A review of the types of childhood cancer associated with a medical X-ray examination of the pregnant mother

Abstract

Purpose: For 65 years the interpretation of the statistical association between the risk of cancer in a child and a prior diagnostic X-ray examination of the abdomen of the pregnant mother has been debated. The objections to a direct cause-and-effect explanation of the association vary in their strength, but one of the most notable grounds for controversy is the finding from the first and largest case-control study reporting the association, the Oxford Survey of Childhood Cancers (OSCC), of an almost uniformly raised relative risk (RR) for nearly all of the types of cancer that are most frequent in children. Here we compare the antenatal X-ray associations found in the OSCC for different types of childhood cancer with the results of all other case-control and case-cohort studies appropriately combined in meta-analyses, and we also review the findings of the few cohort studies that have been conducted. Conclusions: From the case-control/case-cohort studies other than the OSCC there are consistent and clear elevations of risk for all types of childhood cancer combined, all leukemia, and all cancers except leukemia combined. This compatibility of the findings of the OSCC with those of the combined other studies is less clear, or effectively absent, when some categories containing smaller numbers of incident cases/deaths are considered, but lack of precision of risk estimates due to sparse data presents inferential challenges, although there is a consistent absence of an association for bone tumors. Further, more recent studies almost certainly address lower intrauterine doses, with an anticipated decrease in estimated risks, which could be misleading when comparisons involve a limited number of studies that are mainly from later years, and a similar problem arises when having to employ all types of antenatal X-ray exposures for a study because data for abdominal exposures are absent. The problem of low statistical power is greater for cohort studies, and this, together with other shortcomings identified in the studies, limits the interpretational value of results. The findings of non-medical intrauterine exposure studies are constrained by sparse data and make a limited contribution to an understanding of the association. Certain aspects of the various studies require a need for caution in interpretation, but overall, the appropriate combination of all case-control/case-cohort studies other than the OSCC lends support to the inference that low-level exposure to radiation in utero proportionally increases the risk of the typical cancers of childhood to around the same level.

Review of the risk of cancer following low and moderate doses of sparsely ionising radiation received in early life in groups with individually estimated doses

“…A literature search of PubMed was last performed on 16th May 2021 using the search terms given in the Supplementary Methods . Additionally, recent UNSCEAR reports ( United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2008 ; 2013 ; 2018 ) were scanned to assess additional literature, as well as recent review articles ( Kendall et al 2021 ; Linet et al 2009 ; Linet et al 2012 ; Wakeford and Bithell 2021 ). We restricted attention to those studies of persons exposed in utero or in childhood (age 20 y or less) and with individually estimated organ/tissue doses.…”

Melanoma in pregnancy: Diagnosis and management in early-stage and advanced disease

“…Ionising radiation has a threshold dose above which these effects may occur, and the potential severity of these effects is dose-dependent above this threshold [84]. In addition to this, there are potential carcinogenic and mutagenic risks to the foetus, with ongoing debate as to whether this leads to any significant subsequent risk of childhood malignancy [85,86]. In reality, there is no 'safe' level of ionising radiation exposure in pregnancy that is universally accepted, and the general consensus is that attempts should be made to minimise exposure whilst obtaining sufficient clinical information [87].…”

Areas of research to support the system of radiological protection

“…There is growing evidence from epidemiologic studies of dose–risk relationships at dose levels down to about 100 mGy or less, for all cancers and for several specific cancer sites (see for example Grant et al 2017 ; Richardson et al 2015 ; Little et al 2017 ; Lubin et al 2017 ; Hauptmann et al 2020 ; Wakeford and Bithell 2021 ). Although risk models are available for many cancer sites that incorporate modifying factors such as sex, age at exposure and time since exposure (Cahoon et al 2017 ; Brenner et al 2018 , 2020 ; Mabuchi et al 2021 ), there are still large uncertainties related to radiation-induced risks at low doses and the shape of the dose-risk relationships.…”

“…Much of the current guidance relies on animal research and limited epidemiological data (ICRP 2003a ), but some new results were published in the recent years. Results show smaller head and chest size at birth, increased risks of paediatric leukaemia and cancer, increased systolic blood pressure at adolescence, and increased risk of cancer in women at late adulthood (Nakashima et al 2007 ; Hatch et al 2017 ; Sugiyama et al 2021 ; Wakeford and Bithell 2021 ). Further research is needed in understanding the long-term health effects from in utero low dose exposures.…”