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

Abstract

results are not independent. Those for the present paper, however, are based on more cases, and the method of analysis is entirely different and, in particular, does not use the controls from the other studies. Although (with some minor and possibly questionable exceptions) the results of the present analyses are not significant and there is no suggestion of a doubling of the risk of malignant disease arising from the use of intramuscular vitamin K, the findings for childhood leukaemia are compatible with an increased risk of around 20-30%, as, by using the same argument as at the end of the section on statistical methods, it can be shown that an individual relative risk of 1.25 gives a risk ratio of 1.14, and such values occur in table 3. These largely negative results are in agreement with those from our own casecontrol study and with most of the other papers on this subject, the results and implications of which are discussed in the accompanying paper by Passmore et al. 3 Various colleagues are thanked in the accompanying paper. We are very grateful to Dr Hey and the members of the Scottish Neonatal Network for providing carefully validated information on numbers of births and vitamin K prophylaxis policies in Scottish hospitals.Contributors: SJP and GD initiated the study and designed the protocol. PB was responsible for setting up and manipulating computer databases. Statistical analyses were carried out by GD and MK. The paper was written jointly by SJP and GD, who are guarantors for the paper.Funding: This work was funded by the Department of Health; the views expressed in this publication are those of the authors and not necessarily those of the Department of Health.Conflict of interest: None. 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 Key messages+ Intramuscular vitamin K given to babies is known to be effective in the prevention of vitamin K deficiency bleeding but it has been suggested that these preparations, or one of their constituents, may increase the risk of childhood cancer + Most studies have not shown a significant association between childhood cancer and vitamin K but are unable to exclude the possibility that its use increases the risk of childhood cancer ...

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

“…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). To investigate this further, a metaanalysis of the results published by Roman et al (2002) and the results reported here has been undertaken.…”

“…vitamin K and any diagnostic group, with the pooled OR for ALL diagnosed between 12 and 71 months being: OR ¼ 0.98, 95% CI ¼ 0.79 -1.22 (based on 1201 cases). In light of all the available evidence, the most likely explanation for the finding of Parker et al (1998) would seem to be chance. Accordingly, 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.…”

“…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.…”

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

“…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).…”

“…In order to investigate this topic in more depth, a pooled analysis of individual patient data from the six major case -control studies (Golding et al, 1992;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) has been undertaken. The principal aims were to use consistent definitions of exposure and potential confounders to:…”