Association of maternal intake of nitrate and risk of birth defects and preterm birth: a systematic review and dose-response meta-analysis

In this study, the high versus low analysis method was applied to evaluate the association of maternal nitrate intake and risk of heart defect, limb deficiency, cleft lip, and preterm birth. Also, linear and non-linear dose-response associations between maternal intake of nitrate and risk of heart defects were investigated. In high versus low intake, the risk of heart defects in infants is directly associated with the level of nitrate exposure, but no significant relationship was found between the cleft lip, limb deficiency, and preterm birth. The linear dose-response meta-analysis was associated with risk of heart defects (RR: 1.03; 95% CI: 1.00 to 1.05, P = 0.400, I2= 0%, P heterogeneity= 0.602, n = 3) and nonlinear dose-response meta-analysis showed that maternal intake of nitrate higher than ∼4 mg/day is positively associated with heart defects risk (P non-linearity= 0.012).