For many mums-to-be it is advised that taking regular folic acid supplements during pregnancy, and whilst trying to conceive, has significant health benefits for their unborn baby, namely around reducing the risk of neural tube defects such as spina bifida (NHS, 2013). However, do these supplements also affect the risk of the unborn baby developing Autistic Spectrum Disorders (ASDs) as they grow in life post birth?

A recent cohort study by Suren et al. (2013) aimed to look at this link. In their paper, they suggest that taking folic acid supplements during pregnancy may be associated with a reduced risk in developing ASDs, which include autism (AD), Asperger’s (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS).

This video by The Dutch Autism Association can help us understand how ASDs can affect individuals:

Methods

In order to examine this claim, Suren et al. used a population based cohort of 85,176 pairs of mothers and babies recruited in Norway. These children were born from 2002-2008; meaning by the end of the study in March 2012 the age of children was 3.3 years to 10.2 years, increasing the likelihood that they could assess any presence of ASD within this age bracket. Due to it being unethical to deceive mothers with a non-folic acid placebo, the authors decided to compare mothers who themselves had either decided to take supplements or not.

Mums-to-be were recruited at around 18 weeks pregnant and were interviewed about their use of folic acid supplements from the interval of 4 weeks prior to conception to 8 weeks pregnant. Subsequent information about folic acid intake was recorded using a supplement diary that the mums completed. Additionally, cases of ASDs in children after they had been born were also identified from a sub-study using three approaches:

1. Questionnaire interview with mothers when their children were at 36 months, 5 years and 7 years old
2. Referrals made to professionals of suspected ASD cases, or
3. Identified using a patient registry which collects data of diagnoses.

Any child who was identified using these three approaches was also invited to join the study.

Results

Using regression analysis, results showed in the study sample that:

• 270 (0.32%) of children were diagnosed with ASDs
• In children whose mum had taken folic acid, 0.1% had developed  AD
• In children whose mum had not taken folic acid, 0.21% had developed AD
• The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90)
• There was no relation between folic acid and the development of Asperger’s, or PDD-NOS.

Conclusions

Maternal use of folic acid supplements from 4 weeks before to 8 weeks of pregnancy is associated with a lower risk of developing autistic disorder

Maternal use of folic acid supplements from 4 weeks before to 8 weeks of pregnancy is associated with a lower risk of developing autistic disorder. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.

Strengths of the study:

• Cohort design enabled a large sample size
• Combination of data collection to analyse in-depth information, such as referrals, interviews and screening for ASDs provided the opportunity to study rich data

Limitations of the study:

• Sample not representative to typical population when compared nationwide: mums in the study sample tended to be first time mums, have a partner, higher educational status, less likely to smoke and have a higher mean age.
• The study couldn’t control which type of folic acid supplements the mothers were choosing to use.
• There were discrepancies in some mothers under-reporting whether or not they had consumed folic acid during pregnancy.
• Incomplete picture of ASD cases in the cohort as mothers with severely affected children were less likely to respond
• The sub groups of ASDs defined in this paper may be unreliable, as there is the potential for them to be removed altogether from DSM-V classification system.

Summary

So, in summary, what can we take from this study? The results do suggest that in the study sample maternal folic acid was associated with a slightly lower risk of children developing ASDs. However, despite the large sample size and thorough methods of data collection, the limitations are strong and confounding. The sample size was not representative, and the response and reporting rate suggest discrepancies in the data collected.

Let’s take a moment to think about all those mums out there who did take folic acid during pregnancy and their precious new-born developed AD down the line. This elf  feels we need to be careful in attributing the causality of folic acid and autism until there is more valid and generalizable data, especially when this is a sensitive subject that affects the lives of families and their children in many different, often severe, ways.

Is it worth taking folic acid when pregnant?

Yes, consumption of folic acid has come highly recommended by many health professionals due to the well documented health benefits associated with reducing the risk of neural tube deficits in growing babies. However, it seems we do need more evidence to suggest it might lower the risk of ASDs as well before we can be sure of this additional potential benefit.

Links

Surén P., Roths,C., Bresenhan,M.,Hauge,M., Hornig,M., Hirtz,D.,Lie,K,K.,Lipkin,W., Magnus,P., Reichbron-Kjennerud,T., Scholberg,S., Smith.,D., Oyen,A., Susser,E., and Stolenberg,C. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013; 309(6):570-7. [PubMed abstract]

NHS Choices: Supplements in Pregnancy, 2013.