Use of computer simulation to evaluate a putative cluster of genetic or teratologic outcomes: Adjustment for “multiple hypotheses” and application to a reported excess of Down's syndrome

Hook, Ernest B.; Carothers, Andrew D.

doi:10.1002/(sici)1098-2272(1997)14:2<133::aid-gepi3>3.0.co;2-8

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…Recently, the problem of interpreting clusters has been emphasised by Hook and Carothers25 who analysed a reported excess of Down's syndrome in births to young mothers in Norway during 1985–6, and concluded that it was likely to have arisen by chance.…”

Section: Discussionmentioning

confidence: 99%

Investigation of a cluster of children with Down's syndrome born to mothers who had attended a school in Dundalk, Ireland

Dean

Nevin²,

Mikkelsen³

et al. 2000

Occup Environ Med

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Objectives-To investigate a reported cluster of Down's syndrome in oVspring of former pupils of a girls' school in Ireland, to establish the prevalence of Down's syndrome among live births in the area around the school, and to review the literature on the possible causes of reported clusters of Down's syndrome. ), although only four of these mothers were attending the school at any one time. The origin of the non-disjunction was found to be maternal first meiotic in four children, mitotic after fertilisation in another (with the youngest mother), and in the remaining one could not be determined. The marked excess of Down's syndrome in births to young mothers did not extend to oVspring of former pupils of the other Dundalk girls' school surveyed, or to live births in County Louth generally or in adjacent Newry and Mourne District. Conclusion-A striking, highly localised, excess of Down's syndrome in births to young mothers who had attended a girls' school in Dundalk during 1956-57 has been confirmed. However, not all of the mothers of the aVected children attended the school concurrently and the origin of non-disjunction in one child was an error occurring after conception. Some exposure essentially confined to girls attending the school at this time is a possible, although unlikely, explanation, but a review of potential risk factors does not suggest what this could be. Previous suggestions that an influenza epidemic or contamination from the Windscale nuclear reactor fire might be implicated, both of which occurred in October 1957, can be eVectively dismissed because three of the women with aVected oVspring had left the school by then and had moved away from Dundalk, and Down's syndrome in the child of another mother originated in an error after fertilisation. Owing to the retrospective nature of the investigation and the characteristics of the cases, chance is the most likely explanation for the cluster.

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Section: Discussionmentioning

confidence: 99%