Induced Labor Linked to Increased Risk for Autism

Deborah Brauser

August 14, 2013

Induced labor and/or augmentation during childbirth may be linked to an increased risk for autism spectrum disorder (ASD) in children, new research suggests. However, researchers are quick to point out that more research is needed before any conclusions regarding causality can be drawn.

A retrospective study of more than 625,000 live births showed that children of mothers who received labor augmentation and induction had 23% increased odds of having ASD than children whose mothers did not undergo induced or augmented labor.

In addition, this association was even stronger in boys.

"We're hoping this can contribute to the discussion about environmental factors which could contribute to the development of autism or to a subset of the ASDs," lead author Simon G. Gregory, PhD, associate professor at the Duke Institute of Molecular Physiology at Duke University Medical Center in Durham, North Carolina, told Medscape Medical News.

"It's a complex disorder that can be a combination of genes and the environment. And it could be that what we're seeing is an environmental factor that's contributing to elevated risk, whether or not it's on top of a genetic predisposition," said Dr. Gregory. "With all of these diseases, it's important to chip away at what the causes are."

The researchers note that, to their knowledge, "this is the first large-scale study to address the relationships among birth induction/augmentation and autism."

However, they caution that "further research is needed to differentiate among potential explanations of the association," including underlying pregnancy conditions, events leading up to the induction/augmentation, and specific medications and dosing patterns used.

The study was published online August 12 in JAMA Pediatrics.

Environmental Risk Factors

According to the investigators, approximately 1 out of every 88 children in the United States has ASD. Previous studies have examined both genetic and environmental factors that may influence the development of ASD — and led the current researchers to assess a possible link with induction and/or augmentation during childbirth.

Induction is "stimulating uterine contractions prior to the onset of spontaneous labor," and augmentation is "increasing the strength, duration, or frequency of uterine contractions," they explain.

The investigators evaluated data on 625,042 live births from 1990 to 1998 linked with school reports from 1997 to 1998 and 2007 to 2008 from the North Carolina Detailed Birth Record and Education Research databases. Of these children, 5500 had a documented exceptionality designation for autism (1.3% of all boys and 0.4% of all girls).

"We looked at this population and analyzed for the traditional risk factors that have been identified and implicated in the development of autism from a birth perspective," said Dr. Gregory.

Dr. Simon Gregory

"Then we wanted to drill down and control for these factors to see if the associations with birth induction and augmentation were still significant," he added.

Results showed that after controlling for male sex only, children of mothers who underwent induction and augmentation had significantly higher odds of being diagnosed with autism than children whose mothers did not undergo induction or augmentation (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02 - 1.47).

Compared with the "neither induced nor augmented" category, the induced-only and augmented-only categories had ORs of 1.10 and 1.15, respectively.

In addition, "the inclusion of successive sets of potential confounders related to socioeconomic status, maternal health, and pregnancy-related events and conditions did not substantively alter the estimated ORs," report the researchers.

No Cause and Effect Established

"One possible explanation for the induction/augmentation-ASD association is through exposure to exogenous oxytocin," write the investigators, noting that 50% to 70% of women who undergo induction receive this medication. And past research has suggested that it is a contributor to the development of ASD.

Further analysis showed ORs for autism of 1.25 for fetal distress during labor and delivery, 1.22 for meconium, and 1.25 for being born at or at less than 34 weeks' gestation compared with no fetal distress or meconium and being born full term, respectively.

Compared with mothers who did not have diabetes mellitus, those with the condition had 23% higher odds of having a child with autism.

When examining the specific sexes, the researchers found that boys of mothers who received both induction and augmentation had 35% higher odds of having autism, and those of mothers who had induction only had 18% higher odds than those who had mothers who had neither.

"In contrast, there was no real elevated risk for females in the induced and augmented group. It was primarily coming from the males," said Dr. Gregory. However, he noted that in the augmented-only groups, the girls had 18% higher odds of having autism and the boys had 15% higher odds.

Although significant overall associations were shown, the researchers stress that causation was not determined.

"Our results are not sufficient to suggest altering the standard of care regarding induction or augmentation; our results do suggest that additional research is warranted," they write.

"We are being very, very careful to not say that we've established cause and effect. It's the maternal health and the health of the baby in utero and the circumstances that required the physician to say the birth should be induced or augmented — or it could be the augmentation process itself," added Dr. Gregory.

"Still, we don't want moms to worry and at the time of birth say, 'Don't induce because it will cause autism.' Negative consequences of not inducing can far outweigh those risks."

The study was funded by a grant from the United States Environmental Protection Agency. The study authors have disclosed no relevant financial relationships.

JAMA Pediatr. Published online August 12, 2013. Abstract


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