Fetal Thermal Effects of Diagnostic Ultrasound

Processes that can produce a biological effect with some degree of heating (ie, about 1°C above the physiologic temperature) act via a thermal mechanism. Investigations with laboratory animals have documented that pulsed ultrasound can produce elevations of temperature and damage in biological tissues in vivo, particularly in the presence of bone (intracranial temperature elevation). Acoustic outputs used to induce these adverse bioeffects are within the diagnostic range, although exposure times are usually considerably longer than in clinical practice. Conditions present in early pregnancy, such as lack of perfusion, may favor bioeffects. Thermally induced teratogenesis has been shown in many animal studies, as well as several controlled human studies; however, human studies have not shown a causal relationship between diagnostic ultrasound exposure during pregnancy and adverse biological effects to the fetus. All human epidemiologic studies, however, were conducted with commercially available devices predating 1992, that is, with acoustic outputs not exceeding a spatial‐peak temporal‐average intensity of 94 mW/cm 2 . Current limits in the United States allow a spatial‐peak temporal‐average intensity of 720 mW/cm 2 for fetal applications. The synergistic effect of a raised body temperature (febrile status) and ultrasound insonation has not been examined in depth. Available evidence, experimental or epidemiologic, is insufficient to conclude that there is a causal relationship between obstetric diagnostic ultrasound exposure and obvious adverse thermal effects to the fetus. However, very subtle effects cannot be ruled out and indicate a need for further research, although research in humans may be extremely difficult to realize. This article analyzes thermal effects of fetal ultrasound exposure. The normal core human body temperature is generally accepted to be 37°C with a diurnal variation of ±0.5°C to 1°C, 1 , 2 although 36.8°C ± 0.4°C (95% confidence interval) may be closer to the actual mean for large populations. 3 During the entire gestation, the temperature of the human embryo/fetus is higher than the maternal core body temperature 4 and gradually rises until, in the final trimester (near term), it exceeds that of the mother by 0.5°C. 5 Thermally induced teratogenesis has been shown in many animal studies, as well as several controlled human studies. 6 Edwards 7 and others have shown that hyperthermia is teratogenic for numerous animal species, including the human, and suggested a 1.5°C temperature elevation above the normal value as a universal threshold. 8 An elevated maternal temperature in early gestation has been associated with an increased incidence of congenital anomalies. 9 Tolerance to increased temperature (thermotolerance) is an important aspect of thermal teratogenesis. Thermotolerance is induced by the production of heat shock proteins (HSPs), which occurs (up to a limit) during a relatively slow (10‐ to 15‐minute) temperature increase of the whole body. 10 Diagnostic ultrasound exposures of mammalian embryos or fetuses in vivo and in vitro do not cause a whole‐body temperature increase in the mother but can potentially do so in the embryo. In principle, heating with ultrasound could occur so rapidly that the protective effects of HSPs might not come into play. There are data on effects of hyperthermia and measurements of in vivo temperature induced by pulsed ultrasound but not in the human. 11 – 14 These data have been widely reviewed. 15 – 20 However, there is a serious lack of data on the effects of ultrasound while rigorously excluding other confounding factors. A number of epidemiologic studies of possible developmental effects of obstetric ultrasound were performed before 1992, when exposures of the fetus, if anything, were lower on average than they are today. The results overall were negative. Around 1992, the maximum permitted acoustic output of clinical ultrasound instruments operating in the obstetric mode was allowed to increase by a factor of almost 8. 21 Potentially of even greater significance, no report clearly defines the duration of actual exposure. Epidemiology, of course, cannot be expected to reveal subtle effects. Today, ultrasound is so much a part of obstetric care that it would be very difficult to design an ethically acceptable epidemiologic study. The material in this article will be presented in the following manner: “Definitions,” “Mechanisms of Tissue Heating,” “Measured Temperature Rise in Human Fetal Tissue,” “Intracranial Temperature Elevation,” “Epidemiologic Data,” “Clinical Studies,” “Discussion Regarding Obstetric Issues in the Human,” and “Conclusions and Recommendations.”