Mining leachate contamination and subfecundity among women living near the United States-Mexico border

Design and sample We conducted a retrospective cohort study on pregnancy cases of women living across the watershed area of the Sonora River, in those municipalities directly affected by the environmental disaster: Arizpe, Banámichi, Huépac, San Felipe de Jesús, Aconchi, Baviácora, Ures, and some villages belonging to the state capital Hermosillo (Molino de Camou, Topahue, San Francisco de Batuc, El Tronconal and San Pedro El Saucito) (Lammers., 2014). In addition, we included Magdalena de Kino as a non-exposed community, whose water supply source is different from the resting municipalities, but shares common climate and ecological characteristics (Figure 1). Participants were first identified by the local health centers and then visited at home, where they were asked to participate before signing the informed consent. Inclusion criteria were women being older than 18 years, planned pregnancy, conception of pregnancy in municipalities considered as exposed and non-exposed in this study after the disaster or before up to 10 years prior, with the possibility of including more than one pregnancy for each participant. Among the criteria for exclusion were having a physical or mental disability to adequately respond the questionnaire or refused to sign the consent. The study sample size had enough statistical power according to the Freedman table (Freedman., 1982), taking into account that previous studies exploring fecundity and metal exposure worked with samples between 41 and 300 pregnancies (Snijders., 2012). The study was approved by either ethical review board of the University of Sonora, Mexico, and the Industrial University of Santander, Colombia. Statistical methods Univariate and bivariate descriptive analysis were made after completing the database, using chi-square, Student’s t, and Mann-Whitney U to test for differences between variables. Fecundability odds ratios (fOR) obtained from discrete time analogue of Cox’s proportional hazard models were used to estimate associations with logistic regression models using the macro dthaz (Dinno., 2011). For multiple analysis, variables included in the model had p<0.25 in the bivariate Wald-test or had effect changes > 20%. Models were adjusted for age at pregnancy, age at first pregnancy, pregnancy order, maternal occupation, father’s occupation, father’s age, and father history of hyperthyroidism. Finally, for each approach to measure exposure (acute, acute plus non-affected zone, and pollution gradient), we developed three models: model 1 included all pregnancies with TTP up to 12 months; model 2 excluded pregnancies with TTP = 1; whereas model 3 only included first time pregnancies in order to control for obstetric history of participants (Idrovo et al., 2005; Weinberg et al., 1994 ). All assumptions and adjustments were evaluated, and Stata 14 was the statistical software used to carry out all the analysis (Stata Corporation, College Station, USA).研究设计与样本 本研究针对索诺拉河流域范围内受此次环境灾难直接影响的自治市：阿里斯佩（Arizpe）、巴纳米奇（Banámichi）、韦帕克（Huépac）、圣费利佩德赫苏斯（San Felipe de Jesús）、阿孔奇（Aconchi）、巴维阿科拉（Baviácora）、乌雷斯（Ures），以及墨西哥索诺拉州州府埃莫西约（Hermosillo）下辖的部分村落：卡莫磨坊（Molino de Camou）、托帕韦（Topahue）、圣弗朗西斯科德巴图克（San Francisco de Batuc）、埃尔特龙科纳尔（El Tronconal）与圣佩德罗埃尔萨西托（San Pedro El Saucito）的女性妊娠病例开展回顾性队列研究（Lammers，2014）。此外，本研究纳入马格达莱纳德基诺（Magdalena de Kino）作为非暴露社区，该社区供水水源与其余自治市不同，但气候与生态特征与研究涉及区域一致（图1）。 参与者首先由当地卫生中心初步识别，随后由研究人员上门家访，在签署知情同意书前征询其参与意愿。纳入标准为：年龄满18周岁以上的女性、计划妊娠、于本研究划定的暴露或非暴露自治市，在灾难发生后或灾难发生前10年内受孕，每名参与者可纳入多次妊娠记录。排除标准包括：存在无法有效完成问卷的躯体或精神障碍，或拒绝签署知情同意书。本研究样本量依据Freedman表（Freedman，1982）具备足够统计效力；既往针对生育力与金属暴露的相关研究，样本量多介于41至300例妊娠之间（Snijders，2012）。本研究经墨西哥索诺拉大学伦理审查委员会与哥伦比亚桑坦德工业大学伦理审查委员会批准。 统计分析方法 数据库搭建完成后，本研究开展单变量与双变量描述性分析，采用卡方检验、Student t检验及曼-惠特尼U检验比较变量间差异。采用离散时间版Cox比例风险模型计算生育概率比（fecundability odds ratios, fOR），并借助宏程序dthaz结合逻辑回归模型评估暴露与结局的关联效应（Dinno，2011）。多因素分析中，纳入模型的变量需满足双变量Wald检验p<0.25，或效应改变率超过20%。模型校正因素包括：妊娠时年龄、首次妊娠年龄、妊娠次数、母亲职业、父亲职业、父亲年龄及父亲甲状腺功能亢进病史。 针对三种暴露测量方式（急性暴露、急性暴露加非暴露区域、污染梯度），本研究分别构建三类模型：模型1纳入所有妊娠等待时间（time to pregnancy, TTP）≤12个月的妊娠；模型2排除妊娠等待时间为1个月的妊娠；模型3仅纳入首次妊娠的病例，以控制参与者的产科病史（Idrovo等，2005；Weinberg等，1994）。所有分析假设与校正方案均经过评估，本研究采用Stata 14统计软件完成全部分析（美国Stata公司，大学城站）。