Doria-Rose and Edwards Respond to "Parity and Down’s Syndrome"

V. Paul Doria-Rose1,2  and Karen L. Edwards1

1 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA.
2 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.

Received for publication May 14, 2003; accepted for publication May 23, 2003.

We agree with Dr. Chan (1) that our findings (2) should be interpreted cautiously, based on issues of underascertainment in our data. We accounted for differential termination of Down’s syndrome pregnancies between low-parity and high-parity women by attempting to exclude women who had received prenatal diagnosis. Unfortunately, our data sources could not identify all such women. Thus, our adjustment for the differential termination effect was incomplete, biasing our resulting odds ratios upwards. Nevertheless, given the magnitude of the odds ratios, we find it unlikely that this bias accounts for all of the observed association (2). Chan also mentions our inability to identify all liveborn cases of Down’s syndrome for some of the study years. In our view, this was less of a concern with regard to the validity of our study. Restriction of the data to years for which the Birth Events Record Database was available still resulted in a strong association between parity and Down’s syndrome, and this strong association was present regardless of the source of case identification.

Chan refers to the fact that, in our study population, cases were more likely than controls to be Hispanic and less likely to have reported a prior induced abortion. Hispanic women may be less likely to undergo prenatal diagnosis (3), and women with a previous induced abortion might be more willing to terminate a Down’s syndrome pregnancy. In fact, it is precisely this type of case-control difference that led us to restrict the data to women not receiving amniocentesis. Cases and controls in this subanalysis were more similar on the basis of ethnicity and prior abortion than were members of the full study population (table 1). Had we been able to accurately identify all women who had received prenatal diagnosis, it seems likely that these case-control differences would have been diminished even further.


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TABLE 1. Selected characteristics of mothers of children with and without Down’s syndrome for the full study sample and for women reporting no amniocentesis during the index pregnancy, Washington State, 1984–1998
 
We disagree with Chan’s assertion that it is "essential to include both births and terminations" in a study of parity and Down’s syndrome (1). Our approach of restricting the data to women who had not received prenatal diagnosis removed any effect of differential termination, since the remaining women would not have known whether they were carrying a Down’s syndrome fetus and thus could not have chosen to terminate the pregnancy on that basis. While it remains possible that this restriction introduces another bias, we find it less plausible that a biologic association between parity and Down’s syndrome should differ in women who choose not to receive prenatal diagnosis.

There are differences between our analysis and the Chan et al. study that included Down’s syndrome births and terminations (4) which go beyond the method used to account for differential prenatal diagnosis. Chan et al. found no association even when they restricted their data to liveborn cases, despite the association between parity and use of prenatal diagnosis in their population (4, 5). It is unclear what other factors might account for differences between the studies. We feel that the Chan et al. approach is reasonable, with the understanding that any true effect of parity on Down’s syndrome losses late in pregnancy could be obscured (2). However, in the presence of this known, if small, bias, it is worthwhile to consider an alternative approach. We suggest one such alternative. Both of the above methods of accounting for differential pregnancy termination have their own strengths and limitations. Perhaps the use of both methods in tandem in a population for which both Down’s syndrome and prenatal diagnosis could be reliably ascertained would shed additional light on the association, or lack thereof, between parity and risk of Down’s syndrome.


    NOTES
 
Correspondence to Dr. V. Paul Doria-Rose, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, MP-381, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: pdoriaro{at}fhcrc.org). Back


    REFERENCES
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  1. Chan A. Invited commentary: parity and the risk of Down’s syndrome—caution in interpretation. Am J Epidemiol 2003;158:509–11.[Free Full Text]
  2. Doria-Rose VP, Kim HS, Augustine ET, et al. Parity and the risk of Down’s syndrome. Am J Epidemiol 2003;158:503–8.[Abstract/Free Full Text]
  3. Wilson MG, Chan LS, Herbert WS. Birth prevalence of Down syndrome in a predominantly Latino population: a 15-year study. Teratology 1992;45:285–92.[ISI][Medline]
  4. Chan A, McCaul KA, Keane RJ, et al. Effect of parity, gravidity, previous miscarriage, and age on risk of Down’s syndrome: population based study. BMJ 1998;317:923–4.[Free Full Text]
  5. Halliday J, Lumley J, Watson L. Comparison of women who do and do not have amniocentesis or chorionic villus sampling. Lancet 1995;345:704–9.[ISI][Medline]

Related articles in Am. J. Epidemiol.:

Parity and the Risk of Down’s Syndrome
V. Paul Doria-Rose, Han S. Kim, Elizabeth T. J. Augustine, and Karen L. Edwards
Am. J. Epidemiol. 2003 158: 503-508. [Abstract] [FREE Full Text]  

Invited Commentary: Parity and the Risk of Down’s Syndrome—Caution in Interpretation
Annabelle Chan
Am. J. Epidemiol. 2003 158: 509-511. [Extract] [FREE Full Text]  




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