Association of prenatal arsenic exposure with gestational hypertension and preeclampsia
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摘要:
目的 基于妊娠期高血压（GH）与子痫前期（PE）同属妊娠期高血压疾病谱、病程呈进展性的临床特点，本研究旨在探讨孕期尿砷（U-As）、胎盘砷（P-As）暴露与两类疾病发病风险及母体血压水平的关联，并分析剂量-反应关系，以期为妊娠期高血压疾病的环境病因防控提供流行病学参考依据。 方法 采用1∶1匹配病例对照研究，以年龄、分娩孕周为匹配条件，纳入妊娠期高血压疾病病例70例（仅包含GH患者38例、PE患者32例，排除慢性高血压相关类型）、健康孕妇对照70例；检测孕妇U-As、P-As浓度，运用多因素多项logistic回归分析、混合线性回归分析，并进一步分析剂量-反应关系。 结果 病例组P-As浓度高于对照组[6.489(5.675, 8.073)μg/kg vs. 5.038（4.312, 5.766）μg/kg, P＜0.001]，2组U-As水平差异无统计学意义；U-As与P-As浓度呈显著正相关（P＜0.05）。多项logistic回归显示，P-As可能是GH、PE发病的独立危险因素，U-As仅与GH发病风险存在关联趋势；混合线性回归分析结果显示，U-As、P-As均与收缩压、舒张压、平均动脉压呈显著正相关，P-As的关联效应相对更稳定，且P-As暴露与孕期血压存在显著剂量-反应递增趋势。 结论 孕期砷暴露与妊娠期高血压疾病的发生及孕期血压变化存在一定关联，且不同暴露标志物的效应存在差异。P-As蓄积水平与GH、PE发病风险升高相关，并可呈剂量依赖性影响母体血压水平，其宫内暴露指示价值相较于U-As更为突出。加强孕期环境砷暴露防护，或对降低妊娠期高血压疾病发生风险具有一定的参考意义。 Abstract:Objective Based on the clinical characteristics that gestational hypertension (GH) and preeclampsia (PE) belong to the spectrum of hypertensive disorders of pregnancy with progressive disease courses, this study aimed to investigate the associations of urinary arsenic (U-As) and placental arsenic (P-As) exposure during pregnancy with the risk of these two disorders and maternal blood pressure levels, as well as to analyze their dose-response relationships, so as to provide epidemiological evidence for the prevention and control of environmental etiology of hypertensive disorders of pregnancy. Methods A 1∶1 matched case-control study was conducted. A total of 70 cases with hypertensive disorders of pregnancy (including 38 GH patients and 32 PE patients, excluding cases related to chronic hypertension) and 70 healthy pregnant women as controls were enrolled, matched by maternal age and gestational week at delivery. Concentrations of U-As and P-As were measured. Multinomial logistic regression analysis and linear mixed model analysis were performed, followed by further dose-response relationship analysis. Results The P-As concentration in the case group was significantly higher than that in the control group [6.489 (5.675, 8.073)μg/kg vs. 5.038 (4.312, 5.766) μg/kg, P < 0.001], while no statistically significant difference in U-As levels was observed between the two groups. A significant positive correlation was found between U-As and P-As concentrations (P < 0.05). Multinomial logistic regression analysis indicated that P-As might be an independent risk factor for the onset of GH and PE, whereas U-As only showed a marginal association trend with GH risk. Linear mixed model analysis revealed that both U-As and P-As were significantly positively correlated with systolic blood pressure, diastolic blood pressure and mean arterial pressure. The association effect of P-As was relatively more stable, and a significant increasing dose-response trend was identified between P-As exposure and blood pressure during pregnancy. Conclusion Arsenic exposure during pregnancy is associated with the development of hypertensive disorders of pregnancy and changes in maternal blood pressure, with differential effects across different exposure biomarkers. Elevated placental arsenic accumulation is correlated with increased risks of GH and PE, and exerts dose-dependent effects on maternal blood pressure, showing a superior indicative value of in-utero exposure compared with urinary arsenic. Strengthening the prevention of environmental arsenic exposure during pregnancy may contribute to reducing the risk of hypertensive disorders of pregnancy. -
表 1 病例组与对照组孕产妇基本资料比较
Table 1. Comparison of basic characteristics between the non-HDP group and the HDP group
项目 对照组(n=70) 病例组(n=70) 统计量 P值 分娩孕周(x±s，周) 37.91±1.41 37.73±1.82 1.933a 0.057 孕妇年龄[M(P25, P75), 岁] 30.00(27.00, 32.00) 29.00(26.00, 32.25) -1.110b 0.267 孕妇身高[M(P25, P75), cm] 160.00(157.75, 163.00) 162.00(158.00, 166.25) -1.275b 0.202 孕前体重[M(P25, P75), kg] 55.00(51.00, 59.25) 60.00(53.50, 70.00) -3.487b ＜0.001 孕前BMI[M(P25, P75)] 21.09(19.55, 23.22) 22.76(20.93, 26.58) -3.216b 0.001 怀孕次数[M(P25, P75), 次] 2(1, 3) 2(1, 3) -1.714b 0.086 生育次数[M(P25, P75), 次] 1(1, 2) 1(1, 2) -1.333b 0.182 孕期体重增长(x±s，kg) 14.59±4.41 14.21±5.54 0.443a 0.658 糖尿病或妊娠期糖尿病[例(%)] 24(34.29) 29(41.43) 0.725c 0.384 妊娠合并甲减或亚甲减[例(%)] 8(11.43) 12(17.14) 0.933c 0.334 妊娠期肝内胆汁淤积症[例(%)] 2(2.86) 3(4.29) 0.207c 0.649 大学及以上学历[例(%)] 47(67.14) 50(71.43) 0.302c 0.583 注：a为t值，b为Z值，c为χ2值。 
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表 2 病例组与对照组砷暴露指标比较
Table 2. Comparison of arsenic exposure indicators between the case group and the control group
组别 例数 P-As
[M(P25, P75)，μg/kg]U-As
[M(P25, P75)，μg/L]对照组 70 5.038(4.312, 5.766) 10.696(5.440, 16.131) 病例组 70 6.489(5.675, 8.073) 12.852(7.988, 19.835) Z值 -5.001 -1.261 P值 ＜0.001 0.207
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表 3 U-As与P-As的混合线性回归分析
Table 3. Mixed linear regression analysis of U-As and P-As
变量 SE t值 P值 β 95% CI 模型1：U-As与P-As的单因素混合线性回归模型 lnAs-U 0.030 2.741 0.007 0.083 0.023~0.142 模型2：U-As与P-As多因素混合线性回归模型 lnAs-U 0.030 2.940 0.004 0.087 0.028~0.145 注：模型2校正了孕前BMI、孕期体重增长、产次、妊娠合并甲状腺功能减退(含亚临床甲减)及糖尿病/妊娠期糖尿病病史混杂因素。
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表 4 砷暴露与血压的混合线性模型
Table 4. The mixed linear model of arsenic exposure and blood pressure
变量 SBP DBP MAP β(95% CI) P值 β(95% CI) P值 β(95% CI) P值 模型1：尿砷与血压的混合线性模型 lnAs-U 2.994(0.173~5.816) 0.038 2.373(0.309~4.437) 0.025 2.580(0.351~4.809) 0.024 模型2：胎盘砷与血压的混合线性模型 lnAs-P 17.750(10.132~25.369) ＜0.001 9.558(3.767~15.350) 0.001 12.289(6.139~18.439) ＜0.001 注：各分析模型均校正了孕前BMI、孕期体重增长、产次、妊娠合并甲状腺功能减退(含亚临床甲减)及糖尿病/妊娠期糖尿病病史混杂因素。SBP：产前最高收缩压；DBP：产前最高舒张压；MAP：产前平均动脉压。
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表 5 砷暴露与产前血压的剂量-反应关系(混合线性模型)
Table 5. The dose-response relationship between arsenic exposure and prenatal blood pressure (mixed linear model)
变量 SBP DBP MAP β(95% CI) P值 β(95% CI) P值 β(95% CI) P值 模型1：尿砷暴露与血压的剂量-反应关系(以低暴露为参照组) 中暴露 -1.643(-7.765~4.478) 0.596 -2.381(-6.834~2.072) 0.292 -2.135(-6.957~2.687) 0.383 高暴露 3.563(-2.561~9.687) 0.252 2.790(-1.665~7.245) 0.218 3.048(-1.776~7.872) 0.214 模型2：胎盘砷暴露与血压的剂量-反应关系(以低暴露为参照组) 中暴露 6.662(0.842~12.483) 0.025 0.790(-3.625~5.204) 0.724 2.747(-1.958~7.452) 0.250 高暴露 13.048(7.113~18.982) ＜0.001 6.339(1.838~10.840) 0.006 8.575(3.778~13.372) 0.001 注：各分析模型均校正了孕前BMI、孕期体重增长、产次、妊娠合并甲状腺功能减退(含亚临床甲减)及糖尿病/妊娠期糖尿病病史混杂因素。
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表 6 U-As、P-As与GH、PE的多项logistic回归分析
Table 6. Multivariate logistic regression analysis of U-As, P-As, GH, and PE
变量 GH PE β SE OR(95% CI) P值 β SE OR(95% CI) P值 模型1：U-As与妊娠期高血压疾病严重程度的多项logistic回归分析 lnAs-U 0.654 0.276 1.923(1.120~3.300) 0.018 0.288 0.262 1.333(0.797~2.229) 0.273 模型2：P-As与妊娠期高血压疾病严重程度的多项logistic回归分析 lnAs-P 3.659 0.879 38.835(6.941~217.287) ＜0.001 2.866 0.884 17.563(3.106~99.306) 0.001 注：各分析模型均校正了孕前BMI、孕期体重增长、产次、妊娠合并甲状腺功能减退(含亚临床甲减)及糖尿病/妊娠期糖尿病病史混杂因素。
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