Wartime evacuation and mortality from childhood leukaemia in England and Wales in 1945-9.

OBJECTIVE--To discover whether the wartime government evacuation of children from London and other population centres to rural districts was associated with any increase in childhood leukaemia. DESIGN--Observational study of mortality from leukaemia among the childhood population of England and Wales in relation to the unique population movements during the second world war. The 476 rural districts of England and Wales were ranked according to the ratio of government evacuees (two thirds of them children) to local children in September 1941. The districts were divided into three categories, each with similar numbers of children in 1947 but with different ratios of evacuees to local children ("low," "intermediate," "high"). Mortality from childhood leukaemia was examined in these three rural categories in 1945-9. Urban areas were also examined according to their exposure to evacuees. SETTING--Local authority areas of England and Wales. SUBJECTS--Children aged under 15. RESULTS--47% excess of leukaemia at ages 0-14 years occurred in 1945-9 in the rural "high" category for evacuees relative to the "low" category, with a significant trend across the three categories. There were increases in both the 0-4 and 5-14 year age groups, but these were larger in the older age group. Rates 25% lower than average occurred in rural areas with few evacuees. CONCLUSION--These findings suggest that wartime evacuation increased the incidence of childhood leukaemia in rural areas and that other forms of population mixing may have contributed to the increases in past decades. Overall, they add to the appreciable evidence for an infective basis in childhood leukaemia.     

Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland,including the area near Dounreay nuclear site.

OBJECTIVE--To determine if any excess of childhood leukaemia and non-Hodgkin''s lymphoma was associated with certain striking examples of population mixing in rural Scotland produced by the North Sea oil industry. DESIGN--Details were traced for over 30,000 workers involved in the construction of the large oil terminals in the Shetland and Orkney islands in northern Scotland or employed offshore. Home addresses of the 17,160 Scottish residents were postcoded, integrated with census data, and then classified as urban or rural. Rural postcode sectors, ranked by proportion of oil workers, were grouped into three categories with similar numbers of children but contrasting densities of oil workers. The incidence of leukaemia and non-Hodgkin''s lymphoma was examined in these rural (and also in urban) categories in the periods 1974-8, 1979-83 and 1984-8. SETTING--Scotland. SUBJECTS--Young people below age 25. RESULTS--A significant excess of leukaemia and non-Hodgkin''s lymphoma was found in 1979-83 in the group of rural home areas with the largest proportion of oil workers, following closely on large increases in the workforce. The area near the Dounreay nuclear installation, where an excess of leukaemia is already well known, was within the rural high oil category. CONCLUSION--The findings support the infection hypothesis that population mixing can increase the incidence of childhood leukaemia in rural areas. They also suggest that the recent excess in the Dounreay-Thurso area is due to population mixing linked to the oil industry, promoted by certain unusual local demographic factors.     

Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

OBJECTIVE--To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father''s testes shortly before conception. DESIGN--Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING--Nordic countries. SUBJECTS--Children aged under 15 years. MAIN OUTCOME MEASURES--Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS--During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS--Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures.     

Fallout from Chernobyl and incidence of childhood leukaemia in Finland, 1976-92.

OBJECTIVE--To assess effects of fallout from Chernobyl on incidence of childhood leukaemia in Finland. DESIGN--Nationwide cohort study. External exposure measured for 455 Finnish municipalities with instruments driven 19,000 km throughout the country. Values specific to municipalities corrected for shielding due to houses and fallout from A bomb testing. Internal exposure estimated from whole body measurements on a random sample of 81 children. Mean effective dose for two years after incident calculated from these measurements. Data on childhood leukaemia obtained from Finnish cancer registry and verified through hospitals treating childhood cancers. SETTING--Finland, one of the countries most heavily contaminated by the Chernobyl accident; the population was divided into fifths by exposure. SUBJECTS--Children aged 0-14 years in 1976-92. MAIN OUTCOME MEASURES--Standardised incidence ratio of childhood leukaemia and relative excess risk of childhood leukaemia per mSv. From incidence data of Finnish cancer registry for 1976-85, expected numbers specific to sex and age group (0-4, 5-9, and 10-14 years) were calculated for each municipality for three periods (1976-85, 1986-8, and 1989-92) and pooled as exposure fifths. Dose response was estimated as regression slope of standardised incidence ratios on mean doses for fifths for each period. RESULTS--Population weighted mean effective doses for first two years after the accident were 410 microSv for the whole country and 970 microSv for the population fifth with the highest dose. In all Finland the incidence of childhood leukaemia did not increase 1976-92. The relative excess risk 1989-92 was not significantly different from zero (7% per mSv; 95% confidence interval -27% to 41%). CONCLUSIONS--An important increase in childhood leukaemia can be excluded. Any effect is smaller than eight extra cases per million children per year in Finland. The results are consistent with the magnitude of effect expected.     

Survival and the HL-A System in Acute Lymphoblastic Leukaemia

The relation between the HL-A antigens and survival has been studied in 58 patients with acute lymphoblastic leukaemia. Patients with the HL-A9 antigen had the best estimated median survival times, the highest ratio of survivors to non-survivors, and the lowest median age at diagnosis. The data suggest that resistance to acute lymphoblastic leukaemia may be associated with the HL-A9 antigen.     

Childhood leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities in relation to nuclear establishments in the vicinity.

During the years 1972-85, 89 children aged 0-14 were registered with leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities. Two nuclear establishments are located within the health authorities, and a third is situated nearby. Fifty of the 143 electoral wards in the two district health authorities lie wholly within, or have at least half their area lying within, a circle of radius 10 km around the establishments. In those 50 electoral wards 41 children aged 0-14 were registered with leukaemia, 28.6 registrations being expected on the basis of leukaemia registration rates in England and Wales (incidence ratio = 1.4, p less than 0.05). This excess was confined to children aged 0-4, among whom there were 29 registrations of leukaemia, 14.4 being expected (incidence ratio = 2.0, p less than 0.001). In the remaining 93 electoral wards there was a small and non-significant increase in the number of registrations of leukaemia at age 0-14 (48 observed, 40.8 expected; incidence ratio = 1.2). There was no obvious trend in the incidence of childhood leukaemia over the 14 years and the overall occurrence of the malignancy in the 143 electoral wards was consistent with a random distribution. In the surrounding Oxford and Wessex Regional Health Authorities the number of registrations of leukaemia at age 0-14 was virtually identical with that expected on the basis of registration rates in England and Wales (362 observed, 372.5 expected; incidence ratio = 1.0). These data indicate that in the two district health authorities studied there was an excess incidence of childhood leukaemia during 1972-85 in the vicinity of the nuclear establishments. In the West Berkshire and Basingstoke and North Hampshire District Health Authorities an average of 60,000 children aged 0-14 lived within a 10 km radius of a nuclear establishment each year. The normal expectation of leukaemia in these children was two cases a year, whereas the recorded incidence was three cases per year, representing one extra case of leukaemia each year among these 60,000 children.     

Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction sites,with a comparison with Sellafield nuclear site.

OBJECTIVE--To determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin''s lymphoma. DESIGN--A study of the incidence of leukaemia and non-Hodgkin''s lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. For periods before 1962 mortality was studied. SETTING--Areas within 10 km of relevant sites, and the highland counties of Scotland with many hydroelectric schemes. SUBJECTS--Children aged under 15. RESULTS--A 37% excess of leukaemia and non-Hodgkin''s lymphoma at 0-14 years of age was recorded during construction and the following calendar year. The excesses were greater at times when construction workers and operating staff overlapped (72%), particularly in areas of relatively high social class. For several sites the excesses were similar to or greater than that near the nuclear site of Sellafield (67%), which is distinctive in its large workforce with many construction workers. Seascale, near Sellafield, with a ninefold increase had an unusually high proportion of residents in social class I. The only study parish of comparable social class also showed a significant excess, with a confidence interval that included the Seascale excess. CONCLUSION--The findings support the infection hypothesis and reinforce the view that the excess of childhood leukaemia and non-Hodgkin''s lymphoma near Sellafield has a similar explanation.     

Risk of acute childhood leukaemia in Sweden after the Chernobyl reactor accident. Swedish Child Leukaemia Group.

OBJECTIVE--To evaluate the risk of acute childhood leukaemia in areas of Sweden contaminated after the Chernobyl reactor accident in April 1986. DESIGN--Population based study of childhood leukaemia diagnosed during 1980-92. SETTING--Coordinates for places of residence of all 1.6 million children aged 0-15 years; aerial mapped areas of Sweden heavily contaminated after the Chernobyl accident. SUBJECTS--888 children aged 0-15 years with acute leukaemia diagnosed in Sweden during 1980-92, identified with place of birth and residence at diagnosis. MAIN OUTCOME MEASURES--Risk of leukaemia in areas contaminated after the Chernobyl accident compared with the rest of Sweden and in the same areas before the accident. RESULTS--During six and a half years of follow up after the accident the odds ratio for acute leukaemia was 0.9 (95% confidence interval 0.6 to 1.4) in highly contaminated areas (> or = 10 kBq/m2) compared with the same areas before the accident. For the subgroup acute lymphoblastic leukaemia in children aged under 5 years at diagnosis the odds ratio was 1.5 (0.8 to 2.6). For all cases diagnosed after May 1986 in highly contaminated areas compared with areas of low contamination the odds ratio was 0.9 (0.7 to 1.3). For acute lymphoblastic leukaemia in children aged under 5 years at diagnosis the odds ratio was 1.2 (0.8 to 1.9) in highly contaminated areas compared with areas of low contamination. Dose-response analysis showed no correlation between the degree of contamination and the incidence of childhood leukaemia. CONCLUSION--There has been no significant increase in the incidence of acute childhood leukaemia in areas of Sweden contaminated after the Chernobyl reactor accident.     

Testicular disease in acute lymphoblastic leukaemia in childhood. Report on behalf of the Medical Research Council's Working Party on leukaemia in childhood.

In three trials conducted by the Medical Research Council on acute lymphoblastic leukaemia in childhood the incidence of testicular infiltration in relation to presenting features and treatment was analysed. Initial severe thrombocytopenia was associated with an increased incidence. Testicular infiltration was occasionally found during treatment in patients with high blood leucocyte counts at diagnosis but the main incidence in patients with all types of disease occurred within one year of stopping treatment. The incidence may be increased when "second-line" drugs, especially cyclophosphamide, have been used. A reappraisal of the value of additional drugs in maintenance treatment of patients with good prognosis is needed.     

Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study.

OBJECTIVE: To explore the possible association between intramuscular vitamin K given to neonates and the subsequent development of childhood cancer. DESIGN: Retrospective case-control study on the basis of hospital records. SETTING: The former Northern Health region of England. SUBJECTS: 685 children who were born and lived in the region and who developed cancer before their 15th birthday, and 3442 controls also born between 1960 and 1991 and matched only for date and hospital of birth. The notes of a further 701 index cases were untraceable. MAIN EXPOSURE MEASURE: Administration of intramuscular vitamin K versus no exposure to vitamin K. RESULTS: There was no association between the administration of vitamin K and the development of all childhood cancers (unadjusted odds ratio 0.89; 95% confidence interval 0.69 to 1.15) or for all acute lymphoblastic leukaemia (1.20; 0.75 to 1.92), but there was a raised odds ratio for acute lymphoblastic leukaemia developing 1-6 years after birth (1.79; 1.02 to 3.15). No such association was seen in a separate cohort-based study not dependent on case note retrieval in which the rates of acute lymphoblastic leukaemia in children born in hospital units where all babies received vitamin K were compared with those born in units where less than a third received prophylaxis. CONCLUSIONS: It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal intramuscular vitamin K administration increases the risk of early childhood leukaemia. Any association may have been masked in earlier studies that did not use controls matched for time and locality by other unidentified factors affecting the spatiotemporal variations in incidence of leukaemia.     

Childhood cancer in relation to distance from high voltage power lines in England and Wales: a case-control study

Objective To determine whether there is an association between distance of home address at birth from high voltage power lines and the incidence of leukaemia and other cancers in children in England and Wales.Design Case-control study.Setting Cancer registry and National Grid records.Subjects Records of 29 081 children with cancer, including 9700 with leukaemia. Children were aged 0-14 years and born in England and Wales, 1962-95. Controls were individually matched for sex, approximate date of birth, and birth registration district. No active participation was required.Main outcome measures Distance from home address at birth to the nearest high voltage overhead power line in existence at the time.Results Compared with those who lived > 600 m from a line at birth, children who lived within 200 m had a relative risk of leukaemia of 1.69 (95% confidence interval 1.13 to 2.53); those born between 200 and 600 m had a relative risk of 1.23 (1.02 to 1.49). There was a significant (P < 0.01) trend in risk in relation to the reciprocal of distance from the line. No excess risk in relation to proximity to lines was found for other childhood cancers.Conclusions There is an association between childhood leukaemia and proximity of home address at birth to high voltage power lines, and the apparent risk extends to a greater distance than would have been expected from previous studies. About 4% of children in England and Wales live within 600 m of high voltage lines at birth. If the association is causal, about 1% of childhood leukaemia in England and Wales would be attributable to these lines, though this estimate has considerable statistical uncertainty. There is no accepted biological mechanism to explain the epidemiological results; indeed, the relation may be due to chance or confounding.     

Time trends and seasonal variations in the diagnosis of childhood acute lymphoblastic leukaemia in France

Background: Several studies have evidenced an increase in the incidence of childhood leukaemia since the 1970s but the variations since 2000 have received little attention. Seasonal variations in incidence have also been widely investigated, with however inconsistent conclusions. The present study aimed to investigate jointly the temporal trends and the seasonal variations in the month of diagnosis of childhood acute lymphoblastic leukaemia (ALL). Methods: All the cases of ALL registered in the French National Registry of Childhood Haematological malignancies during 1990–2007 were included in the study. The overall temporal trend and seasonality of ALL were tested with Poisson regression models on 0–14-year-old ALL cases, and specifically on the B-cell precursor ALL (Bcp-ALL) cases. The analyses were also stratified by age groups and gender. Results: Over 1990–2007, a significant time trend in risk of +0.48% (0.02–0.95%) per year for all ALL and +0.85% (0.33–1.37%) for Bcp-ALL was found. The increase was more marked for 7–14-year-old girls with a trend of +2.84% (1.34–4.36%) per year for Bcp-ALL. Seasonal variations were also evidenced for 1–6-year-old boys, with a standardised incidence ratio of 1.11 (1.04–1.18) for Bcp-ALL in April, August and December. Conclusion: The study showed an increase in childhood ALL risk over 1990–2007, which tended to be stronger for 7–14-year-old Bcp-ALL, particularly in girls (about one case per year, on average). However, although in accordance with the log-linear assumption, the increase in risk seemed less marked after 2001. The study also suggested seasonal variations in the month of diagnosis for 1–6-year-old boys.     

Epipodophyllotoxins,alkylating agents,and radiation and risk of secondary leukaemia after childhood cancer.

OBJECTIVE--To investigate the incidence and aetiology of secondary leukaemia after childhood cancer in Britain. DESIGN--Cohort study and a case-control study. SETTING--Britain and population based National Register of Childhood Tumours. SUBJECTS--Cohort of 16,422 one year survivors of childhood cancer diagnosed in Britain between 1962 and 1983, among whom 22 secondary leukaemias were observed. A case-control study of 26 secondary leukaemias observed among survivors of childhood cancer diagnosed in Britain between 1940 and 1983; 96 controls were selected matched for sex, type of first cancer, age at first cancer, and interval to diagnosis of secondary leukaemia. MAIN OUTCOME MEASURES--Dose of radiation averaged over patients'' active bone marrow and total accumulated dose of epipodophyllotoxins, alkylating agents, vinca alkaloids, antimetabolites, and antibiotics (mg/m2) given for the original cancer. RESULTS--Cumulative risk of secondary leukaemia within the cohort did not exceed 0.5% over the initial five years beyond one year survival, except that after non-Hodgkin''s lymphomas 1.4% of patients developed secondary leukaemia. Corresponding figure for patients treated for non-Hodgkin''s lymphomas in the early 1980s was 4%. The relative risk of secondary leukaemia increased significantly with exposure to epipodophyllotoxins and dose of radiation averaged over patients'' active bone marrow. Ten patients developed leukaemia after having an epipodophyllotoxin-teniposide in nine cases, etoposide in one. Chromosomal translocations involving 11q23 were observed relating to two secondary leukaemias from a total of six for which there were successful cytogenetic studies after administration of an epipodophyllotoxin. CONCLUSIONS--Epipodophyllotoxins acting alone or together with alkylating agents or radiation seem to be involved in secondary leukaemia after childhood cancer.     

Capitation funding: population,age, and mortality adjustments for regional and district health authorities in England.

OBJECTIVE--To assess the effect of each of the components of the national capitation funding formula--population projections and age and mortality weighting--at regional and district level. DESIGN--Application of age-cost and mortality weights to the projected 1997 populations of regions and districts, based on the Department of Health public health common dataset. SETTING--Regional and district health authorities in England. RESULTS--The application of the age-cost and mortality weights to projected populations resulted in greater changes in the shares of weighted populations relative to the estimated 1991 population at district level (mean 0, range -17% to 28%) than at regional level (mean 0, range -9% to 6%). At district level mortality weights had less scope for influence (mean 0, range -9% to 14%) than population projections (mean 0, range -16% to 31%) or age weights (mean 0, range -20% to 30%). CONCLUSIONS--The adjustments to the 1991 population shares due to the application of the national capitation funding formula depend on the interaction of three elements: the projected population by age group, the age-cost weight, and the mortality weight. Since each is open to uncertainty, either in terms of measurement (projected population, particularly for births and the over 85s) or method (derivation of the age-cost and mortality weights), the formula should be implemented cautiously at district level. Ways should be considered of incorporating elements of uncertainty into the model. Further research is required on the elements and degree of uncertainty in each of these components, as well as on the relative health needs of different populations.     

Fallout,radiation doses near Dounreay,and childhood leukaemia.

Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by an underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by an underestimate of the relative biological efficiency of high as compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to the dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other possible explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease, and exposure to some other, unidentified environmental agent. These findings weigh heavily against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated.     

Prognostic implications of chromosomal findings in acute lymphoblastic leukaemia at diagnosis.

Chromosomes were studied on diagnostic bone-marrow samples from 39 children with acute lymphoblastic leukaemia (ALL). The patients were classified, according to the chromosomal characteristics of the major proportion of their leukaemia cells, into five categories; hyperdiploid, pseudodiploid, diploid, hypodiploid, and mixed. Patients in the hyperdiploid category had significantly longer first remissions than those in all other categories, and those in the pseudodiploid category had the shortest. Neither the absence of any normal cells nor the presence of detectable clones appeared to be an adverse feature. We suggest that the proportion of hyperdiploid cells, determined by conventional chromosomal staining techniques, may be used as an additional prognostic feature in childhood ALL.     

Infant leukaemias and cot deaths.

Infant leukaemias differ from childhood leukaemias in ways which suggest that when haemopoietic neoplasms combine fetal origins with rapid growth rates they prevent normal development of the reticuloendothelial system and thus cause the sudden death of apparently healthy babies (stillbirths or cot deaths). Cot deaths are commoner in boys and have a peak incidence during the first half of infancy-that is, during the period most affected by the switch from passive to active immunity. Babies born from July to December, who are intensively exposed to winter conditions form 1 to 5 months of age, are also at special risk. During this period more girls and more children born form January to June die of leukaemia; and within three months of birth an exceptionally high ratio of myeloid to lymphatic leukaemias has been replaced by a low ratio, which persists throughout childhood.     

Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90.

OBJECTIVE--To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN--Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING--England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS--All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES--Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS--Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin''s disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS--During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.     

Vitamin K and childhood cancer: a population based case-control study in Lower Saxony,Germany.

OBJECTIVE--To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. DESIGN--Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. SETTING--State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. SUBJECTS--272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. MAIN EXPOSURE MEASURES--Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. RESULTS--An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. CONCLUSIONS--This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.