Fewer Multiple Births May Cut Autism Risk in ART Kids

Fran Lowry

March 26, 2015

Children conceived with assisted reproductive technology (ART) are twice as likely to receive a diagnosis of autism compared with their counterparts who are conceived naturally, new research shows.

Dr Peter Bearman

But when the researchers delved a little deeper, they found that this increased risk was largely due to complications of pregnancy and birth, especially when such pregnancies were associated with multiple births.

"Multiple births seemed to account for the difference," lead author Christine Fountain, PhD, a sociologist at Fordham University, New York City, told Medscape Medical News.

"We found what an epidemiologist would call a modifiable risk factor. The thing we can do to reduce the risk of autism among ART children would be to transfer only single embryos, rather than multiple embryos. That is the thing that can be changed," Dr Fountain said.

Senior author Peter Bearman, PhD, Jonathan Cole Professor of the Social Sciences in the Department of Sociology and director, Interdisciplinary Center for Innovative Theory and Empirics, Columbia University, concurred.

"The risk of ART with respect to autism appears to be largely modifiable by restricting the procedure to single-embryo transfer. Knowing that one can largely reduce the risk of autism from an ART conception by restricting the procedure to single-egg transfer is important for women, who can then make better informed decisions," he said.

The study was published online March 19 in the American Journal of Public Health.

Rapid Rise

The researchers note that during the past decade, there has been a rapid rise in autism rates in the United States. At the same time, there has been a rapid increase in ART, defined as in vitro fertilization and similar procedures in which both egg and sperm are handled.

"Because of the increasing use of ART as well as the increasing incidence and uncertain etiology of autism, it is important to explore whether these phenomena are associated. We assessed the possible association between ART and diagnosed autism in a 10-year cohort of California children," the investigators write.

In the observational cohort study, the researchers assessed the association between ART and autism in a population-based sample of almost 6 million live births that took place in California from 1997 through 2007.

They used linked records from the California Birth Master Files for those years, the California Department of Developmental Services (DDS) autism caseload records for 1997 to 2011, and the Centers for Disease Control and Prevention's National ART Surveillance System for live births for 1997 to 2007.

"The DDS system coordinates diagnoses, services, and support for persons with developmental disabilities in California, including patients with autistic disorder, but generally not with other ASDs [autism spectrum disorders], such as Asperger's syndrome," said Dr Fountain.

"The vast majority of persons with autism in California are enrolled in the DDS, making it the largest administrative source of data on autism diagnoses. We classified children enrolled in the DDS autism caseload as having a diagnosis of autism on the date of enrollment," she said.

Potential Mechanisms

Of the 5,926,251 children born in California from 1997 to 2007, 48,865 were born through ART; 32,922 children were diagnosed with autism and enrolled in the DDS caseload by June 2011.

The researchers compared births that originated with the use of ART with births that originated without ART for incidence of autism.

They found that the incidence of diagnosed autism was twice as high for ART as non-ART births (12.1 for every 1000 births for ART vs 5.5 per 1000 births for non-ART).

"Specifically, autism was 80% more likely among ART births than non-ART births. But a closer look that adjusted for other known risk factors for autism reduced the hazard ratio down to 74% for mothers aged 20 to 34, and 36% for older mothers," Dr Fountain said.

"ART appears to have a smaller impact on the risk of having a child with autism for older mothers. They are still more likely to have a child with autism, but their chances are smaller," she added.

The authors note that there are many potential mechanisms through which ART could be associated with autism. These include the biological factors related to the underlying fertility or quality of the germ cells, effects of the fertility hormones used during ART, other effects of the ART procedure, and the prenatal and perinatal complications associated with ART treatment.

However, the study was not designed to distinguish between these mechanisms.

"Multiple births played an important role in the association between ART and autism. In fact, the adjusted risk arising from ART was not significantly elevated in singletons, who make up less than half of ART-originated children," said Dr Fountain.

Is It Autism?

"The study is interesting but doesn't really tell us that much, because of the complicating fact of multiple births. These children may not in fact all have autism," said Fred R. Volkmar, MD, Irving B. Harris Professor in the Child Study Center, Yale University School of Medicine, New Haven, Connecticut, who was not part of the study.

Dr Fred Volkmar

"Multiple-birth kids generally have more problems, and issues of diagnosis can be complicated when dealing with very young children. There is a tendency to overrely on school labels, rather than actual assessments, among children with birth-related problems," Dr Volkmar, who is also editor-in-chief of the Journal of Autism and Developmental Disorders, told Medscape Medical News.

"It looks like the authors are relying on data that have been collected without people necessarily having seen the child. This is problematic. The label of autism can get assigned to address needs for service, rather than diagnosis, and this multiple-birth group is already a high-risk group in terms of needs for service," he said.

The research was supported by the National Institutes of Health Director's Pioneer Award program and the National Institutes of Mental Health. Dr Fountain and Dr Volkmar report no relevant financial relationships.

Am J Public Health. Published online March 19, 2015. Abstract

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