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Maternal dietary nitrate intake and risk of neural tube defects: A systematic review and dose-response meta-analysis

Kakavandi, Nader Rahimi, Hasanvand, Amin, Ghazi-Khansari, Mahmoud, Sezavar, Ahmad Habibian, Nabizadeh, Hassan, Parohan, Mohammad
Food and chemical toxicology 2018 v.118 pp. 287-293
confidence interval, congenital abnormalities, dose response, meta-analysis, models, neural tube defects, nitrates, observational studies, risk, systematic review, teratogenicity, toxicology
Despite growing evidence for the potential teratogenicity of nitrate, knowledge about the dose-response relationship of dietary nitrate intake and risk of specific birth defects such as neural tube defects (NTDs) is limited. Therefore, the aim of this meta-analysis was to synthesize the knowledge about the dose-response relation between maternal dietary nitrate intake and the risk of NTDs. We conducted a systematic search in PubMed, ISI Web of Science and Scopus up to February 2018 for observational studies. Risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated using a random-effects model for highest versus lowest intake categories. The linear and non-linear relationships between nitrate intake and risk of NTDs were also investigated. Overall, 5 studies were included in the meta-analyses. No association was observed between nitrate intake and NTDs risk in high versus low intake (RR: 1.33; 95% CI: 0.89–1.99, p = 0.158) and linear dose-response (RR: 1.03; 95% CI: 0.99–1.07, p = 0.141) meta-analysis. However, there were positive relationships between nitrate intake and risk of NTDs in non-linear (pnon-linearity<0.05) model. Findings from this dose-response meta-analysis indicate that maternal nitrate intake higher than ∼3 mg/day is positively associated with NTDs risk.