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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 persistent shortage of ADHD medications has been more than a simple annoyance for patients at the pharmacy; the inconsistent availability of these medications has had deep impacts on the daily lives of those struggling without them. While public discourse has pointed fingers at over-prescribing or at restrictive DEA quotas, a recent economic evaluation in JAMA Health Forum suggests we’ve been looking in the wrong direction for an answer to what is causing this.
The reality of the shortage is less about increased demand and more about a fragile, globalized supply chain that snapped at a critical link.
Debunking the "Quota Myth":
The prevailing narrative suggested that the Drug Enforcement Administration (DEA) was stifling production by refusing to raise quotas. However, the data tells a different story. In 2022, manufacturers collectively met only about 70% of their allotted production quotas.
So we know that the problem wasn't that this DEA quota ceiling was too low. In fact, most manufacturers couldn't even reach it. Even when accounting for exports and domestic retail, production remained significantly below the legal limit. Even if the DEA had doubled its quotas, these medications still likely wouldn't have magically appeared on pharmacy shelves.
The most striking finding in the study is the correlation between the shortage and a sharp decline in the import of raw Active Pharmaceutical Ingredients (APIs). For the past decade, Germany has accounted for over 85% of US amphetamine imports. In 2022, these imports dropped by approximately 36.7%. When the API doesn't arrive at the factory, production for medium and small manufacturers grinds to a halt. Unlike larger pharmaceutical giants, these smaller players often lack the inventory cushion or flexibility to quickly pivot to a new supplier.
When the primary supply of amphetamine-based stimulants (like Adderall) faltered, it triggered a secondary crisis. Patients and clinicians, seeking alternatives, shifted toward lisdexamfetamine (Vyvanse) and methylphenidate (Ritalin/Concerta).
If we view this shortage purely through a regulatory or clinical lens, we miss the underlying cause of the crisis. The pharmaceutical industry has become a victim of its reliance on "just-in-time manufacturing” and highly concentrated sourcing. Because over 30% of APIs for the US market are produced in just one or two facilities globally, the system isn't just inefficient; it’s brittle. We are, in a sense, trapped in a system that prioritizes cost-reduction over the resilience required for public health.
The researchers suggest several policy shifts to prevent a repeat of this supply chain failure:
The ADHD medication shortage wasn't a failure of clinical oversight or a sudden surge in "TikTok-driven diagnoses”, as many have suggested. It was a failure of logistics. It reminds us that the path from a lab in Germany to a patient's hand in the US is far more precarious than we realized.
ADHD is a neurodevelopmental condition rooted in delayed or atypical maturation of the prefrontal cortex (the brain region that governs self-regulation). This maturational lag underlies the hallmark difficulties with attention, hyperactivity, and impulsivity, and also impairs what researchers call executive function: the cognitive toolkit we rely on for working memory, impulse control, mental flexibility, emotional regulation, and the ability to tolerate delays in reward.
The Background:
Standard treatments work through two main routes. Stimulant and non-stimulant medications are considered very safe and effective treatments, but are not without risk of side effects and are not appropriate for every ADHD patient. Behavioral and psychosocial interventions can improve self-regulation and social functioning, but they require sustained effort and produce variable results. These limitations have kept the search for better alternatives active.
One candidate that has drawn growing attention is transcranial direct current stimulation (tDCS). The technique is appealingly simple: a weak electrical current is applied to the scalp through small electrodes, modulating the excitability of neurons in the underlying cortex without requiring surgery, anesthesia, or significant discomfort. Its safety profile and ease of use have made it attractive to researchers.
The Study:
A newly published meta-analysis set out to give the technique its most rigorous test yet, pooling results from randomized controlled trials, including crossover designs, that compared active tDCS against sham stimulation in people with ADHD across all age groups.
The Results:
The findings were consistently null. Across seven trials enrolling 303 participants, tDCS produced no significant reduction in overall ADHD symptom severity compared with sham. Breaking symptoms into their components made no difference: neither hyperactivity/impulsivity nor inattention improved. Turning to executive function, 18 studies with 872 participants found no meaningful gain in inhibitory control, and 12 studies with 506 participants found the same for working memory. Smaller bodies of evidence, including three studies on cognitive flexibility (122 participants) and two on hot executive function, the motivational and emotional dimension of self-regulation (86 participants), similarly came up empty. Variation in outcomes across studies was small to moderate, and there was no evidence of publication bias skewing the picture.
The authors’ conclusion was succinct: tDCS was well tolerated but “did not demonstrate significant overall efficacy for core ADHD symptoms or executive functions.”
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Disordered eating (a broad category of persistent, harmful patterns in eating or weight control) affects between 5% and 22% of children and adolescents worldwide, with similar rates seen in the United States. The consequences are far-reaching: these conditions are linked to bone fractures, anemia, malnutrition, dental erosion, obesity, diabetes, hypertension, and elevated cholesterol and triglycerides. They also carry one of the highest mortality rates of any psychiatric illness.
Eating disorders rarely occur in isolation. They frequently arise alongside other psychiatric and neurological conditions. Yet, until now, no large-scale study had examined these co-occurrences in a nationally representative U.S. sample. A new study addresses that gap, focusing on children and adolescents aged 6–17 and the conditions most commonly associated with disordered eating, including ADHD.
The Study:
Researchers drew on data from the 2022–2023 National Survey of Children's Health (NSCH), a nationally representative, cross-sectional survey covering all 50 states and Washington, D.C. Households were selected using stratified, address-based sampling, and parents or guardians completed surveys about one randomly selected child per household. The final sample included 68,000 children and adolescents.
Results:
After accounting for factors including sex, age, race and ethnicity, household income, educational attainment, insurance status, and household language, children and adolescents with ADHD were 2.6 times more likely to have some form of disordered eating compared to their typically developing peers.
The elevated risk appeared across a range of specific behaviors:
A greater tendency toward using diet pills, laxatives, or diuretics was also observed in the ADHD group, though this finding did not reach statistical significance.
The Take-Away:
These findings underscore a need to improve both prevention and treatment strategies for disordered eating, particularly in children and adolescents who have ADHD. Clinicians working with this population are advised to screen for a wide spectrum of disordered eating behaviors.
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