Meta-analysis with Millions of Participants Finds No Link Between Antipsychotic Use in Pregnancy and ADHD in Offspring

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.

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Study Background:

Animal-assisted interventions (AAIs) involve structured interactions with animals, designed and carried out by mental health teams assisted by trained human–animal professionals, to achieve specific therapeutic or educational goals. While a wide variety of animals may be used, horses and dogs tend to predominate. These interventions often involve physical contact, imitation, and play aimed at reducing stress and generating affection. Previous research has suggested that AAI to those with a range of developmental and mental health conditions.

Just how effective are they for treating ADHD in children and adolescents? Recent years have seen an increase in studies into AAIs for children with ADHD, but previous systematic reviews have not included quantitative meta-analysis to evaluate efficacy.

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The Study:

A Chinese study team based in Nanjing set out to remedy that with a systematic search of the peer-reviewed published medical literature aimed at performing meta-analyses of efficacy.

The team limited its search to randomized controlled trials (RCTs) and pre–post single-group studies involving children and adolescents diagnosed with ADHD.

Meta-analysis of five studies with a combined total of 95 participants reported no significant effect of AAIs on ADHD symptom severity. There was negligible variation (heterogeneity) in outcomes among the studies.

Similarly, meta-analysis of the six studies encompassing 323 individuals found no significant improvements in social behavior. There was no heterogeneity and no sign of publication bias. Breaking that down into subcategories of social interaction (4 studies, 190 persons), social skill (3 studies, 53 persons), and problem behavior (4 studies, 80 participants) made no difference.

Likewise, meta-analysis of the three studies encompassing 61 individuals found no significant improvements in emotional control. Again, there was no heterogeneity and no sign of publication bias.

Three studies combining 56 participants reported no significant reductions in anxiety and depression, again with no heterogeneity and no sign of publication bias.

However, meta-analyses of five studies encompassing 194 individuals found a medium effect size association between AAIs and declines in attention problems, and a medium-to-large effect size improvement in learning and cognition. Heterogeneity was negligible to low.

Finally, meta-analysis of three studies combining 95 participants reported a large effect size improvement in motor proficiency, with moderate heterogeneity.

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The Conclusion:

The team concluded, “As an ADHD management strategy complementary to gold-standard approaches, such as medication or multimodal interventions, AAIs did not appear to be more effective in improving the majority of core ADHD outcomes in children. Future studies should incorporate rigorous study designs with large sample sizes and a standard protocol to achieve more valid and reliable conclusions.”

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A recent Finnish study offers important insights into how symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD) in adolescence can shape academic performance, and even influence educational outcomes well into adulthood.  Children and teens with ODD often show a pattern of angry, irritable moods, arguing with adults, and defying rules or requests. They may lose their temper easily, be quick to blame others for mistakes, and deliberately annoy people. 

The researchers followed participants from the Northern Finland Birth Cohort of 1986, a large, population-based study. They looked at over 6,000 teens whose parents reported symptoms of ADHD and ODD when the children were 15–16 years old. The team then tracked their academic performance at age 16 and their highest level of education by age 32.

ADHD, ODD, and Academic Performance

ADHD is well-known for affecting school performance, often linked to difficulties with attention, impulse control, and executive functioning. ODD, characterized by patterns of irritability, defiance, and hostility toward authority figures, is less studied in this context, especially when it appears without ADHD.

The study found that both disorders, whether occurring separately or in combination, were associated with poorer grades at age 16. However, teens with ADHD symptoms performed worse than those with only ODD symptoms. Interestingly, students with both ADHD and ODD symptoms had the most pronounced academic struggles, but their performance didn’t significantly differ from the ADHD-only group at that age.

Long-Term Educational Impact

By age 32, the effects were even more striking. Participants with both ADHD and ODD symptoms were the least likely to attend or graduate from higher education institutions. Only about 10% of them reached that level, compared to over 40% of those without these symptoms.

Even after accounting for other influences, such as parental education, family structure, and additional psychiatric conditions, the findings held. This suggests that the combination of ADHD and ODD symptoms in adolescence may uniquely disrupt the educational path.

For adolescent girls with ODD symptoms, the impact was particularly notable: they were significantly more likely to complete only the mandatory nine years of schooling.

Why This Matters

These results underscore the lasting effects that behavioral and emotional challenges in adolescence can have. While schools often focus on immediate academic outcomes, this study highlights the importance of early identification and support, not just for ADHD but for ODD as well.

Parents and educators play a crucial role in shaping future outcomes for children and adolescents with ADHD. Recognizing early signs of attention problems, emotional dysregulation, or defiance—and responding with appropriate interventions—could help redirect educational trajectories and open up opportunities down the line.

In short, it’s not just about managing classroom behavior. It’s about supporting long-term potential. When ADHD and ODD symptoms show up in adolescence, they don’t just make school harder—they can limit a student’s entire educational future. Early support and understanding can make a lasting difference.

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