Meta-analysis of Two Nationwide Population Studies Finds No Harm to Offspring from Taking ADHD Medications During Pregnancy

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

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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

How To Best Manage ADHD During Pregnancy to Minimize Risk to Offspring

How can women best manage ADHD during pregnancy to minimize risk to their babies?

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."

June 18, 2021

Meta-analysis Finds People with ADHD Twice as Likely to Self-harm

Background: 

Non-suicidal self-injury (NSSI) means intentionally hurting yourself without trying to end your life. Common examples include cutting, scratching, or burning yourself. This behavior is most common in teenagers, affecting 13-20% of adolescents. It’s also called self-harm or deliberate self-injury. 

Young people who struggle with managing emotions, act impulsively, or have mental health conditions like depression are more likely to self-harm. 

Because ADHD involves impulsivity and often occurs alongside emotional difficulties, researchers have suspected a link between ADHD and self-injury. However, previous studies have tended to be small, unrepresentative, and inconsistent, making it hard to draw clear conclusions. 

The Study: 

Researchers combined results from 14 different studies involving nearly 30,000 people to get a clearer picture. They looked at children, teenagers, and adults with ADHD from various settings—including hospitals, community programs, and general population studies. 

To be included, studies had to confirm ADHD diagnosis through professional evaluation or validated testing methods. 

Key findings 

  • About 1 in 4 people with ADHD (27%) have engaged in self-injury. This rate was similar for adults (25%) and teenagers (28%).
  • People with ADHD had more than twice the odds (2.25 times higher) of self-injury compared to people without ADHD 
  • Girls and women with ADHD were at highest risk—they had four times higher rates of self-injury than boys and men with ADHD 

Conclusion: 

The researchers concluded that roughly one in four people with ADHD have engaged in non-suicidal self-harm. The findings suggest that ADHD and self-harm share overlapping vulnerabilities. 

Overall, this meta-analysis strengthens evidence that people with ADHD face a significantly elevated risk of non-suicidal self-injury, likely reflecting overlapping challenges with impulsivity, emotional regulation, and co-occurring mental health conditions. Importantly, this does not mean self-harm is inevitable in ADHD. It does, however, highlight the need for early screening, supportive environments, and targeted mental-health care to help reduce risk and support healthier coping strategies.

March 5, 2026

Meta-analysis Identifies Resilience Factors Associated with Improved Outcomes in Children and Adolescents with ADHD

Background:

While ADHD is generally linked to negative childhood outcomes, individual variability exists. Researchers have found that factors like cognition, emotion, parenting, and social interactions can help some adversity-exposed children develop better than expected. This variability has driven extensive resilience research, which now views resilience not as a single trait, but as a combination of biological, psychological, social, and ecological processes supporting adaptation. 

The Study:

This meta-analysis sought to address several key research gaps. First, while many potential resilience factors have been identified, no previous meta-analysis has quantitatively synthesized evidence focused specifically on children with ADHD. Second, relatively little research has clarified how particular resilience factors relate to specific developmental outcomes. Third, there is currently no integrated conceptual model of resilience processes tailored to children and adolescents with ADHD. 

To keep the analysis focused and clinically relevant, the authors examined psychosocial and ecological resilience factors only. Biological factors (such as genetics or cardiovascular health) and non-modifiable demographic characteristics (such as age and sex) were excluded, as they do not readily inform interventions. The analysis also focused strictly on outcomes for children and adolescents with ADHD, excluding adult outcomes and those reported for parents or teachers. Only studies based on clinical ADHD diagnoses were included. 

In total, 28 studies involving more than 11,600 participants met the inclusion criteria. Fifteen studies were rated as high quality and 13 as fair quality; none were rated low quality. However, the evidence base was relatively thin for many analyses. Of the 50 components examined, only one included five studies, six included four studies, ten included three studies, and most (33) were based on just two studies. While some components involved large samples, most did not, meaning the findings should be viewed as suggestive rather than definitive. 

Results:

Unsurprisingly, academic skills and cognitive functioning – specifically including working memory and intelligence – were strongly associated with better educational outcomes for children and adolescents with ADHD. In contrast, social skills and proactive attitudes or behaviors showed no significant link to educational attainment

Well-being outcomes showed a different pattern. Proactive attitudes and behaviors, cognitive functioning, and parental resources were associated with small-to-moderate improvements in well-being. Emotional regulation and positive parenting or attachment, however, were not significantly related to well-being in this analysis. 

For relationship outcomes, peer relationships – especially close friendships – stood out as particularly important, showing strong associations with better relational functioning. Social skills and positive parenting or attachment were linked to moderate improvements, although positive parenting alone had no significant effect. This suggests that the observed benefit likely stemmed from parental warmth and secure parent–child attachment rather than parenting practices in isolation. Parental resources (such as parental social support) and school-based support (including student–teacher relationships) showed no significant association with relationship outcomes. 

The study also examined behavioral symptoms. Externalizing symptoms refer to outward-directed behaviors that affect others or the environment, such as aggression, defiance, impulsivity, hyperactivity, and rule-breaking. Peer relationships were linked to a modest reduction in these behaviors, while positive relationships with adults were associated with a strong reduction. In contrast, disciplinary parenting – particularly harsh punishment – was strongly associated with increased externalizing symptoms. 

Internalizing symptoms involve inward-directed distress, such as anxiety, depression, withdrawal, excessive worry, and unexplained physical complaints. Here again, positive relationships with adults were important, showing a moderate association with fewer internalizing symptoms. Emotional regulation was also linked to small-to-moderate improvements. 

Conclusion: 

Overall, the findings highlight that resilience factors tend to be closely tied to specific outcomes rather than broadly protective across domains. For example, emotional regulation was associated with lower levels of both internalizing and externalizing symptoms but showed no significant link to well-being, educational achievement, or relationship quality. This suggests that emotional regulation may play a particularly important role in protecting mental health in children with ADHD, rather than driving broader developmental gains – consistent with evidence that emotional dysregulation is a core difficulty in ADHD. 

Similarly, academic skills, social competence, and prosocial behaviors were linked mainly to their most closely related outcomes. Cognitive functioning was associated with both educational and well-being outcomes, but its impact was much stronger in education and more modest for well-being. Together, these context-specific patterns underscore the importance of designing interventions that target particular resilience factors with strategies tailored to specific developmental goals, rather than assuming that any single factor will promote resilience across all areas of life. 

Key takeaway: resilience is individual and resilience isn’t one trait; different types of support help different individuals, in different areas.

Higher Relative Fat Mass (RFM) Associated with Lower ADHD Risk in Boys but Higher ADHD Risk in Girls

Background: 

Traditional measures of obesity, like body mass index (BMI) and waist circumference, have been linked to ADHD risk — but they aren’t great at capturing where fat is actually stored in the body. A newer index called relative fat mass (RFM), which combines height and waist circumference, does a better job of estimating overall body fat and predicting metabolic risks like heart disease and metabolic syndrome. Because those conditions share some underlying biological mechanisms with ADHD, researchers wondered whether RFM might also help explain the relationship between obesity and ADHD — particularly in children. 

That question is complicated by the fact that ADHD doesn't look the same in boys and girls. Boys tend to display more hyperactive and impulsive behavior, making their ADHD easier to spot. Girls more often show inattention, which is quieter and frequently goes undiagnosed. 


The Study: 

A new study set out to test whether RFM is associated with ADHD in children, and whether that association differs between sexes. Using data from the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2004, the researchers narrowed a large initial pool of over 31,000 participants down to 5,089 children and adolescents aged 6 to 14 who had complete data on height, waist circumference, ADHD screening, and other relevant variables. 

After adjusting for age, race/ethnicity, Poverty-Income Ratio, maternal age at delivery, maternal smoking during pregnancy, health insurance coverage, and birth weight, the results revealed a striking split along sex lines.  

In boys, higher RFM was associated with lower odds of ADHD. Compared to boys in the lowest fat-mass quartile, those in the second quartile had about 10% lower odds of ADHD, rising to over 30% lower in the third quartile and nearly 40% lower in the highest. In girls, the pattern reversed entirely. While girls in the second quartile showed similar odds to those with the lowest RFM, girls in the third and fourth quartiles had 60% to 70% greater odds of ADHD. 

Conclusion & Why This Matters:  

In recent years, the relationship between obesity and ADHD has become an increasingly important focus in pediatric neurodevelopmental research. Studies have reported higher rates of ADHD symptoms among children and adolescents with obesity compared with their non-obese peers, and difficulties with peer relationships have also been linked to increased obesity risk (Sönmez et al., 2019). From a neurobiological standpoint, both conditions may involve shared underlying mechanisms, particularly dysfunction in dopaminergic pathways.

The authors concluded that higher body fat levels appear to lower ADHD risk in boys while raising it in girls. This finding highlights why sex-specific analysis matters in ADHD research. The underlying biological reasons for this divergence, however, remain an open question and open the door for future research.