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DOI: 10.1055/a-1394-6194
How safe is it to use ultrasound in prenatal medicine? Facts and contradictions – Part 2 – Laboratory experiments regarding non-thermal effects and epidemiological studies
Wie sicher ist Ultraschall in der Pränatalmedizin? Fakten und Widersprüche – Teil 2 – Laborversuche zu nichtthermischen Effekten und epidemiologische StudienAbstract
The first part of this CME article (issue 5/20) provided a detailed examination of the biophysical effects of ultrasound waves, the exposure values, and in particular the thermal effect. In vivo and in vitro measurements have shown that the temperature increase in tissue associated with B-mode ultrasound is far too low to pose a potential risk. Even experiments with exposure values in the range of pulsed Doppler have shown that temperature increases of over 1.5 °C can only occur in areas in direct contact with the probe, thus making a limited exposure time particularly in the case of transvaginal application advisable. The second part of this CME article describes various laboratory and animal experiments for evaluating non-thermal effects and also presents the most important epidemiological studies in the last 30 years in the form of an overview and review. In addition to direct insonation of isolated cells to examine possible mutagenic effects, the blood of patients exposed in vivo to ultrasound was also analyzed in multiple experiments. Reproducible chromosome aberrations could not be found in any of the studies. In contrast, many experiments on pregnant rodents showed some significant complications, such as abortion, deformities, and behavioral disorders. As in the case of thermal effects, the results of these experiments indicate the presence of an intensity- or pressure-dependent effect threshold. Numerous epidemiological studies examining possible short-term and long-term consequences after intrauterine ultrasound exposure are available with the most important studies being discussed in the following. In contrast to information presented incorrectly in the secondary literature and in the lay press, health problems could not be seen in the children observed in the postpartum period in any of these studies.
Zusammenfassung
Im ersten Teil dieses CME-Artikels (Heft 5/20) waren die biophysikalischen Effekte von Ultraschallwellen, die Expositionsgrößen und insbesondere die Wärmewirkung ausführlich behandelt worden. In-vivo- und In-vitro-Messungen hatten gezeigt, dass insbesondere die mit dem B-Modus einhergehende Temperaturerhöhung im Gewebe weit unterhalb jeglichen Gefährdungspotenzials lag. Selbst aus Versuchen mit Expositionen im Leistungsbereich gepulster Doppler war hervorgegangen, dass lediglich im direkten Kontaktbereich der Sonden Temperaturerhöhungen von über 1,5 °C auftreten können – Erwärmungen, die insbesondere bei transvaginaler Applikation eine zeitliche Befristung der Expositionsdauer nahelegen. Dieser zweite Teil des CME-Artikels beschreibt zum einen verschiedene Labor- und Tierversuche zur Evaluierung von nichtthermischen Effekten und stellt des Weiteren die wichtigsten epidemiologischen Studien der letzten 30 Jahre in Form eines Überblicks und Reviews vor. Neben der direkten Beschallung von isolierten Zellen zur Untersuchung eventueller mutagener Folgen war in mehreren Versuchen auch das Blut von in vivo exponierten Patienten analysiert worden. In keiner der Studien konnte reproduzierbar eine Chromosomenaberration gefunden werden. Demgegenüber zeigten viele Versuche an trächtigen Nagern teils signifikante Komplikationen, wie Aborte und Fehlbildungen der Nachkommen sowie Verhaltensauffälligkeiten. Die Ergebnisse dieser Versuche deuten – vergleichbar mit den thermischen Effekten – auf das Vorhandensein einer leistungs- oder druckabhängigen Wirkungsschwelle hin. Epidemiologische Studien zur Untersuchung etwaiger Kurz- und Langzeitfolgen nach intrauterinen Ultraschallexpositionen stehen in großer Vielzahl zur Verfügung, wobei die wichtigsten Arbeiten nachfolgend besprochen werden. Anders als in der Sekundärliteratur und in der Laienpresse teilweise verfälscht wiedergegeben, konnte in keiner dieser Studien eine gesundheitliche Beeinträchtigung der post partum beobachteten Kinder gefunden werden.
Publication History
Article published online:
09 April 2021
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References
- 1 Bundesgesetzblatt Jahrgang 2018 Teil I Nr. 41, ausgegeben zu Bonn. am 5. Dezember 2018
- 2 Macintosh IJ, Davey DA. “Chromosome aberrations induced by an ultrasonic fetal pulse detector.”. British medical journal 1970; 4: 92-93
- 3 Coakley WT, Hughes DE, Slade JS. et al “Chromosome aberrations after exposure to ultrasound.”. British medical journal 1971; 1: 109-110
- 4 Abdulla U, Talbert D, Lucas M. et al “Effect of ultrasound on chromosomes of lymphocyte cultures.”. British medical journal 1972; 3: 797-799
- 5 Rott H, Soldner R. The effect of ultrasound on human chromosomes in vitro. Humangenetik 1973; 20: 103-112
- 6 Bobrow M, Blackwell N, Unrau AE. et al Absence of any observed effect of ultrasonic irradiation on human chromosomes. J Obstet Gynaecol Br Commonw 1971; 78: 730-736
- 7 Buckton KE, Baker NV. An investigation into possible chromosome damaging effects of ultrasound on human blood cells. Br J Radiol 1972; 45: 340-342
- 8 Watts PL, Hall AJ, Fleming JE. Ultrasound and chromosome damage. Br J Radiol 1972; 45 (533) 335-339
- 9 Coakley WT, Slade JS, Braeman JM. et al Examination of lymphocytes for chromosome aberrations after ultrasonic irradiation. The British Journal of Radiology 1972; 45: 328-332
- 10 Liebeskind D, Bases R, Mendez F. et al. Sister chromatid exchanges in human lymphocytes after exposure to diagnostic ultrasound. Science 1979; 205: 1273-1275
- 11 Barnett SB, Barnstable SM, Kossoff G. Sister chromatid exchange frequency in human lymphocytes after long duration exposure to pulsed ultrasound. J Ultrasound Med 1987; 6: 637-642
- 12 Ciaravino V, Brulfert A, Miller MW. et al Diagnostic ultrasound and sister chromatid exchanges: failure to reproduce positive findings. Science 1985; 227: 1349-1351
- 13 Morris SM, Palmer CG, Fry FJ. et al Effect of ultrasound on human leucocytes. Sister chromatid exchange analysis. Ultrasound Med Biol 1978; 4: 253-258
- 14 Wegner RD, Obe G, Meyenburg M. Has diagnostic ultrasound mutagenic effects?. Hum Genet 1980; 56: 95-98
- 15 Brulfert A, Ciaravino V, Miller MW. Lack of ultrasound effect on in vitro human lymphocyte sister chromatid exchange. Ultrasound Med Biol 1984; 10: 309-313
- 16 Miller MW, Wolff S, Filly R. et al Absence of an effect of diagnostic ultrasound on sister-chromatid exchange induction in human lymphocytes in vitro. Mutat Res 1983; 120: 261-268
- 17 Lucas M, Mullarkey M, Abdulla U. Study of chromosomes in the newborn after ultrasonic fetal heart monitoring in labour. Br Med J 1972; 3: 795-796
- 18 Watts PL, Stewart CR. The effect of fetal heart monitoring by ultrasound on maternal and fetal chromosomes. J Obstet Gynaecol Br Commonw 1972; 79: 715-716
- 19 Abdulla U, Dewhurst CJ, Campbell S. et al Effect of diagnostic ultrasound on maternal and fetal chromosomes. Lancet 1971; 2: 829-831
- 20 Blettner M, Jahn A, Langner I. et al. Machbarkeit von Studien zur schädigenden Wirkung von diagnostischem Ultraschall in der Schwangerschaft auf die Gesundheit der Nachkommen, Bundesministerium für Umwelt, Naturschutz und Reaktorsicherheit. 2003
- 21 Stolzenberg SJ, Torbit CA, Edmonds PD. et al Effects of ultrasound on the mouse exposed at different stages of gestation: Acute studies. Radiat Environ Biophys 1980; 17: 245-270
- 22 Kimmel CA, Stratmeyer ME, Galloway WD. et al Developmental exposure of mice to pulsed ultrasound. Teratology 1989; 40: 387-393
- 23 Angles JM, Walsh DA, Li K. et al Effects of pulsed ultrasound and temperature on the development of rat embryos in culture. Teratology 1990; 42: 285-293
- 24 Carnes KI, Hess RA, Dunn F. Effects of in utero ultrasound exposure on the development of the fetal mouse testis. Biol Reprod 1991; 45: 432-439
- 25 Vorhees CV, Acuff-Smith KD, Weisenburger WP. et al A teratologic evaluation of continuous‐wave, daily ultrasound exposure in unanesthetized pregnant rats. Teratology 1991; 44: 667-674
- 26 Hande MP, Devi PU. Effect of prenatal exposure to diagnostic ultrasound on the development of mice. Radiat Res 1992; 130: 125-128
- 27 Hande MP, Devi PU. Effect of in utero exposure to diagnostic ultrasound on the postnatal survival and growth of mouse. Teratology 1993; 48: 405-411
- 28 Tarantal AF, Gargosky SE, Ellis DS. et al. Hematologic and growth-related effects of frequent prenatal ultrasound exposure in the long-tailed macaque (macaca fascicularis) Ultrasound Med. Biol 1995; 21: 1073-1081
- 29 Ramnarine KV, Nassiri DK, McCarthy A. et al Effects of pulsed ultrasound on embryonic development: an in vitro study. Ultrasound Med Biol 1998; 24: 575-585
- 30 Pellicer B, Herraiz S, Táboas E. et al Ultrasound bioeffects in rats: quantification of cellular damage in the fetal liver after pulsed Doppler imaging. Ultrasound Obstet Gynecol 2011; 37: 643-648
- 31 Devi PU, Suresh R, Hande MP. Effect of fetal exposure to ultrasound on the behavior of the adult mouse. Radiat Res 1995; 141: 314-317
- 32 McClintic AM, King BH, Webb SJ. et al Mice exposed to diagnostic ultrasound in utero are less social and more active in social situations relative to controls. Autism Res 2014; 7: 295-304
- 33 Jensh RP, Lewin PA, Poczobutt MT. et al Effects of prenatal ultrasound exposure on adult offspring behavior in the Wistar rat. Proc Soc Exp Biol Med 1995; 210: 171-179
- 34 Fisher Jr JE, Acuff-Smith KD, Schilling MA. et al Behavioral effects of prenatal exposure to pulsed-wave ultrasound in unanesthetized rats. Teratology 1996; 54: 65-72
- 35 Ang Jr ES, Gluncic V, Duque A. et al Prenatal exposure to ultrasound waves impacts neuronal migration in mice. Proc Natl Acad Sci U S A 2006; 103: 12903-12910
- 36 Hartman C, Child SZ, Mayer R. et al Lung damage from exposure to the fields of an electrohydraulic lithotripter. Ultrasound Med Biol 1990; 16: 675-679
- 37 Child SZ, Hartman CL, Schery LA. et al Lung damage from exposure to pulsed ultrasound. Ultrasound Med Biol 1990; 16: 817-825
- 38 Tarantal AF, Canfield DR. Ultrasound-induced lung hemorrhage in the monkey. Ultrasound Med Biol 1994; 20: 65-72
- 39 Frizzell LA, Chen E, Lee C. Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung hemorrhage. Ultrasound Med Biol 1994; 20: 53-63
- 40 Zachary JF, O'Brien Jr WD. Lung lesions induced by continuous- and pulsed-wave (diagnostic) ultrasound in mice, rabbits, and pigs. Vet Pathol 1995; 32: 43-54
- 41 Baggs R, Penney DP, Cox C. et al Thresholds for ultrasonically induced lung hemorrhage in neonatal swine. Ultrasound Med Biol 1996; 22: 119-128
- 42 Zachary JF, Sempsrott JM, Frizzell LA. et al Superthreshold behavior and threshold estimation of ultrasound-induced lung hemorrhage in adult mice and rats. IEEE Trans Ultrason Ferroelectr Freq Control 2001; 48: 581-592
- 43 O'Brien Jr WD, Yang Y, Simpson DG. et al Threshold estimation of ultrasound-induced lung hemorrhage in adult rabbits and comparison of thresholds in mice, rats, rabbits and pigs. Ultrasound Med Biol 2006; 32: 1793-1804
- 44 Miller DL, Dong Z, Dou C. et al Pulmonary Capillary Hemorrhage Induced by Different Imaging Modes of Diagnostic Ultrasound. Ultrasound Med Biol 2018; 44: 1012-1021
- 45 Meltzer RS, Adsumelli R, Risher WH. et al Lack of lung hemorrhage in humans after intraoperative transesophageal echocardiography with ultrasound exposure conditions similar to those causing lung hemorrhage in laboratory animals. J Am Soc Echocardiogr 1998; 11: 57-60
- 46 Bernstine RL. Safety studies with ultrasounic Doppler technique: A clinical followup of patients and tissue culture study. Obstet Gynecol 1969; 34: 707-709
- 47 Abdulla U, Dewhurst CJ, Campbell S. et al. Effect of diagnostic ultrasound on maternal and fetal chromosomes. Lancet 1971; 2: 829-831
- 48 Serr DM, Padeh B, Zakat H. et al. Studies on the effekt of ultrasound waves on the fetus. In: Huntingdon PJ, Beard RW, Hutten EE. et al. ed. Proceeding of the second European Congress on perinatal medicine. London: 1971: 302
- 49 Falus M, Koranyi G, Sobel M. et al. [Follow-up studies on infants examined by ultrasound during fetal age]. [Hungarian] Orvosi Hetilap 1972; 113: 2119-2121
- 50 Watts PL, Stewart CR. The effect of fetal heart monitoring by ultrasound on maternal and fetal chromosomes. Journal of Obstetrics & Gynaecology of the British Commonwealth 1972; 79: 715-716
- 51 Ikeuchi T, Sasaki M, Osimura M. et al. Ultrasound and embryonic chromosoms. BMJ 1973; 1: 112
- 52 Lyons EA, Coggrave-Toms M. Long term follow-up study of children exposed to ultrasound in utero. Proceedings of the 24th annual meeting of AIUM, Montreal, Canada. 1979 27. 11
- 53 Stark CR, Orleans M, Haverkamp AD. et al. Short- and long-term risks after exposure to diagnostic ultrasound in utero. Obstetrics & Gynecology 1984; 63: 194200
- 54 Ewigman BG, Crane JP, Frigoletto FD. et al. Effect of prenatal ultrasound screening on perinatal outcome. RADIUS Study Group New England Journal of Medicine 1993; 329: 821-827
- 55 Cartwright RA, McKinney PA, Hopton PA. et al. Ultrasound examinations in pregnancy and childhood cancer. Lancet 1984; 2: 999-1000
- 56 Wilson LL, Waterhouse J. Obstestric ultrasound and childhood malignacies. Lancet 1984; 2: 997-999
- 57 Lyons EA, Dyke C, Toms M. et al. In utero exposure to diagnostic ultrasound: a 6-year follow-up. Radiology 1988; 166: 687-690
- 58 Bakketeig LS, Eik-Nes SH, Jacobsen G. et al. Randomised controlled trial of ultrasonographic screening in pregnancy. Lancet 1984; 2: 207-211
- 59 Eik-Nes SH, Okland O, Aure JC. et al. Ultrasound screening in pregnancy: a randomised controlled trial. Lancet 1984; 1: 1347
- 60 Saari-Kemppainen A, Karjalainen O, Ylostalo P. et al. Ultrasound screening and perinatal mortality: controlled trial of systematic one-stage screening in pregnancy. The Helsinki Ultrasound Trial. Lancet 1990; 336: 387-891
- 61 Salvesen KA, Bakketeig LS, Eik-nes SH. et al. Routine ultrasonography in utero and school performance at age 8-9 years. Lancet 1992; 339: 85-89
- 62 Grisso JA, Strom BL, Cosmatos I. et al. Diagnostic ultrasound in pregnancy and low birth weight. American Journal of Perinatology 1994; 11: 297-301
- 63 Salvesen KA, Vatten J, Bakketeig LS. et al. Routine ultrassonography in utero and speech development. Ultrasound Obste. Gynecol 1994; 4: 101-103
- 64 Shu XO, Jin F, Linet MS. et al. Diagnostic X-ray and ultrasound exposure and risk of childhood cancer. British Journal of Cancer 1994; 70: 531-536
- 65 Sorahan T, Lancashire R, Stewart A. et al. Pregnancy ultrasound and childhood cancer: a second report from the Oxford Survey of Childhood Cancers. British Journal of Obstetrics & Gynaecology 1995; 102: 831-832
- 66 Kieler H, Haglund B, Waldenstrom U. et al Routine ultrasound screening in pregnancy and the children's subsequent growth, vision and hearing. British Journal of Obstetrics & Gynaecology 1997; 104: 1267-1272
- 67 Kieler H, Ahlsten G, Haglund B. et al. Routine ultrasound screening in pregnancy and the children's subsequent neurologic development. Obstetrics & Gynaecology 1998; 91: 750-775
- 68 Kieler H, Axelsson O, Haglund B. et al. Routine ultrasound screening in pregnancy and the children's subsequent handedness. Early Human Development 1998; 50: 233-245
- 69 Naumburg E, Bellocco R, Cnattingius S. et al. Prenatal ultrasound examinations and risk of childhood leukaemia: case-control study. BMJ 2000; 320: 282-283
- 70 Campbell JD, Elford RW, Brant RF. Case-control study of prenatal ultrasonography exposure in children with delayed speech. CMAJ 1993; 149: 1435-1440
- 71 Newnham JP, Doherty DA, Kendall GE. et al Effects of repeated prenatal ultrasound examinations on childhood outcome up to 8 years of age: follow-up of a randomised controlled trial. Lancet 2004; 364: 2038-2044
- 72 Taskinen H, Kyyronen P, Hemminki K. et al Effects of ultrasound, shortwaves, and physical exertion on pregnancy outcome in physiotherapists. Journal of Epidemiology & Community Health 1990; 44: 196-201
- 73 Scheidt PC, Stanley F, Bryla DA. One-year follow-up of infants exposed to ultrasound in utero. American Journal of Obstetrics & Gynecology 1978; 131: 743-748
- 74 Newnham JP, Evans SF, Michael CA. et al. Effects of frequent ultrasound during pregnancy: a randomised controlled trial. Lancet 1993; 342: 887891
- 75 Moore RM, Barrick MK, Hamilton PM. Effect of sonic radiation on growth and development. Proceedings of the meeting of the society for epidemiologic Research, Cincinnati. 1982: 16-18
- 76 Waldenström U, Axelsson O, Nilsson S. et al. Effects of routine one-stage ultrasound screening in pregnancy: a randomised controlled trial. Lancet 1988; 2: 585-588
- 77 Salvesen KA, Vatten LJ, Eik-Nes SH. et al Routine ultrasonography in utero and subsequent handedness and neurological development. BMJ 1994; 307: 159-164
- 78 Kieler H, Cnattingius S, Haglund B. et al. Sinistrality-a side-effect of prenatal sonography: A comparative study of young men. Epidemiology 2001; 12: 618-623
- 79 Heikkilä K, Vuoksimaa E, Oksava K. et al Handedness in the helsinki ultrasound trial. Ultrasound Obstet Gynecol 2011; 37: 638-642
- 80 Salvesen KÅ. Ultrasound in pregnancy and non-right handedness: meta-analysis of randomized trials. Ultrasound Obstet Gynecol 2011; 38: 267-271
- 81 Ocklenburg S, Schmitz J, Moinfar Z. et al Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries. Elife 2017; 6: e22784 . Published 2017 Feb 1.
- 82 Hepper PG, McCartney GR, Shannon EA. Lateralised behaviour in first trimester human foetuses. Neuropsychologia 1998; 36: 531-534
- 83 McClintic AM, King BH, Webb SJ. et al Mice exposed to diagnostic ultrasound in utero are less social and more active in social situations relative to controls. Autism Res 2014; 7: 295-304
- 84 Grether JK, Li SX, Yoshida CK. et al. Journal of Autism and Developmental Disorders 2010; 40: 238-245
- 85 Höglund Carlsson L, Saltvedt S, Anderlid BM. et al Prenatal ultrasound and childhood autism: long-term follow-up after a randomized controlled trial of first- vs second-trimester ultrasound. Ultrasound Obstet Gynecol 2016; 48: 285-288
- 86 Rosman NP, Vassar R, Doros G. et al Association of Prenatal Ultrasonography and Autism Spectrum Disorder. JAMA Pediatr 2018; 172: 336-344
- 87 Hobbs K, Kennedy A, Dubray M. et al A retrospective fetal ultrasound study of brain size in autism. Biol Psychiatry 2007; 62: 1048-1055
- 88 Davies JA, Gallivan S, Spencer JA. Randomised controlled trial of Doppler ultrasound screening of placental perfusion during pregnancy. Lancet 1992; 340: 1299-1303
- 89 Doppler French Study Group. A randomised controlled trial of Doppler ultrasound velocimetry of the umbilical artery in low risk pregnancies. Br J Obstet Gynaecol 1997; 104: 419-424
- 90 Fatemi M, Ogburn PL, Greenleaf JF. “Quiet, Please!" Says the Fetus, Presented Monday Afternoon, December 3, 2001 142nd ASA Meeting, Fort Lauderdale, FL.
- 91 Arulkumaran S, Talbert DG, Nyman M. et al Audible in utero sound caused by the ultrasonic radiation force from a real-time scanner. J Obstet Gynaecol Res 1996; 22: 523-527
- 92 Friedrichs A, Kollmann C. Fötale Exposition bei modernen Screening-Verfahren. Ultraschall in Med – European Journal of Ultrasound 2012; 33
- 93 Hepper PG, Shahidullah BS. Development of fetal hearing. Arch Dis Child Fetal Neonatal Ed 1994; 71: F81-F87
- 94 Pujol R, Lavigne-Rebillard M, Uziel A. Development of the human cochlea. Acta Otolaryngol Suppl 1991; 482: 7-13
- 95 https://www.zentrum-der-gesundheit.de/artikel/schwangerschaft/ultraschall-untersuchung-ia
- 96 Lorenz RP, Comstock CH, Bottoms SF. et al Randomized prospective trial comparing ultrasonography and pelvic examination for preterm labor surveillance. Am J Obstet Gynecol 1990; 162: 1603-1610
- 97 Liebeskind D, Bases R, Koenigsberg M. et al Morphological changes in the surface characteristics of cultured cells after exposure to diagnostic ultrasound. Radiology 1981; 138: 419-423
- 98 Liebeskind D, Padawer J, Wolley R. et al. Diagnostic ultrasound time-lapse and transmission electron microscopic studies of cells insonated in vitro. Br J Cancer Suppl 1982; 5: 176-186
- 99 Taylor KJ. A prudent approach to ultrasound imaging of the fetus and newborn. Birth 1990; 17: 218-221 , 223; discussion 221-222. doi:10.1111/j.1523-536x.1990.tb00026.x. PMID: 2285442
- 100 http://www.initiative.cc/Artikel/2006_10_06_Sanft%20ins%20Leben.htm
- 101 https://wavegenetics.org/de/publikatsii/osnovnye-publikatsii/
- 102 http://www.gesundheitlicheaufklaerung.de/ultraschall-mehr-fluch-als-segen/
- 103 https://www.zeitenschrift.com/stichwort/ultraschall
- 104 https://www.greenbirth.de/de/