Prenatal exposure to ionizing radiation: sources, effects and regulatory aspects

Knowledge and awareness of physicians and the general public concerning the risks of prenatal exposure to ionizing radiation are important when developing a correct attitude to ionizing radiation. This is particularly important in the justification of medical diagnostic exposure of pregnant women and in case of possible accidents. The present paper reviews the most recent data on the effects of prenatal exposure to ionizing radiation reported in the scientific literature and in documents of international organizations dealing with this subject. Potentially significant exposure for women of childbearing age in medical diagnostics, working conditions and environmental contamination following the Chernobyl accident are reported. Some examples of doses associated with medical exposure in the course of diagnostic examinations with X-rays and radiopharmaceuticals, and occupational exposure in workplaces are given. Lastly, the regulatory aspects of the European Union directives and the Italian legislation on medical and occupational exposure of women during pregnancy or in reproductive age are reviewed.     

Radiological protection for diagnostic examination of pregnant women

ABSTRACT  Application of diagnostic X-ray examination to pregnant women is complicated since risks to both mother and embryo/fetus must be considered. Embryos and fetuses are more sensitive to radiation than adults or children. The threshold doses for fetal death, malformations and mental retardation which are deterministic effects, are reported to be 100–200 mGy or higher. The relative risk for childhood cancer due to radiation at an absorbed dose of 10 mGy during embryonic/fetal development has been estimated at 1.4. However, the absorbed dose of the embryo/fetus during X-ray diagnostic examination in which the X-ray beam does not irradiate the embryo/fetus directly such as maternal skull and chest X-ray is extremely low, less than 0.01 mGy. Thus these diagnostic procedures are not a problem from the perspective of radiological protection of the embryo/fetus. However, for pelvic CT scan and barium enema in which the uterus is directly within the X-ray beam, the absorbed doses to the embryo/fetus are about 20–80 mGy and 10–20 mGy, respectively. Therefore, medical staff must pay careful attention to the embryo/fetus in application of these examinations. Pregnant women who were not aware of pregnancy at the time of their diagnostic exposure have great anxiety about radiation from such X-ray examinations. However, fetal doses below 100 mGy should not be considered a reason for terminating a pregnancy.     

Cancer risks following diagnostic and therapeutic radiation exposure in children

The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life.     

Chornobyl radiation—congenital anomalies: A persisting dilemma

We report population prevalence rates of neural tube defects (NDT) and microcephaly (MIC) as well as levels of incorporated Cs137 by pregnant women in two areas of the Rivne Province of Ukraine, a northern half (Polissia) polluted by Chornobyl radiation and not‐Polissia areas. Monitoring of congenital malformations was conducted with adherence to methods adopted by a European surveillance network (EUROCAT). Incorporated Cs137 (Bq/kg) by pregnant women residing in the Polissia and not‐Polissia areas were obtained concurrently with prenatal ultrasound examinations. In Polissia, the incorporated Cs137 levels by pregnant women as well as the prevalence rates of NDTs and MIC are significantly higher than in not‐Polissia. In Polissia, the prevalence rates of NDTs and MIC are among the highest in Europe. The debate concerning the teratogenic impact of chronic exposures to low levels of ionizing radiation was re‐ignited by our 2010 report. Health agencies uphold the notion that exposure to Chornobyl radiation levels are too low to be teratogenic, which is inconsistent with our observations. Further investigations in Rivne by international teams can, we believe, contribute facts to the ongoing debate. Our monitoring system, experience and data can facilitate concurrent investigations of teratogenic risks from exposures to other sources of ionizing radiation, alcohol, folate, and zinc deficiencies, among other risk factors. Study of genomic impacts can likewise be undertaken.     

Imaging in pediatric patients: Time to think again about surveillance

Background

Despite concerns regarding ionizing radiation exposures from diagnostic imaging procedures in pediatric patients, many are deemed unavoidable or even mandated by treatment protocols. A prior review at our institution found patients with lymphoma had a higher median cumulative radiation exposure (191 mSv) versus other oncology subgroups (61 mSv).

Purpose

Estimations of cumulative diagnostic radiation exposures were tabulated for 5 years from the first diagnostic scan for 30 consecutive lymphoma patients diagnosed in 2001. Each individual imaging procedure was reviewed and classified as protocol mandated or discretionary (for disease surveillance, good patient care or radiologist request).

Results

Almost all patients (28/29) received chemotherapy; one had surgery only. Individual cumulative radiation exposures ranged from 10 to 642 mSv. Over 5 years, 690 procedures were performed; 303 (44%) X‐rays, 203 (29%) CTs, 157 (23%) radionucleotide, and 27 (4%) interventional procedures. Of these, 238 (34%) were protocol required and 452 (66%) discretionary (224 as part of good patient care for a co‐morbid illness and 228 for evaluation of possible disease progression/surveillance). A total of 86/217 (40%) studies (including 43 CTs and 38 radionucleotide scans) were performed when the recurrence risk was low (>2 years off therapy).

Conclusions

The majority of ionizing radiation procedures in this lymphoma cohort were discretionary. Given the excellent outcome of this group and the long‐term risks; rational use of discretionary surveillance procedures is necessary. Guidelines for the appropriate use of surveillance imaging based on probability of risk recurrence must be developed in order to minimize ionizing radiation exposure. Pediatr Blood Cancer. 2010;55:407–413. © 2010 Wiley‐Liss, Inc.     

The cause and prevention of human birth defects: What have we learned in the past 50 years?

ABSTRACT This review article dealig with the subject of “The Cause and Prevention of Human Birth Defects” was prepared in celebration of the 40th anniversary of the Japanese Teratology Society. It begins with recollections of some of the important contributions of Japanese scientists in the fields of teratology and embryology and a summary of the many scientific and medical accomplishments of the past 50 years in the fields of teratology, genetics, developmental biology, epidemiology and genetics. The review includes a summary of the drugs, chemicals and physical agents that have been documented to result in congenital malformations and reproductive effects when pregnant women are exposed during pregnancy. The principles of teratology were also summarized and emphasize that 1) no teratogenic agent can be described qualitatively as a teratogen, since a teratogenic exposure must include not only the agent, but also the dose and the time in pregnancy when the exposure occurs. 2) Even agents that have been demonstrated to result in malformatins cannot produce every type of malformation. 3) Known teratogens can be presumptively identified by the spectrum of malformations they produce. 4) It is easier to exclude an agent as a cause of birth defects than to definitively conclude that it was responsible for birth defects. 5) When evaluating the risk of exposures, the dose is a crucial component in determining the risk. 6) Teratogenic agents follow a toxicological dose response curve. This means that each teratogen has a threshold dose, below which, there is no risk of teratogenensis, no matter when in pregnancy the exposure occurred. 7) The evaluation of a child with congenital malformations connot be adequately performed unless it is approached with the same scholarship and detail, as is any other complicated medical problem. 8) Each physician must recognize the consequences of providing erroneous reproductive risks to pregnant women exposed to drugs and chemicals during pregnancy or alleging that a child's malformations are due to an environmental agent without performing a complete and scholarly evaluation.     

Paternal occupational exposure to electro-magnetic fields as a risk factor for cancer in children and young adults: a case-control study from the North of England

BACKGROUND: Numerous studies have implied that paternal occupational exposures, in particular electromagnetic fields (EMF) and ionizing radiation, may be involved in the etiology of childhood cancers. We investigated whether an association exists between paternal occupations at birth involving such exposures and cancer risk in offspring, using data from the Northern Region Young Persons' Malignant Disease Registry (NRYPMDR). PROCEDURE: Cases (n=4,723) were matched, on sex and year of birth, to controls from two independent sources: (i) all other patients from the NRYPMDR with a different cancer, (ii) 100 cancer-free individuals per case from the Cumbrian Births Database. An occupational exposure matrix was used to assign individuals to exposure groups. RESULTS: There was an increased risk of leukemia among the offspring of men employed in occupations likely to be associated with EMF or radiation exposures (OR 1.31, 95% CI 1.02-1.69), particularly in males aged less than 6 years (OR 1.81, 95% 1.19-2.75). No significant association was seen in females. Increased risks were also seen for chondrosarcoma (OR 8.7, 95% CI 1.55-49.4) and renal carcinoma (OR 6.75, 95% CI 1.73-26.0). These associations were consistent between control groups and remained after adjustment for socio-economic status. CONCLUSIONS: This large case-control study identified a significantly increased risk of leukemia among the offspring of men likely to have been occupationally exposed to EMF, with differing associations between males and females. Increased risks of chondrosarcoma and renal carcinoma were also seen, although based on smaller numbers. Further detailed investigations in this area are required to understand this association.     

Pediatric Hodgkin lymphoma: are we over-scanning our patients?

Despite the favorable outcome of most pediatric patients with Hodgkin lymphoma (HL), there is rising concern about risks of carcinogenesis from both diagnostic and therapeutic radiation exposure for patients treated on study protocols. Although previous studies have investigated radiation exposure during treatment, radiation from post-treatment surveillance imaging may also increase the likelihood of secondary malignancies. All diagnostic imaging examinations involving ionizing radiation exposure performed for surveillance following completion of therapy were recorded for 99 consecutive pediatric patients diagnosed with HL from 2000 to 2010. Cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. In the first 2 years following completion of therapy, patients in remission received a median of 11 examinations (range 0-26). Only 13 of 99 patients relapsed, 11 within 5 months of treatment completion. No relapse was detected by 1- or 2-view chest radiographs (n = 38 and 296, respectively), abdomen/pelvis computed tomography (CT) scans (n = 211), or positron emission tomography (PET) scans alone (n = 11). However, 10/391 (2.6%) of chest CT scans, 4/364 (1.1%) of neck CT scans, and 3/47 (6.4%) of PET/CT scans detected relapsed disease. Thus, only 17 scans (1.3%) detected relapse in a total of 1358 scans. Mean radiation dosages were 31.97 mSv for Stage 1, 37.76 mSv for Stage 2, 48.08 mSv for Stage 3, and 51.35 mSv for Stage 4 HL. Approximately 1% of surveillance imaging examinations identified relapsed disease. Given the very low rate of relapse detection by surveillance imaging stipulated by current protocols for pediatric HL patients, the financial burden of the tests themselves, the high cure rate, and risks of second malignancy from ionizing radiation exposure, modification of the surveillance strategy is recommended.     

Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations

In the context of health care, risk assessment is the identification, evaluation and estimation of risk related to a particular clinical situation or intervention compared to accepted medical practice standards. The goal of risk assessment is to determine an acceptable level of risk for a given clinical treatment or intervention in association with the provided clinical circumstances for a patient or group of patients. In spite of the inherent challenges related to risk assessment in pediatric cross-sectional imaging, the potential risks of ionizing radiation and sedation/anesthesia in the pediatric population are thought to be quite small. Nevertheless both issues continue to be topics of discussion concerning risk and generate significant anxiety and concern for patients, parents and practicing pediatricians. Recent advances in CT technology allow for more rapid imaging with substantially lower radiation exposures, obviating the need for anesthesia for many indications and potentially mitigating concerns related to radiation exposure. In this review, we compare and contrast the potential risks of CT without anesthesia against the potential risks of MRI with anesthesia, and discuss the implications of this analysis on exam selection, providing specific examples related to neuroblastoma surveillance imaging.     

Stage Differences in Developmental Disorders in ICR Mouse Embryos Irradiated with Gamma-Rays

This study was designed to determine precisely the radiosensitive period in the development of ICR mouse embryos during which external malformations and growth retardation tend to occur. Female and male mice were placed together for only three hours to allow fairly precise identification of the time of conception. The pregnant mice were divided into 31 groups, which were irradiated in turn with 1.5 Gy gamma radiation at 6-hour intervals during the period of organogenesis. They were then observed on day 18 of gestation. Items recorded were intrauterine death, external malformations, sex ratio and fetal body weight. Death of the embryo/fetus, especially death in the early period of organogenesis, was most frequent in mice irradiated between days 6.75 and 8.25 of gestation, but there was no statistically significant difference in the frequency of early- and late-period deaths between irradiated and control groups. The types and frequencies of external malformations observed differed according to the exposure period. The most highly sensitive period for each malformation lasted no more than 12 hours. Reduction of fetal body weight was a good indicator of radiation effects, and was observed mostly in the groups irradiated between days 9.75 and 11.00 of gestation. The sex ratio was not affected by the period in which irradiation was performed.     

CT utilization: the emergency department perspective

CT scan utilization in the pediatric emergency department (ED) has dramatically increased in recent years. This likely reflects the improved diagnostic capability of CT, as well as its wider availability. However, the utility of CT is tempered by the high radiation exposure to patients as well as cost. In this review we will consider the magnitude of changes in CT use in the pediatric ED, and we will examine some of the driving forces behind these increases. In addition, we will consider strategies to limit growth in CT scan utilization or even result in reductions in CT use in the future. These strategies include better physician and patient education, application of existing clinical decision rules to reduce CT utilization and development of new rules, technical alterations in CT protocols to reduce per-exam exposures, use of alternative imaging modalities such as US and MRI that do not expose patients to ionizing radiation, and expanded use of clinical observation in place of immediate diagnostic imaging. Reform of liability laws might alleviate another driving force behind high CT utilization rates. Protocols must be designed to maximize patient safety by limiting radiation exposures while preserving rapid and accurate diagnosis of time-sensitive conditions.     

Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations

While the etiology of most childhood cancers is largely unknown, epidemiologic studies have consistently found an association between exposure to medical radiation during pregnancy and risk of childhood cancer in offspring. The relation between early life diagnostic radiation exposure and occurrence of pediatric cancer risks is less clear. This review summarizes current and historical estimated doses for common diagnostic radiologic procedures as well as the epidemiologic literature on the role of maternal prenatal, children’s postnatal and parental preconception diagnostic radiologic procedures on subsequent risk of childhood malignancies. Risk estimates are presented according to factors such as the year of birth of the child, trimester and medical indication for the procedure, and the number of films taken. The paper also discusses limitations of the methods employed in epidemiologic studies to assess pediatric cancer risks, the effects on clinical practice of the results reported from the epidemiologic studies, and clinical and public health policy implications of the findings. Gaps in understanding and additional research needs are identified. Important research priorities include nationwide surveys to estimate fetal and childhood radiation doses from common diagnostic procedures, and epidemiologic studies to quantify pediatric and lifetime cancer risks from prenatal and early childhood exposures to diagnostic radiography, CT, and fluoroscopically guided procedures.     

Welcome

Issues pertaining to control of radiation dose exposures in pediatric imaging are on the forefront of patient care worldwide. Certain factors contribute to appropriate—or inappropriate—use of ionizing radiation in pediatric medical imaging. Such issues include naiveté regarding cancer risk and the role of medical imaging in its development, misinformation about exposure to ionizing radiation, resource availability, staffing, scheduling “snags,” costs, limited evidence-based imaging practice information and shrinking funding. These issues will be introduced in this paper.     

Glucocorticoids,inflammation and the perinatal lung

Many women delivering preterm infants at less than 30 weeks gestation have subclinical chorioamnionitis. Based on current guidelines, maternal glucocorticoid treatment is given to induce lung maturation. Fetal exposure to proinflammation can cause acute and chronic injury, but inflammation also can induce fetal lung maturation. Both antenatal glucocorticoids and inflammation modulate lung development, by inducing the surfactant system, inducing structural maturation, and inhibiting alveolarization. The opportunities for the future are to develop new safer strategies to mature the preterm foetus, and the risks are potential adverse interactions of repetitive glucocorticoid exposures and unrecognized fetal exposure to inflammation.     

Optimization of a fluoroscope to reduce radiation exposure in pediatric imaging

Background. A new children's hospital provided the impetus to investigate radiation dose and image quality in a fluoroscope that was specially engineered for pediatric fluoroscopy. Radiation protection management recommends radiation exposures that are as low as reasonably achievable, while still maintaining diagnostic image quality.¶Objectives. To obtain comparative phantom imaging data on radiation exposure and image quality from a newly installed fluoroscope before and after optimization for pediatric imaging.¶Materials and methods. Images were acquired from various thickness phantoms, simulating differing patient sizes. The images were evaluated for visualization of high- and low-contrast objects and for radiation exposure. Effects due to use of the image intensifier anti-scatter grid were also investigated.¶Results. The optimization of the new fluoroscope for pediatric operation reduced radiation exposure by about 50 % (compared to the originally installed fluoroscope), with very little loss of image quality. Pulsed fluoroscopy was able to lower radiation dose to less than 10 % of continuous fluoroscopy, while still maintaining acceptable phantom image quality.¶Conclusion. Radiation exposure in pediatric fluoroscopy can be reduced to values well below the exposure settings that are typically found on unoptimized fluoroscopes. Pulsed fluoroscopy is considered a requisite for optimal pediatric fluoroscopy.     

Congenital malformations. Cleft palate, congenital heart disease, absent tibiae, and polydactyly.

A girl had cleft palate, micrognathia, Wormian bones, congenital heart disease, dislocated hips, absent tibiae, bowed fibulae, preaxial polydactyly of the feet, and abnormal dermal patterns at birth. She was born after a pregnancy complicated by exposure to multiple medications. This combination of malformations may represent a distinct entity unrelated to the medication or may be a complication of the intrauterine drug exposure.     

Pediatric Burkitt's Lymphoma and Diffuse B-Cell Lymphoma: Are Surveillance Scans Required?

Outcomes in pediatric B-Non-Hodgkin Lymphoma (B NHL) have improved with intensive chemotherapy protocols, with long-term survival now over 80%. However, long-term adverse effects of therapy and poor outcomes for patients who relapse remain challenges. In this study, we aimed to evaluate the potential risks and benefits of routine relapse surveillance imaging after the completion of therapy. We reviewed 44 B NHL patients diagnosed and treated at Texas Children's Cancer Center in the period between 2000 to 2011. All cross-sectional diagnostic imaging examinations performed for disease assessment after completion of chemotherapy were reviewed and cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. Only 3 patients of the 44 relapsed (6.8%), though none of the relapses were initially diagnosed by computed tomography (CT) or fludeoxyglucose positron emission tomography (FDG-PET) scans. Median effective dose of ionizing radiation per patient was 40.3 mSv with an average of 49.1 mSv (range 0–276 mSv). This single-institution study highlights the low relapse rate in pediatric B-NHL with complete response at the end of therapy, the low sensitivity of early detection of relapse with surveillance CT or FDG-PET imaging, and the costs and potential increased risk of secondary malignancies from cumulative radiation exposure from surveillance imaging. We propose that routine surveillance CT or FDG-PET scans for these patients may not be necessary.     

Guidelines for imaging retinoblastoma: imaging principles and MRI standardization

Retinoblastoma is the most common intraocular tumor in children. The diagnosis is usually established by the ophthalmologist on the basis of fundoscopy and US. Together with US, high-resolution MRI has emerged as an important imaging modality for pretreatment assessment, i.e. for diagnostic confirmation, detection of local tumor extent, detection of associated developmental malformation of the brain and detection of associated intracranial primitive neuroectodermal tumor (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic evaluation of retinoblastoma or mimicking lesions are presented, based on consensus among members of the European Retinoblastoma Imaging Collaboration (ERIC). The most appropriate techniques for imaging in a child with leukocoria are reviewed. CT is no longer recommended. Implementation of a standardized MRI protocol for retinoblastoma in clinical practice may benefit children worldwide, especially those with hereditary retinoblastoma, since a decreased use of CT reduces the exposure to ionizing radiation.