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Down Syndrome Abstract
of the Month: Sept 1998

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Is there evidence of clustering in Down syndrome?

Morris JK, Alberman E, Mutton D
Int J Epidemiol 1998 Jun;27(3):495-498

Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.

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BACKGROUND: Associations between environmental hazards and the occurrence of congenital anomalies may be detectable by seeking evidence of non-random occurrence of cases (clusters). There have been a number of anecdotal reports of occurrences of clusters of Down syndrome (DS).
METHODS: Data from a national register of cytogenetic diagnoses of Down syndrome births and legal terminations occurring between 1989 and 1995 were used to examine the possibility of clustering. Space-time clustering at Regional Health Authority (RHA) level was examined by comparing the expected monthly number of DS pregnancies given the maternal age distribution, with the observed numbers. Seasonality was also investigated by comparing monthly expected and observed numbers of DS pregnancies. Time clustering was examined by using the scan statistic to determine whether a statistically significant excess of pregnancies in any 3-month period occurred in any individual or adjacent groups of District Health Authority (DHA).
RESULTS: The numbers of DS pregnancies were no higher than expected in the same RHA over consecutive months. There was no evidence of any seasonality of DS pregnancies. Only two individual DHA and three pairs of adjacent DHA had significantly high scan statistics, but as over 400 statistical tests had been completed 12 clusters would be expected to have occurred due to chance alone.
CONCLUSION: There was no evidence of any space-time clustering in DS at DHA level.

My comments:

Most of this article deals with the statistics the authors used to determine their outcome. This is now the third study to rule out clustering. The bottom line here is that Down syndrome does not appear to have environmental causes in the cases studied.

One possible limitation is that the authors could not include spontaneous miscarriages. (It has been estimated that 90 to 95% of all conceptions with trisomy 21 do spontaneously miscarry.) So the study may not have had a large enough sample to find significant clustering. Also, since we still don't know why some fetuses with DS make it to term, could the difference be that the ones that miscarry have a more environmental cause than the ones that make it to term, so that clustering would occur in the miscarried babies and not the live births? That's possible, but not logical.

Another limitation is geographic.Here, only births in the UK were considered. While it is still possible that clustering may occur outside England, there's no reason why that should occur. England is an industrialized country with all the environmental contaminants one might expect to have an influence on chromosomal abnormalities. If the study was done in a non-industrialized country, then that would be a major limitation.

It is worthwhile to note that two other studies(1,2) have also found no evidence of clustering. There has been some research on births of children with Down syndrome in Eastern Europe after the Chernobyl incident, but those studies have been conflicting.

Finally, one study out of Hungary(3) did find a cluster of babies with Down syndrome in mothers who ate contaminated fish from a plant that used the chemical trichlorfon.
  1. Rothman KJ; Fabia JJ. Place and time aspects of the occurrence of Down's syndrome. Am J Epidemiol 103(6):560-4, 1976.
  2. Stark CR; Mantel N. Lack of seasonal- or temporal-spatial clustering of Down's syndrome births in Michigan. Am J Epidemiol 86(1):199-213, 1967.
  3. Czeizel AE et al. Environmental trichlorfon and cluster of congenital abnormalities. Lancet 27;341(8844):539-42, 1993.
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