Autism Not Linked to Labor Induction, Augmentation

  • SAN DIEGO — Birth complications during labor and delivery do not increase a child’s risk for autism spectrum disorder, delegates heard here at the Society for Maternal-Fetal Medicine (SMFM) 2015 Annual Pregnancy Meeting.

The findings conflict with a previous study on this issue, even though the epidemiologic approaches of the two studies were similar and both groups used birth records and an education research base to identify autism (JAMA Pediatr. 2014;168:191-192).

The conflicting results could be related to “differences in population characteristics and methodologic approach, including the management of confounding variables,” explained investigator Erin Clark, MD, from the University of Utah in Salt Lake City.

In the United States, one in every 68 children is diagnosed with autism, according to the Centers for Disease Control and Prevention. From 2002 to 2010, its prevalence increased 120%.

“The explanation for this increase is multifactorial and at least partially due to changes in case ascertainment,” Dr Clark said. “How much is due to a legitimate increase in case prevalence is unclear, but it is a source of great concern. The hunt for risk factors is on, as we seek etiologic clues and possible prevention and treatment strategies.”

Environmental Triggers, Genetic Risk

Autism arises most often when environmental triggers combine with genetic risk. Data on perinatal risk factors are conflicting. However, because alterations in oxytocin and oxytocin signaling have been linked to autism, the induction and augmentation of labor have been of interest.

Previous research has demonstrated an association between induction or augmentation and autism that persisted after confounders were controlled for, but a meta-analysis found no link (Pediatrics.2011;128:344-355).

Dr Clark and her team obtained data from the Utah Registry of Autism and Developmental Disabilities. The collaborative program of the Utah Department of Health and the University of Utah identifies children with autism in a four-county surveillance area, which represents 70% of Utah’s population.

The team examined the records of children born from 1998 to 2006. They compared 2547 children who had received a diagnosis of autism before 2012 with 166,238 children who were born without congenital anomalies or aneuploidy at 24 to 42 weeks of gestation and who weighed at least 400 g at birth. They obtained information on induction and augmentation from birth certificates.

The prevalence of autism in the study cohort was one in 65. The breakdown by sex was one in 45 males and one in 130 females, which is consistent with the prevalence in the United States of 3 males to 1 female. Overall, 33% of the deliveries involved the induction of labor and 25% involved augmentation.

After potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth cohort were controlled for, the odds of a diagnosis of autism were not significantly higher in children exposed to induction or augmentation than in those not exposed to either.

Table 1. Association Between Autism and Induction or Augmentation

Patient Group Adjusted Odds Ratio 95% Confidence Interval PValue
Induction and augmentation 0.897 0.753–1.070 .23
Induction only 0.959 0.864–1.065 .43
Augmentation only 0.978 0.870–1.100 .71

A sex-stratified analysis of 85,956 males and 82,874 females yielded similar results.

“In adjusted models, males had a three-fold higher risk of autism, compared with females,” Dr Clark reported. “Other variables had a relatively small but statistically significant association with autism spectrum disorder.”

Table 2. Other Variables Associated With Autism

Variable Adjusted Odds Ratios
Male sex 3.00
Composite neonatal morbidity 1.70
Birth before 34 weeks of gestation 1.46
Large for gestational age 1.31
Smoking 1.29
Small for gestational age 1.26
First child 1.25
Cesarean delivery 1.14
Prepregnancy body mass index 1.04
Pregnancy weight gain 1.01
Maternal age 1.01

One of the strengths of this study, said Dr Clark, is that it “carefully considered the relevant confounders.”

She explained that the findings join the “preponderance of current literature, including a meta-analysis, that refutes the association” between induction or augmentation of labor and autism.

“Our findings support the current recommendation from the SMFM and ACOG, which advises against a change in current guidance regarding counseling and indications for, and methods of, labor induction and augmentation,” she said.

“This is a brilliant paper and I think in these days of hysteria, it is very timely,” said Laxmi Baxi, MD, from the New York University Langone Medical Center and Columbia University in New York City.

Interest High

The study is a “wonderful model to show how we can perform evidence-based public health studies,” added Qing Li, MD, DrPH, from the Medical University of South Carolina in Charleston.

However, some concerns were raised because the study lacked information on the exact method and the agent used for induction or augmentation. “Not having this information makes the study less reliable,” said a member of the audience.

“Not knowing the oxytocin variables is critical,” said Dr Clark. “We think a huge step forward would be to have detailed exposure data from a modern obstetric cohort with well-validated case ascertainment. That would give us additional reassurance on this subject.”

The findings from this study “conflict with previous studies,” but it provides more detail than others have, Brian Mercer, MD, from the MetroHealth Medical Center at Case Western Reserve University in Cleveland, who is immediate past president of the SMFM.

“However, no study yet provides the depth of detail one would want to answer all the questions,” Dr Mercer told Medscape Medical News.

Dr Clark and Dr Mercer have disclosed no relevant financial relationships.

Society for Maternal-Fetal Medicine (SMFM) 2015 Annual Pregnancy Meeting: Abstract 6. Presented February 5, 2015.