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    Study: No association between prenatal ultrasound duration and autism

    According to a study published in JAMA Pediatrics, there is no association between diagnosis with autism spectrum disorder (ASD) and duration of prenatal ultrasound. In children with ASD, however, mean depth of first- and second-trimester ultrasonography was significantly greater than in children without the disorder. 

    In a case-controlled study that included 107 patents with ASD, 104 control patients with developmental delay, and 209 controls with typical development, the researchers explored whether there is an association between fetal ultrasound exposure and later ASD. Criteria for inclusion in the study were maternal prenatal care at the academic safety net medical center used in the study, birth at the medical center between July 1, 2006 and December 31, 2014, and gestational age at birth ≥ 37 weeks. Diagnosis of ASD was performed by a developmental-behavioral pediatrician and based on ICD-9 codes, as was diagnosis of non-ASD developmental delays. The researchers identified children with ASD and then included 1 control individual with developmental delay and 2 controls with typical development to correspond to each ASD patient by sex, birthdate (± 90 days), and maternal age (± 3 years). Data collected from each ultrasound scan included gestational age at scan, total time of exposure, time-weighted mean depth, frame rate (ultrasound pulses per second), mechanical index, soft-tissue thermal index, total time of Doppler use, and total time using 3-D and 4-D imaging.   

    No statistically significant differences were found in the timing of the initial ultrasound scans, number of scans, or total time of exposure in the ASD group compared with the developmental delay group. However, during the first trimester, time-weighted mean depth of scans was greater in the ASD group (12.5 cm; 95% CI, 12.0-13.0 cm) than in the developmental delay group (11.6 cm; 95% CI, 11.1-12.1 cm). The ASD group also had longer duration of 4-D imaging exposure (6.6 seconds, 95% CI, 1.0 to 12.2 seconds) than the developmental delay group (0.8 seconds; 95% CI, -4.7 to 6.2 seconds). Time-weighted mean depth of penetration was higher in the ASD group in all trimesters compared to the typical development group: first trimester (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.3-12.0 cm]), second (12.9 cm [95% CI, 12.6-13.3 cm] vs 12.5 cm [95% CI, 12.2-12.7 cm]), and third trimester (15.1 cm [95% CI, 14.7-15.5 cm] vs 14.8 cm [95%CI, 14.5-15.0 cm]). However, fewer patients in the ASD group had first-trimester scans but the mean number in the first trimester was not significantly different (0.5 [95%CI,0.4-0.6] vs0.6 [95%CI,0.5-0.7]). The authors noted, however, that the mean number of total scans was more than 5, which is considerably higher than the 1 to 2 scans recommended by the American College of Obstetricians and Gynecologists in low-risk pregnancies.

    Mothers of children with ASD were more likely to be obese (body mass index [BMI] ³ 30) compared to mothers of children with developmental delay (28 [26.2%] versus 15 [14.4%]). The researchers did not find any other significant differences in maternal demographic factors between these two groups. They were also more likely to be 35 years or older than mothers of children with typical development (32 [29.9%] versus 41 [19.6%]). Mothers of children with ASD were also more likely to be late registrants for prenatal care compared with mothers of children with typical development.      

    The authors noted a few limitations to the study. The study was retrospective, which may have underestimated or underrepresented exposure duration. The study also excluded preterm infants, who are at a higher risk for ASD but receive fewer ultrasounds due to a shorter gestational period. The researchers said they did not have access to maternal smoking history, which is associated with a higher risk of ASD. They believe the findings of this study suggest that more research is necessary, but that their data illustrate the need for updating ultrasound procedures and safety measures.


    Putting the study in perspective

    Dr. CopelThis is a deeply flawed study which failed to find any connection between ASD and ultrasound, yet its abstract cited a connection. There was no difference in the number of ultrasounds in any trimester (actually the ASD group had FEWER first-trimester scans), or in any demographic factors between the studied groups: children with ASD, other developmental delays and normal.

    The authors claimed in this retrospective study that they could measure total duration of ultrasound, based on when still images were obtained. Anyone who performs ultrasonography knows that there is, at best, an indirect correlation between time from first to last stored image and total time the transducer is on the maternal abdomen. For example, time waiting for a physician to come and check the scan could result in long intervals when no ultrasound exposure is occurring.

    More concerning is the introduction of an alleged measure of ultrasound exposure, the “time weighted-mean depth.” The Safety Committee of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), an international group of experts in ultrasound safety and bioeffects, released a statement about this at the time of the paper’s publication. None of these experts had ever encountered this measure before, and it is totally unvalidated. (Full disclosure: I am President of ISUOG.)

    To understand the irrelevance of the “time weighted-mean depth,” consider that the depth of an ultrasound image, selected to include only relevant structures, does not mean that the ultrasound energy somehow knew to stop at the depth displayed on the monitor. To make matters worse, the authors do not present data on or statistical control for maternal BMI, and maternal obesity naturally increases the depth at which we look at the fetus and in some studies, is associated with ASD.

    NEXT: Can a placenta-on-a-chip be used to analyze placental perfusion?

    Ben Schwartz
    Ben Schwartz is Associate Editor, Contemporary OB/GYN.
    Judith M. Orvos, ELS
    Judith M. Orvos, ELS, is an editorial consultant for Contemporary OB/GYN.


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