assessments used to evaluate newborns’ health minutes after birth. 

With these adjustments, infants who had neonatal seizures were twice as likely to subsequently be diagnosed with ADHD and three times as likely to be subsequently diagnosed with autism spectrum disorder.  

The authors emphasized that because the study was observational, it cannot demonstrate a direct cause-and-effect relationship between neonatal seizures and outcomes. Factors like seizure frequency, genetics, and socioeconomic status are thought to significantly impact the prognosis of affected children, but these could not be included in this study due to data limitations. 

March 18, 2026