Representative and misrepresentative associations of birth defects in livebirths. Conditions under which relative risks greater than unity in livebirths necessarily imply relative risks greater than unity in all conceptuses.
One may express the relative risk of defect in all conceptuses, r(def), as a function of the relative risk of defect in livebirths, r(def,lb), and in embryonic and fetal deaths, r(def,efd), as r(def) = C(lb)r(def,lb) + C(efd)r(def,efd), where C(lb) and C(efd) are coefficients defined in terms of conceptus and defect viability and lethality. If the relative risk of birth defect in livebirths, r(def,lb), is greater than unity, but the relative risk of defect in all conceptuses, r(def), is equal to or less than unity (or the reverse pattern holds), then the relative risk of defects in livebirths may be said to be "distorting" or "misrepresentative" because it does not reflect the nature of the association in all conceptuses. The authors define and present an explicit expression for a boundary upon the relative risk of defect in livebirths. If the relative risk of defect in livebirths is (validly) greater than this boundary value, then the relative risk in all conceptuses must be greater than unity and the observed relative risk of defect in births is "representative" and not distorting. The authors show that the boundary value is equal to 1/C(lb), where C(lb) is a simple function of the lethality of all unexposed conceptuses, the lethality of unexposed conceptuses with defect, and the relative risk of any embryonic and fetal death. Tables of the boundary relative risk for various values of these variables are presented. Over a very wide range of reference variables, a (valid) relative risk of defect in livebirths of 3.5 or greater implies a positive association with defect in all (recognized) conceptuses in the population studied.
Hook
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School of Public Health, University of California, Berkeley 94720.
Regal
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D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D004622:Embryo, Mammalian / Q000002:abnormalities; D005260:Female; D005313:Fetal Death / Q000453:epidemiology / Q000209:etiology; D005333:Fetus / Q000002:abnormalities; D006801:Humans; D007231:Infant, Newborn; D015233:Models, Statistical; D011247:Pregnancy; D012306:Risk; D013792:Thalidomide / Q000009:adverse effects
D013792:Thalidomide