“We appreciate the concerns raised and welcome constructive discussion. We would like to clarify several important points regarding our study, including:

Folic acid supplementation is already recommended in routine prenatal care

In Australia and many other countries, guidelines already recommend folic acid supplementation (e.g., Elevit or equivalent) at least one month before conception and during early pregnancy to prevent neural tube defects. Therefore, our findings do not introduce a new intervention and should not be interpreted as a call for new clinical practice changes. They merely suggest that existing prenatal folate recommendations may also have additional neurodevelopmental benefits, although more research is needed.

We do not claim causation, nor convincing evidence - only an association classified as “highly suggestive”

Our study clearly states that the findings show an association, not proof that folic acid or multivitamins prevent ASD. We explicitly discuss the limitations of observational data—including unmeasured confounding, heterogeneity in study designs, and potential publication bias. We also recommended future research focusing on conducting large-scale prospective cohort studies and randomised controlled trials (RCTs) to confirm and expand these findings.

This was not a primary study - it is a review of existing reviews

Our research is an umbrella review, which synthesises results from previously published systematic reviews and meta-analyses. We did not collect new data, and we do not claim new evidence. Our work simply summarises what the existing literature already shows.

In conclusion, our umbrella review does not make any causal claims and does not propose the use of prenatal supplements as a strategy for ASD prevention. It summarises existing evidence showing an association – not proof – between prenatal folic acid or multivitamin use and ASD risk. Folic acid supplementation is already part of routine pregnancy care, and our findings should be interpreted within this context without implying any new clinical or public health recommendations. Prenatal multivitamins are considered safe and are already commonly used during pregnancy, so our findings do not introduce any additional burden, cost, or health risk for women.

Importantly, supplements should complement rather than replace nutritionally adequate diets, and a stronger public health priority should remain on whole-food dietary patterns that provide folate and other nutrients that supplements cannot replicate.”

"The evidence from this umbrella review of eight systematic reviews and meta-analyses supports the existing Australian recommendations for folic acid supplementation one month before pregnancy and during the first three months. This timing is well established for the prevention of neural tube defects and is where autism-related benefit is most plausible. However, evidence for benefits beyond early pregnancy remains uncertain, and it is unlikely that all women require folic acid throughout the entire pregnancy.

The findings on multivitamin use should be interpreted cautiously. This umbrella review included three relevant systematic reviews/meta-analyses, and one showed no association with reduced autism risk. Multivitamins can influence a range of other maternal health and their differing formulations make their overall benefits difficult to interpret. For example, higher-dose or high-frequency supplementation has been linked to increased risks such as gestational diabetes, and one of the most common prenatal supplements in Australia contains double the dose of folic acid that is most associated with the protective effects reported in this new study. These issues require careful consideration before recommending prolonged multivitamin use for all pregnant women. There is certainly a place for targeted supplementation but it is unlikely to be necessary for everyone, and not for the entire duration of pregnancy.

A stronger public health priority should remain on whole-food dietary patterns, which provide folate along with other nutrients, such as fibre, that supplements cannot replicate. Supplements have a role, but they should complement and not replace nutritionally adequate diets."

"Folate and/or multivitamins supplementation pre-pregnancy are widely recommended and used, especially in high-income countries. This review on the association between periconceptional folate and multivitamins and a reduced risk of childhood autism spectrum disorder (ASD) is timely. It is of considerable interest given that it comes on the back of recent concerns about a possible link between maternal paracetamol ingestion and ASD.

This is an ‘umbrella review’ summarising results of eight systematic reviews and meta-analyses published by others, containing data from over 100 studies involving more than 2 million women. It concludes that there is a 30% reduction in ASD for children of women who took supplements. The bulk of the data come from studies involving folate only, but multivitamin studies are also associated with a slightly reduction. Multivitamins usually include folate, so it is difficult to clarify what is of significance in such studies. The review uses standard, rigorous methodology, is well-written, and recognises limitations.

One issue not discussed is if these results should lead to recommending folate supplementation throughout pregnancy, as opposed to current guidelines aimed at reducing the risk of neural tube defects by taking periconceptional folate. The authors discuss the biological plausibility how ASD could be influenced by folate supplementation, but if the mechanisms involve an effect beyond the periconceptional period, it may be that supplementation should continue beyond this time."

"Autism Spectrum Disorder (ASD) encompasses a wide range of behaviours and developmental challenges, making synthesis and comparison of different research findings difficult. Diagnostic criteria vary, and studies often examine different aspects of ASD.

This umbrella review evaluated eight systematic reviews exploring the relationship between maternal vitamins and folic acid intake and ASD risk. Findings were inconsistent from the original papers included in this ‘umbrella’ review with some papers reported a potential association, while others found no significant link.

The review’s conclusions are constrained by methodological limitations. The quality of the included studies varied, and some datasets may overlap. Because the analysis did not return to primary data for synthesis, there is a risk of confounding, reducing the reliability of the findings. Consequently, the evidence presented is not compelling and should be interpreted as demonstrating a possible association and not a causation.

There is very sound rational for women planning a pregnancy to take additional folic acid. Folic acid is critical for the foetus neural tube development, during the first trimester of pregnancy. This scientific evidence underpins recommendations for folic acid supplementation pre-conception and during the first trimester. However, the role of folic acid in ASD risk remains to be proven.

This paper does highlight that pregnancy is time when the diet quality is crucial. That is, ensuring that the diet contains sufficient range of micronutrients to meet the needs of both the mother and to ensure that the growing baby has all the micronutrients they need for optimal growth and development. This may include the use of  multivitamins (including folic acid) supplements especially for women who do not have access to a safe, adequate and secure food supply.

The authors advocate for further research to establish causal relationships between micronutrients during pregnancy and risk of ASD in children. This topic would indeed be worthwhile to provide solid foundations for public health advice."

"This new paper adds to a growing body of research suggesting that inadequate folate intake in early pregnancy may increase the risk of autism spectrum disorder (ASD).

Folate is well established as essential in the earliest weeks of pregnancy for neural tube development, including the formation of the brain and spinal cord. It also supports healthy methylation processes, reduces inflammation, and helps protect against oxidative stress — all biological pathways that have been implicated in ASD risk.

Although most Australian women take a prenatal multivitamin during pregnancy, ASD rates continue to rise. As a fertility and prenatal dietitian, I see first-hand that this isn’t simply about whether a woman takes a prenatal. Certain groups have higher or more complex folate requirements and may not receive what they need from a standard supplement alone.

My concern is particularly for:
a) those who conceive without planning and miss the critical early window for folate,
b) women with higher-than-average folate needs — such as those with a BMI over 30, malabsorptive conditions, or who smoke, and
c) individuals who do not metabolise folic acid efficiently and may require a different form of folate or a tailored dose.

It’s also important to highlight that folate follows a U-shaped curve in relation to ASD risk: too little or too much may be associated with increased risk. This reinforces why personalised assessment matters.

If we genuinely want to curb ASD rates in Australia, a proactive approach is needed. Making dietitian consultations a routine part of preconception and early pregnancy care would help ensure women receive individualised folate guidance rather than relying on a one-size-fits-all prenatal. The modest cost of personalised nutrition care has the potential to save the government millions in long-term ASD-related health and support services — and, more importantly, give children the best possible start to life."

"This review concludes that maternal prenatal folic acid and multivitamin supplementation is associated with a reduced risk of ASD in offspring.

It is intuitively appealing to find universal and simple solutions to complex problems, including ADHD. By combining studies of various designs and populations we result in a poorly resolved summary with conflicting results. From the highest quality papers, it is indeed plausible that there will be a benefit for some with a particular genetic makeup that predisposes them to poor metabolism of folic acid.

However, the authors, perhaps in search of simplicity, state that 'Healthcare providers should encourage women to start supplementation during the pre-conception period and continue throughout pregnancy.'

This recommendation is entirely premature.

We, and others, have published that supplemental folic acid throughout pregnancy is associated with an increased risk of recurrent asthma in childhood in a time and dose-dependent fashion.

The authors in the present study acknowledge that 'variations in supplementation timing, dosage, and formulation across studies posed challenges for interpretation'.

It is therefore imperative that we further examine the diverse and complex relationship of folic acid and fetal development before advocating mass prescriptions on the current maternal population and next generation."