Note: The main intent of this blog is to call attention to the fact that inadequate use of ultrasound is clearly dangerous and may be tied to the ever increasing prevalence of some neurodevelopmental conditions. Urgent action by the government is clearly needed to regulate the use of this technique. Selling equipment to non-health professionals (e.g. Amazon.com or eBay) should be prohibited. Furthermore, the use of ultrasound for nonmedical purposes, e.g., keepsake images, should be banned.

Introduction

The term ultrasound refers to oscillating sound waves that travel through a medium, either gaseous, liquid, or solid, at a very high frequency. Sounds waves in physics are also known as compression waves because they produce alternating compression and rarefaction (a push and pull effect) when traveling through a medium. Audible sound usually travels at 10 to 20 thousand cycles per second. By comparison, ultrasound waves travel at a much higher frequency, that is, several million cycles per second. In the animal kingdom, bats, whales and dolphins use ultrasound for echolocating objects in their surroundings allowing them to both navigate and capture their prey.

The idea of using ultrasound for practical purposes came after the sinking of the Titanic at the turn of the century when sonar (sound navigation and ranging) was proposed as a way of screening for the submerged component of an iceberg. In fact, the first ultrasound machine was capable of detecting an iceberg 2 miles away! A few years later the threat of German submarines during World War I (1914-1918) created an impetus for further developing ultrasound technology. During World War II (1939-1945) submarines comprised less than 2% of the US Navy but sunk over 55% of Japan’s navy. Detection of submarines by ultrasound was therefore prioritized thus promoting an emerging technology.

In the mid 1950’s a Scottish physician by the name of Ian Donald borrowed an ultrasound machine, that had been used to detect flaws in metallurgy, in order to investigate differences in tissue densities in biopsied abdominal masses obtained from over one hundred patients. His results, published in The Lancet were well received within the medical field. The potential to use the technique in order to visualize the human fetus was soon realized and its use spread quickly. Commercial equipment became available in 1963, and by the late 1970’s ultrasound was part of the standard of care in obstetrics.

Ultrasound Use in Obstetrics

The main uses of ultrasonography in obstetrics are:

Diagnosis and confirmation of early pregnancy
Vaginal bleeding in early pregnancy
Determination of gestational age and assessment of fetal size
Diagnosis of fetal malformation
Placental localization
Multiple pregnancies
Changes in quantity of amniotic fluid
Nuchal (neck) scans (to help identify chromosomal disorders)(see: http://en.wikipedia.org/wiki/Nuchal_scan)

Ultrasound is used in obstetrics in order to visualize the embryo or fetus within the mother’s womb. Despite its wide use, there does not appear to be a clear benefit for using ultrasound in low risk pregnancies. Multiple Cochrane Collaborative Database studies as well as the American College of Obstetricians and Gynecologists have concluded that:

“…neither a reduction in perinatal morbidity (disease) and mortality (death) nor a lower rate of unnecessary interventions can be expected from routine diagnostic ultrasound.”

In spite of the lack of benefit for using ultrasound in low risk pregnancy its use has increased exponentially over last few decades. In Canada, the average number of ultrasound exams experienced by a low risk pregnant woman varies between 3 to
4. In the US practically all low risk pregnancies receive the study, usually between 18 and 20 weeks when it is referred to as “routine prenatal ultrasound” (see: http://bit.ly/1cYtjWq).
Along with the increased usage of ultrasound, a number of significant poor pregnancy outcomes have been noted, as an example, there has been an increased risk for unnecessary Cesarean sections when ultrasound was used during third trimester screening. Ultrasound may also mistakenly lead to termination of pregnancy (abortion) whenever the severity of an underlying fetal anomaly is confused. Furthermore, since about 10% of ultrasounds give unclear results, mothers are subjected to additional exams and continuous anxiety until the end of their pregnancy. It is therefore not surprising that a review of the literature has condemned the use of ultrasound for the purposes of dating, second semester organ scan, biophysical profile, and amniotic fluid assessment.

Ultrasound and Autism

The use of ultrasound was deregulated in the 1990’s as a result of an obesity epidemic. In this regard, an eightfold increase in energy was allowed by the FDA in order to better visualize the babies of obese women. This time frame coincides with the escalating prevalence of autism in our country. This sort of correlation does not imply causality (see: http://bit.ly/JVs8jz). Truthfully, none of the supportive evidence that I will provide shows a causal relationship. However, they indicate a need for further studies and to apply caution when using the technique.

My inclination to consider ultrasound as a possible risk factor for autism spectrum disorders (ASD) is derived from several lines of evidence:

1) Adverse outcomes of ultrasound are commonly seen in autism. The use of ultrasound has been reported to produce growth retardation, delayed speech, learning difficulties (dyslexia), and increased prevalence of left handedness. All of these factors are commonly seen in autism spectrum disorders (ASD).

2) Risk factors that would promote either an increased number of ultrasound exams during pregnancy or an increased energy are also risk factors for ASD. This commonality is evident in pregnancies where the mother is obese, older, multiparous (having twins or triplets) or there is evidence of threatened abortion.

3) Epidemiological studies in third world countries (Somalia) where the prevalence of autism appears to be low (along with diminished use of ultrasound) skyrockets when they immigrate to industrialized nations. Also, select populations within industrialized nations (e.g., Amish) that tend to forgo the use of ultrasound seemingly have a lower prevalence of autism.

4) Animal studies in different species (both chicks and rodents) have shown changes in-keeping with an autism phenotype, e.g. changes in learning, locomotor activity, and socialization (the latter not caused by anxiety).

5) The mode of action of ultrasound could well explain the neuropathology of autism. Ultrasound has well established effects on germinal cell populations and its ability to regulate growth factors. The FDA has allowed ultrasound to be used to trigger tissue regeneration in bone fractures, and a similar growth effect has been observed for cartilage. In previous blogs and publications I have detailed how autism (both idiopathic and syndromic) appears to be the result of a single pathophysiological mechanism: the division of germinal cells and their anomalous migration during brain development (see Casanova et al., 2013 and the following blogs: http://bit.ly/1eDrlSS and http://bit.ly/18iI4pw ).

6) The potential effect on germinal cells could help explain the gender bias in autism due to the protecting effects of estrogen receptors on these cells. A similar gender bias is noted in other conditions affecting periventricular germinal cells (e.g., hemorrhages in extreme prematurity).

7) Migrational abnormalities follow the heterochronic division of germinal cells. Clusters of cells are seen in the white matter of autism spectrum disorders individuals leading to cortical laminar effacement and a derangements in their minicolumnar organization. There are clusters of misplaced neurons in the subventricular zone, along the white matter, and in the subplate of autistic individuals. The cortex shows evidence of malformation (dysplasia) explained by migratory defects. In prenatal ultrasound, Ang et al (2006), using a mouse model, showed migrational abnormalities and cortical derangements.

None of the above evidence provides a causal relationship but indicate the necessity for further research.

Discussion

Ultrasound is not an inert technique with innocuous side effects. Stanton and colleagues (2001) have reported that mice exposed to dosages typical of diagnostic obstetric ultrasound exhibit a significant decrease in cell division and cell death when the small intestine is studied. These effects are typically the end-result of thermal and mechanical actions caused by high frequency sound waves. In effect, side effects such as those described by Stanton were observed after the initial use of the technique. When high-power ultrasound waves were first used for sonar, schools of dead fish floated on the surface water. More recently the use of sonar has led to the stranding and mass extinction of whales. Mass stranding have been reported in the Canary Islands, Greece, Madeira, the US Virgin Islands, and many other locations (http://www.nrdc.org/wildlife/marine/sonar.asp ). The lethal effect of ultrasound on fish has called for the regulation of this technique for maritime purposes, but no similar attempts are undertaken to protect humans! For those individuals who believe that Ultrasound is innocuous and is only a way of obtaining a pretty picture of your baby, please see how these high frequency sound waves can actually move objects: http://t.co/gvhTzz3iYz

Findings, such as dead fish caused by sonar, called attention to important and unexpected bioeffects of the technique. The thermal effects of ultrasound led to further research that propitiated use of this technique for tissue heating and healing. Ultrasound is presently used by physical and occupational therapists in order to break up scar tissue and adhesions as well as to reduce inflammation, swelling and calcium deposits. Ultrasound is also commonly used for dispersing emulsions. Highly intensive ultrasound disperses liquid from one phase into a second phase (e.g., oil into water). Emulsification is accomplished by small bubbles imploding and causing extreme shock waves and high velocity liquid jets into the surrounding liquid.

A lack of skepticism bordering on overconfidence has led the medical community to overuse ultrasound in obstetrics. During the first few decades of ultrasound’s use in prenatal care, the FDA strictly regulated absolute intensity levels according to the specific application. Now, however, risk is assessed by real-time thermal and cavitational indices only available on the device itself. This has shifted control away from a regulatory authority dictating absolute exposure levels, to the end user who interprets machine output and adapts usage based on medical experience (Barnett et al. 2000). To complicate matters, machine reliability is being called into question. Recently, a series of studies assessing ultrasound transducer error rates revealed that, of seven manufacturer’s equipment tested across 676 different transducers, on average 40% of those transducers were defective (Mårtensson et al. 2009). All companies tested exhibited a minimum of 20% error rates, while one company tested as high as 67%. A separate study by the same research group sampled additional ultrasound transducers in a single hospital setting, finding 81 of 299 actively-used ultrasound machines to be defective (Mårtensson et al. 2010). Not only for the purpose of image quality and diagnostics is it imperative that ultrasound machines perform as they are intended: faulty transducers lead one to question whether the safety indices are accurately gauging exposure levels and, if not, what the true range of exposure levels may be. With faulty equipment, there is no way to ensure that exposures are not reaching harmful levels.

In addition to questionable transducer performance, practitioners and sonographers who routinely utilize ultrasound in their practices appear to be poorly educated as to the possible risks of ultrasound exposure. In a survey of 130 end users, 82.3% failed to demonstrate understanding of the term “thermal index” which gauges temperature levels within exposed tissue, 96.2% failed to demonstrate understanding of “mechanical index” which measures cavitational levels within the tissue, and, alarmingly, only 20 % of end users knew where these safety indices were located on the machines (Sheiner et al. 2007). While patient safety is now dependent on machine performance and sonographer judgment, it is clear that earlier FDA deregulations have placed the onus of that safety on the shoulders of faulty equipment and under-educated end users.

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References

Ang ES, Gluncic V, Duque A, Schager ME, Rakic P. Prenatal ultrasound waves impacts neuronal migration in mice. Proc Natl Acad Sci USA 103(34):12903-10, 2006.
Barnett SB, Ter Haar GR, Ziskin MC, Rott HD, Duck FA, Maeda K. International recommendations and guidelines for the safe use of diagnostic ultrasound in medicine. Ultrasound Med Biol. 2000; 26, 355–66
Casanova MF, El-Baz A, Kamat SS, Dombroski BA, Khalifa F, Elnakib A, Soliman A, Allison-McNutt A, Switala AE. Focal cortical dysplasias in autism spectrum disorders. Acta Neuropathol Commun 1(1):67, 2013.
McClintic AM, King BH, Webb SJ, Mourad PD. Mice exposed to diagnostic ultrasound in utero are less social and more active in social situations relative to controls. Autism Res doi: 10.1002/aur.1349 (Epub ahead of print)
Mårtensson M, Olsson M, Segall B, Fraser AG, Winter R, Brodin LA. High incidence of defective ultrasound transducers in use in routine clinical practice. Eur J Echocardiogr. 2009; 10: 389–94
Sheiner E, Shoham-Vardi I, Abramowicz JS. What do clinical end users know regarding safety of ultrasound during pregnancy? J Ultrasound Med. 2007; 26: 319–25
Stanton MT, Ettarh R, Arango D, Tonra M, Brenann PC. Diagnostic ultrasound induced changes within numbers of cryptal mitotic and apoptotic cells in small intestine. Life Sc i68(13):1471-5, 2001.