Pat Ansell

Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study

Objective To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days). Design Case-control study. Setting England and Wales. Participants 2690 childhood cancer cases and 4858 age, sex, and region matched controls from the United Kingdom Childhood Cancer Study (UKCCS), born 1976-96. Main outcome measures Risk of all childhood cancer, leukaemia, lymphoma, and central nervous system tumours, measured by odds ratios. Results Logistic regression models conditioned on matching factors, with adjustment for maternal age and child’s birth weight, showed no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. Some indication existed of a slight increase in risk after in utero exposure to x rays for all cancers (odds ratio 1.l4, 95% confidence interval 0.90 to 1.45) and leukaemia (1.36, 0.91 to 2.02), but this was not statistically significant. Exposure to diagnostic x rays in early infancy (0-100 days) was associated with small, non-significant excess risks for all cancers and leukaemia, as well as increased risk of lymphoma (odds ratio 5.14, 1.27 to 20.78) on the basis of small numbers. Conclusions Although the results for lymphoma need to be replicated, all of the findings indicate possible risks of cancer from radiation at doses lower than those associated with commonly used procedures such as computed tomography scans, suggesting the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages.

Malignant neoplasms of the brain during childhood: the role of prenatal and neonatal factors (United Kingdom)

AbstractObjectives: To evaluate whether factors in pregnancy and around birth influence the risk of childhood malignant neoplasms of the brain or other parts of the nervous system. Methods: The distribution of certain characteristics of pregnancy and birth among 83 cases of malignant neoplasms of the brain and other parts of the nervous system (diagnosed between 0 and 14 years of age) and 166 controls (individually matched on date of birth, sex, and hospital of birth) were compared. Odds ratios (OR), 95% confidence intervals (95% CI) and two-sided p-values were calculated using conditional logistic regression for matched sets. Results: Children whose mothers had documented evidence of a clinically diagnosed viral infection during pregnancy had an approximately 11-fold increase in risk of developing a malignant neoplasm of the brain or other part of the nervous system (OR = 10.6, 95% CI = 1.1–503.2). In addition, non-statistically significant increased risks were observed among children who had a non-cephalic presentation (OR = 3.3, 95% CI = 0.8–13.9) or a low 1-minute apgar score (OR = 2.7, 95% CI = 1.0–7.4). No other aspects of the index pregnancy, delivery, or maternal characteristics were associated with an increased risk of childhood brain tumors. Conclusions: The results reported here provide limited evidence for the role of prenatal and neonatal factors in the etiology of childhood malignant neoplasms of the brain. The finding for maternal viral infection during pregnancy warrants further investigation.

Health of children born to medical radiographers

OBJECTIVES: To develop a reliable method for collecting information on reproductive outcome in an occupational setting; and to investigate the health of children born to medical radiographers. METHODS: The study population comprised 6730 members of the College of Radiographers who were, at the time of survey; aged between 30 and 64 years, on the current membership file of the College, and were resident in Britain. RESULTS: The postal method developed proved to be reliable, with around 87% of questionnaires being returned. The observed frequencies of reproductive events were broadly in line with findings from other studies: of the 9208 pregnancies reported, 83% were livebirths, 12% were miscarriages (gestational age < 20 weeks), 1% were stillbirths (gestational age > or = 20 weeks), and 1% were other rarer spontaneous adverse events (ectopic pregnancy, blighted ovum, and hydatidiform mole). There was little difference between men and women in the frequency of adverse reproductive events reported, with the exception that male radiographers reported fewer medical terminations, the proportions being 3.1% and 1.4% for women and men respectively. Among children, the overall risks of major congenital malformation (RR 1.0, 95%CI 0.9-1.2), chromosomal anomaly (RR 1.4, 95%CI 0.8-2.3), and cancer (RR 1.2 95%CI 0.7-2.0) were as expected based on general population rates. Borderline excesses of chromosomal anomalies other than Downs syndrome in the children of female radiographers (RR 3.9, 95%CI 1.3-9.0, based on five observations), and cancer in the children of male radiographers (RR 2.7, 95%CI 0.9-6.5, based on five observations) were noted. The numbers on which these risks are based are small and the findings should be interpreted cautiously. CONCLUSIONS: The postal methods developed for obtaining information about reproductive events and child health proved to be reliable in men, as well as in women. Overall, the findings for medical radiographers are reassuring. Dose-response relations could not, however, be examined as long term dose records of radiographers are not routinely kept in an accessible form.

Vitamin K and childhood cancer: analysis of individual patient data from six case–control studies

To investigate the hypothesis that neonates who receive intramuscular vitamin K are at an increased risk of developing cancer, particularly leukaemia, a pooled analysis of individual patient data from six case–control studies conducted in Great Britain and Germany has been undertaken. Subjects comprised 2431 case children diagnosed with cancer before 15 years of age and 6338 control children. The retrospective assessment of whether or not an individual baby received vitamin K is not straightforward. In many cases no record was found in stored medical notes and two types of analysis were therefore conducted; in the first it was assumed that where no written record of vitamin K was found it had not been given, and in the second, where no written record of administration was found, information on hospital policy and perinatal morbidity was used to ‘impute’ whether or not vitamin K had been given. In the first analysis, no association was found between neonatal administration of intramuscular. vitamin K and childhood cancer: odds ratios adjusted for mode of delivery, admission to special care baby unit and low birth weight were 1.09 (95% confidence interval 0.92–1.28) for leukaemia and 1.05 (0.92–1.20) for other cancers. In the second analysis, the adjusted odds ratios increased to 1.21 (1.02–1.44) for leukaemia and 1.10 (0.95–1.26) for other cancers. This shift did not occur in all studies, and when data from the hypothesis generating Bristol study were excluded, the adjusted odds ratios for leukaemia became 1.06 (0.89–1.25) in the first analysis and 1.16 (0.97–1.39) when data on prophylaxis imputed from hospital policy and perinatal morbidity were used. We conclude that whilst the broad nature of the diagnostic groups and the poor quality of some of the vitamin K data mean that small effects cannot be entirely ruled out, our analysis provides no convincing evidence that intramuscular vitamin K is associated with childhood leukaemia.

Allergy and risk of childhood leukaemia : Results from the UKCCS

We investigated the relationship between childhood leukaemia and preceding history of allergy. A nationwide case–control study of childhood cancers was conducted in the United Kingdom with population‐based sampling of cases (n = 839) and controls (n = 1,337), matched on age, sex and region of residence. Information about clinically diagnosed allergies was obtained from primary care records. More than a third of subjects had at least one allergy diagnosed prior to leukaemia diagnosis (cases) or pseudo‐diagnosis (controls). For both total acute lymphoblastic leukaemia (ALL) and common‐ALL/precursor B‐cell ALL (c‐ALL), a history of eczema was associated with a 30% significant reduction in risk: the odds ratios (OR) and 95% confidence intervals (CI) were 0.70 (0.51–0.97) and 0.68 (0.48–0.98), respectively. Similar associations were observed for hayfever (OR = 0.47; 95% CI: 0.26–0.85 and OR = 0.62; 95% CI: 0.33–1.16 for ALL and c‐ALL, respectively). No such patterns were seen either for asthma and ALL, or for any allergy and acute myeloid leukaemia. A comparative analysis of primary care records with parents recall of allergy revealed only moderate agreement with contemporaneous clinical diagnoses for both cases and controls—confirming the unreliability of parental report at interview. Our finding of a reciprocal relationship between allergy and ALL in children is compatible with the hypothesis that a dysregulated immune response is a critical determinant of childhood ALL.

Vitamin K and childhood cancer: a report from the United Kingdom Childhood Cancer Study

The relationship between neonatal vitamin K received by the intramuscular (i.m.) route and the development of leukaemia or other cancers was investigated as part of a national case–control study of childhood cancer, using data abstracted from obstetric and neonatal records. The analyses included 2530 children diagnosed with cancer before 15 years of age, 1174 of whom had leukaemia and 4487 control children without cancer. Overall, 39% of cases and 42% of controls had records of i.m. vitamin K administration, while 24% of cases and 22% of controls had no record of whether or not they had received vitamin K. Using subjects who received i.m. vitamin K as the baseline group, our analyses found no association between the administration of i.m. vitamin K and either leukaemia or other cancers as a group. We conclude that there is no convincing evidence that neonatal vitamin K administration, irrespective of the route by which it is given, influences the risk of children developing leukaemia or any other cancer.

Survival from childhood acute lymphoblastic leukaemia: the impact of social inequality in the United Kingdom

BACKGROUND Survival from childhood acute lymphoblastic leukaemia (ALL) has continued to improve in economically-developed regions of the world, but 20% of patients still die within 5-years of diagnosis. Treatment is prolonged and complex; and as survival rates plateau, factors relating to socio-economic status and/or treatment adherence are increasingly scrutinised as potentially important determinants of outcome. METHODS Predicated on the frame-work of the United Kingdom (UK) NHS, the relationship between socio-demographic factors and ALL survival is examined here using data from a large follow-up study conducted in the 1990s. One thousand five hundred and fifty nine children (0-14 years) diagnosed in England, Scotland &Wales during the era of the national UKALL XI randomized-controlled trial (RCT) were followed-up for an average of 15.9 years (20,826.3 person-years). Area-based deprivation scores and fathers occupational social class at the time of the childs birth were used as markers of socio-economic status. Information on deaths was obtained from the NHS Information Centre for Health and Social Care. All children were included in the analyses, irrespective of RCT enrolment or participation in the founding epidemiological study (www.UKCCS.org).Survival effects were assessed using proportional hazards regressions models. RESULTS Survival varied with both area-based deprivation at diagnosis (hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.05-1.57) and fathers occupational social class at birth (HR 1.12; 95% CI 0.97-1.29); the divergence beginning 6-9 months after diagnosis, and widening thereafter during home-administered therapy. The findings became more marked when analyses were restricted to those enrolled in UKALL XI (n = 1341). As expected, survival differences were also observed with sex, and age at diagnosis. CONCLUSION The existence of significant social disparities in ALL survival, which are not due to treatment accessibility, is of major clinical importance. Trends should be monitored and further research into potentially modifiable risk factors conducted.

Infectious Illness in Children Subsequently Diagnosed With Acute Lymphoblastic Leukemia: Modeling the Trends From Birth to Diagnosis

Although there is increasing evidence that immune dysregulation in children who develop acute lymphoblastic leukemia (ALL) is detectable from birth, debate about the role of infectious exposures in infancy continues. With the aim of quantifying childrens infectious exposures, investigators have used a number of infection exposure proxies, but there is a lack of consistency in findings, with some markers indicating increased ALL risks and others decreased risks, the disparity being evident both within and between studies. Accordingly, the authors conducted an in-depth analysis of key infection exposure proxies used in the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted over the period 1991-1996, which combined data from medical records, parental interview, and population census. This longitudinal approach revealed the marked deterioration in immune response that emerged around 5 months prior to ALL diagnosis and confirmed that infectious diagnoses in the first year of life were significantly increased (P < 0.05) in children who developed leukemia between 2 and 14 years of age, as well as in those who had birth orders >1, were not breastfed, lived in deprived areas, or were diagnosed with eczema. By contrast, no association between infectious illness and preschool activity was detected, the lower infection levels among controls whose mothers reported attendance contributing to a significantly reduced ALL odds ratio.

Investigation of the sources of residential power frequency magnetic field exposure in the UK Childhood Cancer Study.

There is an unexplained association between exposure to the magnetic fields arising from the supply and use of electricity, and increase in risk of childhood leukaemia. The UK Childhood Cancer Study (UKCCS) provides a large and unique source of information on residential magnetic field exposure in the UK. The purpose of this supplementary study was to investigate a sample of UKCCS homes in order to identify the particular sources that contribute to elevated time-averaged exposure. In all, 196 homes have been investigated, 102 with exposures estimated on the basis of the original study to be above 0.2 microT, and 21 higher than 0.4 microT, a threshold above which a raised risk has been observed. First, surveys were carried out outside the property boundaries of all 196 study homes, and then, where informed consent had been obtained, assessments were conducted inside the properties of 19 homes. The study found that low-voltage (LV) sources associated with the final electricity supply accounted together for 77% of exposures above 0.2 microT, and 57% of those above 0.4 microT. Most of these exposures were linked to net currents in circuits inside and/or around the home. High-voltage (HV) sources, including the HV overhead power lines that are the focus of public concern, accounted for 23% of the exposures above 0.2 microT, and 43% of those above 0.4 microT. Public health interest has focused on the consideration of precautionary measures that would reduce exposure to power frequency magnetic fields. Our study provides a basis for considering the options for exposure mitigation in the UK. For instance, in elevated-exposure homes where net currents are higher than usual, if it is possible to reduce the net currents, then the exposure could be reduced for a sizeable proportion of these homes. Further investigations would be necessary to determine whether this is feasible.

Brain Tumor Signs and Symptoms: Analysis of Primary Health Care Records From the UKCCS

OBJECTIVE: To compare the frequency of brain tumor signs and symptoms in children with and without brain tumors. METHODS: This was a UK population-based retrospective analysis of primary care records. Participants were 195 children (1–14 years) newly diagnosed with brain tumors and 285 controls matched by age, gender, and region. Comparisons included total number of prediagnosis consultations, number with ≥1 symptom suggestive of a brain tumor, total number of symptoms, number of different symptoms, and number of visits with specific combinations of symptoms. RESULTS: On average, cases consulted more often than controls between birth and diagnosis/pseudodiagnosis with brain tumor signs and symptoms. Their consultation rate with ≥1 suggestive symptom escalated in the 2 years before diagnosis. Symptom prevalence was higher among cases than controls, a relative difference of 3.29 times as many consultations with ≥1 suggestive symptom (95% confidence interval [CI]: 2.82–3.83) and 7.01 as many with more than 1 (95% CI: 5.38–9.13). In each 6-month period in the 4 years before diagnosis, cases had at least twice as many consultations with ≥1 suggestive symptom (20.81 times as many in the 6 months before diagnosis [95% CI: 14.29–30.30]) and 2–3 times more records of suggestive symptoms (28.35 times more in the 6 months before diagnosis [95% CI: 19.05–42.19]). Symptoms rarely or not observed among control children included head tilt, odd head movements, odd posture, back or neck stiffness, and unsteadiness without obvious cause. CONCLUSION Key to identifying the 1 child among many who merits prompt investigation is recognition of unusual symptoms, or specific symptom patterns.