RESUMO
BACKGROUND: Amine-containing (nitrosatable) drugs can react with nitrite to form N-nitroso compounds, some of which are teratogenic. Data are lacking on whether dietary intake of nitrates and nitrites modifies the association between maternal nitrosatable drug exposure and neural tube defects (NTDs) in offspring. METHODS: We examined nitrosatable drug exposure and NTD-affected pregnancies in relation to dietary nitrite and total nitrite intake in a case-control study of Mexican American women. We interviewed 184 women with NTD-affected pregnancies and 225 women with normal live births, including questions on periconceptional drug exposures and dietary intake. For 110 study participants, nitrate was also measured in the usual source of drinking water. RESULTS: Women who reported taking drugs classified as nitrosatable were 2.7 times more likely to have an NTD-affected pregnancy than women without this exposure (95% confidence interval [CI] = 1.4-5.3). The effect of nitrosatable drugs was observed only in women with higher intakes of dietary nitrite and total nitrite (dietary nitrite + 5% dietary nitrate). Women within the highest tertile (greater than 10.5 mg/day) of total nitrite were 7.5 times more likely to have an NTD-affected pregnancy if they took nitrosatable drugs (95% CI = 1.8-45.4). The association between nitrosatable drug exposure and NTDs was also stronger in women whose water nitrate levels were higher. CONCLUSIONS: Findings suggest that effects of nitrosatable drug exposure on risk for neural tube defects in offspring could depend on the amounts of dietary nitrite and total nitrite intake.
Assuntos
Suplementos Nutricionais , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/etnologia , Nitratos/efeitos adversos , Nitritos/efeitos adversos , Compostos Nitrosos/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Intervalos de Confiança , Interações Medicamentosas , Feminino , Seguimentos , Humanos , Incidência , Idade Materna , Americanos Mexicanos , Nitratos/administração & dosagem , Nitritos/administração & dosagem , Compostos Nitrosos/administração & dosagem , Razão de Chances , Gravidez , Gravidez de Alto Risco , Cuidado Pré-Natal , Valores de Referência , Medição de Risco , Inquéritos e Questionários , Texas/epidemiologiaRESUMO
Fumonisins are a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly Fusarium moniliforme), a common fungal contaminant of maize. Fumonisins inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism (sphinganine and other sphingoid bases and derivatives) as well as depletion of complex sphingolipids, which interferes with the function of some membrane proteins, including the folate-binding protein (human folate receptor alpha). Fumonisin causes neural tube and craniofacial defects in mouse embryos in culture. Many of these effects are prevented by supplemental folic acid. Recent studies in LMBc mice found that fumonisin exposure in utero increases the frequency of developmental defects and administration of folate or a complex sphingolipid is preventive. High incidences of neural tube defects (NTD) occur in some regions of the world where substantial consumption of fumonisins has been documented or plausibly suggested (Guatemala, South Africa, and China); furthermore, a recent study of NTD in border counties of Texas found a significant association between NTD and consumption of tortillas during the first trimester. Hence, we propose that fumonisins are potential risk factors for NTD, craniofacial anomalies, and other birth defects arising from neural crest cells because of their apparent interference with folate utilization.