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October 1, 2025
Background:
Since the first in vitro fertilization (IVF) in 1978, assisted reproductive technology (ART) has led to over 10 million births worldwide.
There are four types of embryo transfers, depending on whether they are fresh or frozen, and on their developmental stage.
Fresh cleavage stage embryos are transferred on day 2 or 3 following fertilization and typically contain four to eight relatively large, undifferentiated cells. Fresh blastocyst embryos are transferred on day 5 or 6 after fertilization. At this point, they have developed over a hundred cells and have differentiated into two types: the inner cell mass, which develops into the fetus, and the outer cell layer, which forms the placenta.
Globally, more children are now born through assisted reproductive technology using frozen-thawed embryo transfer than fresh embryo transfer.
Research suggests that ART-conceived offspring may face increased risks of cardiovascular, musculoskeletal, chromosomal, urogenital diseases, and cancers. Might they also be at increased risk for ADHD?
Study:
Taiwan’s single-payer health insurance covers over 99% of people and records all their healthcare activity. Since 1998, it has kept an ART database for all couples registered for IVF treatment.
A Taiwanese research team reviewed all records for the five-year period from 2013 through 2017, ultimately analyzing 3,125 live singleton births from fresh cleavage stages, 1,332 from fresh blastocysts, 1,465 from frozen cleavage stages, and 4,708 from frozen blastocysts, alongside 878,643 naturally conceived singleton births.
The team controlled for the following potential confounders: pregnancy-induced hypertension, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, unhealthy lifestyle, placenta previa, placenta abruption, preterm premature rupture of membrane, and postpartum hemorrhage.
Results:
With these adjustments, cleavage stage embryo transfers, whether fresh or frozen, were associated with a seven-fold higher rate of ADHD diagnosis in offspring than natural conception.
Frozen blastocyst embryo transfers were likewise linked to a seven-fold increase in ADHD diagnoses in offspring compared to natural conception. Notably, fresh blastocyst transfers showed a 19-fold increase, likely due to the smaller number of cases in this category.
The team concluded, “Compared to natural conception, ART is associated with higher risks, particularly for preterm birth, ADHD, and developmental delay.”
Conclusion:
This large national cohort suggests that ART-conceived singletons face higher rates of several adverse outcomes, including preterm birth, ADHD, and developmental delay. Clinicians and prospective parents should therefore weigh these potential associations when counseling and planning care, prioritize optimized ART protocols and perinatal management, and ensure early developmental surveillance for ART-conceived children so concerns can be identified and addressed promptly.
It is important to note that the findings also point to the likely contribution of underlying parental infertility in these developmental outcomes. Future research should aim to disentangle parental- versus procedure-related risks to clarify absolute risk magnitudes. As always, associations of this time should not be interpreted as causal due to the inability of observational studies to rule out all possible confounding factors.
Chih-Ting Chang, Shih-Feng Weng, Hui-Yu Chuang, Chia-Yi Hsu, and Eing-Mei Tsai, “Impact of embryo transfer strategies on children health outcomes: a retrospective national cohort study in Taiwan,” Frontiers in Endocrinology (2025) 16:1630293, https://doi.org/10.3389/fendo.2025.1630293.
The Background:
Down syndrome (DS) is a genetic disorder resulting from an extra copy of chromosome 21. It is associated with intellectual disability.
Three to five thousand children are born with Down syndrome each year. They have higher risks for conditions like hypothyroidism, sleep apnea, epilepsy, sensory issues, infections, and autoimmune diseases. Research on ADHD in patients with Down syndrome has been inconclusive.
The Study:
The National Health Interview Survey (NHIS) is a household survey conducted by the National Center for Health Statistics at the CDC.
Due to the low prevalence of Down syndrome, a Chinese research team used NHIS records from 1997 to 2018 to analyze data from 214,300 children aged 3 to 17, to obtain a sufficiently large and nationally representative sample to investigate any potential association with ADHD.
DS and ADHD were identified by asking, “Has a doctor or health professional ever diagnosed your child with Down syndrome, Attention Deficit Hyperactivity Disorder (ADHD), or Attention Deficit Disorder (ADD)?”
After adjusting for age, sex, and race/ethnicity, plus family highest education level, family income-to-poverty ratio, and geographic region, children and adolescents with Down syndrome had 70% greater odds of also having ADHD than children and adolescents without Down syndrome. There were no significant differences between males and females.
The Take-Away:
The team concluded, “in a nationwide population-based study of U.S. children, we found that a Down syndrome diagnosis was associated with a higher prevalence of ASD and ADHD. Our findings highlight the necessity of conducting early and routine screenings for ASD and ADHD in children with Down syndrome within clinical settings to improve the effectiveness of interventions.”
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/24566677, https://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.
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.
The Background:
Many studies have tried to determine whether exercise improves executive function in children and adolescents with ADHD, but their conclusions have not always agreed. To bring the evidence together more clearly, the research team re-analyzed the available randomized controlled trials using a statistical approach designed to handle the kinds of data common in this field.
Executive functions are skills that help us control attention and behavior. The three core components are inhibitory control (the ability to stop or override impulses), working memory (holding and manipulating information in mind), and cognitive flexibility (switching between tasks or perspectives). Because a single study often reports multiple tests that tap these different skills, one study can contribute several related results (called effect sizes). Traditional meta-analysis typically treats each effect size as independent; when they are actually correlated, that can bias the combined estimate or force reviewers to discard useful data.
To avoid those problems, the team used a three-level meta-analysis. In this model, variance in the data is separated into three sources:
(1) sampling variance: the random error in each measured effect
(2) within-study variance: differences between multiple effect sizes reported in the same study
(3) between-study variance: differences in effects from one study to another
Accounting for all three levels makes it possible to include every eligible effect size from each study, which preserves information and statistical power and reduces the risk that correlations among effect sizes will overstate results.
The Study:
The review focused on long-term exercise interventions and also tested whether certain factors might change (or moderate) the effects. These potential moderators included participant age, which executive-function subcomponent was measured, the type of exercise, how long each session lasted, the total length of the intervention, and how often sessions occurred.
To be included, studies had to be randomized controlled trials (RCTs) of children or adolescents aged 6–18 diagnosed with ADHD. RCTs randomly assign participants to an intervention or a comparison group and are considered a strong design for testing cause-and-effect. The exercise programs had to be structured and last at least six weeks. Comparison groups varied by study and could include usual care, medication, sedentary activities, health education, waiting lists, or everyday life without the specific exercise program. Fifteen studies including 658 participants met these criteria.
The Results:
The three-level meta-analysis showed that long-term exercise interventions were associated with moderate-to-strong improvements in overall executive function. When statistical outliers were removed, the result remained positive: 13 RCTs with 598 participants showed moderate improvements. In plain terms, this suggests improvements that are noticeable and meaningful on average, not just tiny changes that are unlikely to matter in daily life.
Those moderate gains appeared across all three executive-function domains (inhibitory control, working memory, and cognitive flexibility, meaning the benefits were not limited to a single cognitive skill. The authors also examined exercise type:
“Open-skill” activities, which require reacting to changing situations (for example, many team sports, martial arts sparring, or racket sports), produced moderate-to-large improvements.
“Closed-skill” activities, which are more predictable and repetitive (for example, running or stationary cycling), showed only small, non-significant improvements in this analysis.
The review also found dose-related patterns. Interventions lasting at least twelve weeks were about three times more effective than interventions of six to twelve weeks, and sessions longer than an hour were about twice as effective as shorter sessions. Benefits were largest among adolescents aged 13 and older.
These patterns suggest that longer, more intensive programs, and those that involve open-skill activities, may produce larger gains. However, the authors caution that the overall certainty of the evidence was low. “Low certainty” means that limitations in the available studies (for example, small sample sizes, variability in methods, or possible bias) make it difficult to be confident that the observed effects will hold up exactly the same way in future research. Some subgroup findings (age, intervention duration, and others) were based on only a small number of effect sizes, so those moderator results should be treated as exploratory rather than definitive.
The Take-Away:
In short, this three-level meta-analysis suggests that regular, structured exercise (particularly longer programs and open-skill activities) may help improve executive functions in children and adolescents with ADHD. The evidence is promising but not yet strong enough to be considered conclusive, and the authors recommend more, larger randomized trials to confirm specifically which types and doses of exercise are most effective. Moreover, neither this meta-analysis or others show that exercise can replace standard treatments for reducing the core symptoms of ADHD (inattention, hyperactivity, impulsivity).
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When a patient sits down in an examination room today, their physician is rarely the first voice they have heard regarding their symptoms. More often, an algorithm got there first.
According to a nationwide survey by The Physicians Foundation conducted with Medscape, medical misinformation is no longer a peripheral nuisance; it is a daily clinical crisis. Nearly all surveyed physicians (99.9%) reported that their patients had been influenced by medical misinformation over the past year.
While misinformation affects every discipline from oncology to cardiology, few conditions sit as squarely in the algorithmic crosshairs as ADHD. From viral 30-second video clips trivializing complex executive dysfunction to predatory wellness campaigns attacking evidence-based medications, the attack on evidence directly threatens the well-being of children and adults living with ADHD.
Key Findings from The Physicians Foundation
The survey, which captured perspectives from over 1,000 practicing physicians, paints a sobering picture of how unverified information disrupts modern medicine:
The challenge is especially acute in communities already facing systemic healthcare hurdles:
As the survey illustrates, 38% of rural physicians encounter "a great deal" of health misinformation, far exceeding their suburban (21%) and urban (25%) peers. In rural and underserved regions, where access to developmental pediatricians and psychiatrists is already scarce, online narratives frequently fill the void left by provider shortages.
Why ADHD Is Ground Zero for Health Misinformation
Despite decades of neurobiological research confirming its validity, ADHD remains uniquely vulnerable to digital distortions in three distinct ways:
1. The Dueling Traps: "Life Hack" Trivialization vs. Denialism
Social media platforms host billions of views under ADHD-related tags. While digital awareness has helped destigmatize mental health, it frequently collapses nuanced clinical criteria into broad, relatable personality traits such as zoning out during a boring meeting, misplacing keys, or feeling restless.
This creates two opposing misinformation hazards:
2. Medication Stigma and Treatment Nonadherence
The survey found that 49% of doctors frequently encounter medication nonadherence and 45% face treatment refusal due to misinformation.
In ADHD care, this finding is acutely visible around stimulant pharmacotherapy. First-line stimulant medications have high response rates and extensive safety profiles spanning decades. Yet online narratives persistently frame them as dangerous narcotics, accusing parents of "drugging their children" or claiming medications permanently alter a child's brain.
Terrified parents frequently delay initiating care or discontinue effective regimens without clinical oversight, turning instead to unproven, expensive alternative supplements, unverified nootropics, or restrictive elimination diets.
3. Escalating Anxiety and Parental Guilt
With 66% of physicians observing increased patient anxiety driven by online health claims, the emotional toll on families cannot be overstated. Parents of newly diagnosed children are inundated with contradictory advice: one post warns that failing to medicate guarantees academic failure, while another claims that medicating guarantees addiction.
Adults navigating a new diagnosis experience similar distress, second-guessing their lived experiences and feeling deep shame over their executive dysfunction.
4. The 15-Minute Primary Care Bottleneck
Because pediatricians and family physicians handle most ADHD diagnoses and management, the survey’s warning that 70% of primary care providers feel hamstrung by misinformation hits ADHD patients first.
Deconstructing a viral video, explaining the difference between therapeutic stimulant dosing and substance misuse, and addressing years of internalized stigma takes time. In a standard 15-to-20-minute primary care visit, providers are forced to choose between rushing through diagnostic assessments or leaving patients' misinformed fears unaddressed.
Rebuilding the Partnership: Steps for Patients, Families, and Providers
Addressing the erosion of trust requires practical, collaborative shifts from both sides of the examination table:
For Patients and Caregivers
For Healthcare Providers and Systems
Medical misinformation thrives in the gap between a patient's vulnerability and the clinical system's time constraints. By recognizing how digital noise distorts ADHD, patients and clinicians can work together to replace viral anxiety with evidence-based care.
The Background:
Adults with ADHD often struggle more at work than their peers without ADHD. They tend to underperform on job tasks, advance less in their careers, miss more workdays, and face higher rates of unemployment. Research from several countries, including Japan, points to two main channels through which ADHD erodes workplace productivity: absenteeism, or missing work entirely, and presenteeism, showing up but performing below one’s usual capacity. Both problems typically trace back to ADHD’s core symptoms: difficulty sustaining attention, managing time, staying organized, and navigating relationships with coworkers and supervisors.
Stigma compounds these challenges. Employers and the public often have limited understanding of how ADHD manifests in adults, which can translate into unfair treatment or diminished job opportunities. That fear of judgment, in turn, discourages some people from seeking a psychiatric evaluation in the first place, delaying diagnosis and treatment, and with it, delaying access to support that could improve both their work performance and daily functioning.
Japan does offer medical care and workplace support for adults with ADHD. Options include social skills training, which teaches practical strategies for communication and collaboration; self-reliance support programs that help with daily living and job management; and, in more severe cases, a disability pension for those unable to work. Still, it remains unclear whether these employment-support services are robust enough to help people who want to work actually secure and hold onto steady jobs.
The impact of ADHD extends beyond the individual diagnosed. Supporting a family member with ADHD can be emotionally and logistically demanding, often cutting into a caregiver’s own capacity to work and earn, meaning that the economic toll of ADHD ripples outward.
The Research:
Most prior research on the economic costs of ADHD, in both children and adults, has come from the United States and Europe, focusing on medical expenses, lost productivity, and social support spending. Until recently, no one had attempted a comparable estimate for adult ADHD in Japan or elsewhere in Asia.
To address that gap, a Japanese research team conducted a cross-sectional observational study (meaning they gathered data at a single point in time and examined existing patterns rather than testing an intervention). They drew on three sources: a retrospective review of medical insurance claims, a web-based survey of affected individuals, and official government statistics. Combining these, they estimated annual costs from a societal perspective, accounting for medical expenses, lost work productivity, and government welfare spending, as well as productivity losses among family caregivers.
The claims analysis relied on JMDC, a nationwide database of insurance receipts and medical examination records spanning multiple health insurers and covering 14 million residents. Within it, the researchers identified 30,730 adult outpatients diagnosed with ADHD.
The Results:
Annual medical costs per adult with ADHD (combining outpatient visits and medication) averaged 284,000 yen (about $1,750). Scaling this figure to match the age and sex distribution of Japan’s adult population produced a nationwide estimate of 74 billion yen (about $455 million).
A separate web-based survey found that, after statistical matching, nearly half of adults with ADHD received a disability pension, yielding a nationwide estimate of 95 billion yen (about $585 million) in ADHD-related pension payments. Including public employment support services, total social welfare spending reached 390 billion yen (about $2.4 billion).
Workplace productivity losses were substantial as well. With an unemployment rate more than four percentage points higher than the general population, unemployment-related losses among adults with ADHD totaled an estimated 50 billion yen. Lower average incomes among those employed accounted for a further 315 billion yen. Once absenteeism and presenteeism were factored in, total productivity losses reached 570 billion yen (about $3.5 billion).
Family members bore a comparable burden: productivity losses among adult relatives of people with ADHD were estimated at 540 billion yen (about $3.3 billion).
Taken together, these figures point to a nationwide socioeconomic burden of 1.6 trillion yen (roughly $11 billion), equivalent to nearly $30,000 per adult with ADHD.
The Take-Away:
“This study, the first estimate of the annual socioeconomic burden of adult ADHD in Japan, underscores the necessity of providing appropriate support to adult patients with ADHD and their families and the prevention of comorbidities,” the research team concluded. “In particular, measures to support participation in the workplace to improve patients’ quality of life and reduce the social and economic burden should be explored. Furthermore, it is hoped that estimating the annual socioeconomic burden of adult ADHD will help clarify policy priorities in Japan.”
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