The odds of autism increased significantly in children whose mothers gave birth with induced or augmented labor, a study of more than 600,000 births showed.
Overall, the likelihood of autism increased by 23% in association with induced or augmented labor as compared with children whose mothers had unassisted labor, Simon G. Gregory, PhD, of Duke University, and colleagues reported inJAMA Pediatrics.
Induction only, augmentation only, or the combination all were associated with significantly increased odds of autism. The magnitude of increased risk was similar to that associated with fetal distress, meconium, prematurity, and maternal diabetes, they said.
"While these results are interesting, further investigation is needed to differentiate among potential explanations of the association including underlying pregnancy conditions requiring the eventual need to induce/augment, the events of labor and delivery associated with induction/augmentation, and the specific treatments and dosing used to induce/augment labor," the authors concluded.
Autism has a prevalence of about 1.1% among children in the U.S. Etiology remains unknown, but most studies have focused on genetic predisposition. Some of the same studies, however, have yielded discordant results suggesting a potential contribution of environmental factors toward dysregulation of developmental processes, the authors noted.
A recent study of twins provided evidence that environmental factors may influence susceptibility to autism during prenatal and early postnatal development. Within that time frame, one potential contributor is labor induction or augmentation.
To investigate the role of induced or assisted labor in autism, Gregory and colleagues analyzed data from the North Carolina Education Research Data Center, which maintains records on all children in North Carolina public schools, including a designation for autism.
The study included birth records of children born during 1990 to 1998 linked to educational data from the school years 1997-1998 and 2007-2008. Using designators employed by the North Carolina Detailed Birth Record, investigators separated births into four classifications: no labor induction or augmentation, labor induction only, augmentation only, or both induction and augmentation.
The final analysis included 625,042 live births, including 5,648 children with a designation for autism. Statistical analyses included a variety of covariates within the categories of events of labor and delivery, mode of delivery, maternal medical conditions, and birth outcome status.
Consistent with the known sex distribution of autism, boys accounted for three-fourths of the cases. Induced/augmented labor occurred more often in association with autism in both sexes. Children with autism also had higher rates of fetal distress or meconium.
The results showed a consistent pattern of increased odds for autism among children whose mothers had induced or augmented labor:
- Induced/augmented versus none: odds ratio 1.23 (95% CI 1.02-1.47)
- Induced only: OR 1.10 (95% CI 1.01-1.19)
- Augmented only: OR 1.15 (95% CI 1.07-1.24)
- Induction and augmentation: OR 1.27 (95% CI 1.05-1.52)
Compared with girls, boys exhibited increased odds of autism diagnosis (OR 3.04, 95% CI 2.86-3.24).
Other factors associated with increased odds of an autism diagnosis were fetal distress (OR 1.25, 95% CI 1.15-1.36), meconium (OR 1.22, 95% CI 1.11-1.34), birth ≤34 weeks (OR 1.25, 95% CI 1.11-1.41), and maternal diabetes (OR 1.23, 95% CI 1.07-1.41).
Non-Hispanic black race/ethnicity, older maternal age, higher maternal education, and first born in birth order also increased the odds of an autism diagnosis. Mode of delivery (vaginal versus cesarean) did not affect the odds.
Given the documented benefits of labor induction and augmentation and lack of understanding about the nature of the association with autism, the authors emphasized that the results "are not sufficient to suggest altering the standard of care regarding induction or augmentation; our results do suggest that additional research is warranted."
"We haven't established cause and effect," Gregory told MedPage Today. "We know that there are circumstances surrounding birth which have resulted in an elevated risk in autism, but we can't establish that it's the induction or augmentation process itself. It could be maternal health, it could be fetal health, or it could be the induction or augmentation process itself. We haven't made that link yet."
Despite the study's large, diverse, modern population sample, the need for more research is clear, said Susan Hyman, MD, of the University of Rochester in New York.
"I would urge families to have open lines of communication with their healthcare provider so they can discuss indications for induction," Hyman told MedPage Today. "However, the literature regarding the improvements in neonatal morbidity and mortality cannot be forgotten."
The American Academy of Pediatrics recommends general developmental screening that includes autism-specific screening of children at 18 and 24 months and ongoing surveillance for all children, irrespective of labor induction or augmentation, she added.
Reviewed by Robert Jasmer, MD
; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner