5. Geelen JA. Hypervitaminosis A induced teratogenesis. ;6:-

7. Rosa FW. Teratogenicity of isotretinoin.  ;2:-

24. Rothman KJ. Modern epidemiology. Boston: Little, Brown, 1986.

We then evaluated the effects of a high intake of vitamin A from food and supplements after stratifying the data according to potential confounding factors. We found little confounding by any single factor. We also constructed several multiple logistic-regression models incorporating vitamin A intake from food and supplements, with additional terms for the age, education, and race of the mother, the family history of birth defects, use of folate supplements during early pregnancy, treated maternal diabetes, alcohol consumption, genital herpes infection, fever (temperature, >38.3°C during the first trimester), and use of antiseizure medication, retinoids, or exogenous hormones. The estimates of the effects of vitamin A from both food and supplements were similar to the corresponding estimates from , even when both factors were in the same model. Thus, there was little aggregate confounding from the factors mentioned.

8. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy.  ;313:-

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We analyzed the data first by obtaining contingency tables for the main study variables, from which we calculated the prevalence of birth defects according to the mothers' retinol-intake category, along with prevalence ratios and approximate 95 percent confidence intervals. We then stratified the contingency tables according to each of several possible confounding variables, which included the age, education, and race of the mother and the maternal history or family history of birth defects. We also fitted a multiple logistic-regression model to the data that controlled for the above variables as well as folate intake, alcohol consumption, genital herpes infection, treated maternal diabetes, fever (temperature, >38.3°C [101°F]) during the first trimester of pregnancy, and the use of antiseizure medication, retinoids, or exogenous hormones.

9. Use of supplements containing high-dose vitamin A -- New York State, 1983-1984 ;36:-

Some data on the multivitamin brand, the week vitamin use began, the frequency of intake, or the dosage of single-vitamin supplements were missing for 201 women. For these women, we substituted median values for the missing values. For example, if the week of first vitamin use was missing and the brand was a prenatal formulation, we used the median starting week for all users of prenatal vitamins. We also analyzed the data after excluding women for whom we had made such substitutions.


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The study cohort was originally recruited to evaluate risk factors for neural-tube defects. Between October 1984 and June 1987, women from the practices of more than 100 participating obstetricians were identified when they either had a maternal serum alpha-fetoprotein measurement or underwent amniocentesis. The study protocol was reviewed and approved by the Boston University Medical Center's Institutional Review Board for Human Research.

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For 106 women, information on some, but fewer than half, of the retinol-containing foods was missing. For these foods, we assigned values for retinol intake, using the median daily intake for all women in the study. We excluded from our analyses 6 women for whom information for half or more of the retinol-containing foods was missing and 1 woman for whom we lacked information on vitamin supplements; these additional exclusions left 22,748 women for whom we had completed interviews and usable data on retinol intake from both foods and vitamin supplements.

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Information on the outcome of pregnancy was obtained from a questionnaire mailed to the obstetrician around the expected time of delivery. If the physician did not respond, the same questionnaire was mailed to the mother. Information requested on the follow-up form included the presence of any birth defects as well as other information about complications and outcome of pregnancy. Physicians supplied the information for 76.5 percent of the pregnancies; the mothers supplied the information for the remainder.

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Data on the teratogenicity of vitamin A in humans are scant. Here we report on the relation between birth defects and the intake of vitamin A from food and supplements in a prospectively studied population of more than 22,000 pregnant women.