A clinical look at the problem of drugs in pregnancy and their effect on the fetus.

The first annual W. E. Upjohn Lecture concerned itself with the interrelationship between administration of drugs to the pregnant woman and fetal outcome. The epidemiology of drug intake (both prescribed and self-administered drugs) during pregnancy is reviewed, using data derived from several surveys conducted both in the United States and in Scotland. The complexities of establishing a causal relationship between drug intake during pregnancy and effects upon the fetus are considered. Special emphasis is given to the adverse effects of aspirin and cigarette smoking. The shortage of data is critical and the need for further research is stressed.     

Present and future magnetic resonance sources of exposure to static fields

This paper considers the exposure of humans to static magnetic fields due to magnetic resonance imaging (MRI) procedures. It briefly introduces the types of magnetic fields associated with MRI. It then discusses trends in the number of people exposed to MRI, the field strength of the magnets used in MRI, and the types of applications of MRI. It also considers the types of staff who are exposed to magnetic fields due to MRI, and the alternative techniques that would be used in the absence of MRI.     

Maternal Smoking during Pregnancy and Fetal Organ Growth: A Magnetic Resonance Imaging Study

Objective

To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta.

Design

A case-control study, with operators performing the image analysis blinded.

Setting

Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom.

Participants

A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy.

Methods

Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA).

Main outcome measures

Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes.

Results

Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume.

Conclusion

Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.     

Health effects of static magnetic fields--a review of the epidemiological evidence

Potential health effects of static magnetic fields have received far less attention than, for example, power frequency or radiofrequency fields. Static fields are found in certain occupational settings, e.g. in the aluminium and chloralkali industries, in arc-welding processes, and certain railways systems. Magnetic resonance imaging (MRI) for medical diagnosis is another source. This paper summarizes the epidemiological evidence of static magnetic field exposure and long-term health effects. There are only a few epidemiological studies available, and the majority of these have focused on cancer risks. There are some reports on reproductive outcomes, and sporadic studies of other outcomes. Overall, few occupational studies have focused specifically on effects of static magnetic field exposure, and exposure assessment have consequently been poor or non-existent. Results from studies that have estimated static magnetic field exposure have not indicated any increased cancer risks, but they are generally based on small numbers of cases and crude exposure assessment. Control of confounding has been limited, and it is likely that the “healthy worker” effect have influenced the results. A few studies have reported results on reproductive outcomes among aluminium workers and MRI operators, but limitations in study designs prevent conclusions. A problem in epidemiological studies of static magnetic fields is that workers in exposed occupations are also exposed to a wide variety of other potentially harmful agents, including some known carcinogens. In conclusion, the available evidence from epidemiological studies is not sufficient to draw any conclusions about potential health effects of static magnetic field exposure.     

The effects of continuous exposure to 20-kHz sawtooth magnetic fields on the litters of CD-1 mice.

Mated CD-1 mice were exposed to 20-kHz sawtooth magnetic fields similar to those associated with video display terminals (VDT). Four groups of animals were continuously exposed from day 1 to day 18 of pregnancy to field strengths of 0, 3.6, 17, or 200 microT. There were no less than 185 mated dams in each exposure group. On day 18, the dams were sacrificed and assessed for weight gain and pregnancy. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral and skeletal malformations, and fetal weights. There were no less than 140 pregnant females in each group, and there were no significant differences between any of the exposure groups and the sham group (0 microT) for any of the end points. The results of this study do not support the hypothesis that the 20-kHz VLF magnetic fields associated with video display terminals are teratogenic in mammals.     

Comparison of residential power-frequency magnetic fields away from appliances in different countries

The purpose of this paper is to review measurements of residential power-frequency magnetic fields made in different countries and to determine whether average magnetic fields away from appliances are higher in some countries than in others. The paper includes 27 studies reporting measurements of residential magnetic fields in samples of homes: 14 from North America, 5 from the United Kingdom, and 8 from other European countries. Various factors that might make the results from individual studies unrepresentative of average fields in the relevant country are identified and discussed. Because distributions of magnetic fields generally are approximately log-normal, they are summarised by their geometric means. The best estimate of the geometric means of long-term average background fields in the United States is 60-70 nT and in the United Kingdom approximately 36-39 nT. In other countries, there are insufficient studies to draw firm conclusions on average fields. Measurements of personal exposure are higher than measurements of background fields, perhaps because they include exposures from appliances and other sources in the home. The ratio of personal exposure to background field seems, on average, to be approximately 1.4.     

Employee Attitudes about the Impact of Visitation Dogs on a College Campus

Therapy and visitation dogs are becoming more common on college campuses to provide comfort and support to students, but little attention has been given to the concerns of faculty and staff who share space with the dogs in their workplaces. The purpose of this study was to assess the perceptions of faculty and staff with regard to both the benefits and the hazards (e.g., dander, bites, fleas) and risks associated with the presence of visitation dogs in their workplaces. One hundred and thirty-eight employees who worked in buildings with resident visitation dogs completed an online survey about their perceptions of the hazards and risks of the dogs and the effects of dogs on the wellbeing of both students and employees. In general, employees perceived that the dogs presented minimal risks, and most employees believed that they can reduce stress and provide comfort to students on campus. There were a few employees, however, who reported that the dogs did not improve the work environment and conferred no benefits to the staff or students. The findings of the present survey support the mostly positive attitudes that people have for dogs in the workplace, but they also highlight a potential challenge: accommodating individuals who believe very strongly that dogs do not belong in work environments.     

妊娠合并甲状腺功能亢进症23 例临床分析

目的:探讨妊娠合并甲状腺功能亢进症的孕妇的妊娠结局,对母体造成的影响,抗甲状腺药物的使用情况及分娩方式。方法:对23例甲状腺功能亢进孕妇进行了回顾性分析,观察该病对孕妇的影响,对母儿造成的不良结局。结果:23例甲状腺功能亢进孕妇合并轻度妊娠高血压综合征的2例,中度4例,重度2例。合并心衰6例,合并胎膜早破5例,胎盘粘连2例,甲状腺危象1例,胎盘早剥1例,产后出血1例,前置胎盘1例。23例甲状腺功能亢进顺产6例,产钳1例,胎头吸引1例,剖宫产15例。出现早产9例,其中5例为医源性早产。胎儿宫内窘迫6例,死胎1例。结论:妊娠合并甲状腺功能亢进症常危及母婴健康,为降低母儿风险,孕前需很好地控制病情,孕期密切监控,合理治疗。     

Effects of exercise on maternal glycogen storage patterns and fetal outcome in mature rats.

The purpose of the present study was to examine the effects of exercise on maternal glycogen storage patterns and fetal outcome in mature (approximately 12 months of age) Sprague-Dawley rats. The exercise consisted of treadmill running at 30 m.min-1, on a 10 degree incline, for 60 min, 5 days per week, for 4 weeks prior to pregnancy, which continued until day 19 of gestation. In mature animals, chronic exercise increased (p < 0.05) liver glycogen concentration in both pregnant and nonpregnant rats. In pregnant exercised animals, the glycogen concentration of the maternal liver increased almost twofold (p < 0.05) compared with the sedentary pregnant group. There was no difference in the amount of glycogen stored in the gastrocnemius or soleus muscles in response to training, pregnancy, or chronic maternal exercise in the mature rat. In the pregnant groups, there were fewer (p < 0.05) viable fetuses and more (p < 0.05) resorption sites than in young rats. In addition, exercise during pregnancy in the mature animal decreased (p < 0.05) fetal body weight. These results demonstrate that a conflict may exist between maternal exercise and fetal demands for energy in the mature rat. This conflict seems to favour the maternal system, as evidenced by the enhanced maternal liver glycogen storage and the negative effect on fetal growth.     

恒定磁场出生前暴露对小鼠胚胎发育的影响

目的:探讨不同强度恒定磁场对小鼠胚胎发育的影响。方法:将52只受孕母鼠分别暴露于不同强度的恒定磁场下(0.04T、0.08T、0.12T),17只怀孕雌鼠作为对照,孕18日时处死母鼠,解剖后记录仔鼠总数,活胎数、吸收胎数,并称重胎重,测量胎仔身长、尾长以及计算心脏、肝、脑、肾脏与体重的比值。结果:在0.08T及0.12T磁场暴露下,平均活胎数较对照组明显减少。平均吸收胎数明显增加,与对照组相比差异有显著性(P<0.05)。胎鼠尾长、心、肝、脑、肾与体重比值各组间无显著性差异,但体重与身长在0.12T磁场环境中要较另外三组显著增加(P<0.05)。0.12T磁场暴露下畸形胎仔增加,其中外表畸形较另外三组差异有显著性。结论:磁场对小鼠胚胎发育有一定的影响,并且其影响与磁场强度相关。     

Obstetric Anaesthesia Services in the United Kingdom

In a survey of obstetric anaesthetic services in the United Kingdom questionnaires were sent to 398 hospital maternity units and 347 general-practitioner maternity units, of which 344 and 272 respectively were returned. Many hospitals were unable to provide an anaesthetist for obstetric surgery only, and few consultant anaesthetist sessions were allocated to obstetric surgery, particularly in regional hospitals in England and Wales. Constant supervision of junior anaesthetic staff with under 12 months'' experience was lacking in several hospitals. Endotracheal intubation is widely used throughout the United Kingdom. Though regional analgesic techniques are used by most anaesthetists it is impossible to provide a 24-hour regional analgesic service in all but a few hospitals.     

Interaction of static and extremely low frequency electric and magnetic fields with living systems: health effects and research needs

An international seminar was held June 4-6, 1997, on the biological effects and related health hazards of ambient or environmental static and extremely low frequency (ELF) electric and magnetic fields (0-300 Hz). It was cosponsored by the World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), the German, Japanese, and Swiss governments. Speakers provided overviews of the scientific literature that were discussed by participants of the meeting. Subsequently, expert working groups formulated this report, which evaluates possible health effects from exposure to static and ELF electric and magnetic fields and identifies gaps in knowledge requiring more research to improve health risk assessments. The working groups concluded that, although health hazards exist from exposure to ELF fields at high field strengths, the literature does not establish that health hazards are associated with exposure to low-level fields, including environmental levels. Similarly, exposure to static electric fields at levels currently found in the living and working environment or acute exposure to static magnetic fields at flux densities below 2 T, were not found to have demonstrated adverse health consequences. However, reports of biological effects from low-level ELF-field exposure and chronic exposure to static magnetic fields were identified that need replication and further study for WHO to assess any possible health consequences. Ambient static electric fields have not been reported to cause any direct adverse health effects, and so no further research in this area was deemed necessary.     

Increased resorptions in CBA mice exposed to low-frequency magnetic fields: An attempt to replicate earlier observations

This paper has two aims. First, it reports the findings of a study on the effects of low-frequency magnetic fields on reproduction. Second, it serves as an example of an attempt to replicate the results of an experimental study in an independent laboratory and discusses some of the problems of replication studies. To try to replicate the findings of a study reporting increased resorptions (fetal loss) in mice exposed to 20 kHz magnetic fields with sawtooth waveform and to study the possible effects of 50 Hz sinusoidal fields, pregnant mice were exposed to magnetic fields from day 0 to 18 of pregnancy, 24 h per day. The flux densities of the vertical magnetic fields were 15 μT (peak-to-peak) at 20 kHz and 13 or 130 μT (root mean square) at 50 Hz. Two strains of animals were used: CBA/S mice imported from the laboratory reporting the original observations, and a closely related strain CBA/Ca. The CBA/S mice were cleaned of pathogenic microbes and parasites before they were imported into our laboratory. The magnetic field exposures did not affect resorption rate in CBA/Ca mice. In CBA/S, the frequency of resorptions was higher in the exposed mice than in the control group. However, the increase was not significantly different from either the no-effect hypothesis or the results of the original study we were attempting to replicate. Differences between the two studies and difficulties in interpreting the results are discussed. It is concluded that the results tend more to support than argue against increased resorptions in CBA/S mice exposed to the 20 kHz magnetic field. The results demonstrate that animal strain is an important variable in bioelectromagnetics research: even closely related strains may show different responses to magnetic field exposure. Bioelectromagnetics 18:410–417, 1997. © 1997 Wiley-Liss, Inc.     

Effects of Gestational Magnetic Resonance Imaging on Methylation Status of Leptin Promoter in the Placenta and Cord Blood

Over the past two decades, magnetic resonance imaging (MRI) has been widely used for diagnosis in gestational women. Though it has several advantages, animal and human studies on the safety of MRI for the fetus remain inconclusive. Epigenetic modifications, which are crucial for cellular functioning, are prone to being affected by environmental changes. Therefore, we hypothesized that MRI during gestation may cause epigenetic modification alterations. Here, we investigated DNA methylation patterns of leptin promoter in the placenta and cord blood of women exposed to MRI during gestation. Results showed that average methylation levels of leptin in the placenta and cord blood were not affected by MRI. We also found that the methylation levels in the placenta and cord blood were not affected by different magnetic fields (1.5T and 3.0T MRI). However, if pregnant women were exposed to MRI at 15 to 20 weeks of gestation, the methylation level of leptin in cord blood was visibly lower than that of pregnant women exposed to MRI after 20-weeks of gestation (P = 0.037). mRNA expression level of leptin in cord blood was also altered, though mRNA expression of leptin in the placenta was not significantly affected. Therefore, we concluded that gestational MRI may not have major effects on the methylation level of leptin in cord blood and the placenta except for MRI applied before 20 weeks of gestation.     

Genotoxic effects of 3 T magnetic resonance imaging in cultured human lymphocytes

The clinical and preclinical use of high-field intensity (HF, 3 T and above) magnetic resonance imaging (MRI) scanners have significantly increased in the past few years. However, potential health risks are implied in the MRI and especially HF MRI environment due to high-static magnetic fields, fast gradient magnetic fields, and strong radiofrequency electromagnetic fields. In this study, the genotoxic potential of 3 T clinical MRI scans in cultured human lymphocytes in vitro was investigated by analyzing chromosome aberrations (CA), micronuclei (MN), and single-cell gel electrophoresis. Human lymphocytes were exposed to electromagnetic fields generated during MRI scanning (clinical routine brain examination protocols: three-channel head coil) for 22, 45, 67, and 89 min. We observed a significant increase in the frequency of single-strand DNA breaks following exposure to a 3 T MRI. In addition, the frequency of both CAs and MN in exposed cells increased in a time-dependent manner. The frequencies of MN in lymphocytes exposed to complex electromagnetic fields for 0, 22, 45, 67, and 89 min were 9.67, 11.67, 14.67, 18.00, and 20.33 per 1000 cells, respectively. Similarly, the frequencies of CAs in lymphocytes exposed for 0, 45, 67, and 89 min were 1.33, 2.33, 3.67, and 4.67 per 200 cells, respectively. These results suggest that exposure to 3 T MRI induces genotoxic effects in human lymphocytes.     

Potentialities of magnetic resonance imaging in the complex of prenatal radiation diagnosis of fetal malformations

The purpose of the study was to investigate the potentialities of magnetic resonance imaging (MRI) in the complex of prenatal radiation diagnosis of fetal malformations. Twenty-eight female patients with suspected fetal malformations were examined. Ultrasound study was supplemented by MRI according to a specially developed protocol. Various fetal CNS malformations were diagnosed. These included the Arnold-Chiari syndrome, the Dandy-Walker syndrome, occlusive hydrocephaly, lobular holoprosencephaly, porencephaly, diaphragmatic hernias, anomalies of the abdomen and retroperitoneal space, as well as anomalies of facial structures, including median clefts, and dacryocystocele. The use of MRI in the complex prenatal radiation diagnosis makes it possible to visualize fetal malformation more clearly, contributes to the more adequate prediction of the outcome of pregnancy and to the choice of a management policy for a female patient.     

Setting standards in the presence of developing scientific understanding

The setting of standards for potential hazards as result of the application of a new technology depends on both the philosophy with respect to risk and the state of knowledge about the circumstances under which the technology can cause damage. Typically, biological damage is first observed for high levels of exposure and short times. As our understanding of the technology and its effects on the biology improve, biological effects are observed at lower levels and longer exposure times. For extended low-level exposures it also becomes more difficult to demonstrate a hazard that is independent of other influences. This has been true for electric and magnetic fields both at low and radio frequencies. In this article it is recognized that a set number is needed for both manufactures and system operators to meet if the technology is to serve the public. It is also recommended that the public be presented with tables of relative risks that include levels of exposure and other risks for comparison. Three tables of relative risks are included as a possible starting point.     

Estimation and reduction of the radiation dose to the fetus from external-beam radiotherapy

The appearance of a malignant disease during pregnancy is relatively rare. The use of external-beam radiation therapy is limited to non-pelvic tumors which are usually located above the diaphragm. However, supradiaphragmatic radiotherapy unavoidably exposes the fetus to secondary radiation due to head leakage, scatter from the machine and scatter produced inside the patient. This fetal exposure may be associated with an elevated risk for the development of deterministic harmful effects and/or carcinogenesis. The decision about the administration of radiotherapy in a pregnant patient is influenced by the fetal dose which must always be estimated before the patient’s treatment course. The methods employed for fetal dosimetry in external-beam radiotherapy are described in this review study. Direct dose measurements using thermoluminescent dosemeters or large ionization chambers placed on physical phantoms may be used. Monte Carlo simulations on computational phantoms may also provide accurate fetal dose calculations. The physical and/or computational phantoms need to simulate the full-scatter geometry of the pregnant patient. Typical fetal dose values attributable to radiation therapy for brain tumors, head and neck cancer, breast carcinoma and Hodgkin lymphoma at the first, second and third trimesters of gestation are presented. The effectiveness of different shielding devices for fetal dose reduction in radiotherapy is discussed. The effect of the dimensions and setup of the shielding material on the radiation dose received by the fetus is described. Moreover, practical methods for reducing the fetal dose by selecting the appropriate irradiation parameters are presented.