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This article was originally published in The Tan Sheet

Executive Summary

VITAMIN C, FOLATE AND IRON SUPPLEMENT USE IN MATERNAL DIET show protective benefits against the development of primitive neuroectodermal brain tumors in young children, according to the results of a case-control study reported in the Aug. 19 New England Journal of Medicine. Conducted by Greta R. Bunin, PhD, University of Pennsylvania, et al., the study was initiated as an exploration of the inhibitory effect of vitamins C and E on the formation of nitrosamines believed to be a risk factor for primitive neuroectodermal brain tumors, but eventually concluded that its results could not support the nitrosamines hypothesis. "Strong protective dose-response relations were observed for maternal consumption of fruit, vegetables, vitamin C, nitrate, and folate," the study authors concluded. "Protective effects of early multivitamin use and iron supplements were also observed." The case group involved 166 mothers of children under the age of six who had been diagnosed with primitive neuroectodermal brain tumors between 1986 and 1989. The group was culled from North American families of eligible patients registered with the Children's Cancer Group; of the 166 eligible patients, 147 "were confirmed as neuroectodermal tumors" by a reviewing pathologist, while "about three of the 19 tumors without pathological review were probably not primitive." Control families were selected through "random-digit telephone dialing" and "matched to case patients according to area code and the next five digits of the telephone number, date of birth (+/-one year) and race (black or nonblack)," according to Bunin et al. Dietary intake was determined through "trained interviewers" who conducted telephone interviews of a mean length of 62 minutes. The interview was structured with a "food frequency questionnaire with 53 food items similar in design to Block et al.," plus fruits and vegetables that reflect "geographic and ethnic diversity in diet," as well as "other items, such as coffee, tea, diet soda, and raw meat." The Bunin group calculated intake of nine dietary components (vitamins A, C and E, beta carotene, retinol, nitrate, nitrite, dimethylnitrosamine, and folate), using the data base of Block et al. to fix on "portion size and content," using "medium portions for women of reproductive age." Bunin et. al found that "the highest quartile groups for vitamin C, nitrate and folate intake were associated with significantly decreased odds ratios, and the trends were significant. Although the odds ratio for the highest quartile of vitamin A consumption was not significant," the authors observed that the trend toward a decreased risk was significant. "The results for beta carotene were virtually identical to those for vitamin A," the study found, "whereas retinol had no association with risk." The study also indicated that "multivitamin use in the first six weeks after the last menstrual period was associated with an odds ratio of .56 (95% confidence interval, .32 to .96; P = .02)," and observed a "significant protective effect" with vitamin C, calcium and iron supplementation. In the NEJM article, the group called the iron findings "puzzling, since all prenatal multivitamin supplements contain iron." Bunin et al. speculated that the finding might be attributable "to some effect of very large amounts of iron or an effect early in gestation." Folate, vitamin C and calcium supplements demonstrated "stronger" protective effects among mothers who had not taken multivitamins in the first six weeks of their pregnancy than among mothers in the multivitamin group, according to the study. "The observed protective effects of folate and multivitamin use early in pregnancy are the most intriguing because of their specificity for primitive neuroectodermal tumor and the biologic plausibility of a causal similarity between primitive neuroectodermal tumor and neural tube defects," Bunin et al. concluded. The Bunin group findings also suggested that supplemental daily multivitamin use during the first year of life significantly decreased the odds of neuroectodermal tumor by .68 (P = .11), at a confidence interval of 95%, as did the child's subsequent use of multivitamins (odds ratio .51; P = .07). Other significant factors included "no consumption of fruit" and "frequent consumption of apple juice." Brain tumors account for about one childhood cancer in five, according to the study.

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