Induction of labor was not associated with an increased risk of autism among the offspring, a large Swedish cohort study found.

In a fixed-effects model examining exposure-discordant siblings (meaning siblings who were born via induced labor compared with those who were not), there was no link between induction of labor and autism spectrum disorder, reported Anna Sara Oberg, PhD, of Harvard T.H. Chan School of Public Health in Boston, and colleagues, writing in JAMA Pediatrics.

"Our findings suggest that concern for autism should not need to be factored into the decision about whether to induce labor," Oberg told MedPage Today separately via email. "Failing to find support for a causal link between the intervention to induce labor and the risk of autism, this study aligns with the ACOG committee recommendation to not change current guidelines regarding labor induction."

While the comparison between exposure-discordant siblings showed no association between induction of labor and autism spectrum disorder (adjusted hazard ratio 0.99, 95% CI 0.88-1.10), there was a 32% increased risk when examining the baseline population (HR 1.32, 95% CI 1.27-1.38).



That association remained significant even after adjusting for maternal characteristics (adjusted HR 1.31, 95% CI 1.26-1.37) and even maternal and birth-specific characteristics (adjusted HR 1.19, 95% CI 1.13-1.24). The authors argued that using a comparison between siblings accounts for shared factors.

"Since a potential difference between siblings cannot be due to any of the things they have in common, the comparison controls for many of the factors that could lead to both induction and ASD (e.g., shared maternal, socioeconomic or genetic factors)," said Oberg.

Overall, 3.5% of induced offspring had been diagnosed with autism spectrum disorder by the age of 20 compared with 2.5% of non-induced offspring.

The link between induction of labor and autism is mainly thought to be due to the use of oxytocin, a neurotransmitter that is involved in social behavior and cognition and may also be linked with downregulation of neuroreceptors, the authors wrote.

But induction of labor is only one of several associated factors that may lead to increased risk of autism spectrum disorder. Use of SSRIs during pregnancy and pregnancy via assisted reproductive technology may also contribute to the risk of the child developing this condition.

An accompanying editorial by Daniel L. Coury, MD, of Nationwide Children's Hospital in Columbus, Ohio, argued that clinicians should be cautious whenever a new study about the link between a particular prenatal intervention and the risk of autism spectrum disorder.

"It might ... be helpful to have medical professionals exercise restraint in their embracing of each new study," he wrote. "[Presenting an] interpretation of the effect in lay terms ... might allow families to make more reasoned decisions regarding their health choices."

Oberg and colleagues examined 1,362,950 live births from the Swedish Multi-Generation Register from 1992 to 2005. Overall, 22,077 offspring (1.6%) were diagnosed with autism spectrum disorder from ages 8 to 21 years. Overall, 11% of live births in Sweden during that time were preceded by labor induction, which was more likely to occur in primiparous women who were older and had a higher BMI than the general population. Induction of labor was also more likely to be associated with pregnancy complications -- with 23% of inductions performed at ≥42 weeks gestation, 15% performed on women with preeclampsia and 7% on those with intrauterine growth restriction.

Oberg acknowledged these limitations, and said that they require further investigation, as do their findings here.

"Most importantly, this finding needs to be verified in different study settings and using different methods/designs," she noted.

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