Maternal Obesity Linked to Autism, Other Developmental Disorders

Deborah Brauser

April 12, 2012

April 12, 2012 — Metabolic conditions in pregnant women may be associated with increased risk for autism and other neurodevelopmental disorders in their offspring, new research suggests.

In a cohort study of more than 1000 children between the ages of 2 and 5 years, those who had mothers classified as having "metabolic conditions" (which included diabetes, hypertension, and obesity) during pregnancy were at a significantly higher risk of developing an autism spectrum disorder (ASD) and developmental delays than the children with mothers who did not have metabolic conditions.

In addition, mothers who were obese were 1.6 times more likely to have a child with ASDs and more than twice as likely to have a child with other developmental problems. Maternal diabetes alone was associated with significant risk for overall developmental problems and lower expressive language skills in their children.

"The prevalence of obesity and diabetes among US women of childbearing age is 34% and 8.7%, respectively," senior author Irva Hertz-Piccioto, PhD, University of California, Davis, and colleagues write.

"With obesity rising steadily, [our] results appear to raise serious public health concerns," they add.

The study was published online April 9 in Pediatrics..

CHARGE Data

The investigators evaluated data for 1004 children from the ongoing Childhood Autism Risks from Genetics and the Environment (CHARGE) study. This included 517 participants with ASDs, 172 with other developmental disorders, and 315 who were developing typically ("healthy control" participants).

Children who entered the study with a diagnosis of ASD were reevaluated by the researchers using the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R).

The Social Communication Questionnaire was also given to parents of the children in the developmental delay and healthy control participant groups as a screen for ASD. Children who had a score of 15 or over were reassessed with the ADI-R and the ADOS; and if ASD criteria were met, they were moved into the ASD group.

Other measurements administered to all children included the Mullen Scales of Early Learning (MSEL) and the Vineland Adaptive Behavior Scales (VABS). Maternal demographic and medication information was obtained from birth files, medical records, and the telephone-based CHARGE Environmental Exposure Questionnaire.

For this study, obesity was defined as a body mass index (BMI) during pregnancy ≥30. In addition, the researchers validated self-reported information on diabetes and hypertension in a subset of 560 of the women.

"Serious" Public Health Implications

Results showed that metabolic conditions during pregnancy were associated with a higher risk for an ASD (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.10 - 2.37) and of developmental delays (OR, 2.35; 95% CI, 1.43 - 3.88) compared with not having metabolic conditions.

For women who were obese during pregnancy, the risk was also significantly higher for having a child with ASD (OR, 1.67; 95% CI, 1.10 - 2.56) or other developmental delays (OR, 2.08, 95% CI, 1.20 - 3.61) compared with the women who were not obese.

The women who had diabetes during pregnancy (defined as either gestational diabetes or type 2 diabetes) were significantly more likely to have a child with developmental delays than those who did not have diabetes (OR, 2.33; 95% CI, 1.08 - 5.05).

No statistically significant associations were found between diabetes and ASD, or between hypertension and ASD or developmental delays.

When examining only the children with ASD, those with mothers who had diabetes during pregnancy showed lower expressive language scores on the MSEL (standard deviation [SD], 0.37; P = .01) than the children of mothers who did not have any metabolic conditions.

When assessing only the children without an ASD, those with mothers with diabetes had significantly lower MSEL receptive and expressive language scores (SD, 0.5; P = .03 for both subscales) and significantly lower VABS socialization scores (SD, 0.49; P = .01) than those of mothers without diabetes.

In addition, the children without an ASD but with mothers who had had any metabolic condition showed significantly lowers scores on all MSEL subscales and composites and on all VABS domains and composites (SD, at least 0.4 on all; P ≤ .01 on all) compared with those with mothers who did not have metabolic conditions.

"Our findings raise concerns that these maternal conditions may be associated with neurodevelopmental problems in children and therefore could have serious public health implications," write the investigators.

Avoid Obesity

Max Wiznitzer, MD, associate professor of pediatrics and neurology at Case Western Reserve University and pediatric neurologist at Rainbow Babies and Children's Hospital in Cleveland, Ohio, told Medscape Medical News that it was "interesting" that this study showed no significant associations for hypertension.

Dr. Max Wiznitzer

"There was a very modest association found for developmental disorders for diabetes. And there was a relationship between obesity and autism, but it was bigger for other developmental disorders," he said. "When they combined all the numbers and called it metabolic conditions, which I'm hesitant about using, then autism was there. But that's because the obesity number was thrown in."

Dr. Wiznitzer, who is also the neurology liaison to the Autism Subcommittee for the American Academy of Pediatrics, said that the real question is about the interpretation of the results.

"They found an association, but we don't have enough evidence to tell us what the association means. Is it causal? Or is there a maternal factor that's contributing to the obesity, which then increases the risk of these developmental problems, including autism? We need more information, and it needs to be replicated."

Nonetheless, Dr. Wiznitzer noted that if the study's results can influence women to better manage their weight and overall health before and during pregnancy, "more power to them."

"If this is going to be a motivator to make a mom go closer to the expected BMI, that's fine. I would definitely not fault people for thinking that way. That's a win-win for the fetus and the mom. And a win for after the baby is born," he said.

"There is no downside to saying that obesity should be avoided during pregnancy," concluded Dr. Wiznitzer.

The study was supported by the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at the University of California, Davis, and by grants from the National Institutes of Health and the US Environmental Protection Agency through the Science to Achieve Results program. Dr. Wiznitzer and all study authors but one have disclosed no relevant financial relationships. The other study author reported receiving grant support from Autism Speaks.

Pediatrics. Published online April 9, 2012. Abstract

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