Copyright © 2004 by the Johns Hopkins Bloomberg School of Public Health
LETTERS TO THE EDITOR |
RE: "PARITY AND THE RISK OF DOWN’S SYNDROME"
Department of Occupational and Environmental Medicine, Regions Hospital, University of Minnesota, St. Paul, MN 55101
Although Doria-Rose et al.’s Journal article (1) presents convincing data that Down’s syndrome livebirth increases with parity, their interpretation ignores a well-established pitfall in reproductive epidemiology. Over two decades ago, a convincing correlation between spontaneous abortion and gravidity was detected and debated at length (Wilcox and Gladen (2)). A consensus emerging from this debate held that the causative mechanism was not biologic. Rather, it was recognized that individual women always know the outcomes of their previous pregnancies and, knowingly or not, use this information in making future reproductive decisions. When a greater proportion of women with a history of adverse pregnancy outcomes than those without such outcomes decides in favor of further attempts at reproduction, this increases the cohort of women who are attempting reproduction while at greater risk.
Risk heterogeneity is a prerequisite for the selective-fertility mechanism (2) to be operative and sufficiently account for the parity-related artifact. Evidence from the literature does, however, suggest that individual women differ intrinsically in their risk of Down’s syndrome livebirth. This evidence is demonstrated by documentation that a Down’s syndrome livebirth is more likely for women with a history of repeat spontaneous abortion (3). Similarly, it has clearly been demonstrated that the recurrence risk of Down’s syndrome is higher than the incidence risk (4, 5). One apparent explanation for the greater recurrence risk is that Down’s syndrome occurrences include cases due to heritable mutations, including translocations, rather than trisomy 21. In addition, some occurrence of Down’s syndrome may reflect germline mosaicism for trisomy 21 among oocytes (6). If this hypothesis were to prove valid, it also should enhance recurrence risk.
Could the confounding effect of selective fertility be controlled by the conditional logistic regression used by Doria-Rose et al. (1)? My answer is that this is unlikely. Although women giving birth to their first or second child may be said to have a reproductive history already, properly matching their experiences with those of more parous mothers is a very difficult task.
REFERENCES
- 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] - Wilcox AJ, Gladen BC. Spontaneous abortion: the role of heterogeneous risk and selective fertility. Early Hum Dev 1982;7:165–78.[CrossRef][ISI][Medline]
- Hook EB, Cross PK. Spontaneous abortion and subsequent Down syndrome livebirth. Hum Genet 1983;64:267–70.[CrossRef][ISI][Medline]
- Carter CO, Evans KA. Risk of parents who have one child with Down’s syndrome (mongolism) having another child similarly affected. Lancet 1961;2:785–8.[CrossRef]
- Stene J, Stene E, Mikkelsen M. Risk for chromosome abnormality at amniocentesis following a child with a non-inherited chromosome aberration. A European Collaborative Study on Prenatal Diagnoses 1981. Prenat Diagn 1984;4S:81–95.
- Zheng CJ, Byers B. Oocyte selection: a new model for the maternal-age dependence of Down syndrome. Hum Genet 1992;90:1–6.[CrossRef][ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. P. Doria-Rose and K. L. Edwards TWO AUTHORS REPLY Am. J. Epidemiol., September 15, 2004; 160(6): 611 - 611. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||