Link between labor induction and autism spectrum disorder?

Findings from a study using a family comparison design to control for environmental and genetic factors conferring risk for labor induction and autism spectrum disorder (ASD) do not support there being any causal association between labor induction and offspring ASD.

The Swedish population-based study included data from 1,362,950 live births that occurred between 1992 and 2005.¹ Induction prevalence was 11%, and 22,077 (1.6%) children were diagnosed with ASD by ages 8 years through 21 years.

The analyses showed a statistically significant association between labor induction and ASD in the full cohort (hazard ratio [HR], 1.32;95% confidence interval [CI], 1.27–1.38). The strength of the association was reduced but remained statistically significant  (HR 1.19;95% CI, 1.13–1.24) in a multivariate model controlling for measured maternal factors and pregnancy conditions prespecified as potential confounders because of their known or plausible association with both labor induction and ASD. 

Labor induction was no longer independently associated with ASD, however, in a fixed-effects model that controlled for unmeasured risk factors by including only sibling pairs discordant with respect to exposure to labor induction (HR, 0.99; 95% CI, 0.88-1.10).

Jeffrey L Ecker, MD, is a coauthor of the published paper and Chief, Department of Obstetrics & Gynecology, Massachusetts General Hospital, Boston. He told Contemporary OB/GYN, “At least one prior study suggested an association between induction or augmentation and ASD, but that study could not control for many genetic and environmental factors. Because induction and augmentation are commonly undertaken in the process of labor and delivery, it seemed important to understand whether the previously suggested association with ASD remained after controlling for these potential confounders.”

“Our study mined the richness of the Scandinavian database and used siblings as controls to account shared genetic and socioeconomic factors. As we found no association between induction and ASD, I believe clinicians should not alter present management and their use of induction or augmentation based on concerns related to risk for ASD.”

The population-based study that raised particular concern about an association between ASD and labor induction and augmentation was published in 2013.² Conducted using data from North Carolina, the study found that exposure to labor induction or augmentation increased the risk for ASD by approximately 1.3-fold.

The investigation conducted by Dr Ecker and colleagues extracted data from the Medical Birth Register, which contains information for ≥96% of live births in Sweden since 1973, and population registers of familial relations. Information on ASD diagnosis was obtained from the National Patient Register.

The strengths of the study lie in its large size, the completeness of the Medical Birth Register that minimizes the potential for selection bias, and the availability of long-term follow-up of children for the development of ASD. Unlike the North Carolina study, information on labor augmentation was not available. Neither study analyzed a potential influence of labor induction method on ASD development.

References

1. Oberg AS, D’Onofrio BM, Ricker ME, et al. Association of labor induction with offspring risk of autism spectrum disorders. JAMA Pediatr. 2016;e160965. [Epub ahead of print].

2. Gregory SG, Anthopoulos R, Osgood CE, Grotegut CA, Mirand ML Association of autism with induced or augmented childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) databases. JAMA Pediatr.  2013;167(10):959-966.