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Re: "Parity and the risk of Down's Syndrome."

Zheng CJ
Am J Epidemiol 2004 Jun; 160(6):609-610
Although Doria-Rose et al.'s Journal article 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. 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 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. Similarly, it has clearly been demonstrated that the recurrence risk of Down's syndrome is higher than the incidence risk. 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. 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.? 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.
Biological-function; Cell-biology; Cellular-function; Cytology; Epidemiology; Genes; Genetics; Germ-cells; Pregnancy; Reproduction; Reproductive-system; Reproductive-effects; Risk-analysis
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American Journal of Epidemiology
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University of Minnesota Twin Cities
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