A systematic review of human evidence for the intergenerational effects of exposure to ionizing radiation

Reference: Jade Stephens, Alexander J. Moorhouse, Kai Craenen, Ewald Schroeder, Fotios Drenos & Rhona Anderson (2024) A systematic review of human evidence for the intergenerational effects of exposure to ionizing radiation, International Journal of Radiation Biology, DOI: 10.1080/09553002.2024.2306328

 

Background to research

The question of whether exposure of a parent to ionising radiation can lead to adverse effects in their unexposed children, remains poorly understood and controversial. It was the major concern after the Japanese atomic bombings and, after reports of increases in leukaemia and non-Hodgkin's lymphoma among children living near the Sellafield nuclear facility in the UK. The current scientific consensus based upon health (epidemiological) studies suggests human health not to be significantly affected. This is contrasted however by evidence gained from cellular and animal studies which generally supports the potential for detrimental outcomes.

A ‘systematic review’ is a method whereby much of the relevant peer-reviewed published research is pooled together for the purpose of assessing the ‘body of evidence’ surrounding a particular question. The process includes pre-defined inclusion and exclusion criteria as set out in a protocol, meaning the potential for any selection bias, i.e. cherry-picking of studies, is reduced. In this way, published studies are systematically gathered and assessed in order to evaluate the body of the collected evidence.

What was the aim of the research?

The aim was to conduct a systematic review to examine the published evidence for the occurrence of human health effects in children of parents who were exposed to ionizing radiation before conception.

What did the research involve?

The researchers followed the Office of Health Assessment and Translation/National Toxicology (OHAT) guidelines for systematic reviews.
This involved:

    1. Search and selection of eligible published peer-reviewed research using international databases (2441 studies identified).
    2. Eligibility determined using pre-defined set of ‘inclusion and exclusion’ criteria.
    3. Relevant data extracted from all eligible (127) publications e.g. information on the study, the human population, all parental exposure details, other potential confounder exposures and, the findings.
    4. Flaws in the experimental design and procedures, data analysis and reporting of observations can lead to over- or under-estimating of an effect. Therefore, for each individual publication, a series of questions were asked, designed to assess studies for potential sources of bias.
    5. The most important of these was on the ‘timing of parental exposure’ whereby, a probable risk of bias relates to ‘suspected’ exposure after conception e.g. in utero or after birth, whereas a high risk of bias is where the study provides ‘evidence’ that this is the case.
    6. The information from each study was then grouped into health outcomes consisting of (i) pregnancy outcomes, (ii) genomic anomalies, (iii) solid and non-solid cancer, and (iv) other non-cancer diseases and mortality. For each health outcome, studies were further grouped by exposure situations. These include occupational exposure, non-cancer associated medical exposure, exposure to radiation from atomic bombs, and environmental exposure.
    7. The next step involved assessing and rating the ‘confidence’ in the body of evidence for each group. This involved making judgements based on the assessments of each publication in steps 4 and 5.
    8. Conclusions were then made. This conclusion was based upon the authors conclusions of the individual studies which comprise that body of evidence and, the direction of any statistical effect reported in the majority of the studies.

What did we find?

A summary of the evidence for each health outcome group is shown below.

What is the evidence for adverse pregnancy outcomes?

    • The majority of studies examining adverse pregnancy outcomes looked at the occurrence of congenital abnormalities.
    • There was a large variation in results reported between differently exposed populations. For instance, for occupational (e.g. nuclear workers) and medically exposed parents, for which there is greater confidence in the timing of exposure, most studies show an effect for congenital abnormalities, however the small number of studies available for analysis limits the strength of this finding. Indeed, for occupationally exposed parents with a good-high rating that parent(s) were exposed preconceptionally only, no conclusions could be drawn due to inconsistencies in the results.
    • There is some evidence to suggest an increase in neural tube defects amongst offspring of exposed populations.
    • For A-bomb survivor studies, which represent the largest cohort studied, a non-significant increase in new-born diseases is seen.
    • No evidence of a dose effect was seen across any of the studies.
    • Environmentally exposed populations represent the majority of studies whereby a mixture of effects/no effects were reported; however, these studies all lack critical information on the timing of exposure in relation to conception.

In summary, occupational and medically exposed populations (parents), for which there is greater confidence that exposure occurred before conception, show mostly an effect for congenital abnormalities, however the small number of studies available for analysis limits the strength of this finding. When ‘all’ exposure situations are considered, the evidence is rated as inadequate due to inconsistencies in the effects reported.

What is the evidence for increased genomic anomalies?

    • An examination of the evidence from DNA mutation/chromosomal studies in occupationally exposed parents was found to be inadequate to make any conclusions, due to inconsistencies with the authors conclusions.
    • All A-bomb survivor studies report no effect in the unexposed offspring.

What is the evidence for increased cancer rates?

    • An evidence confidence rating of high was given for those studies examining solid cancer amongst offspring of occupationally exposed individuals however this translated to inadequate evidence due to inconsistencies in the authors conclusions. This included where authors interpreted observed effects as being unlikely to be as a consequence of parental radiation exposure.
    • Solid cancer in offspring of A-bomb survivors was investigated in five studies, all of which showed no effect, however there is high likelihood of overlap in populations between studies.
    • The confidence in the body of evidence for non-solid cancers in occupational exposure studies was moderate. Inconsistencies in the reported conclusions translated into inadequate evidence.

What is the evidence of increased non-cancer diseases and mortality rates?

None of the studies examined showed any association between non-cancer disease incidence and mortality in offspring born to exposed parents. No studies assessing non-cancer diseases and mortality within offspring of occupationally or medically exposed parents were identified in this review.

What does this mean?

For the majority of the adverse health groups, we find there to be inadequate evidence from which to determine whether the health effect was, or was not, associated with parental pre-conceptional radiation exposure. This was largely due to variation between individual study’s findings and conclusions within each group and, the limited number of studies within each group. We did observe one health grouping (congenital abnormalities) in occupationally exposed populations, where an increase in effect relative to their controls or large magnitude of effects, were reported, although it is noted that the individual study’s findings were previously interpreted as not being associated with parental radiation exposure.

Overall, we find there to be a lack of evidence to enable the formal assessment of radiation-related adverse effects in offspring of exposed humans. This is not the same as there being no clear evidence that effects may occur but does infer that if adverse health effects do arise in children of exposed parents, then these effects are small and difficult to reproducibly measure. So, although a vast amount of research has been published over many decades there are large differences in the design of the studies and, in the reporting of the results. Inconsistencies are unavoidable, however we highlight the need for an element of standardisation and, more sharing of primary datasets as part of open access initiatives, in order for future reviews to make reasonable conclusion.

Who did this research?

This study was carried out by researchers at Brunel University London.

This work was, in part, supported by the Nuclear Community Charity Fund (NCCF) through funds received by The Armed Forces Covenant Fund Trust under the Aged Veterans Fund Grant AVF16 and Brunel University London.

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Supporting Resources

 

 

 

Key Messages

There is a lack of sufficient detail in the available evidence to enable the formal assessment of radiation-related adverse effects in unexposed human offspring after parental exposure

This is not the same as there being no clear evidence that effects may occur but does infer that if adverse health effects do arise in children of exposed parents, then these effects are small and difficult to reproducibly measure

Of those studies which do report some effect most show no evidence of any dose effect

Further understanding of the mechanistic processes which may be associated with intergenerational effects are needed

There is a need for an element of standardisation across the field to make reasonable conclusions and to enable the pooling of statistical data for meta-analysis

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Links to the research paper

This is a peer-reviewed study meaning that other scientists have reviewed this work before the authors published it in International Journal of Radiation Biology in 2024.