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Original Investigation
April 2018

Association of Prenatal Ultrasonography and Autism Spectrum Disorder

Author Affiliations
  • 1Department of Pediatrics, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
  • 2Department of Neurology, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
  • 3Division of Pediatric Neurology, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
  • 4Departments of Pediatrics and Neurology, Division of Pediatric Neurology, Boston Medical Center, Boston, Massachusetts
  • 5medical student at Boston University School of Medicine, Boston, Massachusetts
  • 6Department of Pediatrics, Benioff Children’s Hospital, University of California, San Francisco
  • 7Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  • 8graduate student at Boston University School of Public Health, Boston, Massachusetts
  • 9Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts
  • 10Division of Pediatric Neurology, Puerto Rico Children’s Hospital, Bayamón, Puerto Rico
  • 11Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, Massachusetts
JAMA Pediatr. 2018;172(4):336-344. doi:10.1001/jamapediatrics.2017.5634
Key Points

Question  Is prenatal ultrasonography frequency, timing, duration, or strength associated with later diagnosis of autism spectrum disorder?

Findings  In this case-control study of 420 children, those with autism spectrum disorder were exposed to greater mean depth of ultrasonographic penetration during the first and second trimesters compared with typically developing children and during the first trimester compared with developmentally delayed children. No association between the number of scans or duration of ultrasound exposure and later autism spectrum disorder was found.

Meaning  Increased depth of prenatal ultrasonographic penetration may be associated with perturbations in fetal neuronal cortical migration and later autism spectrum disorder; this correlation deserves further study.

Abstract

Importance  The prevalence of autism spectrum disorder (ASD) has been increasing rapidly, with current estimates of 1 in 68 children affected. Simultaneously, use of prenatal ultrasonography has increased substantially, with limited investigation into its safety and effects on brain development. Animal studies have demonstrated that prenatal ultrasonography can adversely affect neuronal migration.

Objective  To quantify prenatal ultrasound exposure by the frequency, timing, duration, and strength of ultrasonographic scans in children with later ASD, developmental delay, and typical development.

Design, Setting, and Participants  This case-control study included 107 patients with ASD, 104 control individuals with developmental delay, and 209 controls with typical development. Participants were identified from medical records based on prenatal care and delivery at Boston Medical Center, a diverse, academic, safety-net medical center, from July 1, 2006, through December 31, 2014, with a gestational age at birth of at least 37 weeks. Data were analyzed from May 1, 2015, through November 30, 2017.

Exposures  Ultrasonographic exposure was quantified by the number and timing of scans, duration of exposure, mean strength (depth, frame rate, mechanical index, and thermal index), and time of Doppler and 3- and 4-dimensional imaging.

Main Outcomes and Measures  Among participants with ASD and controls with developmental delay and typical development, ultrasound exposure was quantified and compared per trimester and for the entire pregnancy, with adjustment for infant sex, gestational age at birth, and maternal age.

Results  A total of 420 participants were included in the study (328 boys [78.1%] and 92 girls [21.9%]; mean age as of January 1, 2016, 6.6 years; 95% CI, 6.5-6.8 years). The ASD group received a mean of 5.9 scans (95% CI, 5.2-6.6), which was not significantly different from the 6.1 scans (95% CI, 5.4-6.8) in the developmental delay group or the 6.3 scans (95% CI, 5.8-6.8) in the typical development group. Compared with the typical development group, the ASD group had shorter duration of ultrasound exposure during the first (290.4 seconds [95% CI, 212.8-368.0 seconds] vs 406.4 seconds [95% CI, 349.5-463.3 seconds]) and second (1687.6 seconds [95% CI, 1493.8-1881.4 seconds] vs 2011.0 seconds [95% CI, 1868.9-2153.1 seconds]) trimesters but no difference in the number of scans. The ASD group had greater mean depth of ultrasonographic penetration than the developmental delay group in the first trimester (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.1-12.1 cm]). The ASD group had greater mean depth than the typical development group during the first (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.3-12.0 cm]) and the second (12.9 cm [95% CI, 12.6-13.3 cm] vs 12.5 cm [95% CI, 12.2-12.7 cm]) trimesters.

Conclusions and Relevance  This study found significantly greater mean depth of ultrasonographic penetration in the ASD group compared with the developmental delay group in the first trimester and compared with the typical development group in the first and second trimesters. Further research is needed to determine whether other variables of ultrasound exposure also have adverse effects on the developing fetus.

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