Translational Neuroscience

, Volume 4, Issue 1, pp 81–87 | Cite as

Reassessment of teratogenic risk from antenatal ultrasound



Science has shown that risk of cavitation and hyperthermia following prenatal ultrasound exposure is relatively negligible provided intensity, frequency, duration of exposure, and total numbers of exposures are safely limited. However, noncavitational mechanisms have been poorly studied and occur within what are currently considered “safe” levels of exposure. To date, the teratogenic capacity of noncavitational effectors are largely unknown, although studies have shown that different forms of ultrasound-induced hydraulic forces and pressures can alter membrane fluidity, proliferation, and expression of inflammatory and repair markers. Loose regulations, poor end user training, and unreliable ultrasound equipment may also increase the likelihood of cavitation and hyperthermia during prenatal exposure with prolonged durations and increased intensities. The literature suggests a need for tighter regulations on the use of ultrasound and further studies into its teratogenicity.


Cavitation Microstreaming Sonoporation Teratogens Ultrasonography Prenatal 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Connolly C., Pond J., The possibility of harmful effects in using ultrasound for medical diagnosis, Biomed. Eng., 1967, 2, 112–115Google Scholar
  2. [2]
    Woo J., A short history of the development of ultrasound in obstetrics and gynecology. History of ultrasound in obstetrics and gynecology, Part 1, 2008, retrieved on 10/12/2009 from Google Scholar
  3. [3]
    Dewhurst C.J., The safety of ultrasound, Proc. R. Soc. Med., 1971, 64, 996–997PubMedGoogle Scholar
  4. [4]
    Dognon A., Simonot Y., 1951. Cavitation et hémolyse par ultrasons de fréquences différentes, C. R. Hebd. Séances Acad. Sci., 1951, 232, 2411–2413PubMedGoogle Scholar
  5. [5]
    Křížek V., Kolominsky J., Tepelné účinky ultrazvuku ve tkánäch, Čas. Lék. Čes., 1951, 90, 482–486Google Scholar
  6. [6]
    Johns L.D., Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis, J. Athl. Train., 2002, 37, 293–299PubMedGoogle Scholar
  7. [7]
    Newnham J.P., Evans S.F., Michael C.A., Stanley F.J., Landau L.I., Effects of frequent ultrasound during pregnancy: a randomised controlled trial, Lancet, 1993, 342, 887–891PubMedCrossRefGoogle Scholar
  8. [8]
    Tarantal A.F., Hendrickx A.G., Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): I. neonatal/infant observations, Teratology, 1989, 39, 137–147PubMedCrossRefGoogle Scholar
  9. [9]
    You J.J., Alter D.A., Stukel T.A., McDonald S.D., Laupacis A., Liu Y., et al., Proliferation of prenatal ultrasonography, Can. Med. Assoc. J., 2010, 182, 143–151CrossRefGoogle Scholar
  10. [10]
    Holland C.K., Apfel R.E., Thresholds for transient cavitation produced by pulsed ultrasound in a controlled nuclei environment, J. Acoust. Soc. Am., 1990, 88, 2059–2069PubMedCrossRefGoogle Scholar
  11. [11]
    Frizzell L.A., Biological effects of acoustic cavitation, In: Suslick K.S. (Ed.), Ultrasound: its chemical, physical and biological effects, VCH, New York, 1988, 287–303Google Scholar
  12. [12]
    Kremkau F.W., Bioeffects and safety, In: Diagnostic ultrasound: principles, instrumentation and exercises, 2nd ed., Grune and Straton, New York, 1984, 166–277Google Scholar
  13. [13]
    Nyborg W.L., Carson P.L., Miller D.L., Miller M.W., Ziskin M.C., Carstensen E.L., et al., Biological effects of ultrasound: mechanisms and clinical Implications, National Council on Radiation Protection and Measurement, Bethesda, 1983Google Scholar
  14. [14]
    National Institutes of Health Consensus Committee, Diagnostic ultrasound imaging in pregnancy, 1984, NIH Pub. No. 84-667Google Scholar
  15. [15]
    Ziskin M.S., Petitti D.B., Epidemiology of human exposure to ultrasound: a critical review, Ultrasound Med. Biol., 1988, 14, 91–96PubMedCrossRefGoogle Scholar
  16. [16]
    Grether J.K., Li S.X., Yoshida C.K., Croen L.A., Antenatal ultrasound and risk of autism spectrum disorders, J. Autism Dev. Disord., 2010, 40, 238–245PubMedCrossRefGoogle Scholar
  17. [17]
    Tezel A., Sens A., Mitragotri S., Investigations of the role of cavitation in low-frequency sonophoresis using acoustic spectroscopy, J. Pharm. Sci., 2002, 91, 444–453PubMedCrossRefGoogle Scholar
  18. [18]
    Counce S.J., Selman G.G., The effects of ultrasonic treatment on embryonic development of Drosophila melanogaster, J. Embryol. Exp. Morphol., 1955, 3, 121–141Google Scholar
  19. [19]
    Suslick K.S., The chemical effects of ultrasound., Sci. Am., 1989, 260, 80–86CrossRefGoogle Scholar
  20. [20]
    Basile A., Biziato D., Sherbet G.V., Comi P., Cajone F., Hyperthermia inhibits cell proliferation and induces apoptosis: relative signaling status of P53, S100A4, and Notch in heat sensitive and resistant cell lines, J. Cell. Biochem., 2008, 103, 212–220PubMedCrossRefGoogle Scholar
  21. [21]
    Kampinga H.H., Thermotolerance in mammalian cells: protein denaturation and a aggregation, and stress proteins, J. Cell Sci., 1993, 104, 11–17PubMedGoogle Scholar
  22. [22]
    Yatvin M.B., The influence of membrane lipid composition and procaine on hyperthermic death of cells, Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 1977, 32, 513–521PubMedCrossRefGoogle Scholar
  23. [23]
    Riesz P., Kondo T., Free radical formation induced by ultrasound and its biological implications, Free Radic. Biol. Med., 1992, 13, 247–270PubMedCrossRefGoogle Scholar
  24. [24]
    Davies K.J., Protein damage and degradation by oxygen radicals, I. General aspects, J. Biol. Chem., 1987, 262, 9895–9901PubMedGoogle Scholar
  25. [25]
    Quinlan G.J., Gutteridge J.M., Hydroxyl radical generation by the tetracycline antibiotics with free radical damage to DNA, lipids and carbohydrate in the presence of iron and copper salts, Free Radic. Biol. Med., 1988, 5, 341–348PubMedCrossRefGoogle Scholar
  26. [26]
    Stadtman E.R., Levine R.L., Free radical-mediated oxidation of free amino acids and amino acid residues in proteins, Amino Acids, 2003, 25, 207–218PubMedCrossRefGoogle Scholar
  27. [27]
    Macintosh I.J., Davey D.A., Relationship between intensity of ultrasound and induction of chromosome aberrations, Br. J. Radiol., 1972, 45, 320–327PubMedCrossRefGoogle Scholar
  28. [28]
    Newcomer E.H., Wallace R.H., Chromosomal and nuclear aberrations induced by ultrasonic vibrations, Am. J. Bot., 1949, 36, 230–236PubMedCrossRefGoogle Scholar
  29. [29]
    Krasovitski B., Kimmel E., Shear stress induced by a gas bubble pulsating in an ultrasonic field near a wall, IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 2004, 51, 973–979PubMedCrossRefGoogle Scholar
  30. [30]
    Koshiyama K., Yano T., Kodama T., Self-organization of a stable pore structure in a phospholipid bilayer, Phys. Rev. Lett., 2010, 105, 018105PubMedCrossRefGoogle Scholar
  31. [31]
    Deng C.X., Sieling F., Pan H., Cui J., Ultrasound-induced cell membrane porosity, Ultrasound Med. Biol., 2004, 30, 519–526PubMedCrossRefGoogle Scholar
  32. [32]
    Carafoli E., Calcium signaling: a tale for all seasons, Proc. Natl. Acad. Sci. USA, 2002, 99, 1115–1122PubMedCrossRefGoogle Scholar
  33. [33]
    Zhou Y., Shi J., Cui J., Deng C.X., Effects of extracellular calcium on cell membrane resealing in sonoporation, J. Control. Release, 2008, 126, 34–43PubMedCrossRefGoogle Scholar
  34. [34]
    Reddy A., Caler E.V., Andrews N.W., Plasma membrane repair is mediated by Ca2+-regulated exocytosis of lysosomes, Cell, 2001, 106, 157–169PubMedCrossRefGoogle Scholar
  35. [35]
    Yang F., Gu N., Chen D., Xi X., Zhang D., Li Y., et al., Experimental study on cell self-sealing during sonoporation, J. Control. Release, 2008, 131, 205–210PubMedCrossRefGoogle Scholar
  36. [36]
    Al-Karmi A.M., Dinno M.A., Stolz D.A., Crum L.A., Matthews J.C., Calcium and the effects of ultrasound on frog skin, Ultrasound Med. Biol., 1994, 20, 73–81PubMedCrossRefGoogle Scholar
  37. [37]
    Mihran R.T., Barnes F.S., Wachtel H., Temporally-specific modification of myelinated axon excitability in vitro following a single ultrasound pulse, Ultrasound Med. Biol., 1990, 16, 297–309PubMedCrossRefGoogle Scholar
  38. [38]
    Tufail Y., Yoshihiro A., Pati S., Li M.M., Tyler W.J., Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound, Nat. Protoc., 2011, 6, 1453–1470PubMedCrossRefGoogle Scholar
  39. [39]
    Pébay A., Peshavariya H., Wong R.C.B., Dusting G.J., Non-classical signalling mechanisms in stem cells, In: Atwood C.S. (Ed.), Embryonic stem cells: the hormonal regulation of pluripotency and embryogenesis, Intech, ijeka, 2011, 317–336Google Scholar
  40. [40]
    American Institute of Ultrasound in Medicine, AIUM practice guideline for the performance of obstetric ultrasound examinations, J. Ultrasound Med., 2010, 29, 157–166Google Scholar
  41. [41]
    Sheiner E., Shoham-Vardi I., Abramowicz J.S., What do clinical end users know regarding safety of ultrasound during pregnancy?, J. Ultrasound Med., 2007, 26, 319–325PubMedGoogle Scholar
  42. [42]
    Washington State Health Care Authority, Ultrasonography (ultrasound) in pregnancy: health technology assessment, 2010, taken on 08/28/2012 from Google Scholar
  43. [43]
    Alberta Clinical Practice Guidelines Working Group for Prenatal Ultrasound, Guideline for the use of prenatal ultrasound: First trimester, Alberta Medical Association, Edmonton, 1998Google Scholar
  44. [44]
    Mårtensson M., Olsson M., Brodin, L.-Å. Ultrasound transducer function: annual testing is not sufficient, Eur. J. Echocardiogr., 2010, 11, 801–805PubMedCrossRefGoogle Scholar
  45. [45]
    Mårtensson M., Olsson M., Segall B., Fraser A.G., Winter R., Brodin L.-Å. High incidence of defective ultrasound transducers in use in routine clinical practice, Eur. J. Echocardiogr., 2009, 10, 389–394PubMedCrossRefGoogle Scholar
  46. [46]
    Rados C., FDA cautions against ultrasound’ keepsake’ images, FDA Consum., 2004, 38, 12–16PubMedGoogle Scholar
  47. [47]
    Williams E.L., Casanova M.F., Prenatal ultrasound: it’s not just a photograph, Autism Sci. Dig., 2011, 1, 58–60Google Scholar
  48. [48]
    Abbott J.G., Rationale and derivation of MI and TI — a review, Ultrasound Med. Biol., 1999, 25, 431–441PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Department of Anatomical Sciences and NeurobiologyUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of Psychiatry and Behavioral SciencesUniversity of Louisville School of MedicineLouisvilleUSA

Personalised recommendations