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

Abstract

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.

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).…”

“…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. In order to do this, the analyses reported here were repeated comparing oral þ given unknown route þ not given þ no record (baseline group) with i.m.…”

“…However, a recently published pooled analysis of data from the six major case -control studies concluded that there was 'no convincing evidence that i.m. vitamin K is associated with childhood leukaemia', including ALL diagnosed between 12 and 71 months of age (Roman et al, 2002). Given the concerns associated with the administration of i.m.…”

Vitamin K, an update for the paediatrician

“…A risk of solid tumours can now almost definitely be ruled out, but a small risk of leukaemia cannot be excluded. [17,35]. When cases of late VKDB started to reappear, Denmark, Canada, Australia and New Zealand responded by reintroducing universal IM prophylaxis, offering oral prophylaxis with repeated doses to those parents refusing the IM injection at birth.…”

Fat-soluble vitamins in breast-fed preterm and term infants

“…Plasma vitamin K 1 in VLBW was very high at 1 week of age compared to earlier studies in healthy newborns (Shearer et al, 1982;Greer et al, 1988) and in preterm infants (Kumar et al, 2001;Costakos et al, 2003). Several authors, although not confirmed in randomized studies, have suggested deleterious side effects from high vitamin K levels such as childhood leukemia and hepatoblastoma (Roman et al, 2002). At present, it is not known whether high plasma vitamin K concentration in the neonatal period increases disease risks.…”