Search

Research Question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?, Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence ratio (SIR) was derived as the ratio of observed to expected cases. Exact 95% CI were calculated., Results: In total, 118,155 children born after ART contributed 796,633 person-years follow-up (average follow-up 6.74 years). Eight cases of LCH were identified, compared with 3.75 cases expected (SIR 2.135, 95% CI 0.92-4.21; P = 0.074). Significantly more cases were associated with intracytoplasmic sperm injection (ICSI) (SIR 4.02, 95% CI 1.31-9.39) and male factor infertility (SIR 5.41, 95% CI 1.47-13.84). Most cases of LCH had single-system disease (n = 6)., Conclusions: This study found that significantly more cases of LCH were identified in children born after ICSI and in children whose parents had male factor infertility. A non-significant excess of cases in children born after ART was identified. Absolute excess risk was small. Given the rarity of LCH and the small number of cases included in this large cohort, further studies into the risk of LCH in children born after ART are indicated., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A fire in one of the Windscale nuclear reactors at Sellafield (Cumbria, England) in October 1957 released 1,800 TBq of 131 I (half-life, 8 days) to atmosphere. Measurements of 131 I activity in thyroids of exposed children showed typical thyroid doses of tens of milligray, but with some exceeding 100 mGy. Radiation exposure in childhood is known to increase the risk of thyroid cancer. Consequently, an investigation was conducted into whether raised numbers of thyroid cancer cases occurred in those exposed to 131 I as young children in Cumbria. A database of Cumbrian births from 1950 onwards allowed cohorts of 56,086 births during 1950-1958 and 137,444 births during 1959-1980 to be constructed, periods including children potentially exposed and unexposed, respectively, to 131 I. Three areas of Cumbria with different 131 I contamination levels were identified from monitoring data, and births assigned to these three areas for the two periods of birth. Members of these six sub-cohorts were linked to incident thyroid cancer cases in Great Britain during 1981-2020 using national cancer registration databases, providing thyroid cancer incidence rates. Incidence rate ratios (IRRs), with the lowest contamination area as a reference, were computed. No IRR differed discernibly from unity. For births during 1950-1958, the IRR for the combined highest and intermediate 131 I contamination areas was 0.68 (95% confidence interval: 0.24, 1.56), and no case of thyroid cancer was found in the small cohort born in the highest contamination area. In conclusion, no increased risk of thyroid cancer in those exposed to 131 I as young children in Cumbria in 1957 was detected. This study adds to the evidence on the long-term risk of thyroid cancer following childhood exposure to low and moderate levels of 131 I, such as occurred following the Fukushima nuclear accident in 2011., Competing Interests: Declarations. Ethics approval and consent to participate: Permission for the study was given on 30 July 2018 by the Newcastle University, Faculty of Medical Sciences Research Ethics Committee (application number: 1530/6677/2018). Approval from the Public Benefit and Privacy Panel for Health and Social Care (reference number 1718 − 0248) was received on 19 March 2019. Data Sharing Agreement (GDPR Compliant) between Public Health England, an executive agency of the Department of Health and Social Care, and the University of Newcastle upon Tyne, dated 9 September 2019. Consent for publication: Not applicable. Competing interests: R.W. is a member of the Technical Working Party of the Compensation Scheme for Radiation-Linked Diseases (http://www.csrld.org.uk). Otherwise, the authors declare no potential conflict of interest., (© 2024. The Author(s).)

Background: Patterns and risks of subsequent primary tumours (SPTs) among long-term survivors of childhood cancer have been extensively described, but much less is known about early SPTs (ESPTs) occurring within 5 years after initial diagnosis., Procedure: We carried out a population-based study of ESPTs following childhood cancer throughout Britain, using the National Registry of Childhood Tumours. The full study series comprised all ESPTs occurring among 56,620 children whose initial cancer diagnosis was in the period 1971-2010. Frequencies of ESPT were calculated for the entire cohort. For analyses of risk, follow-up began 92 days after initial diagnosis., Results: ESPT developed in 0.4% of children overall, 0.52% of those initially diagnosed at age less than 1 year and 0.38% of those diagnosed at age 1-14 years. Standardised incidence ratio (SIR) was 7.7 (95% confidence interval [CI]: 6.7-8.9), overall 9.5 (95% CI: 7.1-12.5) for children initially diagnosed in 1981-1990 and 6.5-7.5 for those from earlier and later decades. SIR by type of first cancer ranged from 4.4 (95% CI: 1.8-9.1) for Wilms tumour to 13.1 (95% CI: 7.7-21.0) for non-Hodgkin lymphoma. SIR by type of ESPT ranged from 2.0 (95% CI: 1.0-3.4) for acute lymphoblastic leukaemia to 66.6 (95% CI: 52.3-83.6) for acute myeloid leukaemia. Predisposition syndromes were known to be implicated in 21% of children with ESPT and suspected in another 5%., Conclusions: This study provides an overview of the patterns and risks of ESPTs in a large population where many children received therapy that is still in widespread use. Further research will be needed to monitor and understand changes in risk as childhood cancer treatment continues to evolve., (© 2023 Wiley Periodicals LLC.)

Background: This nationwide study investigated associations between paternal occupational exposure and childhood bone tumours and soft- tissue sarcomas., Methods: The UK National Registry of Childhood Tumours provided cases of childhood sarcomas born and diagnosed in Great Britain, 1962-2010. Control births, unaffected by childhood cancer, were matched on sex, birth period and birth registration sub-district. Fathers' occupations were assigned to one or more of 33 exposure groups and coded for occupational social class., Results: We analysed 5,369 childhood sarcoma cases and 5380 controls. Total bone tumours, total soft-tissue sarcomas and the subgroups osteosarcoma, rhabdomyosarcoma and Ewing Sarcoma Family of Tumours (ESFT) were considered separately. Significant positive associations were seen between rhabdomyosarcoma and paternal exposure to EMFs (odds ratio = 1.67, CI = 1.22-2.28) and also for ESFT and textile dust (1.93, 1.01-3.63). There were putative protective effects on total bone tumours of paternal dermal exposure to hydrocarbons, metal, metal working or oil mists., Conclusions: Despite the large size and freedom from bias of this study, our results should be interpreted with caution. Many significance tests were undertaken, and chance findings are to be expected. Nevertheless, our finding of associations between ESFT and paternal exposure to textile dust may support related suggestions in the literature.

Objective: To report outcomes to 1 year, in infants born with congenital diaphragmatic hernia (CDH), explore factors associated with infant mortality and examine the relationship between surgical techniques and postoperative morbidity., Design: Prospective national population cohort study., Setting: Paediatric surgical centres in the UK and Ireland., Method: Data were collected to 1 year for infants with CDH live-born between 1 April 2009 to 30 September 2010. Factors associated with infant mortality are explored using logistic regression. Postoperative morbidity following patch versus primary closure, minimally invasive versus open surgery and biological versus synthetic patch material is described. Data are presented as n (%) and median (IQR)., Results: Overall known survival to 1 year was 75%, 95% CI 68% to 81% (138/184) and postoperative survival 93%, 95% CI 88% to 97% (138/148). Female sex, antenatal diagnosis, use of vasodilators or inotropes, being small for gestational age, patch repair and use of surfactant were all associated with infant death. Infants undergoing patch repair had a high incidence of postoperative chylothorax (11/54 vs 2/96 in infants undergoing primary closure) and a long length of hospital stay (41 days, IQR 24-68 vs 16 days, IQR 10-25 in primary closure group). Infants managed with synthetic patch material had a high incidence of chylothorax (11/34 vs 0/19 with biological patch)., Conclusion: The majority of infant deaths in babies born with CDH occur before surgical correction. Female sex, being born small for gestational age, surfactant use, patch repair and receipt of cardiovascular support were associated with a higher risk of death. The optimum surgical approach, timing of operation and choice of patch material to achieve lowest morbidity warrants further evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This nationwide study investigates associations between paternal occupational exposure and childhood lymphoma., Methods: The UK National Registry of Childhood Tumours provided cases of childhood lymphoma born and diagnosed in Great Britain 1962-2010. Control births, unaffected by childhood cancer, were matched on sex, birth period and birth registration sub-district. Fathers' occupations were assigned to one or more of 33 exposure groups and also coded for occupational social class., Results: We analysed 5033 childhood lymphoma cases and 4990 controls. Total lymphoma and the subgroups Hodgkin, Burkitt and non-Hodgkin lymphoma were considered separately. No one exposure was significantly associated with increased risk within all subgroups and for total lymphoma. However, exposure to "ceramics and glass" was significantly associated with increased risk of total lymphoma, Hodgkin and non-Hodgkin lymphoma. Paternal lead exposure was associated with Burkitt lymphoma and exposure to metal fumes was associated with Hodgkin lymphoma., Conclusions: This study provides no support for previous suggestions of an association between childhood lymphoma and paternal occupational exposure to pesticides, solvents/hydrocarbons or infections potentially transmitted by father's social contacts. An association with exposure to "ceramics and glass" was noted for the two major lymphoma subtypes together comprising 80% of total lymphoma.

Purpose: This study aims to describe short-term outcomes of live-born infants with congenital diaphragmatic hernia (CDH) and to identify prognostic factors associated with early mortality., Design: A prospective population cohort study was undertaken between April 2009 and September 2010, collecting data on live-born infants with CDH from all 28 paediatric surgical centres in the UK and Ireland using an established surgical surveillance system. Management and outcomes are described. Prognostic factors associated with death before surgery are explored., Results: Two hundred and nineteen live-born infants with CDH were reported within the data collection period. There were 1.5 times more boys than girls (n=133, 61%). Thirty-five infants (16%) died without an operation. This adverse outcome was associated with female sex (adjusted OR (aOR) 3.96, 95% CI 1.66 to 9.47), prenatal diagnosis (aOR 4.99, 95% CI 1.31 to 18.98), and the need for physiological support in the form of inotropes (aOR 9.96, 95% CI 1.19 to 83.25) or pulmonary vasodilators (aOR 4.09, 95% CI 1.53 to 10.93). Significant variation in practice existed among centres, and some therapies potentially detrimental to infant outcomes were used, including pulmonary surfactant in 45 antenatally diagnosed infants (34%). Utilisation of extracorporeal membrane oxygenation was very low compared with published international studies (n=9/219, 4%). Postoperative 30-day survival was 98% for 182 infants with CDH who were adequately physiologically stabilised and underwent surgery., Conclusion: This is the first British Isles population-based study reporting outcome metrics for infants born with CDH. 16% of babies did not survive to undergo surgery. Factors associated with poor outcome included female sex and prenatal diagnosis. Early postoperative survival in those who underwent surgical repair was excellent., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: We summarise the work of the Childhood Cancer Research Group, particularly in relation to the UK National Registry of Childhood Tumours (NRCT)., Methods: The Group was responsible for setting up and maintaining the NRCT. This registry was based on notifications from regional cancer registries, specialist children's tumour registries, paediatric oncologists and clinical trials organisers. For a large sample of cases, data on controls matched by date and place of birth were also collected., Results: Significant achievements of the Group include: studies of aetiology and of genetic epidemiology; proposals for, and participation in, international comparative studies of these diseases and on a classification system specifically for childhood cancer; the initial development of, and major contributions to, follow-up studies of the health of long-term survivors; the enhancement of cancer registration records by the addition of clinical data and of birth records. The Group made substantial contributions to the UK government's Committee on Medical Aspects of Radiation in the Environment., Conclusion: An important part of the ethos of the Group was to work in collaboration with many other organisations and individuals, both nationally and internationally: many of the Group's achievements described here were the result of such collaborations.

Background: High doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topic METHODS: Most UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling., Results: This paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975-2014., Conclusion: The work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group's work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation.

Our previous study of childhood leukaemia and distance to high-voltage overhead power lines in the UK has been included in an international pooled analysis. That pooled analysis used different distance categories to those we did, which has focussed attention on the effect of that choice. We re-analyse our previous subjects, using finer distance categories. In the 1960s and 1970s, when we principally found an elevated risk, the risk did not fall monotonically with distance from the power line but had a maximum at 100-200 m. This weakens the evidence that any elevated risks are related to magnetic fields, and slightly strengthens the evidence for a possible effect involving residential mobility or other socioeconomic factors.

Background: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines., Methods: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies., Results: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92-1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders., Conclusions: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated.

Objective: The aim of this study was to estimate the incidence of anaphylaxis in pregnancy and describe the management and outcomes in the UK., Design: A population-based descriptive study using the UK Obstetric Surveillance System (UKOSS)., Setting: All consultant-led maternity units in the UK., Population: All pregnant women who had anaphylaxis between 1 October 2012 and 30 September 2015. Anaphylaxis was defined as a severe, life-threatening generalised or systemic hypersensitivity reaction., Methods: Prospective case notification using UKOSS., Main Outcome Measures: Maternal mortality, severe maternal morbidity, neonatal mortality and severe neonatal morbidity., Results: There were 37 confirmed cases of anaphylaxis in pregnancy, giving an estimated incidence of 1.6 (95% CI: 1.1-2.2) per 100 000 maternities. Four cases of anaphylaxis were in women with known penicillin allergies: two received co-amoxiclav and two cephalosporins. Twelve women had anaphylaxis following prophylactic use of antibiotics at the time of a caesarean delivery. Prophylactic use of antibiotics for Group B streptococcal infection accounted for anaphylaxis in one woman. Two women died (5%), 14 (38%) women were admitted to intensive care and seven women (19%) had one or more additional severe maternal morbidities, which included three haemorrhagic events, two cardiac arrests, one thrombotic event and one pneumonia. No infants died; however, in those infants whose mother had anaphylaxis before delivery (n = 18) there were seven (41%) neonatal intensive care unit admissions, three preterm births and one baby was cooled for neonatal encephalopathy., Conclusions: Anaphylaxis is a rare severe complication of pregnancy and frequently the result of a reaction to antibiotic administration. This study highlights the seriousness of the outcomes of this condition for the mother. The low incidence is reassuring given the large proportion of the pregnant population that receive prophylactic antibiotics during delivery., Tweetable Abstract: Anaphylaxis is a rare severe complication of pregnancy and frequently the result of a reaction to antibiotic administration., (© 2017 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Study Question: Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population?, Summary Answer: This study showed no overall increased risk of childhood cancer in individuals born after donor ART., What Is Known Already: Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date., Study Design, Size, Duration: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years)., Participants/materials, Setting, Methods: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles., Main Results and the Role of Chance: In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight., Limitations Reasons for Caution: Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available., Wider Implications of the Findings: This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed., Study Funding/competing Interest(s): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests., Trial Registration Number: N/A., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

We demonstrate a strong correlation between domestic radon levels and socio-economic status (SES) in Great Britain, so that radon levels in homes of people with lower SES are, on average, only about two thirds of those of the more affluent. This trend is apparent using small area measures of SES and also using individual social classes. The reasons for these differences are not known with certainty, but may be connected with greater underpressure in warmer and better-sealed dwellings. There is also a variation of indoor radon levels with the design of the house (detached, terraced, etc.). In part this is probably an effect of SES, but it appears to have other causes as well. Data from other countries are also reviewed, and broadly similar effects seen in the United States for SES, and in other European countries for detached vs other types of housing. Because of correlations with smoking, this tendency for the lower SES groups to experience lower radon levels may underlie the negative association between radon levels and lung cancer rates in a well-known ecological study based on US Counties. Those conducting epidemiological studies of radon should be alert for this effect and control adequately for SES., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We report further analyses from an epidemiological study of childhood cancer and residence at birth near high-voltage power lines in the UK. These results suggest that the elevated risks for childhood leukaemia that we previously found for overhead power lines may be higher for older age at diagnosis and for myeloid rather than lymphoid leukaemia. There are differences across regions of birth but not forming any obvious pattern. Our results suggest the decline in risk we previously reported from the 1960s to the 2000s is linked to calendar year of birth or of cancer occurrence rather than the age of the power lines concerned. Finally, we update our previous analysis of magnetic fields to include later subjects.

Migration, that is the study subjects moving from one residential address to another, is a complication for epidemiological studies where exposures to the agent of interest depend on place of residence [corrected]. In this paper we explore migration in cases from a large British case-control study of childhood cancer and natural background radiation. We find that 44% of cases had not moved house between birth and diagnosis, and about two-thirds were living within 2 km of their residence at birth. The estimated dose at the diagnosis address was strongly correlated with that at the birth address, suggesting that use of just the birth address in this case-control study does not lead to serious bias in risk estimates. We also review other individual-based studies of naturally occurring radiation, with particular emphasis on those from Great Britain. Interview-based case-control and cohort studies can potentially establish full residential histories for study subjects and make direct measurements of radiation levels in the dwellings in question. However, in practice, because of study size and difficulties in obtaining adequate response rates, interview-based studies generally do not use full residential histories, and a substantial proportion of dose estimates often derive from models rather than direct measurements. More seriously, problems of incomplete response may lead to bias, not just to loss of power. Record-based case-control studies, which do not require direct contact with study subjects, avoid such problems, but at the expense of having only model-based exposure estimates that use databases of measurements.

Epidemiological evidence of increased risks for childhood leukaemia from magnetic fields has implicated, as one source of such fields, high-voltage overhead lines. Magnetic fields are not the only factor that varies in their vicinity, complicating interpretation of any associations. Underground cables (UGCs), however, produce magnetic fields but have no other discernible effects in their vicinity. We report here the largest ever epidemiological study of high voltage UGCs, based on 52,525 cases occurring from 1962-2008, with matched birth controls. We calculated the distance of the mother's address at child's birth to the closest 275 or 400 kV ac or high-voltage dc UGC in England and Wales and the resulting magnetic fields. Few people are exposed to magnetic fields from UGCs limiting the statistical power. We found no indications of an association of risk with distance or of trend in risk with increasing magnetic field for leukaemia, and no convincing pattern of risks for any other cancer. Trend estimates for leukaemia as shown by the odds ratio (and 95% confidence interval) per unit increase in exposure were: reciprocal of distance 0.99 (0.95-1.03), magnetic field 1.01 (0.76-1.33). The absence of risk detected in relation to UGCs tends to add to the argument that any risks from overhead lines may not be caused by magnetic fields.

Background: High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers., Methods: We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity., Results: Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours., Conclusions: Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

In the UK, the location of an address, necessary for calculating the distance to overhead power lines in epidemiological studies, is available from different sources. We assess the accuracy of each. The grid reference specific to each address, provided by the Ordnance Survey product Address-Point, is generally accurate to a few metres, which will usually be sufficient for calculating magnetic fields from the power lines. The grid reference derived from the postcode rather than the individual address is generally accurate to tens of metres, and may be acceptable for assessing effects that vary in the general proximity of the power line, but is probably not acceptable for assessing magnetic-field effects.

We previously reported an association between childhood leukaemia in Britain and proximity of the child's address at birth to high-voltage power lines that declines from the 1960s to the 2000s. We test here whether a 'corona-ion hypothesis' could explain these results. This hypothesis proposes that corona ions, atmospheric ions produced by power lines and blown away from them by the wind, increase the retention of airborne pollutants in the airways when breathed in and hence cause disease. We develop an improved model for calculating exposure to corona ions, using data on winds from meteorological stations and considering the whole length of power line within 600 m of each subject's address. Corona-ion exposure is highly correlated with proximity to power lines, and hence the results parallel the elevations in leukaemia risk seen with distance analyses. But our model explains the observed pattern of leukaemia rates around power lines less well than straightforward distance measurements, and ecological considerations also argue against the hypothesis. This does not disprove the corona-ion hypothesis as the explanation for our previous results, but nor does it provide support for it, or, by extension, any other hypothesis dependent on wind direction.

Background: Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analyses relating to areas close to these nuclear installations by considering data from an additional 16 years of follow-up., Methods: Cross-sectional analyses compared cancer incidence rates for 1963-2006 among those aged 0-24 years at diagnosis living in geographically specified areas around either Sellafield or Dounreay with general population rates. Cancer incidence for the period 1971-2006 among the cohort of Cumbrian births between 1950 and 2006 was compared to national incidence for 1971-2006 using person-years analysis. Cancer among those born in the postcode sector closest to Dounreay was compared with that among those born in the three adjoining postcode sectors. Analyses considered both cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia, central nervous system tumours and other malignancies., Results: Apart from previously reported raised risks, no new significantly increased risks for cancer overall or any diagnostic subgroup were found among children or teenagers and young adults living around either nuclear installation. Individuals born close to the installations from 1950 to 2006 were not shown to be at any increased risk of cancer during the period 1971 to date., Conclusions: Analysis of recent data suggests that children, teenagers and young adults currently living close to Sellafield and Dounreay are not at an increased risk of developing cancer. Equally, there is no evidence of any increased cancer risk later in life among those resident in these areas at birth.

Background: We extend our previous study of childhood leukaemia and proximity to high-voltage powerlines by including more recent data and cases and controls from Scotland, by considering 132-kV powerlines as well as 275 and 400 kV and by looking at greater distances from the powerlines., Methods: Case-control study using 53,515 children from the National Registry of Childhood Tumours 1962-2008, matched controls, and calculated distances of mother's address at child's birth to powerlines at 132, 275, and 400 kV in England, Wales and Scotland., Results: Our previous finding of an excess risk for leukaemia at distances out to 600 m declines over time. Relative risk and 95% confidence interval for leukaemia, 0-199 m compared with>1000 m, all voltages: 1960s 4.50 (0.97-20.83), 2000s 0.71 (0.49-1.03), aggregate over whole period 1.12 (0.90-1.38). Increased risk, albeit less strong, may also be present for 132-kV lines. Increased risk does not extend beyond 600 m for lines of any voltage., Conclusions: A risk declining over time is unlikely to arise from any physical effect of the powerlines and is more likely to be the result of changing population characteristics among those living near powerlines.

A small proportion of childhood cancer is attributable to known hereditary syndromes, but whether there is any familial component to the remainder remains uncertain. We explored familial aggregation of cancer in a population-based case-control study using genealogical record linkage and designed to overcome limitations of previous studies. Subjects were selected from the Utah Population Database. We compared risk of cancer in adult first-degree relatives of children who were diagnosed with cancer with the risk in relatives of children who had not had a cancer diagnosed. We identified 1,894 childhood cancer cases and 3,788 controls; 7,467 relatives of cases and 14,498 relatives of controls were included in the analysis. Relatives of children with cancer had a higher risk of cancer in adulthood than relatives of children without cancer [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.11-1.56]; this was restricted to mothers and siblings and was not evident in fathers. Familial aggregation appeared stronger among relatives of cases diagnosed before 5 years of age (OR 1.48, 95% CI 1.13-1.95) than among relatives of cases who were older when diagnosed (OR 1.22, 95% CI 0.98-1.51). These findings provide evidence of a generalized excess of cancer in the mothers and siblings of children with cancer. The tendency for risk to be higher in the relatives of children who were younger at cancer diagnosis should be investigated in other large data sets. The excesses of thyroid cancer in parents of children with cancer and of any cancer in relatives of children with leukemia merit further investigation., (Copyright © 2013 UICC.)

Background: Accurate population-based data are needed on the incidence of cancer in children born after assisted conception., Methods: We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility., Results: The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight., Conclusions: There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).

Background: Retinoblastoma is an eye tumour of childhood that occurs in heritable and non-heritable forms. In the heritable form, there is a predisposition to the development of non-ocular subsequent primary tumours (SPTs)., Methods: This study included 1927 retinoblastoma patients diagnosed in Britain from 1951 to 2004. Ascertainment was through the (UK) National Registry of Childhood Tumours; cases were followed-up for the occurrence of SPTs. Standardised incidence ratios (SIRs) were calculated., Results: We identified 169 SPTs in 152 patients. The SIR analysis included 145 SPTs with cancer registrations from the years 1971 to 2009. These tumours occurred in 132 patients: 112 of the 781 heritable and 20 of the 1075 (presumed) non-heritable cases under surveillance at the start of this period developed at least one registered SPT. The SIRs for all tumours combined were 13.7 (95% confidence interval 11.3-16.5) in heritable cases and 1.5 (0.9-2.3) in non-heritable cases. The main types of SPT in the heritable cases were leiomyosarcoma, (31 cases; SIR 1018.7 (692.2-1446.0)), osteosarcoma (26 cases; SIR 444.6 (290.4-651.4)), and skin melanoma (12 cases; SIR 18.6 (9.6-32.4))., Conclusion: The risk of SPTs in heritable retinoblastoma is extremely high. This has important implications for the clinical follow-up and counselling of survivors and their families.

Background: Paternal occupational exposures have been proposed as a risk factor for childhood central nervous system (CNS) tumours. This study investigates possible associations between paternal occupational exposure and childhood CNS tumours in Great Britain., Methods: The National Registry of Childhood Tumours provided all cases of childhood CNS tumours born and diagnosed in Great Britain from 1962 to 2006. Controls without cancer were matched on sex, period of birth and birth registration sub-district. Fathers' occupations were assigned to one or more of 33 exposure groups. A measure of social class was also derived from father's occupation at the time of the child's birth., Results: Of 11 119 cases of CNS tumours, 5 722 (51%) were astrocytomas or other gliomas, 2 286 (21%) were embryonal and 985 (9%) were ependymomas. There was an increased risk for CNS tumours overall with exposure to animals, odds ratio (OR) 1.40 (95% confidence intervals (CIs) 1.01, 1.94) and, after adjustment for occupational social class (OSC), with exposure to lead, OR 1.18 (1.01, 1.39). Exposure to metal-working oil mists was associated with reduced risk of CNS tumours, both before and after adjustment for OSC, OR 0.87 (0.75, 0.99).Risk of ependymomas was raised for exposure to solvents, OR 1.73 (1.02,2.92). For astrocytomas and other gliomas, risk was raised with high social contact, although this was only statistically significant before adjustment for OSC, OR 1.15 (1.01,1.31). Exposure to paints and metals appeared to reduce the risk of astrocytomas and embryonal tumours, respectively. However, as these results were the result of a number of statistical tests, it is possible they were generated by chance.Higher social class was a risk factor for all CNS tumours, OR 0.97 (0.95, 0.99). This was driven by increased risk for higher social classes within the major subtype astrocytoma, OR 0.95 (0.91, 0.98)., Conclusion: Our results provide little evidence that paternal occupation is a significant risk factor for childhood CNS tumours, either overall or for specific subtypes. However, these analyses suggest that OSC of the father may be associated with risk of some childhood CNS cancers.

We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.

Background: Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain., Methods: The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth., Results: A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes., Conclusion: Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.

Leukemias and lymphomas account for nearly half of all childhood cancers. Although there have been major advances in the treatment of these diseases, what causes them remains largely unknown. There is strong evidence to suggest that leukemia originates in utero, and early life factors may play a role in its etiology. A series of reports illustrate a convincing link between the rate of intrauterine growth and the risk of childhood leukemia. Some studies suggest that this risk relationship also extends to non-Hodgkin lymphoma in children, although, overall, the association with childhood lymphoma is less clear. This review discusses the intricacies of these risk relationships and explores potential explanations of how the rate of fetal growth may influence cancer risk.

Background: High birth weight increases the risk of childhood acute lymphoid leukemia (ALL) through unknown mechanisms. Whether this risk is specific to ALL subtypes is unknown, and low case numbers have prevented investigation of the rarer leukemias. Here we address these associations using a large population-based dataset., Procedure: Using the National Registry of Childhood Tumors, birth weights of 7,826 leukemia cases, defined by immunophenotype and cytogenetic subgroup, were compared with those of 10,785 controls born in England and Wales between 1980 and 2007., Results: The risk for overall leukemia increases 7% with each 0.5 kg increase in birth weight (OR 1.07, 95%CI 1.04-1.10). This risk is limited to the lymphoid leukemias (OR 1.08, 95%CI 1.05-1.12) diagnosed between 1 and 9 years of age. Analysis by cytogenetic feature reveals that there appears to be association with specific chromosomal abnormality: the risk of tumors with high hyperdiploid karyotypes increases 12% per 0.5 kg increase in birth weight (OR 1.12, 95%CI 1.05-1.20), and t(1;19) tumors show an increased risk of 41% per 0.5 kg increase (OR 1.41, 95%CI 1.09-1.84). The risk of acute myeloid leukemia is elevated in high and low birth weight babies. There is no significant risk relationship to other leukemias or myeloproliferative diseases., Conclusions: Birth weight is a risk factor for ALL and AML. Other subtypes of the disease are not significantly affected. There appears to be association with specific chromosomal abnormality, which may aid our understanding of the development of childhood leukemia in utero., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Neuroblastoma is the most common malignancy of infancy but little is known about the aetiological factors associated with the development of this tumour. A number of epidemiological studies have previously examined the risk associated with paternal occupational exposures but most have involved small numbers of cases. Here we present results from a large, population-based, case-control study of subjects diagnosed over a period of more than 30 years and recorded in the national registry of childhood tumours in Great Britain., Methods: A case-control study of paternal occupational data for 2920 cases of neuroblastoma, born and diagnosed in Great Britain between 1962 and 1999 and recorded in the National Registry of Childhood Tumours, and 2920 controls from the general population matched on sex, date of birth and birth registration district. Paternal occupations at birth, of the case or control child, were grouped by inferred exposure using an occupational exposure classification scheme. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), for each of the 32 paternal occupational exposure groups., Results: Only paternal occupational exposure to leather was statistically significantly associated with neuroblastoma, OR=5.00 (95% CI 1.07-46.93). However, this association became non-significant on correction for multiple testing., Conclusion: Our findings do not support the hypothesis that paternal occupational exposure is an important aetiological factor for neuroblastoma.

Objectives: To examine the association between paternal occupational exposures and retinoblastoma using birth registration data for cases from the National Registry of Childhood Tumours (NRCT) and controls from the general population of Great Britain., Methods: A case-control study of paternal occupational data for 1318 cases of retinoblastoma, born and diagnosed in Great Britain between 1962 and 1999, and 1318 controls matched on sex, date of birth and birth registration sub-district. Paternal occupations at birth were grouped according to inferred exposure using an occupational exposure classification scheme. A conditional (matched) case-control analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for each paternal occupational exposure group., Results: For non-heritable retinoblastoma, a statistically significant increased risk was found with father's definite occupational exposure to oil mists in metal working (OR = 1.85 (95% CI 1.05 to 3.36)). Together with a (non-significant) risk (OR = 1.64 (0.73 to 3.83)) amongst the heritable cases, this occupational exposure was also associated with a significant increased risk when all retinoblastoma cases were considered together (OR = 1.77 (1.12 to 2.85)). No statistically significant associations were observed for other exposure groups., Conclusions: Our finding for exposure to oil mists in metal working (a subset of metal workers) is not directly comparable to those for metal working previously reported in the literature. Overall, our findings do not support the hypothesis that paternal occupational exposure is an important aetiological factor for retinoblastoma, however, the study has low power and other methodological limitations.

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the child's conception may be at an increased risk of childhood cancer. An additional 16,964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52,612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.

Background: Several small studies combined have suggested that twins develop fewer childhood cancers than singletons. The national Swedish Family-Cancer Database contains information on a large population of multiple births providing an unbiased dataset for the estimation of cancer risk in twins. Lifelong cancer incidence in these twins has already been reported as similar to that in singleton births. In contrast, the present paper presents robust estimates of a significantly reduced childhood cancer risk in twins to age 15., Methods: Standardised incidence ratios (SIR) were used to measure cancer risk for twins, taking the corresponding rates for singletons as reference. Rates were adjusted for age, sex, period of birth, and residential area. Follow up data cover the period 1958-2002., Results: Overall childhood cancer risk was significantly reduced in all twins (SIR 0.81 [95% CI: 0.69-0.94]) as was the risk for Wilms tumour (SIR 0.34 [95% CI: 0.09-0.88]). These significant reductions in risk were both driven by effects in same sex twins (overall cancer SIR 0.77 [95% CI: 0.64-0.93], Wilms tumour 0.12 [95% CI: 0.00-0.71]). Leukaemia risk was also significantly reduced for same sex twins (SIR 0.69 [95% CI: 0.47-0.97])., Conclusions: Our study provides the evidence that twins experience less childhood cancer than singletons. The risk reduction is most marked for Wilms tumour but may, to a varying extent, be true for a number of childhood neoplasms., ((c) 2008 Wiley-Liss, Inc.)