Study 'links autism to maternal obesity'

“Obese women and those with type 2 diabetes could be increasing their chances of having a child with autism or another development disorder,” BBC News has reported.

This news is based on research examining the possibility of a link between a child's chances of developing one of these conditions and their pregnant mother having one or more of the "metabolic conditions": diabetes, high blood pressure and obesity. To explore any potential links the researchers recruited children with autism spectrum disorder, developmental delay and typical development, and looked at whether their mothers were affected by any of the three metabolic conditions during pregnancy. They found several associations between mothers having metabolic conditions and their children's chances of developmental delays and autism, as well as their likelihood of scoring lower on several markers of development, particularly expressive language.

Due to its design, the study can only show that metabolic conditions during pregnancy are associated with autism and developmental delays, and can’t prove there is a cause-and-effect relationship. However, the study’s results do warrant more research into the effects of maternal metabolic conditions, perhaps with long-term research that can prove that these conditions actively contribute to autism. Although it will be some time before there is any definite proof, staying a healthy weight during pregnancy remains a sensible measure.

Where did the story come from?

The study was carried out by researchers from the University of California and Vanderbilt University in the US. It was funded by the US National Institutes of Health, the US Environmental Protection Agency and the MIND Institute. The study was published in the peer-reviewed journal Pediatrics.

This story was covered accurately by the BBC and The Daily Telegraph.

What kind of research was this?

This was a case-control study that aimed to investigate associations between mothers’ “metabolic conditions” and the chance of their children having autism or developmental delays during early childhood. In the study the researchers classed diabetes, high blood pressure and obesity (body mass index [BMI] greater or equal to 30) as metabolic conditions, and recorded the prevalence of these conditions in mothers who went on to have children with autism spectrum disorder, developmental delay and typical development. They also aimed to determine whether these metabolic conditions were associated with specific developmental effects.

The researchers stated that the prevalence of autism spectrum disorders is 1 in 110 children, making it relatively rare. Case-control studies are a good way to investigate rare events as they look at a group of people with a particular condition and examine their circumstances compared with those of a group of people without the condition. In this way they can look for differences between the two groups that may suggest links to the condition of interest.

Since case-control studies start with people known to have the condition of interest (in this instance, autism) it is possible to enrol a sufficient number of affected patients. Case-control studies also have limitations as they are retrospective, and their control subjects have to be selected carefully in order to minimise the risk of bias. However, it is not always possible to completely remove or minimise bias from the results. Crucially, as they do not follow people up over time they cannot prove cause-and-effect relationships, but only find associations.

What did the research involve?

The researchers recruited 1,004 children aged between two and five years old: 517 with autism spectrum disorder, 172 with developmental delay and 315 children with typical development. The children with typical development were matched to the children with autism spectrum disorder based on age, gender and the region where they lived.

These typically developing children were identified from state birth records. The diagnoses of autism and developmental delay were confirmed clinically and the children’s development was assessed using two recognised assessments of learning and behaviour: the Mullen Scales of Early Learning (MSEL) and the Vineland Adaptive Behaviour Scale (VABS).

Data on the mothers’ health during the pregnancy was obtained from medical records, birth files and from a structured interview with each mother (the Environmental Exposure Questionnaire). The researchers also collected demographic information on the participants.

The researchers analysed the prevalence of the metabolic conditions in the mothers of children with autism spectrum disorder, developmental delay or children with typical development. They then compared mothers with metabolic conditions with mothers with no metabolic conditions and a BMI of less than 25 (a healthy BMI is between 18.5 and 25). When the researchers were carrying out the comparisons, they adjusted for a variety of demographic factors including the child’s age and gender, mother’s age at delivery, race/ethnicity, educational level and whether the delivery was paid for by the government or by private medical insurance.

What were the basic results?

The prevalence of type 2 diabetes and gestational diabetes was higher in mothers who went on to have children with autism spectrum disorder or developmental delay. The prevalence was:

9.3% in the autism spectrum disorder group
11.6% in the developmental delay group
6.4% in the control group (typical development)

Having a mother with type 2 diabetes was significantly more common in the children who had developmental delay than in those with typical development (OR 2.33, 95% CI 1.08 to 5.05). For children who had autism spectrum disorder, the rate of maternal diabetes was not significantly different (in other words, it was not meaningful in statistical terms) compared with mothers of children with typical development.

The prevalence of hypertension was low in all groups, but again more common in mothers of children with autism spectrum disorder or developmental delay:

3.7% in the autism spectrum disorder group
3.5% in the developmental delay group
1.3% in the control group

Hypertension was not significantly more common in the developmental delay or autism spectrum disorder groups compared with the control group.

The prevalence of obesity (a BMI of 30 or more) was also more common in mothers of children with autism spectrum disorder or developmental delay:

21.5% in the autism spectrum disorder group
23.8% in the developmental delay group
14.3% in the control group

Compared with the control group, obesity was significantly more common in the developmental delay and autism spectrum disorder groups (OR 2.08 95% CI 1.20 to 3.61 for developmental delay and OR 1.67 95% 1.10 to 2.56 for autism spectrum disorder).

The researchers then considered all three conditions together, which they called “metabolic conditions”. They found that metabolic conditions were more prevalent in mothers of children with autism spectrum disorder and developmental delay compared with mothers of children developing typically. The prevalence of maternal metabolic conditions was:

28.6% in the autism spectrum disorder group
34.9% in the developmental delay group
19.4% in the control group

When compared with the control group these differences were statistically significant for both the mothers of children with autism spectrum disorder (OR 1.61 95% CI 1.10 to 2.37) and developmental delay (OR 2.35 95% CI 1.43 to 3.88).

The researchers then looked at the children’s development, by assessing factors such as their use of language and their motor skills. Maternal diabetes or any metabolic condition was associated with poorer development in the child, particularly expressive language.

How did the researchers interpret the results?

The researchers concluded that maternal metabolic conditions “may be broadly associated with neurodevelopmental problems in children” and that “with obesity rising steadily, these results appear to raise serious public health concerns”.

Conclusion

This case-control study has found an association between maternal metabolic conditions (diabetes, hypertension and obesity) during pregnancy and the chances of children having autism and developmental delays. These conditions were also associated with lower scores on several markers of development, particularly expressive language.

Due to the study design, this study can only show that metabolic conditions are associated with these outcomes. Case-control studies are useful for investigating rare conditions, such as autism spectrum disorder, as case-control studies start with people known to have the outcome, and therefore allow researchers to have sufficient number of patients to study in a meaningful way. However, case-control studies also have limitations. For example:

The controls were selected carefully, to minimise the risk of bias, but it is still possible mothers could have been generally healthier for a number of reasons, including socioeconomic status. This could partially explain the explain the associations seen in the study.
Also, the study relied partly on the mother’s report of her health during pregnancy. This leaves the possibility that there may have been inaccuracy in recording this information, although the researchers did compare a proportion of the results to medical records, and found good agreement.

The exact causes of autism are still not known, but the latest research is looking at the potential genetic and environmental causes of the condition. While this research has provided results suggesting a potential link to maternal metabolic conditions (defined as obesity, diabetes and blood pressure), it should be remembered that the study only found associations rather than a cause-and-effect relationship.

The authors have raised serious public health concerns about rising levels of obesity and the possibility of a link with autism. However, further studies, perhaps of a prospective nature, are needed to continue assessing this potential link. While waiting for definitive proof, staying a healthy weight during pregnancy remains a good idea.