June 18, 2021

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."

Allison S. Baker, Marlene P. Freeman, "Management of Attention Deficit Hyperactivity Disorder During Pregnancy," Obstetrics and Gynecology Clinics of North America, vol. 45, issue 3 (2018), 495-509.

Related posts

No items found.

Updates on ADHD and Vitamin D

The Background on ADHD and Vitamin D

In a blog published in the early days of The ADHD Evidence Project, we discussed an Iranian study examining the association between Vitamin D levels and ADHD in children. The meta-analysis combined 13 studies for a total of 10,344 participants. The researchers found that youth with ADHD had "modest but significant" lower serum concentrations of 25-hydroxyvitamin D compared to those without ADHD.

They also identified four prospective studies that compared maternal vitamin D levels with the subsequent development of ADHD symptoms in their children. Two of these used maternal serum levels, and two used umbilical cord serum levels. Together, these studies found that low maternal vitamin D levels were associated with a 40% higher risk of ADHD in their children. 

Ultimately, the researchers noted that this result "should be considered with caution" because it was heavily dependent on one of the prospective studies included in the analysis. We concluded our blog by pointing out that further research, including more longitudinal studies, is needed before clinicians should start recommending vitamin D supplementation to ADHD patients. 

Further Research: 

Since publishing that initial blog, several more studies have been published about this association. 

The World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international task force involving 31 leading academics and clinicians from 15 countries between 2019 and 2021. Their goal was to provide a definitive, evidence-based report to assist clinicians in making decisions around the recommendation of nutraceuticals and phytoceuticals for major psychiatric disorders.

For ADHD, the guidelines found only weak support for micronutrients and vitamin D in treatment. Overall, the task force concluded that nutraceuticals and phytoceuticals currently offer very limited evidence‑based benefit for ADHD management.

Another study published in 2023 systematically assessed the results of previously published studies to examine the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and later offspring psychiatric outcomes. This study found a clear association between maternal vitamin D deficiency and subsequent offspring ADHD. They concluded, “Future studies with larger sample sizes, longer follow-up periods, and prenatal vitamin D assessed at multiple time points are needed.”  To that, I will add that studies of this issue should use genetically informed designs to avoid confounding.

Conclusion:

Taking into account the updated research on the topic, there does seem to be an association between low prenatal vitamin D levels and the risk of subsequent offspring ADHD, but it is too soon to say it is a causal relationship due to the possibility of confounding. There is no high-quality evidence, however, that supplementing with vitamin D will significantly reduce symptoms in current ADHD patients. 

July 28, 2025

What Metabolites Tell Us About ADHD — And What This Means for Diet and Treatment

New research has uncovered important links between certain blood metabolites and ADHD by using a genetic method called Mendelian randomization. This approach leverages natural genetic differences to help identify which metabolites might actually cause changes in ADHD risk, offering stronger clues than traditional observational studies.

Key Metabolic Pathways Involved:

The study found 42 plasma metabolites with a causal relationship to ADHD. Most fall into two major groups:

  • Amino acid metabolites from protein metabolism, including those related to tyrosine, methionine, cysteine, and taurine.

  • Fatty acids, especially long-chain polyunsaturated fatty acids (PUFAs) like DHA and EPA, important for brain function.

What Does This Mean for Diet and ADHD?

Since many metabolites come from dietary sources like proteins and fats this supports the idea that diet could influence metabolic pathways involved in ADHD. However, because the study focused on genetic influences on metabolite levels, it doesn’t directly prove that dietary changes will have the same effects.

Notable Metabolites:

  • 3-Methoxytyramine sulfate (MTS): linked to dopamine metabolism, higher genetic levels of MTS were associated with a lower risk of ADHD. Dopamine plays a crucial role in attention and behavior.

  • DHA and EPA: Omega-3 fatty acids abundant in the brain; higher levels were linked to reduced ADHD risk, supporting existing research on omega-3 supplements.

  • N-acetylneuraminate: Involved in brain development and immune function, with higher levels linked to increased ADHD risk, though more research is needed to understand this.

Five metabolites showed bidirectional links with ADHD, meaning genetic risk for ADHD also affects their levels which suggests a complex interaction between brain function and metabolism.

Twelve ADHD-related metabolites are targets of existing drugs or supplements, including:

  • Acetylcysteine: an antioxidant used in various treatments.

  • DHA supplements: widely used to support brain and heart health.

What This Study Doesn’t Show

While these findings highlight biological pathways, they don’t prove that changing diet will directly alter ADHD symptoms. Metabolite levels are shaped by genetics plus environment, lifestyle, and health factors, which require further study.

Conclusion: 

This research provides stronger evidence of metabolic pathways involved in ADHD and points to new possibilities for diagnosis and treatment. Future work could explore how diet or drugs might safely adjust these metabolites to help manage ADHD.

While this study strengthens the link between amino acid and fatty acid metabolism and ADHD risk, suggesting that diet could play a role, ultimately more research is still needed before experts could use this research to give specific nutritional advice.

July 21, 2025

Network Meta-analysis Explores Long-term Efficacy of Nonpharmacological Treatments for Improving Inhibitory Control in Children and Adolescents with ADHD

Background Info:

Executive functions include inhibitory control, working memory, and cognitive flexibility. Inhibitory control is the ability to suppress distractions and focus on goals, which is the main deficit in ADHD. 

Children and adolescents with ADHD often have off-task, unrelated thoughts and are easily distracted, limiting their sustained attention. This makes it difficult for them to focus on tasks and leads to impulsive behaviors that affect their daily life, academics, and social interactions. Improving inhibitory control in ADHD children and adolescents is essential. 

Stimulant medications are commonly used to treat ADHD. However, side effects like insomnia, loss of appetite, and headaches may make parents hesitant to use these medications for their children. 

Non-pharmacological treatments like cognitive training, behavior therapy, and physical exercise have gained attention for their lack of side effects. Research shows that some non-pharmacological methods can improve cognitive outcomes significantly, underscoring their potential in treating ADHD. 

Study:

A Chinese research team identified four key gaps in current research on non-pharmacological treatments for inhibitory control in children with ADHD: 

  • Existing meta-analyses seldom differentiate between short-term and long-term interventions.  
  • Most studies focus primarily on short-term effects and neglect evaluation of maintenance effects through follow-up assessments.  
  • New treatment methods, such as meditation and board games, have not been systematically assessed in meta-analyses for their impact on inhibitory control in children and adolescents with ADHD, leaving their effectiveness uncertain.  
  • Traditional meta-analysis does not tell us which intervention is most effective. Without this comparative analysis, it is difficult to rank efficacy. 

The team therefore performed a network meta-analysis of long-term randomized controlled trials (RCTs) to assess and rank the effectiveness of various non-pharmacological treatments on inhibitory control in children and adolescents with ADHD. 

The team included only RCTs relying on professional diagnoses of ADHD, excluding those based only on parent and teacher rating scales.  

The included studies measured inhibitory control using objective neurocognitive tasks, such as the Stroop test and the Go/No-Go test, to reduce potential subjective bias. Studies relying on parent- or teacher-reported questionnaires were excluded. 

Controls either received no intervention or placebo, such as watching running videos and attending history classes. 

Meta-analysis of 16 studies combining 546 participants found large short-term effect size improvements in inhibitory control from physical exercise. But the two studies with a total of 110 participants that performed a follow-up test reported only a small-to-medium effect size improvement. 

For cognitive training, a meta-analysis of fifteen studies totaling 674 participants reported a medium effect size of short-term improvement in inhibitory control. The ten studies with 563 participants that performed a follow-up test found only a small effect size improvement since treatment initiation. 

For behavioral therapy, meta-analysis of six studies encompassing 244 individuals likewise found a medium effect size short-term improvement in inhibitory control. In this case, however two studies combining 91 participants that performed a follow-up test reported that the medium effect size improvement was maintained. 

For neurofeedback, meta-analysis of seven studies encompassing 186 individuals found a small-to-medium effect size short-term improvement in inhibitory control. The only study that performed a follow-up test reported a small effect size improvement since treatment initiation. 

The two studies with a combined 44 individuals exploring board games found no significant improvement in inhibitory control. Likewise, the two studies combining 32 participants that explored meditation found no significant improvement in inhibitory control. 

There was no indication of publication bias. 

Conclusion:

The team concluded, “Existing evidence shows that physical exercise, behavior therapy, cognitive training, and neurofeedback can effectively improve the inhibitory control of children and adolescents with ADHD. However, meditation, EMG feedback, and board games did not significantly affect inhibitory control. Physical exercise has the best effect among all non-pharmacological treatments, but its impact will be weakened after intervention. Behavior therapy and cognitive training had a slightly lower effect, but they have a better maintenance effect.” 

Ultimately, the study results suggest that non-drug treatments can help children and teens with ADHD improve their ability to control their actions and stay focused. Some methods, like physical exercise, work well at first but may fade once the activity stops. Other methods, like behavioral therapy and cognitive training, may take a little longer to show results but can last longer and make a bigger difference over time. Ultimately, and most importantly, because this work did not study the symptoms of ADHD or its real-world impairments, it provides no reason to change current treatment practices for ADHD.

July 16, 2025