Autism spectrum disorders (ASDs) are etiologically complex. Evidence that the origin begins in utero has made maternal conditions as risk factors during pregnancy the focus of increasing research.
Autism spectrum disorders (ASDs) are etiologically complex. Evidence that the origin begins in utero has made maternal conditions as risk factors during pregnancy the focus of increasing research. As results from these studies emerge, pediatricians must be prepared to discuss the information with families, whether that be in responding to queries from concerned parents of children with ASD or appropriately counseling mothers-to-be.
With these needs in mind, Contemporary Pediatrics reached out to Irva Hertz-Picciotto, PhD, MPH, and Robin L. Hansen, MD, investigators from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study, for perspectives on their research showing associations between maternal metabolic conditions (diabetes, obesity, and hypertension) and neurodevelopmental problems in children.1
Irva Hertz-Picciotto, PhD, MPH. Photo courtesy University of California Regents.“Getting the word out to pediatricians about our findings is critical to raising awareness among the targeted population of women in their reproductive years,” says Hertz-Picciotto, CHARGE principal investigator, professor of Public Health Sciences, and director, University of California, Davis, Medical Investigation of Neurodevelopmental Disorders (MIND) Institute Program in Environmental Epidemiology of Autism and Neurodevelopment.
Determining etiologic contributions of maternal medical conditions to ASD is one of the goals of CHARGE. Being conducted at the UC Davis MIND Institute, it is the first population-based, case-control study designed to comprehensively investigate the underlying nongenetic causes of autism.
Between January 2003 and June 2010, CHARGE enrolled 1004 children aged 2 to 5 years, of which 517 were diagnosed with ASD, 172 with developmental delay (DD), and 315 who were controls developing typically.
Interest in investigating a link between maternal metabolic conditions and autism derived in part from existing evidence associating diabetes during pregnancy with general developmental impairments and recognition that type 2 diabetes, obesity, and hypertension are conditions related by underlying inflammation and insulin resistance.
Using information obtained from maternal medical records and/or structured interview, the study found maternal prevalence rates for each of the metabolic conditions were higher among both children with ASD and those with DD compared with the controls. Overall, about 29% of children with ASD, 35% of children in the DD group, and 19% of controls had a mother with at least one metabolic condition.
Based on logistic regression analysis, mothers with any of the metabolic conditions were 2.35 times more likely than unaffected women to have a child with DD and 1.6 times more likely to have a child with ASD. Adding support to a link between the maternal metabolic conditions and developmental delays were findings that whether analyzing the groups of children with or without ASD, children whose mothers had diabetes scored significantly lower on various development tests compared with children with unaffected mothers.
The findings from the CHARGE study are concerning considering the high and rising rates of obesity and type 2 diabetes in the population. However, determining the clinical implications of any research findings depends on critical appraisal of the study design.
The possibility of misclassification of some women, particularly the chance that women with undetected subclinical conditions were considered “healthy,” is one of the main limitations of the CHARGE analyses, according to Hertz-Picciotto.
However, maternal self-reports of metabolic conditions were well validated through medical records and, importantly, the study had a large, ethnically- and racially-diverse population.
While these features lend strength to the findings and support their generalization, Hertz-Picciotto points out that the study appears to be the first to look at associations between ASD and metabolic conditions as a group.
“Although associations between metabolic conditions and intellectual disabilities have been previously reported, the identified link with autism needs to be replicated before concluding there is a causal effect,” she says.
“In addition, there is more work to be done to understand how metabolic conditions might influence fetal development and hence what the right intervention is once a woman is pregnant. We are now expanding our research by looking at glucose tolerance tests performed during pregnancy and are studying whether the metabolic conditions increase proinflammatory markers in the newborn. At this stage, we are not planning interventional studies.”
In terms of what pediatricians should be communicating to parents, the main messages are for women who are pregnant and mothers-to-be. Specifically, pediatricians should be reminding these women that their own healthcare affects the health of their offspring, says Hansen, professor of Pediatrics and director, UC Davis Center for Excellence in Developmental Disabilities at the MIND Institute.
“Reiterate the importance of achieving optimal prepregnancy health and urge women who are pregnant to obtain good healthcare and careful monitoring as it pertains to their nutrition, weight, and, for women at risk, glucose and blood pressure,” she says.
“However, the clearest take-home message from our research to date,2 and a point which has been replicated by others, is that a woman planning to become pregnant should be taking prenatal vitamins. We now have accumulating evidence that women who increase their intake of folate in the preconception and early postconception periods, which can be accomplished by taking prenatal vitamins, reduce the risk that their future child will develop ASD.”
Hertz-Picciotto echoed these concepts, noting that improving nutrition and losing weight, if done prior to a pregnancy, would appear to be beneficial.
“However, weight loss during pregnancy is a complicated and controversial issue that should be discussed with a clinical nutritionist having expertise in this area,” she says.
In response to mothers who inquire whether their having a metabolic condition during pregnancy caused or might cause autism in their children, pediatricians should choose their words carefully, taking into account how their answer might impart guilt over something done in the past without knowledge of its potential harm and emphasizing that, for any particular child, multiple factors probably contributed to the child’s developmental problems. However, there is a potential message from the study for families who are worried that their child is at risk.
“Considering the links between maternal metabolic conditions and impairments, women who were obese or who had diabetes or hypertension may be counseled to watch out for signs of developmental problems, including in language development and social communications,” Hertz-Picciotto says.
1. Krakowiak P, Walker CK, Bremer AA, et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 2012;129(5):e1121-e1128.
2. Schmidt RJ, Tancredi DJ, Ozonoff S, et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr. 2012;96(1):80-89.
Ms Krader has 30 years of experience as a medical writer. She has worked as both a hospital pharmacist and a clinical researcher/writer for the pharmaceutical industry and is presently a freelance writer in Deerfield, Illinois. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.