October 1, 2025

Taiwanese Nationwide Population Study Finds Strong Association Between Assisted Reproductive Technologies and Offspring ADHD

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

Related posts

U.S. Nationwide Study Finds Down Syndrome Associated with 70% Greater Odds of ADHD

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.” 

June 27, 2025

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

Untreated ADHD Nearly Doubles Risk of Motor Vehicle Crashes

Untreated ADHD nearly doubles risk of motor vehicle crashes, new meta-analysis finds

The Background:

Motor vehicle crashes remain one of the most significant public health challenges in the United States. In 2022 alone, nearly 44,000 people died on American roads, and more than 2.6 million crash-related injuries required emergency care. Most people are familiar with the usual suspects: drunk driving, speeding, and distracted driving from phones. These risks are well-documented and the focus of ongoing public safety campaigns. 

But a serious risk factor has been flying under the radar: untreated ADHD. Despite receiving little attention from the public, policymakers, or transportation safety agencies, it may belong in the same conversation as these better-known dangers. 

ADHD is not currently recognized by the National Highway Traffic Safety Administration as a driving risk factor; yet inattention and impulsivity, two of its defining features, are consistently cited as common contributors to crashes. Beyond these core symptoms, adults with ADHD may also experience emotional dysregulation, which can further impair driving behavior. 

The Research:

Prior studies on ADHD and crash risk have produced estimates ranging from a 5% to a 70% increase. This massive heterogeneity has made it difficult to draw firm conclusions. This new meta-analysis set out to offer some clarity on these numbers. 

Researchers focused specifically on adults aged 18 to 65 with a formal ADHD diagnosis who were not receiving treatment, comparing them to controls without ADHD. Four studies met these criteria, collectively covering more than 2.75 million people. 

The Results:

The findings were striking: untreated ADHD was associated with a 93% increase in crash risk (95% confidence interval: 88%–99%). There was no evidence of publication bias. Although there was meaningful variation across studies, most of it stemmed from the smallest study  (just 36 participants)  which reported an outlier estimate of a 16-fold increase. 

To put the 93% figure in context: a separate meta-analysis found that alcohol use is associated with a 150% increase in crash risk. Another way to understand just how significant this risk really is, untreated ADHD raises crash risk by more than half as much as alcohol does.

The analysis also found a dose-response relationship between ADHD symptom severity and crash risk: each incremental increase in symptom severity corresponded to a 5–6% higher crash risk. At the highest severity levels, crash risk approached that associated with alcohol use. This gradient reinforces that we're not looking at a binary distinction between “has ADHD” and “doesn’t” — the worse the symptoms, the greater the danger on the road. 

The Takeaway:

These findings have practical implications for patients, families, clinicians, and policymakers alike. Untreated ADHD is not a minor footnote in the driving safety literature; rather, it is a substantial, measurable, and potentially modifiable risk factor. The question of whether and how it should be factored into licensing policy, clinical practice, and public health messaging deserves serious attention. 

August 28, 2026

Childhood Exposure to Noise and Air Pollution and ADHD: A Meta-analysis

As populations grow, more children are growing up surrounded by traffic noise and polluted air.   In most cities, these two factors tend to go hand-in-hand; yet, most previous research has examined these exposures separately. Many reviews focused on a single pollutant (such as fine particulate matter, PM2.5), or on a single developmental window, such as pregnancy or early childhood. Few have asked how noise and air pollution compare as risk factors, or how prenatal and postnatal exposures differ in their effects. 

A new meta-analysis set out to address those gaps. It examined evidence on both environmental noise and several major air pollutants in relation to ADHD, compared exposures before versus after birth, and pooled data across countries and regions. Eligible studies involved children and adolescents under 18, used objective measures of environmental exposure, and assessed ADHD using either clinical diagnosis or standardized rating scales. 

Noise 

Nine studies, combining data from over 100,000 children and adolescents  (all in European countries and Canada) found that high noise exposure was associated with 3% greater odds of ADHD. Prenatal noise exposure showed no effect; childhood exposure alone drove the association, at 4% greater odds. This is a negligible effect size that could easily reflect unmeasured confounding factors rather than a true causal relationship. 

Nitrogen dioxide 

Thirteen studies covering nearly one million children and adolescents in Europe, Canada, China, and South Korea found that nitrogen dioxide (NO₂) exposure was associated with 11% greater odds of ADHD. As with noise, prenatal exposure showed no independent effect. When the analysis was restricted to the five studies that used clinical diagnoses alone — generally considered the most reliable measure — the estimated odds rose to between 20% and 80% higher. The wide range reflects substantial variation across studies. 

Pollutants with no significant effect 

Four studies (97,500 participants) examining nitric oxide (NO), three studies (over 63,000 participants) on ozone, and three studies (over 28,000 participants) on sulfur dioxide found no significant associations with ADHD. 

Particulate matter 

The strongest associations emerged for particulate matter. Twelve studies involving nearly 160,000 participants in China, the US, Canada, and Europe found that exposure to fine particles (PM2.5, 2.5 microns in diameter) was associated with 30% greater odds of ADHD. Ten studies covering more than a quarter of a million participants in India, China, South Korea, and Europe found that coarser particles (PM10, 10 microns) were associated with 50% greater odds. In both cases, prenatal exposure showed no association, which is consistent with the fact that fetuses do not breathe air through developed lungs. When restricted to clinically diagnosed ADHD, PM2.5 was associated with roughly 50% greater odds, and PM10 with more than double the odds. 

The Results

Across all exposures examined, particulate matter showed the clearest and strongest associations with ADHD, followed by nitrogen dioxide. Noise reached statistical significance but at a trivially small effect size. Nitric oxide, ozone, and sulfur dioxide showed no significant associations. 

The authors found no evidence of publication bias which strengthens confidence in the overall pattern. However, there was marked heterogeneity across individual studies: results varied considerably, which urges caution in treating any single estimate as definitive. These are associations, not proven causal relationships, and the possibility that unmeasured factors explain part of the signal cannot be ruled out.

New Expert Guidance on "Deprescribing" Stimulants for Adults with ADHD

The Background: 

Over the past two decades, diagnostic rates for adult ADHD have roughly doubled, and stimulant prescriptions in the United States skyrocketed by more than 50% between 2012 and 2023, particularly among girls and women. While these medications help many individuals manage their symptoms, a landmark 2026 article published in European Neuropsychopharmacology tackles an important question that is rarely discussed: When should doctors and patients consider stopping them?  

The Discussion: 

To answer this, the American Society of Clinical Psychopharmacology (ASCP) gathered a task force of 45 international experts spanning 12 countries. Through a rigorous evaluation process, they reached an overwhelming agreement on a framework for "deprescribing", the planned, supervised reduction or cessation of a medication. Here are the core insights from these ground-breaking guidelines and what they mean for adults navigating long-term ADHD treatment.  

When the Treatment Isn’t Yielding Benefits 

One of the most straightforward reasons to consider stopping a stimulant is if it simply isn’t doing its job. The task force agreed that if a patient does not experience an optimal response, measured by actual symptom reduction, improved daily functioning, and a better quality of life, even after trying a high, optimized dose, it may be time to step back and look at alternative options.  

Sometimes, the issue goes back to the initial evaluation. The criteria for diagnosing ADHD have expanded over the years, and brief psychiatric evaluations can occasionally lead to diagnostic inaccuracies. If a thorough reevaluation reveals that the original ADHD diagnosis was incorrect, the expert consensus is clear: stimulant deprescribing is appropriate unless another stimulant-responsive condition is evident. Furthermore, if a patient develops a persistent tolerance to the drug that cannot be resolved by safe dose adjustments, a temporary taper or drug holiday may be recommended.  

When the Risks to Health Outweigh the Rewards 

Our bodies and health needs naturally shift over time, meaning a medication that worked safely years ago might pose a threat to your health today. The experts concluded that deprescribing should be heavily considered if stimulants exacerbate a concurrent medical or psychiatric illness. For example, although rare, stimulants can unintentionally trigger mania or psychosis in adults with unstable or unrecognized comorbid bipolar disorder.  

Physical health developments are equally critical. If an adult develops a newly arising or unstable cardiovascular condition, such as a cardiac arrhythmia, ischemia, or cardiomyopathy, the risk-benefit balance changes dramatically. Additionally, if severe side effects occur that cannot be managed by reducing the dosage, or if dangerous new drug-drug interactions emerge, stopping the medication under medical supervision protects the patient's long-term well-being.  

Addressing Misuse and the Complex Role of Cannabis 

Because stimulant medications target brain reward and wakefulness circuitry, they can foster a propensity for misuse. Studies indicate that more than 1 in 5 adults prescribed stimulants have misused them, and 1 in 6 have diverted their medication to others. The task force emphasizes that deprescribing is warranted if a patient persistently takes doses higher than prescribed against medical advice, uses the medication purely for unauthorized performance enhancement, or has an untreated, coexisting substance use disorder.  

And what about cannabis? This topic sparked the most debate among the experts, falling just short of an official consensus with 71% agreement that regular cannabis use alone shouldn't automatically trigger a stimulant stoppage. Recognizing the complexity, such as how chronic cannabis use can overlap with ADHD executive function deficits, the task force proposed a structured monitoring approach instead of an immediate cutoff. Clinicians are encouraged to track the patient every 1 to 3 months using standardized symptom tools and random urine drug screens to verify whether cannabis use is actively neutralizing the stimulant's therapeutic benefits.  

The Path Forward: Safe Tapering and Lifestyle Support 

If you and your doctor decide that stopping a stimulant is the right path, it shouldn’t happen overnight. The task force strongly recommends that medications be gradually tapered off at a rate tailored to the individual to minimize potential disruptions and distinguish between transient withdrawal and a true return of ADHD symptoms.  

Crucially, stopping a medication doesn't mean stopping treatment. The experts highlight that the success of any deprescribing plan is significantly enhanced when patients focus on optimizing modifiable lifestyle factors. Prioritizing sleep hygiene, staying physically active, and implementing structured behavioral strategies can support executive functioning and help sustain your cognitive gains even as the medication is reduced or eliminated.  

The Takeaway: 

The decision to continue or stop an ADHD medication is a deeply personal one that requires balancing real-world efficacy, safety, and individual health changes. These new consensus recommendations provide an essential roadmap to help adults navigate their long-term mental health journeys safely and effectively.  

Are you or a loved one currently evaluating your long-term relationship with ADHD medication? Consider scheduling a check-in with your healthcare provider to discuss whether your current treatment plan still perfectly matches your health needs today.