Summary: A new study examining variability of symptoms in children with autism found that exposure to diagnostic ultrasound during the first trimester of pregnancy was associated with greater symptom severity in some children.
Source: University of Washington
Researchers say the findings support careful adherence to FDA guidance on prenatal ultrasound
A team of researchers from UW Medicine, University of Washington Bothell and Seattle Children’s Research Institute report that exposure to diagnostic ultrasound during the first trimester of pregnancy is linked to increased symptom severity among children with autism spectrum disorder (ASD). The study, published in Autism Research, does not examine the causes of autism itself but focuses on factors that may influence the degree of symptom severity.
The research analyzed data from the Simons Simplex Collection (SSC), a genetic repository supported by the Simons Foundation Autism Research Initiative. Information from 2,644 families collected across 12 U.S. research sites was used to evaluate whether prenatal ultrasound exposure, genetic vulnerability and timing of exposure relate to differences in outcomes among children diagnosed with ASD.
Corresponding author Pierre D. Mourad, a professor of neurological surgery at the University of Washington and a researcher experienced in ultrasound and brain translational research, emphasized the relevance of the timing of exposure. “Our results are specific to ultrasound exposure during the first trimester,” Mourad said. He noted that analyses of ultrasound exposure in the second and third trimesters did not show a similar association with increased ASD symptom severity.
Lead author Sara Webb, a professor of psychiatry and behavioral sciences at the University of Washington and a researcher at Seattle Children’s, described the project as addressing why outcomes vary so widely among children with autism. “We approached this study with a three-part model: a genetic vulnerability to ASD, an environmental or external stressor, and critical timing of that stressor during development,” Webb explained. In this investigation, the external factor examined was diagnostic ultrasound during early gestation.
The researchers found the strongest association among children who carried particular genetic variations known as copy number variations (CNVs). Approximately 7 percent of the study participants had such genetic variants. Male children with ASD who had CNVs and were exposed to first-trimester ultrasound showed lower nonverbal IQ scores and increased repetitive behaviors compared with male children with ASD and CNVs who were not exposed to ultrasound during the first trimester. These differences suggest that, in the presence of specific genetic vulnerabilities, early prenatal ultrasound exposure may contribute to the heterogeneity of ASD outcomes.
Webb, who also develops biomarkers for children with ASD, said the findings point toward a need for cautious consideration of nonessential ultrasound in early pregnancy. “As a parent, given this information I would avoid first-trimester ultrasound unless there is a clear medical need, such as confirming gestational age,” she said. “Medical procedures often have benefits, but they can also carry risks that deserve careful evaluation.”
The report builds on earlier experimental work by Mourad and colleagues published in 2014, which showed that ultrasound exposure in pregnant mice produced behavioral changes in offspring resembling autistic-like traits. That animal work helped motivate the current human-data analysis, which focused on variability in ASD outcomes rather than incidence.
The research team included clinicians and investigators with diverse expertise in autism, genetics, clinical trials and epidemiology. Among the co-authors were Abbi McClintic, Raphael Bernier, Michelle Garrison and Bryan King, each contributing to analysis, clinical perspective and statistical interpretation of the SSC dataset. The collaborative effort allowed the researchers to examine interactions among genetic risk factors, prenatal exposures and later developmental outcomes.
Funding: This study was supported by grants from the National Institutes of Health (RO1HD064820 and P50HD055782) and by the Simons Simplex Collection (SFARI #89368).
Source: University of Washington (Bobbi Nodell).
Original Research: Abstract for “Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound” by Sara Jane Webb, Michelle M. Garrison, Raphael Bernier, Abbi M. McClintic, Bryan H. King, and Pierre D. Mourad in Autism Research. Published online August 2016. doi:10.1002/aur.1690
Abstract summary
Current evidence suggests that ASD symptom incidence and variability may result from a combination of genetic and environmental factors. Although diagnostic ultrasound is widely used in clinical practice and generally considered safe, experimental data have raised questions about whether exposure early in gestation could affect brain development and behavior. Using a modified “triple hit” framework—genetic predisposition, an environmental stressor, and critical timing—the authors performed a retrospective analysis of SSC data. Their findings indicate that male children with ASD who carry copy number variations and who were exposed to first-trimester ultrasound exhibited lower nonverbal IQ and greater repetitive behaviors than comparable children without first-trimester ultrasound exposure. These results support continued adherence to FDA guidance recommending that prenatal diagnostic ultrasound be used only when medically necessary, and they highlight the importance of further research into how early prenatal environmental exposures may interact with genetic vulnerabilities to influence ASD outcomes.