Association between Drinking Water Nitrate and Adverse Reproductive Outcomes: A Systematic PRISMA Review

Hannah S Clausen,Ninna H Ebdrup,Cecilia H Ramlau-Hansen,Julie Lyngsø,Bjørn Bay,Ulla B Knudsen,Jörg Schullehner,Ida M Barsøe

doi:10.3390/w12082287

Abstract

One in six couples experience fertility problems. Environmental factors may affect reproductive health; however, evidence is lacking regarding drinking water nitrates and outcomes of male and female fertility. The aim of this study was to investigate if exposure to nitrates in drinking water is associated with adverse reproductive outcomes in humans, and animals of fertile age. We conducted a systematic literature search and included case-control studies, cohort studies, and randomized control trials reporting on the association between drinking water nitrate exposure of men, women, or animals and adverse reproductive outcomes, specified as: Semen quality parameters, time to pregnancy (TTP), pregnancy rates, assisted reproductive technologies (ART), and spontaneous abortion. Findings were reported in a narrative synthesis. A total of 12 studies were included. The only human study included reported a decrease in spontaneous abortion at any detectable nitrate level. Overall, the 11 included animal studies support a potential negative effect on semen quality parameters but report equivocal results on TTP and number of offspring produced, and higher risk of spontaneous abortion. In conclusion, animal studies indicate possible effects on semen quality parameters and spontaneous abortion. However, with a few studies, including some with methodological limitations and small sample sizes, caution must be applied when interpreting these results.

Highlights

The toxicology impact on human health for short and long-term exposure of nitrate is complex and not fully explored
The outcomes assessed were measures of subfecundity and infertility (e.g., semen quality parameters, time to pregnancy (TTP), pregnancy rates, use of assisted reproductive technologies (ART)), and spontaneous abortion, which could be an indirect measurement of infertility
CI = Confidence Interval. ↓: decreased risk of adverse reproductive outcomes. a : Cut-off between spontaneous abortion and stillbirth as stated in the study but this definition has changed over time

Summary

Introduction

The toxicology impact on human health for short and long-term exposure of nitrate is complex and not fully explored. Nitrates occur in both drinking water, food and medicine [1]. Water 2020, 12, 2287 nitrates can pass the placental blood barrier, exposing the fetus in utero [5]. Nitrate drinking water contamination is a global issue, especially in areas with agricultural pressure, and 2–3% of the population in U.S and Europe might be exposed to levels exceeding the maximum contaminant level (MCL) for drinking water nitrites and nitrates (3 mg/L and 50 mg/L respectively) set by the

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