Objective: We studied the association between the use of nutritional supplements during the first gestational month and the origin of Down's syndrome.
Methods: We compared 781 subjects with Down's syndrome caused by pure trisomy 21 with their matched controls who had no defect. We also compared subjects who had Down's syndrome with groups of 22 843 patient controls (i.e., subjects with other congenital abnormalities) and 38 151 population controls (without defects). Subjects with Down's syndrome and other congenital abnormalities were identified in the large population-based dataset of the Hungarian Congenital Abnormality Registry between 1980 and 1996, and matched population controls were selected from the National Birth Registry. There were three sources of exposure data: 1) prospective and medically recorded data based on prenatal logbooks, 2) retrospective maternal information based on questionnaires, and 3) home visits in non-respondent cases of Down's syndrome and congenital abnormalities. A possible association between the use of nutritional supplements, mainly folic acid and antioxidant vitamins C and E, during the first month of pregnancy and the incidence of Down's syndrome was studied.
Results: A significant protective effect was seen with large doses of folic acid ( approximately 6 mg/d) and iron (150-300 mg/d of ferrous sulfate) during the first gestational month against Down's syndrome (adjusted odds ratio 0.4, 95% confidence interval 0.2 to 0.7 for both). In general, folic acid and iron were used together, so it was difficult to separate these effects due to the limited number of subjects and controls. Only iron alone showed a protective effect against Down's syndrome (odds ratio 0.4, 95% confidence interval 0.1 to 0.9). The use of antioxidant vitamins was a rare event in the first month of pregnancy.
Conclusion: Pharmacologic doses of folic acid and iron appear to have a preventive effect against Down's syndrome.