Nitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss. We conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996–2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables. No consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest. adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges. No association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.

中文翻译：

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饮用水硝酸盐与流产风险：一项全国性队列研究

硝酸盐污染存在于全世界的饮用水中。硝酸盐可以通过胎盘屏障。尽管有胎儿伤害的暗示性证据，但饮用水中硝酸盐暴露与流产之间的潜在关联仍有待研究。我们旨在调查饮用水中的硝酸盐是否与流产风险相关。我们在 1996 年至 2002 年期间对丹麦国家出生队列 (DNBC) 中的 100,410 名孕妇（在妊娠第 11 周左右登记）进行了一项全国性队列研究。从丹麦国家患者登记处和 DNBC 妊娠访谈中确定了妊娠第 22 周前的自然流产。利用国家饮用水水质监测数据库Jupiter，我们通过将地理编码的孕产妇住宅地址与供水区联系起来，估计了个体和特定时间的硝酸盐暴露。硝酸盐暴露在样条模型中使用对数转换的连续水平进行分析或分为五类。我们使用 Cox 比例风险模型来估计硝酸盐和流产之间的关联，并使用胎龄（天）作为时间尺度，调整人口、健康和生活方式变量。在将暴露作为分类变量进行调查时，没有发现一致的关联，并且在孕期特定分析中也发现了无效结果。在使用连续暴露变量的样条模型中，在 1 至 10 mg/L 之间的硝酸盐暴露量下，妊娠前三个月观察到流产风险适度增加，最高。在 5 mg/L 硝酸盐时调整后的风险比为 1.16（95% CI：1.01, 1.34）。这种趋势在较高的暴露范围内减弱。在将暴露作为分类变量进行调查时，未发现饮用水硝酸盐与流产风险之间存在关联。当我们将暴露建模为连续变量时，发现在妊娠早期的饮用水硝酸盐暴露与流产风险之间存在剂量依赖性关联。本研究未考虑极早期妊娠丢失，应进一步探讨生存偏差是否影响结果。在将暴露作为分类变量进行调查时，未发现饮用水硝酸盐与流产风险之间存在关联。当我们将暴露建模为连续变量时，发现在妊娠早期的饮用水硝酸盐暴露与流产风险之间存在剂量依赖性关联。本研究未考虑极早期妊娠丢失，应进一步探讨生存偏差是否影响结果。在将暴露作为分类变量进行调查时，未发现饮用水硝酸盐与流产风险之间存在关联。当我们将暴露建模为连续变量时，发现在妊娠早期的饮用水硝酸盐暴露与流产风险之间存在剂量依赖性关联。本研究未考虑极早期妊娠丢失，应进一步探讨生存偏差是否影响结果。