{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:02:30Z","timestamp":1786460550041,"version":"build-2736575974"},"reference-count":30,"publisher":"BMJ","issue":"6849","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMJ"],"published-print":{"date-parts":[[1992,8,8]]},"DOI":"10.1136\/bmj.305.6849.341","type":"journal-article","created":{"date-parts":[[2009,3,30]],"date-time":"2009-03-30T12:16:37Z","timestamp":1238415397000},"page":"341-346","source":"Crossref","is-referenced-by-count":259,"title":["Childhood cancer, intramuscular vitamin K, and pethidine given during labour."],"prefix":"10.1136","volume":"305","author":[{"given":"J.","family":"Golding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Greenwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Birmingham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","reference":[{"issue":"6","key":"ref_1","article-title":"As already noted, there were some problems in comparing cases and controls in that cases born before 1971 would be included only if diagnosed after 1970, and births in the 1980s would be included only if diagnosed at a relatively early age. We therefore carried out an analysis of only those babies born between 1971 and 1980, all of whom would have been followed for at least 10 years. We selected those who had had cancer diagnosed before their 10th birthday (89 cancers, 214 controls). Although neither year of birth (x2 = 38, df=4) nor hospital","volume-title":"were significantly associated, these were kept in the model","volume":"1","year":"(x2=","unstructured":"As already noted, there were some problems in comparing cases and controls in that cases born before 1971 would be included only if diagnosed after 1970, and births in the 1980s would be included only if diagnosed at a relatively early age. We therefore carried out an analysis of only those babies born between 1971 and 1980, all of whom would have been followed for at least 10 years. We selected those who had had cancer diagnosed before their 10th birthday (89 cancers, 214 controls). Although neither year of birth (x2 = 38, df=4) nor hospital (x2= 1 6, df= 1) were significantly associated, these were kept in the model. There was a significant association with intramuscular vitamin K"},{"key":"ref_2","article-title":"This study provides an example of the unexpected generation of a hypothesis as the result of a data trawl followed by the testing of that hypothesis on a different data set (none of the index cases in this study were included in the 1970","volume-title":"although methodologically different, have shown similar results strengthens each of those results","unstructured":"This study provides an example of the unexpected generation of a hypothesis as the result of a data trawl followed by the testing of that hypothesis on a different data set (none of the index cases in this study were included in the 1970 cohort). These appear to be the only two studies that have ever looked at intramuscular vitamin K in relation to cancer. The fact that both, although methodologically different, have shown similar results strengthens each of those results."},{"key":"ref_3","article-title":"birth cohort (when it was almost certainly given entirely intramuscularly) had a similar odds ratio (2-6; 95% confidence interval 1-3","author":"the possibility that the association may be causal.","year":"1970","unstructured":"The fact that the association with vitamin K found in the 1970 birth cohort (when it was almost certainly given entirely intramuscularly) had a similar odds ratio (2-6; 95% confidence interval 1-3 to 5 -2) as that for the present study (2-0; 95% confidence interval 1-3 to 3 0) reinforces the possibility that the association may be causal."},{"key":"ref_4","article-title":"As Elwood has described, epidemiologists have identified several criteria which taken together would make it \"more provident to act on the basis that the association is causal rather than to await further evidence.\"'4 The most important criteria, he notes, are biological plausibility as well as strength and consistency between studies. Many epidemiologists would describe an odds ratio of 2 as strong. The fact that two out of two studies have produced similar results provides consistency, though more studies would be even better","unstructured":"As Elwood has described, epidemiologists have identified several criteria which taken together would make it \"more provident to act on the basis that the association is causal rather than to await further evidence.\"'4 The most important criteria, he notes, are biological plausibility as well as strength and consistency between studies. Many epidemiologists would describe an odds ratio of 2 as strong. The fact that two out of two studies have produced similar results provides consistency, though more studies would be even better."},{"issue":"0-25","key":"ref_5","first-page":"12","article-title":"A recent British study identified cases in the British Isles during 1987-90.2' The authors showed that the risk varied from 4 4 per 100 000 in those given no vitamin K prophylaxis to 1-4 per 100 000 in those given oral vitamin K and 0 11 per 100 000 in those given intramuscular vitamin K. A similar study in Germany produced similar results","volume":"4","year":"2,","unstructured":"A recent British study identified cases in the British Isles during 1987-90.2' The authors showed that the risk varied from 4 4 per 100 000 in those given no vitamin K prophylaxis to 1-4 per 100 000 in those given oral vitamin K and 0 11 per 100 000 in those given intramuscular vitamin K. A similar study in Germany produced similar results (7 2, 1 4, 0-25 respectively).'12"},{"key":"ref_6","article-title":"BMJ 1992; 305: 346-7 possible benefits in a population with 700 000 births annually","unstructured":"BMJ 1992;305:346-7 possible benefits in a population with 700 000 births annually."},{"key":"ref_7","article-title":"calculation of the numbers of cancers that might be initiated is as follows. Assume that the incidence of cancer among those who did not receive vitamin K is 1 4 per 1000 by the age of 10 (data from the 1970 cohort study) and that the odds ratio for cancer if given intramuscular vitamin","author":"Conversely","unstructured":"Conversely, calculation of the numbers of cancers that might be initiated is as follows. Assume that the incidence of cancer among those who did not receive vitamin K is 1 4 per 1000 by the age of 10 (data from the 1970 cohort study) and that the odds ratio for cancer if given intramuscular vitamin K is 2-0; then if intramuscular vitamin K is causally related:"},{"key":"ref_8","article-title":"If no one received any vitamin K 980 cancers would occur","volume-title":"1960 cancers would occur","author":"K.","unstructured":"* If no one received any vitamin K 980 cancers would occur. * If all received oral vitamin K 980 cancers would occur. * If all received intramuscular vitamin K 1960 cancers would occur."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1365-3016.1989.tb00371.x","article-title":"Childhood cancers and their association with pregnancy drugs and illnesses","volume":"3","author":"EA, I.Gilman; LM, Kinnear-Wilson; GW, Kneale; JAH, Waterhouse","year":"1989","unstructured":"I Gilman EA, Kinnear-Wilson LM, Kneale GW, Waterhouse JAH. Childhood cancers and their association with pregnancy drugs and illnesses. Paediatr Penrnat Epidemiol 1989;3:66-94.","journal-title":"Paediatr Penrnat Epidemiol"},{"key":"ref_10","first-page":"3","article-title":"Pregnancy x-rays and childhood cancers: effects of exposure age and radiation dose","volume":"3","author":"Gilman, E.A.; Kneale, G.W.; Knox, E.G.; Stewart, A.M.","year":"1988","unstructured":"Gilman EA, Kneale GW, Knox EG, Stewart AM. Pregnancy x-rays and childhood cancers: effects of exposure age and radiation dose. J7ournal ofthe Society for Radiological Protection 1988;3:3-8."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/jnci\/56.5.879","article-title":"Mantel-Haenszel analysis of Oxford data: independent effects of several birth factors including fetal irradiation","volume":"56","author":"Kneale, G.W.; Stewart, A.M.","year":"1976","unstructured":"Kneale GW, Stewart AM. Mantel-Haenszel analysis of Oxford data: independent effects of several birth factors including fetal irradiation. J Nat Cancer Inst 1976;56:879-83.","journal-title":"J Nat Cancer Inst"},{"key":"ref_12","first-page":"279","article-title":"The inter-regional epidemiological study of childhood cancer (IRESCC): a case-control study of aetiological factors in leukaemia and lymphoma..4rch Dis","volume":"62","author":"McKinney, P.A.; Cartwright, R.A.; Saiu, J.M.T.; Mann, JR, Stiller; CA, Draper; G.J.","year":"1987","unstructured":"McKinney PA, Cartwright RA, Saiu JMT, Mann JR, Stiller CA, Draper GJ, et al. The inter-regional epidemiological study of childhood cancer (IRESCC): a case-control study of aetiological factors in leukaemia and lymphoma..4rch Dis Child 1987;62:279-87.","journal-title":"Child"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/bjc.1990.283","article-title":"Factors associated with childhood cancer in a national cohort study","volume":"62","author":"Golding, J.; Paterson, M.; Kinlen, L.J.","year":"1990","unstructured":"Golding J, Paterson M, Kinlen LJ. Factors associated with childhood cancer in a national cohort study. BrJ7 Cancer 1990;62:304-8.","journal-title":"BrJ7 Cancer"},{"key":"ref_14","article-title":"British births volume 1. 7hefirst week oflife","author":"Chamberlain, R.; Chamberlain, G.; Howlett, B.; Claireaux, A.","year":"1975","unstructured":"Chamberlain R, Chamberlain G, Howlett B, Claireaux A. British births volume 1. 7hefirst week oflife. London: Heinemann Medical, 1975."},{"key":"ref_15","article-title":"From birth to five: a study of the health and behaviour of Britain'sfive ylear olds","author":"Butler, N.R.; Golding, J.","year":"1986","unstructured":"Butler NR, Golding J. From birth to five: a study of the health and behaviour of Britain'sfive ylear olds. Oxford: Pergamon, 1986."},{"key":"ref_16","first-page":"781","article-title":"Recent findings of the 1970 Child Health and Education Study: preliminary communication","volume":"75","author":"Butler, N.R.; Golding, J.; Haslum, M.; Stewart-Brown, S.","year":"1982","unstructured":"Butler NR, Golding J, Haslum M, Stewart-Brown S. Recent findings of the 1970 Child Health and Education Study: preliminary communication. JRSocMed 1982;75:781-4.","journal-title":"JRSocMed"},{"key":"ref_17","first-page":"687","article-title":"Maternal smoking during pregnancy and the risk of childhood cancer","volume":"ii:","author":"Stjernfeldt, M.; Ludvigsson, J.; Berglund, K.; Lindsten, J.","year":"1986","unstructured":"Stjernfeldt M, Ludvigsson J, Berglund K, Lindsten J. Maternal smoking during pregnancy and the risk of childhood cancer. Lancet 1986;ii:687-8.","journal-title":"Lancet"},{"key":"ref_18","first-page":"80","article-title":"Children of the nineties. A longitudinal study of pregnancy and childhood based on the population of Avon (ALSPAC)","volume":"105","author":"Golding, J.","year":"1990","unstructured":"Golding J. Children of the nineties. A longitudinal study of pregnancy and childhood based on the population of Avon (ALSPAC). West of England Medical Journal 1990;105:80-2.","journal-title":"West of England Medical Journal"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/oxfordjournals.aje.a114447","article-title":"A general estimator for the variance of the Mantel-Haenszel odds ratio","volume":"124","author":"Robins, J.; Greenland, S.; Breslaw, N.E.","year":"1986","unstructured":"Robins J, Greenland S, Breslaw NE. A general estimator for the variance of the Mantel-Haenszel odds ratio. AmJ_ Epidemiol 1986;124:719-23.","journal-title":"AmJ_ Epidemiol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1365-3016.1992.tb00736.x","article-title":"prophvlaxis-a useful public health measure","volume":"6","author":"von Kries R. Vitamin K","year":"1992","unstructured":"von Kries R. Vitamin K prophvlaxis-a useful public health measure. Paediatr Perinat Epidemiol 1992;6:7-13.","journal-title":"Paediatr Perinat Epidemiol"},{"key":"ref_21","first-page":"543","article-title":"Trends in childhood leukaemia in Britain 1968-1978. Br7 Cancer","volume":"45","author":"Stiller, C.A.; Draper, G.J.","year":"1982","unstructured":"Stiller CA, Draper GJ. Trends in childhood leukaemia in Britain 1968-1978. Br7 Cancer 1982;45:543-51."},{"key":"ref_22","article-title":"Causal relationships in medicine: a practical system for critical appraisal","author":"Elwood, M.J.","year":"1988","unstructured":"Elwood MJ. Causal relationships in medicine: a practical system for critical appraisal. Oxford: Oxford University Press, 1988."},{"key":"ref_23","first-page":"550","article-title":"Analysis of chromosome aberrations and sister chromatid exchanges in peripheral blood lymphocytes of newborns after vitamin","volume-title":"K prophylaxis at birth. Ped Res","volume":"30","author":"Cornelissen, M.; Smeets, D.; Merkx, G.; de Abreu, R.; Kollee, L.; Monnens, L.","year":"1991","unstructured":"Cornelissen M, Smeets D, Merkx G, de Abreu R, Kollee L, Monnens L. Analysis of chromosome aberrations and sister chromatid exchanges in peripheral blood lymphocytes of newborns after vitamin K prophylaxis at birth. Ped Res 1991;30:550-3."},{"key":"ref_24","first-page":"814","article-title":"Plasma concentrations after oral and intramuscular vitamin K1 in neonates..4rch Dis","volume":"60","author":"McNinch, A.W.; Upton, C.; Samuels, M.; Shearer, M.J.; McCarthy, P.; Tripp, P.H.","year":"1985","unstructured":"McNinch AW, Upton C, Samuels M, Shearer MJ, McCarthy P, Tripp PH, et al. Plasma concentrations after oral and intramuscular vitamin K1 in neonates..4rch Dis Child 1985;60:814-8.","journal-title":"Child"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1203\/00006450-198710000-00008","article-title":"Vitamin Kl increases sister chromatid exchange in vitro in human leukocytes and in vivo in fetal sheep cells: a possible role for 'vitamin K deficiency'","volume":"22","author":"Israels, L.G.; Friesen, E.; Jansen, A.H.; Isracls, E.D.","year":"1987","unstructured":"Israels LG, Friesen E, Jansen AH, Isracls ED. Vitamin Kl increases sister chromatid exchange in vitro in human leukocytes and in vivo in fetal sheep cells: a possible role for 'vitamin K deficiency' in the fetus. Ped Res 1987; 22:405-8.","journal-title":"in the fetus. Ped Res"},{"key":"ref_26","first-page":"1130","article-title":"as a regulator of benzo(a)pyrene metabolism, mutagenesis and carcinogenesis. J7 Clin Invest","volume":"71","author":"Israels, L.G.; Walls, G.A.; Ollmann, D.J.; Friesen, E.; Vitamin, Israels E.D.; K.","year":"1983","unstructured":"Israels LG, Walls GA, Ollmann DJ, Friesen E, Israels ED. Vitamin K as a regulator of benzo(a)pyrene metabolism, mutagenesis and carcinogenesis. J7 Clin Invest 1983;71:1130-40."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0020-711X(87)90070-X","article-title":"Vitamin K1 amplification of benzo(a)pyrene metabolism in chick embryos","volume":"19","author":"Dogra, S.C.; Israels, L.G.","year":"1987","unstructured":"Dogra SC, Israels LG. Vitamin K1 amplification of benzo(a)pyrene metabolism in chick embryos. Intj Biochem 1987;19:471-3.","journal-title":"Intj Biochem"},{"key":"ref_28","first-page":"891","article-title":"deficiency and spontaneous metastases","volume":"35","author":"vitamin K, Hilgard P.Experimental","year":"1977","unstructured":"Hilgard P. Experimental vitamin K deficiency and spontaneous metastases. BrJ7 Cancer 1977;35:891-2."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1136\/bmj.303.6810.1105","article-title":"Haemorrhagic disease of the newborn in the British Isles: two year prospective study","volume":"303","author":"McNinch, A.W.; Tripp, J.H.","year":"1991","unstructured":"McNinch AW, Tripp JH. Haemorrhagic disease of the newborn in the British Isles: two year prospective study. BMJ 1991;303:1105-9.","journal-title":"BMJ"},{"key":"ref_30","article-title":"Accepted 24 Julv","year":"1992","unstructured":"(Accepted 24 Julv 1992)"}],"container-title":["BMJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmj.305.6849.341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T10:55:54Z","timestamp":1601117754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.305.6849.341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,8,8]]},"references-count":30,"journal-issue":{"issue":"6849","published-print":{"date-parts":[[1992,8,8]]}},"URL":"https:\/\/doi.org\/10.1136\/bmj.305.6849.341","relation":{},"ISSN":["0959-8138","1468-5833"],"issn-type":[{"value":"0959-8138","type":"print"},{"value":"1468-5833","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,8,8]]}}}