The prevalence of autism has increased during the past few decades. Although some individuals are genetically susceptible to autism, the steep rise in prevalence seems best accounted by the superimposition of environmental exigencies acting at vulnerable times during brain development. This is something that I have called the Triple-Hit Hypothesis of autism. One possible environmental exigency that has increased peri passu with autism has been the use of prenatal ultrasound. Although of great clinical utility in following a pregnancy, ultrasound has been overused in ways that often side steps safety recommendations (see references below). Furthermore, as we get to know more about the effects of ultrasound it seems clear that present day techniques used to monitor safety (e,g., mechanical index, thermal index) are inadequate or insufficient when used by themselves. Indeed, prenatal ultrasound is not just about taking pretty pictures of babies or recording keepsake images. Ultrasound is now used in healing fractures and gastric ulcers (increase mitotic activity), in accelerating the delivery of drugs to the brain (disrupting the blood brain barrier), and in activating areas of the brain as an alternate method to electrophysiological techniques like transcranial magnetic stimulation (TMS). The energy of ultrasound has unintended consequences for the brain, helping create gap junctions between neurons and establishing new pathways of cellular communications. It is for this reason that studies on the safety of this technique are needed in order for consumers to become more informed before taking decisions that may impinge on their health and/or that of their baby.
Today (February 12, 2018), in the Journal of the American Medical Association (JAMA) a new and interesting article has been published entitled, “Prenatal ultrasound and autism spectrum disorder”. The article was written by a team of researchers led by N. Paul Rosman a well-recognized scholar, clinician and humanist who was the perennial chief of pediatric neurology at the Boston City Hospital for Children and the Tufts-New England Medical Center. The study attempted to answer the question of whether there was an association between prenatal ultrasound frequency, timing, duration, or strength and later autism spectrum disorder? The article has a structured abstract that reads as follows:
Importance: The prevalence of autism spectrum disorder (ASD) as been increasing rapidly, with current estimates of 1 in 68 children affected. Simultaneously, use of prenatal ultrasound has increased substantially, with limited investigation into safety and its effects on brain development. Animal studies have demonstrated that prenatal ultrasound can adversely affect neuronal migration.
Objective: The study aimed to quantify prenatal ultrasound exposure by the frequency, timing, duration and strength of scans in fetuses with later ASD, developmental delay (DD), and typical development (TD).
Design: Case-control study.
Setting: Boston Medical Center (BMC), a diverse, academic, safety-net medical center.
Participants: Subjects with ASD (N=107) and controls with DD (N=104) or TD (n=209) were identified from medical records based on prenatal care and delivery at BMC between 1/1/2006-12/31/2014, and gestational age >37 weeks.
Exposures: Ultrasound exposure was quantified by number and timing of scans, duration of exposure, mean strength (depth, frame rate, mechanical index, and thermal index), and time of Doppler, 3D and 4D imaging.
Main Outcome Measures: Among ASD, DD, and TD cases, ultrasound exposure was quantified and compared per trimester and for the entire pregnancy.
Results: The ASD cases received a mean of 5.8 scans (95% CI 5.1-6.5), not significantly different than 5.9 scans (5.2-6.6) in the DD cases or 6.0 scans (5.5-6.6) in the TD cases. ASD cases had shorter duration of ultrasound exposure during the first and second trimesters compared to TD cases, but no difference in number of scans per trimester.
The ASD cases had higher mean depth of ultrasound penetration than DD cases in the first trimester (12.3 cm) vs. 11.5 cm. The ASD cases had higher mean depth than TD cases during the first trimester (12.cm vs. 11.5 cm) and the second trimester (13.0 vs. 12.4 cm).
Conclusion and Relevance: This study found a significantly higher mean depth of ultrasound penetration in the ASD cases compared to the DD cases in the first trimester, and compared to the TD cases in the first and second trimesters. Further research is needed to determine whether other parameters of ultrasound exposure have adverse effects on the developing fetus.
According to the authors, and their review of the literature, this is the most detailed analysis of the 21st century on prenatal ultrasound exposure. The total number of cases in this study was impressive, n=420 children. Furthermore, the techniques, equipment and data generated from them was extraordinary. Among the salient aspects of the study was the fact that the average number of scans in the study was greater than fiver per pregnancy. For low risk pregnancies, the number of scans is not justified. This begs the question of whether clinicians administering this large number of unjustified ultrasound studies were unknowingly increasing the risk of potential complications.
Among the weaknesses of the study, was the total number of different parameters examined, which gave the study an aura of a fishing expedition. Indeed, some of the findings actually pointed towards ultrasound NOT being involved in the genesis of autism. Children with ASD received LESS first and second trimester scans, and LESS time of scans. Only a new variable, “depth of ultrasound penetration” was significant. There were also major confounds that were not addressed adequately through statistics; e.g., the ASD group had more obstetric complications (obesity) and less access to care. These are huge complications each one predisposing by themselves to a higher risk of autism. I also found disturbing the lack of detail inking this new variable (depth of penetration) to known brain findings in autism. It is not that available literature is available, but that the authors were not apparently cognizant of the same. However, it may be that there is a premium in keeping reports short, which may have forced them to remove these mechanistic speculations from their original manuscript. In the end, the main conclusion of the article, although still speculative, merits further study: increased depth of ultrasound penetration may be associated with perturbations of fetal neuronal migration and later autism.
The main page for Cortical Chauvinism has a click button for our Facebook link on safety of prenatal ultrasound. Be sure to click on it and read further material on this subject.
Two of the articles cited in the JAMA article belong to the author (MFC) of this blog:
Williams EL, Casanova MF. Reassessment of teratogenic risk from antenatal ultrasound. Tansl Neurosci 4(1):81-87, 2013.
Williams EL, Casanova MF. Potential teratogenic effects of ultrasound on corticogenesis: implications for autism. Med Hypothesis 75(1):53-58, 2010.
Previous blogs on this subject include: