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ADHD is the most prevalent neurodevelopmental disorder. Nearly 1% of pregnant women in the Nordic countries and more than 1% in the United States are prescribed ADHD medications, ranking these among the most commonly used medications during pregnancy. However, the safety of exposing a fetus to ADHD medications is still uncertain, prompting many expectant mothers to stop using them out of fear for their unborn child’s well-being.
The Study:
A European research team conducted a comprehensive nationwide study on the safety of ADHD medications during pregnancy using populations from Sweden and Denmark. The Swedish population was studied first, followed by inclusion of a separate study of the Danish population. Results were then combined through meta-analysis. Nordic countries, with their single-payer national health insurance systems and national population registers, facilitate the tracking of residents’ health from birth to death, thus providing robust data for such studies.
The team accounted for various potential confounders, including maternal age, year of delivery, whether the mother was a first-time parent, self-reported smoking during pregnancy, and any psychiatric history. They also considered psychiatric inpatient or outpatient treatment received within two years before pregnancy, as well as the dispensing of other psychotropic medications during pregnancy, including antidepressants, antipsychotics, antiseizure medications, and anti-anxiety medications. Additionally, they examined the highest level of maternal education and civil status at delivery (married or cohabiting compared to single, divorced, or widowed).
Out of 861,650 Swedish children, 2,257 were exposed to ADHD medications during pregnancy. Another 3,917 were born to mothers who discontinued ADHD medications before pregnancy.
Children exposed to ADHD medications had lower rates of ADHD, autism spectrum disorder, and overall neurodevelopmental disorders; however, none of these differences were significant.
Limiting the analysis to siblings to control for family environmental influences and genetics likewise found no significant differences.
A meta-analysis combining the Swedish results with a separately conducted nationwide population study in neighboring Denmark similarly found no significant differences between children exposed to ADHD medications during pregnancy and children born to mothers who discontinued ADHD medications before pregnancy.
Conclusion:
The team concluded, “Overall, our study provides reassuring evidence that continuing ADHD medication during pregnancy does not increase the risk of long-term NDDs [neurodevelopmental disorders] in offspring."
Kathrine Bang Madsen, Henrik Larsson, Charlotte Skoglund, Xiaoqin Liu, Trine Munk-Olsen, Veerle Bergink, Jeffrey H. Newcorn, Samuele Cortese, Paul Lichtenstein, Ralf Kuja-Halkola, Zheng Chang, Brian D’Onofrio, Per Hove Thomsen, Kari Klungsøyr, Isabell Brikell, and Miguel Garcia-Argibay, “In utero exposure to methylphenidate, amphetamines and atomoxetine and offspring neurodevelopmental disorders – a population-based cohort study and meta-analysis,” Molecular Psychiatry (2025), https://doi.org/10.1038/s41380-025-02968-4.
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.
Roughly one in thirty adult women have ADHD. Research results indicate that psychostimulants (methylphenidate and amphetamines) offer the most effective course of treatment in most instances. But during pregnancy, such treatment also exposes the fetus to these drugs. Several studies have set out to determine whether such exposure is harmful.
The largest comparison was 5,571 infants exposed to amphetamines and 2,072 exposed to methylphenidate with unexposed infants. It found no increased risks for adverse outcomes due to amphetamine or methylphenidate exposures. Another study studied 3,331 infants exposed to amphetamines, 1,515 exposed to methylphenidate, and 453 to atomoxetine. Comparing these infants to unexposed infants, it found a slightly increased risk of preeclampsia, with an adjusted risk ratio of 1.29 (95% CI 1.11-1.49), but no statistically significant effect for placental abruption, small gestational age, and preterm birth. When assessing the two stimulants, amphetamine, and methylphenidate, together, it found a small increased risk of preterm birth, with an adjusted risk ratio of 1.3 (95% CI 1.10-1.55). There was a statistically significant effect for preeclampsia, placental abruption, or small gestational age. Atomoxetine use was free of any indication of increased risk.
Another study involving 1,591 infants exposed to ADHD medication (mostly methylphenidate) during pregnancy, reported increased risks associated with exposure. The adjusted odds ratio for admission to a neonatal intensive care unit was 1.5 (95% CI 1.3-1.7), and for the central nervous system, disorders were 1.9 (95% CI 1.1-3.1). There was no increased risk for congenital malformations or perinatal death.
Six studies focused on methylphenidate exposure. Two, with a combined total of 402 exposed infants, found no increased risk for malformations. Another, with 208 exposed infants, found a slightly greater risk of cardiovascular malformations, but it was not statistically significant. A fourth, with 186 exposed infants, found no increased risk of malformations but did find a higher rate of miscarriage, with an adjusted hazard ratio of 1.98(95% CI 1.23-3.20). A fifth, with 480 exposed infants, also found a higher rate of miscarriage, with an odds ratio of 2.07 (95% CI 1.51-2.84). But although the sixth, with 382 exposed infants, likewise found an increased risk of miscarriage (adjusted relative risk 1.55 with 95% CI1.03-2.06), it also found an identical risk for women with ADHD who were not on medication during their pregnancies (adjusted relative risk 1.56with 95% CI 1.11-2.20). That finding suggests that all women with ADHD have a higher risk of miscarriage, and that methylphenidate exposure is not the causal factor.
Summing up, while some studies have shown increased adverse effects among infants exposed to maternal ADHD medications, most have not. There are indications that higher rates of miscarriage are associated with maternal ADHD rather than fetal exposure to psychostimulant medications. One study did find a small increased risk of central nervous system disorders and admission to a neonatal intensive care unit. But, again, we do not know whether that was due to exposure to psychostimulant medication or associated with maternal ADHD. If there is a risk, it appears to be a small one.
The question then becomes how to balance that as yet uncertain risk against the disadvantage of discontinuing the effective psychostimulant medication. As the authors of this review conclude. It [ADHD] is associated with significant psychiatric comorbidities for women, including depression, anxiety, substance use disorders, driving safety impairment, and occupational impairment. The gold standard treatment includes behavioral therapy and stimulant medication, namely methylphenidate and amphetamine derivatives. Psychostimulant use during pregnancy continues to increase and has been associated with a small increased relative risk of a range of obstetric concerns. However, the absolute increases in risks are small, and many of the best studies to date are confounded by other medication use and medical comorbidities.
Thus, women with moderate-to-severe ADHD should not necessarily be counseled to suspend their ADHD treatment based on these findings. They advise that when functional impairment from ADHD is moderate to severe, the benefits of stimulant medications may outweigh the small known and unknown risks of medication exposure, and that "If a decision is made to take ADHD medication, women should be informed of the known risks and benefits of the medication use in pregnancy, and take the lowest therapeutic dose possible."
Stimulant medications, such as methylphenidate (Ritalin) and amphetamines (Adderall), are among the most widely prescribed drugs in the world. In the United States alone, prescription rates have climbed more than 50% over the past decade, driven largely by growing awareness of ADHD in both children and adults. Yet stimulants also have a long history of non-medical use, and concerns about their psychological risks persist among patients, families, and clinicians alike.
Two major studies now offer the clearest picture yet of what that risk actually looks like, and who it may affect.
The Background:
Before turning to the research, it helps to understand the landscape. A notable share of stimulant users misuse their medication: roughly one in four takes it in ways other than prescribed, and about one in eleven meets criteria for Prescription Stimulant Use Disorder (PSUD). Counterintuitively, most people with PSUD aren’t obtaining drugs illicitly — they’re misusing their own prescriptions.
This distinction between therapeutic and non-therapeutic use turns out to be critical when evaluating psychosis risk.
The Study:
A comprehensive meta-analysis by Jangra and colleagues pooled data across more than a dozen studies to compare psychotic outcomes in people using stimulants therapeutically versus non-therapeutically. The contrast was striking.
Among therapeutic users (more than 220,000 individuals taking stimulants at prescribed doses under medical supervision), psychotic episodes occurred in roughly one in five hundred people. When symptoms did appear, they typically emerged after prolonged treatment or in individuals with pre-existing psychiatric vulnerabilities, and they usually resolved when the medication was stopped.
Among non-therapeutic users (over 8,000 participants across twelve studies, many using methamphetamine or high-dose amphetamines), nearly one in three experienced psychotic symptoms. These episodes tended to be more severe, involving persecutory delusions and hallucinations, with faster onset and a greater likelihood of recurrence or persistence.
The biology underlying this difference is well understood. When stimulants are taken orally at guideline-recommended doses, they produce moderate, gradual changes in neurotransmitter activity central to attention and executive functions. The brain tolerates these changes relatively well. Non-therapeutic use, by contrast, often involves much higher doses that are frequently delivered through non-oral routes such as injection or smoking. This produces a rapid, excessive surge in dopamine activity, which is precisely the neurochemical pattern associated with psychotic symptoms.
The takeaway here is not that therapeutic stimulant use is risk-free, but that risk is strongly modulated by dose, route of administration, and individual psychiatric history. Clinicians are advised to monitor patients with pre-existing mood or psychotic disorders, particularly carefully.
A Nationwide Study Focuses on Methylphenidate Specifically:
Where the meta-analysis cast a wide net, a large-scale population study by Healy and colleagues drilled into a specific and clinically pressing question: does methylphenidate (the most commonly prescribed ADHD medication, also known as Ritalin) increase the risk of developing a psychotic disorder?
To find out, the researchers analyzed Finland's national health insurance database, tracking nearly 700,000 individuals diagnosed with ADHD. Finland's single-payer system made this kind of comprehensive, long-term tracking possible in a way that fragmented healthcare systems rarely allow.
Critically, the team adjusted for a range of confounding factors that have clouded previous research, including sex, parental education, parental history of psychosis, and the number of psychiatric visits and diagnoses prior to the ADHD diagnosis itself (a proxy for illness severity). After these adjustments, they found no significant difference in the risk of schizophrenia or non-affective psychosis between patients treated with methylphenidate and those who remained unmedicated. This held true even among patients with four or more years of continuous methylphenidate use.
The Take-Away:
When considered together, these studies offer meaningful reassurance without encouraging complacency.
For patients and families weighing ADHD treatment, the evidence suggests that methylphenidate used as prescribed does not increase psychosis risk, even over years of use. The rare cases of stimulant-associated psychosis in therapeutic settings are typically linked to high doses, pre-existing vulnerabilities, or both, and tend to resolve with discontinuation.
For clinicians, the findings reinforce the importance of baseline psychiatric assessment before initiating stimulant therapy, ongoing monitoring in patients with mood or psychotic disorder histories, and clear patient education about the risks of dose escalation or non-oral use.
The picture that emerges is one of a meaningful distinction between a medication used carefully within its therapeutic window and a drug misused outside of it. This distinction matters enormously when communicating risk to patients, policymakers, and the public.
ADHD is commonly treated with medication, but these treatments frequently cause side effects such as reduced appetite and disrupted sleep. Psychological and behavioral therapies exist as alternatives, but they tend to be expensive, hard to scale, and generally do little to address the motor difficulties that many children with ADHD experience — things like clumsy movement, poor handwriting, or difficulty with coordination.
Physical exercise has attracted attention as a more accessible option. But research findings have been mixed, partly because studies vary so widely in how exercise is delivered and what outcomes they measure. This meta-analysis, drawing on 21 studies involving 850 children and adolescents aged 5–20 with a clinical ADHD diagnosis, tries to cut through that noise.
Two types of motor skills
The researchers separated motor skills into two broad categories:
The Data:
Gross motor skills (16 studies, 613 participants)
Overall, exercise produced medium-to-large improvements in gross motor skills. The strongest gains were in:
No significant gains were found in balance or flexibility.
Fine motor skills (13 studies, 553 participants):
Exercise also produced medium-to-large improvements in fine motor skills, specifically:
The Results: What Kind of Exercise Works Best?
Two factors stood out consistently across both gross and fine motor skills: session length and frequency.
The type of exercise mattered; structured programs with clear motor-skill components (rather than unstructured physical activity) yielded stronger results.
These results are not without caveats, however. The authors urge caution in interpreting these findings. A few key limitations include:
The Bottom Line
This meta-analysis provides tentative moderate evidence that structured physical exercise can meaningfully support motor skill development in children and adolescents with ADHD — particularly when sessions run longer than 45 minutes and occur at least three times a week. The benefits appear most robust for object control, locomotion, handwriting, and manual dexterity.
That said, the evidence base still has real gaps. The authors call for better-designed, fully randomized controlled trials with consistent methods, standardized ways of measuring exercise intensity, and greater inclusion of children and adolescents who are not on medication — all of which would help clarify when, how, and for whom exercise works best.
Treatment guidelines for childhood ADHD recommend medications as the first-line treatment for most youth with ADHD. Still, concerns about side effects and long-term outcomes have increased interest in non-pharmacological approaches. Researchers at Saudi Arabian Armed Forces hospitals recently conducted a network meta-analysis comparing several interventions, including mindfulness-based therapy, cognitive behavioral therapy, behavioral parent training, neurofeedback, yoga, virtual reality programs, and digital working memory training.
Although the authors aimed to “provide a rigorous methodological approach to combine evidence from multiple treatment comparisons,” the study illustrates several pitfalls that arise when network meta-analysis is applied to a thin and heterogeneous evidence base.
What Network Meta-analysis Can and Cannot Do:
Network meta-analysis extends conventional meta-analysis by combining:
When the evidence network is large and well-connected, this approach can provide useful estimates of comparative effectiveness among many treatments.
This method is not always best, however, as many networks are sparse. This is especially true in areas such as complementary or behavioral therapies. In sparse networks, estimates rely heavily on indirect comparisons, and single studies can exert disproportionate influence over the results.
Conventional meta-analysis focuses on heterogeneity, meaning differences in results across studies within the same comparison.
Network meta-analysis must additionally evaluate consistency, whether the direct and indirect evidence agree.
However, when comparisons are supported by only one or two studies and the network is weakly connected, statistical tests for heterogeneity and consistency have very little power. In practice, this means the analysis often cannot detect problems even if they are present.
Sparse networks also make publication bias difficult to evaluate. This concern is particularly relevant in fields dominated by small trials and emerging therapies.
Why Such Treatment Rankings Are Appealing, but Potentially Problematic:
Many network meta-analyses summarize results using SUCRA, which estimates the probability that each treatment ranks best.
SUCRA, or Surface Under the Cumulative Ranking, is a key statistical metric in network meta-analyses. It is used to rank treatments by efficacy or safety. This is achieved by summarizing the probabilities of a treatment's rank into a single percentage, where a higher SUCRA value indicates a superior treatment. Ultimately, SUCRA helps pinpoint the most effective intervention among the ones compared.
Again, in well-supported networks, SUCRA can provide a useful summary of comparative effectiveness. But in sparse networks, rankings can create an illusion of precision, because treatments supported by a single small study may appear highly ranked simply due to random variation.
What Did this New Network Meta-analysis Study?
The study includes 16 trials with a total of 806 participants. But the structure of the evidence network is far weaker than this headline number suggests.
Based on the underlying studies:
This produces a very thin network, in which several interventions rely entirely on single studies.
Another challenge is that the included trials measure different outcomes. Some evaluate ADHD symptom severity, while others measure parental stress.
When studies use different outcome scales, meta-analysis typically relies on standardized measures such as the standardized mean difference to allow comparisons across studies. However, the analysis reports only mean-average differences, making it difficult to interpret the relative effect sizes.
Study Issues (including Limited Evidence and Risk of Bias):
The intervention supported by the largest number of studies (family mindfulness-based therapy) was one of the two approaches reported as producing statistically significant results. The other was BrainFit, which is supported by only a single previous trial.
Despite this limited evidence base, the study ranks interventions using SUCRA:
Notably, none of the runner-up interventions demonstrated statistically significant efficacy.
The authors acknowledge methodological limitations in the included studies:
“Blinding of participants and personnel (performance bias) exhibited notable concerns, as blinding for active treatment was not applicable in most studies.”
Such limitations are common in behavioral intervention trials, but they further increase uncertainty in already small evidence networks.
Conclusions:
The study ultimately concludes:
“This network meta-analysis supports MBT and BPT as effective non-pharmacological treatments for ADHD.”
However, the evidence underlying these claims is limited. Some analyses rely on very small numbers of studies and participants, and the network structure depends heavily on indirect comparisons.
Network meta-analysis can be a powerful tool when applied to a large, consistent, and well-connected body of evidence. When the evidence base is sparse, however, the resulting rankings and comparisons may appear statistically sophisticated while resting on a fragile evidentiary foundation.
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