AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 39:499±504 (2001) Pregnancy Outcome Following Exposure to Shortwaves Among Female Physiotherapists in Israel Yehuda Lerman, MD, MPH,1;3 Ruben Jacubovich, MD,1 and Manfred S. Green, MD, PhD2,3 Background The ®ndings of the few epidemiological studies on the possible association between shortwave diathermy use by pregnant physiotherapists and adverse pregnancy outcome are inconsistent. We investigated such an association among physiotherapists in Israel. Methods Individualized data on exposure to shortwaves, ultrasound, and heavy lifting were collected by questionnaires and telephone interviews. Results The 434 studied women included 930 pregnancies: 175 ended in spontaneous abortions, 45 had fetal malformations, 47 were delivered prematurely, and 33 infants had low birth weight. The remaining 630 normal pregnancies comprised the control group. Univariate analysis showed that exposure to shortwaves was associated with a signi®cantly increased odds ratio (O.R.) for congenital malformations (O.R. 2.24, CI 1.27±4.83, P .006) and low birth weight (O.R. 2.99, CI 1.32±6,79, P .006). This effect increased in a dose-related manner. After controlling for potential confounding variables, only low birth weight reached statistical signi®cance (O.R. 2.75, CI 1.07±7.04, P .03). From the potentially confounding variables tested, febrile disease during pregnancy was found to be signi®cantly associated with low birth weight (O.R. 3.37, CI 1.38±8.25, P .01). Conclusions The ®ndings of our study suggest that shortwaves have potentially harmful effects on pregnancy outcome, speci®cally low birth weight. Am. J. Ind. Med. 39:499± 504, 2001. ß 2001 Wiley-Liss, Inc. KEY WORDS: electromagnetic radiation; shortwaves; diathermy; pregnancy outcome; birth weight; prematurity; spontaneous abortion; congenital malformations; physiotherapy INTRODUCTION Shortwave diathermy units heat tissue through absorption of energy from electromagnetic ®elds. Shortwaves are a 1 Occupational Health and Rehabilitation Institute, Ra'annana, Tel-Aviv University, Tel-Aviv, Israel 2 The Israel Center for Disease Control, Gertner Institute,Tel-Hashomer,Tel-Aviv University, Tel-Aviv, Israel 3 The Sackler Faculty of Medicine,Tel-Aviv University,Tel-Aviv, Israel *Correspondence to: Prof. Yehuda Lerman, Occupational Health Center, Sherutei Beriut Clalit, 101Arlozorov St.,Tel-Aviv 62098, Israel. E-mail: ylerman@post.tau.ac.il Accepted 30 January 2001 ß 2001Wiley-Liss, Inc. fraction of the high-frequency band of the non-ionizing electromagnetic spectrum. The wave frequency is typically 27.12 MHz. These devices are widely used in physiotherapy departments. Shortwaves have been shown to cause abortion and abnormal fetal development in animal models [Brown Woodman et al., 1989]. A search of the literature revealed sparse epidemiologic studies on the possible association between shortwave diathermy use by pregnant physiotherapists and adverse pregnancy outcome, and their conclusions were inconsistent. Kallen et al. [1982] showed an excess risk of congenital malformations among the offspring of female physiotherapists who reported working with shortwave diathermy. 500 Lerman et al. Taskinen et al. [1990] reported an excess risk of spontaneous abortion after the 10th week of gestation among Finnish physiotherapists who used ultrasound and shortwave diathermy, but this disappeared when confounders were controlled. In a parallel study, the frequency of using shortwaves was signi®cantly associated with congenital malformations but, interestingly, only in the lower exposure group. Larsen [1991] and Larsen et al. [1991] found no signi®cant association between shortwave exposure and congenital malformations or spontaneous abortions, although they did note a non-signi®cant association between shortwave exposure and low birth weight among male births. Quellet-Hellstrom and Stewart [1993] found no signi®cant association between shortwave use and spontaneous abortions. Finally, Guberan et al. [1994] found no association between shortwave exposure and low birth weight. The results of the works reviewed above are inconsistent in answering the question of whether occupational exposure to physiotherapists is correlated with different pregnancy outcomes. Moreover, in some of them, the study design was that of a simple case control study in which biases are inherent. Also, each of the previous studies analyzed only one or two of the possible adverse pregnancy outcomes. We initiated this study in order to assess whether exposure to shortwave radiation is associated with the four adverse pregnancy outcomesÐspontaneous abortions, congenital malformations, prematurity, and low birth weightÐ within the same group of Israeli physiotherapists. While we included other variables which might affect the pregnancy outcome, our primary objective was to test the hypothesis that shortwave exposure is a reproductive hazard. MATERIALS AND METHODS A detailed questionnaire was sent by mail to all physiotherapists registered as members of the Union of Israeli Physiotherapists. Not all of the registered physiotherapists are actively working in the ®eld, nor is it known what is the percentage of those who are. The target population included Israeli female physiotherapists who had ever been pregnant. We assembled a cohort of female physiotherapists who answered the anonymous questionnaire and provided information on their reproductive history. The investigation was designed as a prevalent case control study. In addition, all physiotherapy departments associated with the sick funds, hospitals, and private clinics were identi®ed and interviewed by telephone in order to achieve a greater response rate. The questionnaire and interview included queries on the outcome of pregnancy and the use of shortwave diathermy, ultrasound, and heavy lifting during pregnancy. The questionnaire was also mailed to male physiotherapists: it included questions on orthopedic problems and was anonymous in order to minimize the selection bias associated with overrepresentation of female physiotherapists who had abnormal delivery outcome. Study Population The groups were divided according to the following pregnancy outcome: Spontaneous abortionÐoccurring before the 28th week of gestation (n 175); Congenital malformationsÐaccording to the ICD codes 740±759.99 (n 45); PrematurityÐdelivery before the 36th week of gestation (n 47); and Low birth weightÐless than 2500 g and delivered after the 36th week of gestation (n 33). A mother could contribute more than one pregnancy as a ``case''. Controls The control group (n 633) consisted of pregnancies of mothers who reported no adverse reproductive outcome (spontaneous abortion, congenital malformations, prematurity and low birth weight) in any of their pregnancies. Normal pregnancies of mothers who had other pregnancies that ended in an abnormal delivery were excluded. Exposure Measurements The duration of exposure to shortwaves and ultrasound per week was estimated on a scale in which 0 no exposure, 1 less than 10 hours/week, and 2 more than 10 hours/ week. For exposure to heavy lifting, the scale was 0 no exposure, 1 5±25 times/week, 2 more than 25 times/ week. Other Retrieved Data The questionnaire and telephone interview also included information about conditions during pregnancy which can act as confounders, such as febrile disease, consumption of alcohol, use of drugs and tobacco during pregnancy, age of the mother at each pregnancy, previous abortions and number of pregnancies. Statistical Methods Crude relationships between pregnancy outcome and exposure to shortwaves, ultrasound, and heavy lifting were estimated by the odds ratio (O.R.) together with the exact 95% con®dence interval (95% CI). The 2 and Fisher exact tests were used to test statistical signi®cance. Multiple Pregnancy Outcome of Shortwave-Exposed Physiotherapists logistic regression analysis was used to control for confounders. TABLE II. The Odds Ratio (O.R.) of Congenital Malformations for Individual Occupational Variables Among Israeli Female Physiotherapists RESULTS There was a total of 774 questionnaires which contributed 1416 pregnancies. The 434 normal pregnancies from mothers who had reproductive hazards in one or more of their pregnancies were excluded from the study (nor were they included in the control group). Another 49 pregnancies from 37 women were excluded because the mother's age was not available. The ®nal study population was comprised of 434 women who contributed 933 pregnancies: 175 pregnancies in the spontaneous abortion group; 45 in the congenital malformation group; 47 in the prematurity group; and 33 in the low birth weight group. The remaining 633 pregnancies from women who reported no adverse outcome in any pregnancy served as the control group. Spontaneous Abortion The O.R. between spontaneous abortion and exposure to shortwaves, ultrasound and heavy lifting are presented in Table I. Shortwaves did not increase the risk of spontaneous abortion (O.R. 0.9). The O.R. was decreased for handling ultrasound equipment and for heavy lifting. The O.R. of the confounding factors showed no signi®cant association. In the multivariate analysis, there was no change in the O.R. for shortwaves. TABLE I. The Odds Ratio (O.R.) of Spontaneous Abortion for Individual Occupational Variable Among Israeli Female Physiotherapists Spontaneous abortion Exposure index Shortwaves No exposure Exposed 1^9 hours/week > 10 hours/week Heavy lifting No exposure Exposed 5^25 times/week > 25 times/week Ultrasound No exposure Exposed 1^9 hours/week > 10 hours/week Cases (n) Controls (n) O.R. 95% CI P 92 80 60 20 323 310 222 88 0.90 0.94 0.79 0.64^1.27 0.65^1.37 0.46^1.36 0.56 0.78 113 59 38 21 306 327 216 111 0.48 0.47 0.51 0.34^0.69 0.31^0.71 0.30^0.85 0.00 0.00 0.01 92 80 36 44 230 403 225 178 0.49 0.40 0.60 0.35^0.69 0.26^0.61 0.41^0.93 0.00 0.00 0.02 501 Congenital malformations Exposure index Shortwaves No exposure Exposed 1^9 hours/week > 10 hours/week Heavy lifting No exposure Exposed 5^25 times/week > 25 times/week Ultrasound No exposure Exposed 1^9 hours/week > 10 hours/week Cases (n) Controls (n) O.R. 95% CI P 13 28 16 12 323 310 222 88 2.24 1.79 3.40 1.27^4.83 1.04^4.33 1.50^7.40 0.006 0.038 0.002 20 21 15 6 306 327 216 111 0.98 1.06 0.82 0.60^2.07 0.65^2.46 0.32^2.11 0.71 0.47 0.69 6 34 15 19 230 403 225 178 3.23 2.55 4.09 1.50^8.68 1.26^8.25 1.60^10.45 0.002 0.01 0.002 Congenital Malformations The O.R. for congenital malformations for individual occupational variables are presented in Table II. Increased exposure to ultrasound and shortwaves increased the O.R. signi®cantly. The O.R. of heavy lifting and the confounding factors showed no signi®cant association with congenital malformations. In the multivariate analysis, only ultrasound exposure showed a signi®cant association with congenital malformations (O.R. 4.19, 95% CI 1.58±11.13, P 0.004). The odds ratio of exposure to shortwaves decreased to 1.33 (95% CI 0.68±2.75, P 0.44). Prematurity No signi®cant association was found between prematurity and exposure to shortwaves, ultrasound, and heavy lifting (Table III). Low Birth Weight Exposure to shortwaves increased the O.R. signi®cantly, and it increased with increasing exposure (Table IV). From the potential confounding factors, febrile disease during pregnancy increased the O.R signi®cantly (O.R. 3.37, 95% CI 1.38±8.25, P 0.01). In the multivariate analysis, exposure to shortwaves showed a signi®cant 502 Lerman et al. TABLE III. The Odds Ratio (O.R.) of Prematurity for Individual Occupational Variables Among Israeli Female Physiotherapists TABLE IV. The Odds Ratio (O.R.) of Low Birth Weight for Individual Occupational Variables Among Israeli Female Physiotherapists Prematurity Exposure index Shortwaves No exposure Exposed 1^9 hours/week > 10 hours/week Heavy lifting No exposure Exposed 5^25 times/week > 25 times/week Ultrasound No exposure Exposed 1^9 hours/week > 10 hours/week Cases (n) Low birth weight Controls (n) O.R. 95% CI P 25 21 18 3 323 310 222 88 0.87 1.04 0.84 0.48^1.59 0.55^1.96 0.13^1.49 0.66 0.88 0.17 28 18 13 5 306 327 216 111 0.60 0.65 0.49 0.32^1.11 0.33^1.29 0.18^1.30 0.10 0.22 0.14 22 24 14 10 230 403 225 178 0.60 0.60 0.60 0.58 0.31^1.10 0.33^1.35 0.27^1.27 0.10 0.20 0.17 association with low birth weight (O.R. 2.75, 95% CI 1.07±7.04, P 0.03). The O.R. for febrile disease was increased but with no statistical signi®cance (O.R. 2.73, 95% CI 1.06±6.99, P 0.1). The gender-speci®c analysis indicated that the risk for low birth weight was greater for boys than for girls (O.R. 3.7 vs. O.R. 2.9, respectively). DISCUSSION In the present retrospective nested case-control study, exposure to shortwave was found to be associated with low birth weight and with an increased risk for male infants. These results are in agreement with those of Larsen et al. [1991] that showed an O.R. of 5.9 (95% CI 1.0±28.6) for low birth weight of boys in the high exposure group versus an O.R. of 0.7 (95% CI 0.0±3.6) for girls. In the same cohort, Larsen [1991] showed that the crude association between the indices of exposure to high frequency electromagnetic radiation and the occurrence of malformations were weak and non-signi®cant because the CIs were wide and included unity. Our results also showed that congenital malformations were not found to be associated signi®cantly with exposure to shortwaves during pregnancy after controlling for the different confounders. Ultrasound equipment was found to be associated with congenital malformations. Different results were reported among physiotherapists in Sweden by Exposure index Shortwaves No exposure Exposed 1^9 hours/week > 10 hours/week Heavy lifting No exposure Exposed 5^25 times/week > 25 times/week Ultrasound No exposure Exposed 1^9 hours/week > 10 hours/week Cases (n) Controls (n) O.R. 95% CI P 8 23 14 9 323 310 222 88 2.99 2.54 4.12 1.32^6.79 1.05^6.17 1.54^11.01 0.006 0.033 0.002 16 15 8 7 306 327 216 111 0.87 0.70 1.20 0.42^1.80 0.29^1.68 0.48^3.01 0.72 0.43 0.68 8 23 11 12 230 403 225 178 1.64 1.40 1.90 0.72^3.70 0.55^3.55 0.77^4.84 0.230 0.47 0.15 Kallen et al. [1982] who demonstrated that the use of shortwave equipment ``often'' or ``daily'' was more common among the cases with malformed or perinatally dead infants than the controls with normal infants (33 vs. 14%, P 0.03). The ®ndings of this study can be random insofar as statistical signi®cance is borderline and multiple comparisons were performed for all subjects. However, it should be borne in mind that the primary objective of this study was to test the hypothesis of one of them, i.e., of a possible harmful effect on pregnant physiotherapists working with shortwave equipment. We cannot exclude the possibility that exposure to shortwave and ultrasound were closely associated or that they were associated with a third unidenti®ed exposure that could be harmful. We controlled for several confounders during the index pregnancy, the ones that were found to be risk factors for adverse pregnancy outcomes, such as the mother's age during each pregnancy, heavy lifting, febrile disease, use of drugs and tobacco, consumption of alcohol during pregnancy, and number of pregnancies. None of them could explain the tendencies of risk associated with shortwave exposure. We could not obtain information from medical records, thus the possibility of misclassi®cation bias cannot be excluded. The information on pregnancy outcome and on the different exposures was based on the physiotherapists' reports, so information bias might have been responsible Pregnancy Outcome of Shortwave-Exposed Physiotherapists for the apparent associations, especially since the hypothesis of the hazard of work with shortwave equipment may well have been known to some of the physiotherapists beforehand. However, two aspects of the results tend to negate this bias. One is the dose±response relationship, i.e., the O.R. for congenital malformations and low birth weight increased with increasing doses of exposure. The second is that we would expect the same trend with spontaneous abortions and prematurity, and this was not the case. Recall bias of the exposures cannot be excluded since varying periods of time had passed since exposure. Exposure evaluation is traditionally based on indirect data, such as those from the kind of interviews conducted by us and by others. For example, Larsen and Skotte [1991] compared the assessment of shortwave exposure based upon observations which included objective measurements of exposure and compared them to the information given by exposed female diathermy operators by means of interviews. According to this study, it was possible to discriminate between recent high and low peak exposure. Moreover, an interview index re¯ecting the duration of the exposure correlated to some extent with the corresponding measurements of that study. We had no access to the registration of all certi®ed physiotherapists in Israel, and we cannot arrive at any conclusions about the compliance of this studied group, thus there is a potential selective participation bias. We took three measures to minimize such a selection bias and to increase participation among physiotherapists: (1) we offered the participants the possibility of answering the questionnaire anonymously; (2) questionnaires were also mailed to male physiotherapists (not included in any analysis); and (3) non-relevant questions (e.g., on orthopedic problems at work) were included in the questionnaire. One obvious issue related to the de®nition of the source population is that some pregnant female physiotherapists may stop working altogether and, therefore, they may drop off the roster of Israeli physiotherapists. This has the potential to bias the ®ndings toward the null if, under the assumption of a deleterious effect of shortwaves, these women were exposed early in their pregnancy, experienced bleeding or some other symptom due to the exposure and then subsequently stopped working and dropped out of the target population. In spite of the potential for a healthy worker effect and its bias toward the null, we provided evidence in this study for the deleterious effects of shortwave on some of the pregnancy outcomes. We had explored exposure to shortwaves in the Israeli physiotherapy departments in an earlier investigation. The electromagnetic ®eld strengths from shortwave diathermy equipment in six physiotherapy departments produced values above the reference levels (61.4 v/m electric ®eld and 0.18 A/m magnetic ®eld) which were detected up to one 503 meter from electrodes and cables when shortwave equipment was used in the continuous mode [Lerman et al., 1996]. Little is known about the mechanisms by which shortwaves might harm the pregnancy or cause fetal damage. In mammals, shortwaves are teratogenic and embryolethal at intensities which produce signi®cant hyperthermia in the dams [Lary et al., 1986]. Others have provided evidence which indicates that increases in mortality and resorption are probably related to peak body temperature and its duration regardless of the method by which the temperature elevation is elicited [Michaelson and Elson, 1996]. Thus, thermal stress appears to be the primary mechanism by which radiofrequency energy absorption exerts a teratogenic action. It is not known whether occupational exposure of physiotherapists could produce hyperthermia in the fetus of pregnant women. In experiments on rats, hyperthermia during speci®c developmental stages produces not only fetal resorption or malformation but also retardation of growth. This might explain an association between exposure to shortwaves early in pregnancy and low birth weight, as was shown in this study, after controlling for possible maternal lifestyle factors also associated with low birth weight, such as smoking. 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