The Need for Further Studies on the Safety of Prenatal Ultrasound

The following is a discussion about the need for further studies on the safety of prenatal ultrasound.  I do believe that ultrasound may pose a risk factor for autism and will discuss my thoughts in a future blog.  In the meanwhile I would like to raise awareness of the problem regardless of its putative link to autism.  The paragraphs are taken from a small grant written conjointly with Emily Williams and Cyndi Corbett. Emily has written extensively about the subject, and you may also want to read her blog: http://insolemexumbra.wordpress.com/2013/01/10/the-biology-of-ultrasound/   Also, Parrish Hirasaki has developed a web site dedicated to advocating for more studies on the safety of prenatal ultrasound: http://www.ultrasound-autism.org/?page_id=19

Significance

Scientists began recognizing the potency of transient ultrasonic cavitation and cavitationally-induced hyperthermia as early as the 1950s; however, knowledge as to additional injurious mechanisms by ultrasound have markedly flourished during the past several years. While there is still much we don’t know about the interaction of ultrasonic waves with biologic tissue at varying intensities and frequencies, we do know that noncavitational and potentially deleterious mechanisms are active below safety cutoffs (Johns 2002). Whether they are actively teratogenic remains unaddressed. Unfortunately, each decade since the introduction of ultrasound to obstetric medicine its popularity and use has continued to skyrocket, increasing the risk of adverse side effects. In modern obstetrics, it is standard practice to utilize ultrasound to diagnose and date the pregnancy as well as to monitor the growth of the fetus, even though studies have suggested that risks may outweigh the benefits in such circumstances (Tarantal & Hendrickx, 1989; Newnham et al. 1993). Even women experiencing non-at-risk pregnancies generally receive multiple unwarranted ultrasounds during a given pregnancy (You et al. 2010). And yet thorough safety studies have not been performed despite the growing evidence that ultrasound is a potentially dangerous tool that requires the utmost delicacy and caution in its application.

Respected researchers in the past have questioned ultrasound safety, despite that the typical range of prenatal exposure does not seem to cause obvious malformations. As Holland and Apfel (1990) report, Frizzell (1988), Kremkau (1984), the National Council on Radiation Protection and Measurement (Nyborg et al. 1983), and the National Institutes of Health Consensus Committee (1984) all reviewed safety studies on ultrasound and each respectively concluded that “diagnostic ultrasound may not be totally innocuous and recommend[ed] that more research be aimed specifically at test systems that would provide a better database for developing reasonable estimates of bioeffects and of risk” (National Institutes of Health Consensus Committee, 1984, p. 2059).

In a 1989 study, Tarantal and Hendrickx exposed prenatal macaques to ultrasound five times per week on gestational days (GD) 21–35, three times per week on GD 36–60, and once a week on GD 61–150. Each exam lasted 10 minutes and spatial-peak temporal-average (i.e., acoustic output) was well within current obstetric ranges. The authors reported altered birth weight and crown-rump length, generally reduced levels of physical activity as compared to control monkeys, and lower white blood cell counts comprising reductions in segmented neutrophils and monocytes. All effects had normalized by age 5–6 months. It is uncertain whether these neonatal phenotypes resulted solely from noncavitational mechanisms or cavitational thresholds had been reached even at the low intensity of 12 mW∙cm⁻². However, mirroring this simian study, frequent ultrasounds in humans have been closely correlated with neonatal birth weight. Newnham et al. (1993) subjected 1415 women with single pregnancies to ultrasound examinations at 18, 24, 28, 34, and 38 weeks of gestation, while a control group of 1419 women received a single ultrasound at week 18. Intrauterine growth restriction was significantly higher in the experimental group as measured by birth weight, such that a significant number of infants fell below the tenth percentile and even the third percentile mark.

Research into transient cavitational and thermal effectors have been considerable, and provided A.L.A.R.A. (As Low As Reasonably Achievable) guidelines are followed, risk from these effectors during prenatal ultrasound should be relatively small; however, work on the bioeffects of noncavitational mechanisms remains sparse and current ultrasound machines do not calculate risk related to stable cavitation and microstreaming.

Ultrasound may have teratogenic effects on cortical development. Ang et al. (2006) were the first to illustrate the cortical migratory abnormalities ultrasound exposure can have on the embryonic brain in mouse. Ultrasound is also well established in the literature for its proliferative effects on various stem cell populations (Young & Dyson 1990; Doan et al. 1999; Zhang et al. 2003) and for its ability to affect the Wnt pathway and production of certain growth factors (Olkku et al. 2010; Burks et al. 2011). In effect, ultrasound can trigger tissue regeneration in bone breaks by activating cellular growth pathways, as evidenced by heightened Wnt activation in osteoblasts (Olkuu et al. 2010). It also has similar growth effects on chondrocytes, activating the P13K/Akt pathway (Takeuchi et al. 2008). The effect of ultrasound on germinal cells could easily explain the migrational abnormalities observed by Ang et al. (2006). Further research is still needed to explore any relationship between ultrasound exposure and abnormal corticogenesis.

Need for Research into Ultrasound Safety

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.

It is therefore of concern that a technique so widely used has enjoyed little in terms of on-going safety studies and less so in terms of enforcing safety standards. In the early 1990’s ultrasound was deregulated and energy levels were allowed to increase by nearly eightfold, from 94 to 720 nW cm^-2 (Nelson et al., 2009; Williams and Casanova, 2013).  The little data presently available on fetal exposure during diagnostic ultrasound and the lack of ongoing research has been called “appalling” (Abramowicz, 2007).

If you are interested in the subject of this blog you will also find it of interest to read Jennifer Margulis’ new book: «The business of baby: what doctors don’t tell you, what corporations try to sell you, and how to put your pregnancy, childbirth, and baby before their bottom line», New York: Scribner, 2013 April 16. Also, David Blake has a petition under change.org advocating for more safety studies on prenatal ultrasound (http://www.change.org/petitions/re-health-risks-of-prenatal-ultrasound-we-need-better-regulation-more-research).

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