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.
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References
Anonymous (1971) Haemorrhage in the newborn. Br Med J 4: 1–2
Anonymous (1978) Vitamin K and the newborn. Lancet 1: 755–757
Ansell P, Bull D, Roman E (1996) Childhood leukaemia and intramuscular vitamin K: findings from a case-control study. Br Med J 313: 204–205
Ansell P, Roman E, Fear NT, Renfrew MJ (2001) Vitamin K policies and midwifery practice: questionnaire survey. Br Med J 322: 1148–1152,
Breslow NE, Day NE (1980) Statistical Methods in Cancer Research, Volume I - The Analysis of Case-Control Studies Scientific Publications No. 32 Lyon, France: IARC
Cornelissen M, von Kries R, Loughan P, Schubiger G (1997) Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. Eur J Pediatr 156: 126–130
Ekelund H, Finnström O, Gunnarskog J, Källén B, Larsson Y (1993) Administration of vitamin K to newborn infants and childhood cancer. Br Med J 307: 89–91
Golding J, Paterson M, Kinlen LJ (1990) Factors associated with childhood cancer in a national cohort study. Br J Cancer 62: 304–308
Golding J, Greenwood R, Birmingham K, Mott M (1992) Childhood cancer, intramuscular vitamin K, and pethidine given during labour. Br Med J 305: 341–346
Hall MA, Pairaudeau P (1987) The routine use of vitamin K in the newborn. Midwifery 3: 170–177
Handel J, Tripp JH (1991) Vitamin K prophylaxis against haemorrhagic disease of the newborn in the United Kingdom. Br Med J 303: 1109
Kaufman T (1999) Vitamin K: an accident waiting to happen or a storm in a teacup? RCM Midwives J 2: 251
Klebanoff MA, Read JS, Mills JL, Shiono PH (1993) The risk of childhood cancer after neonatal exposure to vitamin K. N Engl J Med 329: 905–908
McKinney PA, Juszczak E, Findlay E, Smith K (1998) Case-control study of childhood leukaemia and cancer in Scotland: findings for neonatal intramuscular vitamin K. Br Med J 316: 173–177
McNinch AW, Tripp JH (1991) Haemorrhagic disease of the newborn in the British Isles: two year prospective study. Br Med J 303: 1105–1109
Neuhäuser M, Becher H (1997) Improved odds ratio estimation by post hoc stratification of case-control data. Stats Med 16: 993–1004
Olsen JH, Hertz H, Blinkenberg K, Verder H (1994) Vitamin K regimens and incidence of childhood cancer in Denmark. Br Med J 308: 895–896
Parker L, Cole M, Craft AW, Hey EN (1998) Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study. Br Med J 316: 189–193
Passmore SJ, Draper G, Brownbill P, Kroll M (1998a) Case-control studies of the relation between childhood cancer and neonatal vitamin K administration. Br Med J 316: 178–184
Passmore SJ, Draper G, Brownbill P, Kroll M (1998b) Ecological studies of relation between hospital policies on neonatal vitamin K administration and subsequent occurrence of childhood cancer. Br Med J 316: 184–189
Roman E, Ansell P, Bull D (1997) Leukaemia and non-Hodgkin's lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease? Br J Cancer 76: 406–415
Selvin S (1996) Statistical analysis of epidemiologic data. 2nd Edn New York: Oxford University Press
Sutor AH, von Kries R, Cornelissen EAM, McNinch AW, Andrew M (1999) Vitamin K deficiency bleeding (VKDB) in infancy. Thromb Haemost 81: 456–461
Tripp JH, McNinch AW (1998) The vitamin K debacle: cut the Gordian knot but first do no harm. Arch Dis Child 79: 295–297
United Kingdom Childhood Cancer Study Investigators (2000) The United Kingdom Childhood Cancer Study: objectives, materials and methods. Br J Cancer 82: 1073–1102
von Kries R, Göbel U, Hachmeister A, Kaletsch U, Michaelis J (1996) Vitamin K and childhood cancer: a population based case-control study in Lower Saxony, Germany. Br Med J 313: 199–203
Wariyar U, Hilton S, Pagan J, Tin W, Hey E (2000) Six years' experience of prophylactic oral vitamin K. Arch Dis Child Fetal Neonatal Ed 82: F64–F68
Zipursky A (1996) Vitamin K at birth. Br Med J 313: 179–180
Zipursky A (1999) Prevention of vitamin K deficiency bleeding in newborns. Br J Haematol 104: 430–437
Acknowledgements
We would like to thank all those involved in the original studies, since without their work the present project would not have been possible. We are particularly indebted to researchers from the Bristol and Newcastle study regions for providing us with their data. In addition, we would like to thank Paul Appleby, Ed Juszczak, Uwe Kaletsch and Gillian Reeves for statistical advice, and Ray Cartwright for chairing the various group meetings. This research was funded by The Department of Health and The Leukaemia Research Fund. The views expressed in this publication are those of the authors and not necessarily the Department of Health and give no conflicts of interest.
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Roman, E., Fear, N., Ansell, P. et al. Vitamin K and childhood cancer: analysis of individual patient data from six case–control studies. Br J Cancer 86, 63–69 (2002). https://doi.org/10.1038/sj.bjc.6600007
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DOI: https://doi.org/10.1038/sj.bjc.6600007