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; Habibian, Ahmad; Nabizadeh, Hassan; Parohan, Mohammad

doi:10.1016/j.fct.2018.05.033

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…Fetuses are believed to be at particularly high risk of adverse outcomes from nitrite exposure because they have low levels of MetHb reductase (cytochrome b5 reductase), which converts MetHb back to Hb (Lukens 1987;Gruener et al 1973). Nitrate intake has also been shown to interfere with thyroid function in both animals (Eskiocak et al 2005;Jahreis et al 1986Jahreis et al , 1987 and humans (Aschebrook-Kilfoy et al 2012) and to be teratogenic (Kakavandi et al 2018).…”

Section: Nitrate (No −mentioning

confidence: 99%

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children

Coffman

Jensen

Trabjerg

et al. 2021

Environ Health Perspect

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BACKGROUND: High levels of nitrate (NO − 3) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent. OBJECTIVES: We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term (≥37 wk gestation) live-born singletons. METHODS: We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991-2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable. RESULTS: There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of −9:71 g (95% confidence interval: −14:60, −4:81) was predicted at 25 mg=L (half the value of the European Union drinking water standard) compared with 0 mg=L NO − 3. Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO − 3 and head circumference or LBW. DISCUSSION: Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings.

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Section: Nitrate (No −mentioning

confidence: 99%

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children

Coffman

Jensen

Trabjerg

et al. 2021

Environ Health Perspect

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“…Two previous systematic reviews have assessed the association between maternal nitrate intake and risk of neural tube defects 30 , and between maternal intake of nitrate and risk of birth defects and preterm birth 31 . They reported no association between maternal nitrate intake and the risk of preterm birth, limb deficiency, cleft lip, and neural tube defects through high versus low meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Several epidemiological studies in humans have reported an association between prenatal nitrate exposure and adverse reproductive outcomes, including congenital abnormalities, preterm birth, low birth weight and small-for-gestational-age (SGA) infants 13 , 26 – 29 . Two previous systematic reviews have assessed the association between maternal nitrate intake and risk of neural tube defects 30 , birth defects, and preterm birth 31 , but the exposures included nitrate intake from food and drugs as well as drinking water.…”

Section: Introductionmentioning

confidence: 99%

Nitrate contamination in drinking water and adverse reproductive and birth outcomes: a systematic review and meta-analysis

Lin

Clair

Gamble

et al. 2023

Sci Rep

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Exposure to low levels of nitrate in drinking water may have adverse reproductive effects. We reviewed evidence about the association between nitrate in drinking water and adverse reproductive outcomes published to November 2022. Randomized trials, cohort or case–control studies published in English that reported the relationship between nitrate intake from drinking water and the risk of perinatal outcomes were included. Random-effect models were used to pool data. Three cohort studies showed nitrate in drinking water is associated with an increased risk of preterm birth (odds ratio for 1 mg/L NO3-N increased (OR1) = 1.01, 95% CI 1.00, 1.01, I2 = 23.9%, 5,014,487 participants; comparing the highest versus the lowest nitrate exposure groups pooled OR (ORp) = 1.05, 95% CI 1.01, 1.10, I2 = 0%, 4,152,348 participants). Case–control studies showed nitrate in drinking water may be associated with the increased risk of neural tube defects OR1 = 1.06, 95% CI 1.02, 1.10; 2 studies, 2196 participants; I2 = 0%; and ORp = 1.51, 95% CI 1.12, 2.05; 3 studies, 1501 participants; I2 = 0%). The evidence for an association between nitrate in drinking water and risk of small for gestational age infants, any birth defects, or any congenital heart defects was inconsistent. Increased nitrate in drinking water may be associated with an increased risk of preterm birth and some specific congenital anomalies. These findings warrant regular review as new evidence becomes available.

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“…This distinction is paramount for the consideration of dietary nitrate specifically from plant-based food sources as a conditionally essential nutrient. Table 3 [ [128] , [129] , [130] , [131] , [132] , [133] , [134] , [135] , [136] , [137] , [138] , [139] , [140] ] presents meta-analyses on exposure to nitrate and nitrite and health risks published in the last 10 y. These meta-analyses included, on average, 23 studies that estimated nitrate and nitrite exposure using dietary assessment tools (for example, food frequency questionnaires) and food composition databases.…”

Section: Risks Associated With Dietary Nitrate: Context Mattersmentioning

confidence: 99%

Dietary Nitrate from Plant Foods: A Conditionally Essential Nutrient for Cardiovascular Health

Pinaffi-Langley,

Dajani,

Prater

et al. 2024

Advances in Nutrition

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

Cited by 10 publications

References 27 publications

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children

Prenatal Exposure to Nitrate from Drinking Water and Markers of Fetal Growth Restriction: A Population-Based Study of Nearly One Million Danish-Born Children

Nitrate contamination in drinking water and adverse reproductive and birth outcomes: a systematic review and meta-analysis

Dietary Nitrate from Plant Foods: A Conditionally Essential Nutrient for Cardiovascular Health

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