Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study

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Title:	Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study
Authors:	Jiun-Nong Lin, Cheng-Li Lin, Ming-Chia Lin, Chung-Hsu Lai, Hsi-Hsun Lin, Chih-Hui Yang, Fung-Chang Sung, Chia-Hung Kao
Date:	2015-08
Issue Date:	2016-04-12T07:01:58Z (UTC)
Abstract:	Background The association between enterovirus infections in children and risk of leukaemia is unclear. We aimed toassess the risk of leukaemia after enterovirus infection in children.Methods We did a nationwide retrospective cohort study by analysing data from the National Health InsuranceResearch Database (NHIRD) in Taiwan. Children with enterovirus infections aged younger than 18 years wereidentifi ed. With use of computer-generated random numbers, children not infected with enterovirus were randomlyselected and frequency matched (1:1) with children infected with enterovirus by sex, age, urbanisation level, parentaloccupation, and index year of enterovirus infection. We only included children with complete baseline data for ageand sex and who had at least three clinic visits with the diagnosis of enterovirus infection. The diagnosis date of thefi rst clinic visit for the enterovirus infection was defi ned as the index date for initiation of follow-up person-yearmeasurement and participants. All study patients were followed up until they developed leukaemia, were lost tofollow-up, withdrew from the NHI programme, or until the end of the study without leukaemia (censored). Ourprimary endpoint was a diagnosis of leukaemia during follow-up.Findings Insurance claims data for 3 054 336 children younger than 18 years were randomly selected from all insuredchildren in the NHIRD. We identifi ed 282 360 children infected with enterovirus and 282 355 children not infectedwith enterovirus between Jan 1, 2000, and Dec 31, 2007. The incidence density rates of leukaemia were 3•26 per100 000 person-years for the enterovirus-infected and 5•84 per 100 000 person-years for the non-enterovirus-infectedcohorts. The risk of leukaemia was signifi cantly lower in the enterovirus-infected cohort than in the non-enterovirusinfectedcohort (adjusted subhazard ratio [SHR] 0•44, 95% CI 0•31–0•60; p<0•0001). Children infected withenterovirus have a reduced risk of both lymphocytic leukaemia (adjusted SHR 0•44, 0•30–0•65; p<0•0001) and acutemyeloid leukaemia (adjusted SHR 0•40, 0•17–0•97; p=0•04). Herpangina and hand-foot-and-mouth disease were themain diseases associated with the reduced risk of leukaemia.Interpretation The association between enterovirus infection and the reduced risk of developing leukaemia supportsGreaves’ delayed infection hypothesis for the cause of childhood leukaemia.Funding Taiwan Ministry of Health and Welfare, Academia Sinica, NRPB Stroke Clinical Trial Consortium, Tseng-Lien Lin Foundation, Taiwan Brain Disease Foundation, Katsuzo and Kiyo Aoshima Memorial Funds, China MedicalUniversity Hospital, and Taiwan Ministry of Education.
Relation:	thelancet
Appears in Collections:	[General Education Center] Papers

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