Jul Clemmensen Pernille, Brix Nis, Schullehner Jörg, Lunddorf Lea Lykke Harrits, Ernst Andreas, Ebdrup Ninna Hinchely, Bjerregaard Anne Ahrendt, Hansen Birgitte, Thomas Stayner Leslie, Ingi Halldorsson Thorhallur, Frodi Olsen Sjurdur, Sigsgaard Torben, Kolstad Henrik Albert, Ramlau-Hansen Cecilia Høst
Department of Public Health, Aarhus University, Aarhus, Denmark.
Department of Public Health, Aarhus University, Aarhus, Denmark; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
Environ Int. 2022 Dec;170:107659. doi: 10.1016/j.envint.2022.107659. Epub 2022 Nov 24.
In Western countries, age at pubertal development has declined during the last century in girls, and probably also in boys. No studies have investigated whether nitrate, a widespread environmental exposure with teratogenic and hormone disrupting properties, might affect timing of puberty.
We investigated if prenatal exposure to nitrate from drinking water and diet was associated with timing of puberty.
This cohort study included 15,819 children born from 2000 to 2003 within the Danish National Birth Cohort. Self-reported information on current status of various pubertal milestones was provided every six months by a questionnaire from 11 years of age until 18 years or full maturity, whichever came first. Maternal nitrate intake from diet (mg/day) was derived from a mid-pregnancy food frequency questionnaire and individual level nitrate exposure from drinking water (mg/L) was derived using measurements from Danish public waterworks. Adjusted average differences in months in age at attaining several pubertal milestones as well as the average age difference in age at attaining all the milestones were estimated separately for diet and water using a regression model for interval-censored data. C- and E-vitamin, red meat and processed meat intake were explored as potential effect modifiers in sub-analyses.
No strong associations were observed between prenatal exposure to nitrate and timing of puberty in children. However, sons born of mothers with a nitrate concentration in drinking water at their residential address of > 25 mg/L (half of the World Health Organisation (WHO) guideline value) compared with ≤ 1 mg/L showed a tendency towards earlier age at pubertal development with an average age difference of -1.2 months (95 % confidence interval,-3.0;0.6) for all the pubertal milestones combined.
Studies including more highly exposed children are needed before the current WHO drinking water guideline value for nitrate can be considered safe concerning pubertal development.
在西方国家，上个世纪女孩青春期发育的年龄有所下降，男孩可能也是如此。尚无研究调查硝酸盐这种具有致畸和激素干扰特性的广泛环境暴露因素是否会影响青春期时间。
我们调查了孕期通过饮用水和饮食接触硝酸盐是否与青春期时间有关。
这项队列研究纳入了丹麦国家出生队列中2000年至2003年出生的15819名儿童。从11岁到18岁或发育完全成熟（以先到者为准），每六个月通过问卷提供一次关于各种青春期发育里程碑当前状况的自我报告信息。母亲饮食中硝酸盐摄入量（毫克/天）来自孕中期食物频率问卷，个体饮用水中硝酸盐暴露水平（毫克/升）通过丹麦公共自来水厂的测量数据得出。使用区间删失数据回归模型，分别针对饮食和水估计达到多个青春期发育里程碑时年龄的调整平均差异，以及达到所有里程碑时的平均年龄差异。在亚组分析中探讨了维生素C和E、红肉和加工肉类摄入量作为潜在效应修饰因素。
未观察到儿童孕期接触硝酸盐与青春期时间之间存在强关联。然而，母亲居住地址饮用水中硝酸盐浓度>25毫克/升（世界卫生组织（WHO）指导值的一半）的儿子与≤1毫克/升的儿子相比，青春期发育有提前的趋势，所有青春期发育里程碑综合起来的平均年龄差异为-1.2个月（95%置信区间，-3.0；0.6）。
在考虑当前WHO饮用水硝酸盐指导值对青春期发育安全之前，需要开展纳入更多高暴露儿童的研究。
