Cookie Preferences
By clicking, you agree to store cookies on your device to enhance navigation, analyze usage, and support marketing. More Info
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
June 10, 2025
This new meta-analysis confirms what other meta-analysis have already shown, i.e, that there exists in the population an association between maternal smoking during pregnancy and ADHD in their offspring. But reader beware, association does not mean causation.
The team identified 55 studies with quantitative data suitable for meta-analysis, including 11 case-control, 13 cross-sectional, and 31 retrospective/prospective cohort studies.
Altogether they combined more than four million persons in countries spanning six continents, including the United States, Finland, Sweden, Brazil, the Netherlands, Japan, the UK, Spain, China, Australia, New Zealand, Norway, Canada, France, Sweden, South Korea, Turkey, Romania, Bulgaria, Lithuania, Germany, Denmark, Egypt, and India.
Meta-analysis of all 55 studies found that offspring of mothers who smoked tobacco during pregnancy were about 70% more likely to develop ADHD than offspring of mothers who did not smoke during pregnancy.
Because variation in outcomes across studies was very high, the team performed subgroup analyses to explore potential sources of this heterogeneity.
Comparing study designs, cohort studies reported roughly 50% greater odds of ADHD among children of mothers who smoked during pregnancy, whereas case-control studies reported roughly 70% greater odds and cross-sectional studies 2.3-fold greater odds.
Studies using the most reliable method of determining ADHD – clinical interview/professional diagnosis – reported 90% greater odds, contrasting with 66% through medical records/databases and 58% through self-report by child/parent or through teacher report.
Good quality studies reported roughly 75% greater odds.
Studies with sample sizes above two thousand similarly found 70% greater odds.
There was no sign of publication bias using the more commonly used Egger’s test, but a marginal indication of publication bias using Begg’s test. Performing a standard correction reduced the effect size, indicating that the offspring of mothers who smoked tobacco during pregnancy were over 50% more likely to develop ADHD than the offspring of mothers who did not smoke during pregnancy.
The team concluded, “This systematic review and meta-analysis of 55 studies, encompassing over four million participants, provides compelling evidence that maternal tobacco smoking during pregnancy significantly increases the odds of ADHD in children … These findings underscore the critical need for public health interventions aimed at reducing tobacco smoking during pregnancy.”
However, we disagree with this conclusion; The authors ignore substantial evidence showing that maternal smoking during pregnancy is confounded by maternal ADHD. These mothers transmit ADHD via genetics, not via their smoking. This study should be seen not as "...[further evidence that smoking during pregnancy causes ADHD.] ", but as a lesson in how easy it can be to see correlation as causation.
------
Struggling with side effects or not seeing improvement in your day-to-day life? Dive into a step-by-step journey that starts with the basics of screening and diagnosis, detailing the clinical criteria healthcare professionals use so you can be certain you receive an accurate evaluation. This isn’t just another ADHD guide—it’s your toolkit for getting the care you deserve. This is the kind of care that doesn’t just patch up symptoms but helps you unlock your potential and build the life you want. Whether you’ve just been diagnosed or you’ve been living with ADHD for years, this booklet is here to empower you to take control of your healthcare journey.
Proceeds from the sale of this book are used to support www.ADHDevidence.org.
Mahdi Mohammadian, Lusine G. Khachatryan, Filipp V. Vadiyan, Mostafa Maleki, Fatemeh Fatahian, and Abdollah Mohammadian-Hafshejani, “The association between maternal tobacco smoking during pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring: A systematic review and meta-analysis,” PLOS ONE (2025), 20(2): e0317112, https://doi.org/10.1371/journal.pone.0317112.
Our genes are very important for the development of mental disorders-including ADHD, where genetic factors capture up to 75% of the risk. Until now, the search for these genes had yet to deliver clear results. In the 1990s, many of us were searching for genes that increased the risk for ADHD because we know from twin studies that ADHD had a robust genetic component. Because I realized that solving this problem required many DNA samples from people with and without ADHD, I created the ADHD Molecular Genetics Network, funded by the US NIMH. We later joined forces with the Psychiatric Genomics Consortium (PTC) and the Danish psych group, which had access to many samples.
The result is a study of over 20,000 people with ADHD and 35,000 who do not suffer from it - finding twelve locations (loci) where people with a particular genetic variant have an increased risk of ADHD compared to those who do not have the variant. The results of the study have just been published in the scientific journal Nature Genetics, https://www.nature.com/articles/s41588-018-0269-7.
These genetic discoveries provide new insights into the biology behind developing ADHD. For example, some genes have significance for how brain cells communicate with each other, while others are important for cognitive functions such as language and learning.
Our study used the genome-wide association study (GWAS)methodology because it allowed us to discover genetic loci anywhere on the genome. The method assays DNA variants throughout the genome and determines which variants are more common among ADHDvs. control participants. It also allowed for the discovery of loci having very small effects. That feature was essential because prior work suggested that, except for very rare cases, ADHD risk loci would individually have small effects.
The main findings are:
A) we found 12 loci on the genome that we can be certain harbor DNA risk variants for ADHD. None of these loci were traditional candidate genes' for ADHD, i.e., genes involved in regulating neurotransmission systems that are affected by ADHD medications. Instead, these genes seem to be involved in the development of brain circuits.
B) we found a significant polygenic etiology in our data, which means that there must be many loci(perhaps thousands) having variants that increase the risk for ADHD. We will need to collect a much larger sample to find out which specific loci are involved;
We also compared the new results with those from a genetic study of continuous measures of ADHD symptoms in the general population. We found that the same genetic variants that give rise to an ADHD diagnosis also affect inattention and impulsivity in the general population. This supports prior clinical research suggesting that, like hypertension and hypercholesteremia, ADHD is a continuous trait in the population. These genetic data now show that the genetic susceptibility to ADHD is also a quantitative trait comprised of many, perhaps thousands, of DNA variants
The study also examined the genetic overlap with other disorders and traits in analyses that ask the questions: Do genetic risk variants for ADHD increase or decrease the likelihood a person will express other traits and disorders. These analyses found a strong negative genetic correlation between ADHD and education. This tells us that many of the genetic variants which increase the risk for ADHD also make it more likely that a person will perform poorly in educational settings. The study also found a positive correlation between ADHD and obesity, increased BMI, and type-2 diabetes, which is to say that variants that increase the risk of ADHD also increase the risk of overweight and type-2 diabetes in the population. This work has laid the foundation for future work that will clarify how genetic risks combine with environmental risks to cause ADHD. When the pieces of that puzzle come together, researchers will be able to improve the diagnosis and treatment of ADHD.
A Swedish-Danish-Dutch team used the Swedish Medical Birth Register to identify the almost 1.7 million individuals born in the country between 1980 and 1995. Then, using the Multi-Generation Register, they identified 341,066 pairs of full siblings and 46,142 pairs of maternal half-siblings, totaling 774,416 individuals.
The team used the National Patient Register to identify diagnoses of ADHD, as well as neurodevelopmental disorders (autism spectrum disorder, developmental disorders, intellectual disability, motor disorders), externalizing psychiatric disorders (oppositional defiant and related disorders, alcohol misuse, drug misuse), and internalizing psychiatric disorders (depression, anxiety disorder, phobias, stress disorders, obsessive-compulsive disorder).
The team found that ADHD was strongly correlated with general psychopathology overall (r =0.67), as well as with the neurodevelopmental (r = 0.75), externalizing (r =0.67), and internalizing (r = 0.67) sub factors.
To tease out the effects of heredity, shared environment, and non-shared environment, a multivariate correlation model was used. Genetic variables were estimated by fixing them to correlate between siblings at their expected average gene sharing (0.5for full siblings, 0.25 for half-siblings). Non-genetic environmental components shared by siblings (such as growing up in the same family) were estimated by fixing them to correlate at 1 across full and half-siblings. Finally, non-shared environmental variables were estimated by fixing them to correlate at zero across all siblings.
This model estimated the heritability of the general psychopathology factor at 49%, with the contribution of the shared environment at 7 percent and the non-shared environment at 44%. After adjusting for the general psychopathology factor, ADHD showed a significant and moderately strong phenotypic correlation with the neurodevelopmental-specific factor (r = 0.43), and a significantly smaller correlation with the externalizing-specific factor (r = 0.25).
For phenotypic correlation between ADHD and the general psychopathology factor, genetics explained 52% of the total correlation, the non-shared environment 39%, and the shared familial environment only 9%. For the phenotypic correlation between ADHD and the neurodevelopmental-specific factor, genetics explained the entire correlation because the other two factors had competing effects that canceled each other out. For the phenotypic correlation between ADHD and the externalizing-specific factor, genetics explained 23% of the correlation, shared environment 22%, and non-shared environment 55%.
The authors concluded that "ADHD is more phenotypically and genetically linked to neurodevelopmental disorders than to externalizing and internalizing disorders, after accounting for a general psychopathology factor. ... After accounting for the general psychopathology factor, the correlation between ADHD and the neurodevelopmental-specific factor remained moderately strong, and was largely genetic in origin, suggesting substantial unique sharing of biological mechanisms among disorders. In contrast, the correlation between ADHD and the externalizing-specific factor was much smaller and was largely explained by-shared environmental effects. Lastly, the correlation between ADHD and the internalizing subfactor was almost entirely explained by the general psychopathology factor. This finding suggests that the comorbidity of ADHD and internalizing disorders are largely due to shared genetic effects and non-shared environmental influences that have effects on general psychopathology."
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.
The Background:
Myopia is a growing global health concern linked to conditions like macular degeneration, glaucoma, and retinal detachment. Its prevalence has surged in recent decades; by 2050, an estimated 5 billion people will have myopia. The increase is especially marked in Asia – a survey in Taiwan reports that 84% of students aged 15 to 18 are myopic, with 24% severely affected.
Dopamine is an important neurotransmitter in the retina, involved in eye development, visual signaling, and refractive changes. The dopamine hypothesis, suggesting that retinal dopamine release helps prevent myopia, has emerged as a leading theory of myopia control.
Most studies show ADHD is highly heritable, often involving dopamine system genes. ADHD is strongly associated with dopaminergic abnormalities, especially in dopamine transporter function and release dynamics.
Medications for ADHD, like methylphenidate, atomoxetine, and clonidine, help regulate dopamine to reduce symptoms.
The Study:
Given dopamine’s critical involvement in both ADHD and myopia, a Taiwanese research team hypothesized that medications for ADHD that influence dopaminergic pathways may have a significant effect on myopia risk.
To evaluate this hypothesis, the team conducted a nationwide cohort study using data from Taiwan’s National Health Insurance (NHI) program, which covers 99% of the nation’s 23 million residents and provides access to comprehensive eye care and screenings. Taiwan requires visual acuity screenings beginning at age four, with annual examinations for school-aged children to promote the early detection of visual anomalies such as myopia.
Furthermore, ADHD medication and diagnosis are tracked through compulsory diagnostic codes. This permits an accurate assessment of the effects of dopaminergic medications on myopia risk.
Propensity score allocation using a multivariable logistic regression model was applied to reduce bias from confounding influences, pairing cohorts based on similar scores.
The Results:
Comparing 133,945 individuals with ADHD with an equal number without ADHD, untreated ADHD was associated with a 22% greater risk of myopia.
However, after adjusting for covariates (gender, age, insured premium, comorbidities, location, and urbanization level), the ADHD cohort receiving medication treatment showed a 39% decreased risk of myopia relative to the untreated ADHD cohort.
Narrowing this further to the ADHD cohort receiving dopaminergic medications reduced the risk of myopia by more than half (52%) relative to the untreated ADHD cohort.
Treatment with two dopaminergic medications reduced the risk by well over two-thirds (72%) relative to the untreated ADHD cohort.
There were no significant differences between methylphenidate, atomoxetine, and clonidine. Each reduced risk by about 50%.
The team did not directly compare the ADHD cohort receiving dopaminergic medications with the non-ADHD cohort. But if there were 122 cases of myopia in the ADHD cohort for every 100 cases in the non-ADHD cohort, and dopaminergic medications halved the cases in the ADHD cohort to about 60, that would represent a roughly 40% reduction in myopia risk relative to the non-ADHD cohort.
The team concluded, “our research indicates that pharmacologically treated ADHD children have a reduced risk of myopia. Conversely, untreated ADHD children are at a heightened risk relative to those without ADHD. Moreover, the cumulative effects of ADHD medications were found to notably decrease myopia incidence, emphasizing the protective influence of dopaminergic modulation in these interventions.”
The Take-Away:
Children with untreated ADHD are more likely to develop myopia, but those receiving dopaminergic medications had a substantially lower risk. The findings suggest that ADHD medications may help protect against myopia by boosting dopamine signaling. More research is needed before firmly drawing this conclusion, but this research could open the door to new approaches for preventing myopia in at-risk children.
Background:
ADHD treatment includes medication, behavioral therapy, dietary changes, and special education. Stimulants are usually the first choice but may cause side effects like appetite loss and stomach discomfort, leading some to stop using them. Cognitive behavioral therapy (CBT) is effective but not always sufficient on its own. Research is increasingly exploring non-drug options, such as transcranial direct current stimulation (tDCS), which may boost medication effectiveness and improve results.
What is tDCS?
tDCS delivers a weak electric current (1.0–2.0 mA) via scalp electrodes to modulate brain activity, with current flowing from anode to cathode. Anodal stimulation increases neuronal activity, while cathodal stimulation generally inhibits it, though effects vary by region and neural circuitry. The impact of tDCS depends on factors such as current intensity, duration, and electrode shape. It targets cortical areas, often stimulating the dorsolateral prefrontal cortex for ADHD due to its role in cognitive control. Stimulation of the inferior frontal gyrus has also been shown to improve response inhibition, making it another target for ADHD therapy.
There is an ongoing debate about how effective tDCS is for individuals with ADHD. One study found that applying tDCS to the left dorsolateral prefrontal cortex can help reduce impulsivity symptoms in ADHD, whereas another study reported that several sessions of anodic tDCS did not lead to improvements in ADHD symptoms or cognitive abilities.
New Research:
Two recent meta-analyses have searched for a resolution to these conflicting findings. Both included only randomized controlled trials (RCTs) using either sham stimulation or a waitlist for controls.
Each team included seven studies in their respective meta-analyses, three of which appeared in both.
Both Wang et al. (three RCTs totaling 97 participants) and Wen et al. (three RCTs combining 121 participants) reported very large effect size reductions in inattention symptoms from tDCS versus controls. There was only one RCT overlap between them. Wang et al. had moderate to high variation (heterogeneity) in individual study outcomes, whereas Wen et al. had virtually none. There was no indication of publication bias.
Whereas Wen et al.’s same three RCTs found no significant reduction in hyperactivity/impulsivity symptoms, Wang et al. combined five RCTs with 221 total participants and reported a medium effect size reduction in impulsivity symptoms. This time, there was an overlap of two RCTs between the studies. Wen et al. had no heterogeneity, while Wang et al. had moderate heterogeneity. Neither showed signs of publication bias.
Turning to performance-based tasks, Wang et al. reported a medium effect size improvement in attentional performance from tDCS over controls (three RCTs totaling 136 participants), but no improvement in inhibitory control (five RCTs combining 234 persons).
Wang et al. found no significant difference in adverse events (four RCTs combining 161 participants) between tDCS and controls, with no heterogeneity. Wen et al. found no significant difference in dropout rates (4 RCTs totaling 143 individuals), again with no heterogeneity.
Wang et al. concluded, “tDCS may improve impulsive symptoms and inattentive symptoms among ADHD patients without increasing adverse effects, which is critical for clinical practice, especially when considering noninvasive brain stimulation, where patient safety is a key concern.”
Wen et al. further concluded, “Our study supported the use of tDCS for improving the self-reported symptoms of inattention and objective attentional performance in adults diagnosed with ADHD. However, the limited number of available trials hindered a robust investigation into the parameters required for establishing a standard protocol, such as the optimal location of electrode placement and treatment frequency in this setting. Further large-scale double-blind sham-controlled clinical trials that include assessments of self-reported symptoms and performance-based tasks both immediately after interventions and during follow-up periods, as well as comparisons of the efficacy of tDCS targeting different brain locations, are warranted to address these issues.”
The Take-Away:
Previous studies have shown mixed results on the benefits of this therapy on ADHD. These new findings suggest that tDCS may hold some real promise for adults with ADHD. While the technique didn’t meaningfully shift hyperactivity or impulsivity, it was well-tolerated and showed benefit, especially in self-reported symptoms. However, with only a handful of trials to draw from, it would be a mistake to suggest tDCS as a standard treatment protocol. Larger, well-designed studies are the next essential step to clarify where, how, and how often tDCS works best.
Background:
The development of ADHD is strongly associated with functional impairments in the prefrontal cortex, particularly the dorsolateral prefrontal cortex, which plays a key role in maintaining attention and controlling impulses. Moreover, imbalances in neurotransmitters like dopamine and norepinephrine are widely regarded as major neurobiological factors contributing to ADHD.
Executive functions are a group of higher-order cognitive skills that guide thoughts and actions toward goals. “Executive function” refers to three main components: inhibitory control, working memory, and cognitive flexibility. Inhibitory control helps curb impulsive actions to stay on track. Working memory allows temporary storage and manipulation of information for complex tasks. Cognitive flexibility enables switching attention and strategies in varied or demanding situations.
Research shows that about 89% of children with ADHD have specific executive function impairments. These difficulties in attention, self-control, and working memory often result in academic and social issues. Without timely intervention, these issues can lead to emotional disorders like depression, anxiety, and irritability, further affecting both physical health and social development.
Currently, primary treatments for executive function deficits in school-aged children with ADHD include medication and behavioral or psychological therapies, such as Cognitive Behavioral Therapy (CBT). While stimulant medications do improve executive function, not all patients are able to tolerate these medications. Behavioral interventions like neurofeedback provide customized care but show variable effectiveness and require specialized resources, making them hard to sustain. Safer, more practical, and long-lasting treatment options are urgently needed.
Exercise interventions are increasingly recognized as a safe, effective way to improve executive function in children with ADHD. However, systematic studies on school-aged children remain limited.
Moreover, there are two main scoring methods for assessing executive function: positive scoring (higher values mean better performance, such as accuracy) and reverse scoring (lower values mean better performance, such as reaction time). These different methods can affect how results are interpreted and compared across studies. This meta-analysis explored how different measurement and scoring methods might influence results, addressing important gaps in the research.
The Study:
Only randomized controlled trials (RCTs) involving school-aged children (6–13 years old) diagnosed with ADHD by DSM-IV, DSM-5, ICD-10, ICD-11, or the SNAP-IV scale were included. Studies were excluded if the experimental group received non-exercise interventions or exercise combined with other interventions.
Cognitive Flexibility
Using positive scoring, exercise interventions were associated with a narrowly non-significant small effect size improvement relative to controls (eight RCTs, 268 children). Using reverse scoring, however, they were associated with a medium effect size improvement (eleven RCTs, 452 children). Variation (heterogeneity) in individual RCT outcomes was moderate, with no sign of publication bias in both instances.
Inhibitory Control
Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (ten RCTs, 421 children). Using reverse scoring, there was an association with a medium effect size improvement (eight RCTs, 265 children). Heterogeneity was moderate with no sign of publication bias in either case.
Working Memory
Using positive scoring, exercise interventions were associated with a medium effect size improvement relative to controls (six RCTs, 321 children). Using reverse scoring, the exercise was associated with a medium effect size improvement (five RCTs, 143 children). Heterogeneity was low with no indication of publication bias in both instances.
Conclusion:
The team concluded, “Exercise interventions can effectively improve inhibitory control and working memory in school-aged children with ADHD, regardless of whether positive or reverse scoring methods are applied. However, the effects of exercise on cognitive flexibility appear to be limited, with significant improvements observed only under reverse scoring. Moreover, the effects of exercise interventions on inhibitory control, working memory, and cognitive flexibility vary across different measurement paradigms and scoring methods, indicating the importance of considering these methodological differences when interpreting results.”
Although this work is intriguing, it does not show that exercise significantly improves the symptoms of ADHD in children. This means that exercise, although beneficial for many reasons, should not be viewed as a replacement for evidence-based treatments for the disorder.
_logo%201.svg)
