Vitamin K regimens and incidence of childhood cancer in Denmark

Olsen, Jørgen H.; Hertz, H; K, Blinkenberg; Verder, Henrik

doi:10.1136/bmj.308.6933.895

Cited by 50 publications

(35 citation statements)

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“…vitamin K is associated with childhood leukaemia. These findings are in broad agreement with two other large investigations, whose designs differed from those included in the present pooled analysis (Ekelund et al, 1993;Olsen et al, 1994). In addition, good quality obstetric data on over 2000 children with cancer and twice as many unaffected children have been assembled as part of the United Kingdom Childhood Cancer Study (United Kingdom Childhood Cancer Study Investigators, 2000).…”

Section: Discussionsupporting

confidence: 88%

“…vitamin K prophylaxis became a controversial topic when Golding et al (1992) reported that children who received it by this route were almost three times as likely to develop leukaemia as children who received it orally or not at all. Although subsequent studies failed to confirm these findings (Ekelund et al, 1993;Klebanoff et al, 1993;Olsen et al, 1994;Ansell et al, 1996;von Kries et al, 1996;Roman et al, 1997;McKinney et al, 1998;Parker et al, 1998;Passmore et al, 1998a,b), inconsistencies in their results have left lingering doubts about the safety of I.M. administration (Kaufman, 1999).…”

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confidence: 99%

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

et al. 2002

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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.

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Section: Discussionsupporting

confidence: 88%

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confidence: 99%

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

et al. 2002

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“…administration of vitamin K accords with the majority of individual studies to have reported on this topic (Ekelund et al, 1993;Klebanoff et al, 1993;Olsen et al, 1994;Ansell et al, 1996;von Kries et al, 1996;Roman et al, 1997;McKinney et al, 1998;Passmore et al, 1998a, b) and with the results of an individual record-based pooled analysis of the six major case -control studies (Roman et al, 2002). The one exception is a study carried out in the former Northern Health region of England which, although it found no association for all childhood ALL (OR ¼ 1.20, 95% CI ¼ 0.75 -1.92, based on 207 cases), reported a statistically significantly raised OR for ALL diagnosed between 12 and 71 months of age (OR ¼ 1.79, 95% CI ¼ 1.02 -3.15, based on 144 cases) (Parker et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…vitamin K were raised by Golding et al (1992) in their report associating i.m., but not oral, vitamin K with childhood leukaemia. Since then, most research has failed to find any statistically significant associations (Ekelund et al, 1993;Klebanoff et al, 1993;Olsen et al, 1994;Ansell et al, 1996;von Kries et al, 1996;Roman et al, 1997;McKinney et al, 1998;Passmore et al, 1998a, b), although Parker et al (1998) argued that i.m. vitamin K increases the risk of acute lymphoblastic leukaemia (ALL) diagnosed between 12 and 71 months of age.…”

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confidence: 99%

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

et al. 2003

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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.

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“…The lack of an association between leukaemia and administration of intramuscular vitamin K to the neonate also deserves particular attention as, after the report of Golding and colleagues in 1992, this issue has been the subject of considerable debate (Draper and Stiller, 1992;Ekelund et al, 1993;Olsen et al, 1994;Ansell et al, 1996;von Kreis et al, 1996;Zipursky et al, 1996). The retrospective assessment of whether a baby received vitamin K and by what route is not straightforward (Ansell et al, 1996) and, because of this, we presented our results in two ways, firstly by what was recorded in the notes and secondly by what could be imputed about hospital policy.…”

Section: Characteristics Of the Baby And Neonatal Exposuresmentioning

confidence: 99%

Leukaemia and non-Hodgkin's lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease?

Roman

Ansell²,

Bull³

1997

Br J Cancer

128

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Summary A medical record-based study of leukaemia and non-Hodgkin's lymphoma diagnosed before the age of 30 years was carried out at three hospitals in the south of England. Findings for 177 cases and 354 age-and sex-matched controls are presented here. For documented viral infection in pregnancy, the odds ratio (OR) was 6.0 [95% confidence interval (Cl) 1.2-29.7] for leukaemia and infinity (95% Cl 1.2-) for non-Hodgkin's lymphoma. Mothers of leukaemic cases were more likely to be anaemic, the OR for a pregnancy haemoglobin below 10 g being 3.8 (95% Cl 1.3-11.1). An association with birthweight was found for acute myeloid leukaemia, the OR for birthweights > 3500 g being 6.2 (95% Cl 1.3-29.8). Further, the preceding siblings of those diagnosed with any form of leukaemia were also more likely to weigh > 3500 g at birth (OR 2.2; 95% Cl 1.1-4.4). Overall, leukaemic cases appeared to be comparatively robust at birth with respect to other indicators of well-being, the ORs for jaundice, phototherapy, admission to special care nursery and neonatal intensive care all being less than 1.0. Further, no relation between childhood leukaemia and neonatal administration of intramuscular vitamin K was noted (OR 0.6, 95% Cl 0.3-1.4; for acute lymphoblastic leukaemia diagnosed between the ages of 1 and 6 years).

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Vitamin K regimens and incidence of childhood cancer in Denmark

Cited by 50 publications

References 5 publications

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

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

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

Leukaemia and non-Hodgkin's lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease?

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