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Abstract：
BACKGROUND: Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother\'s arsenic exposure, folic acid, and spina bifida risk in Bangladesh.
METHODS: We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.
RESULTS: We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother\'s arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82).
CONCLUSIONS: Mother\'s arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
METHODS: We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.
RESULTS: We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother\'s arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82).
CONCLUSIONS: Mother\'s arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
摘要：
背景：脊柱裂，脊髓的发育畸形，与高死亡率和致残率有关。尽管基于叶酸的预防策略已成功降低脊柱裂的发生率，由于化学品暴露，一些地区仍然面临更高的风险。孟加拉国通过受污染的饮用水和高脊柱裂的高砷暴露。这项研究考察了母亲的砷暴露之间的关系，叶酸,孟加拉国的脊柱裂风险。
方法：我们在达卡的国家神经科学与医院研究所（NINS＆H）进行了一项基于医院的病例对照研究，孟加拉国,2016年12月至2022年12月。病例为一岁以下患有脊柱裂的婴儿，并由神经外科医生和影像学进一步分类。对照来自在NINS＆H和附近的DhakaShishu医院看到的儿童。母亲报告说怀孕期间使用叶酸，我们通过血清检测来评估叶酸的状态。使用石墨炉原子吸收分光光度法（GF-AAS）估算饮用水中的砷暴露量，并使用电感耦合等离子体质谱法（ICP-MS）估算脚趾甲中的砷暴露量。我们使用逻辑回归分析砷和脊柱裂之间的关系。我们使用分层模型来检查不同砷暴露水平下叶酸与脊柱裂之间的关联。
结果：我们评估了294例脊柱裂和163例对照的数据。我们没有发现母亲砷暴露对脊柱裂风险的主要影响。然而,在分层分析中，在趾甲砷浓度低于中位数0.46µg/g的女性中，使用叶酸与脊柱裂的几率较低（调整后的优势比[OR]：0.50，95％置信区间[CI]：0.25-1.00，p=0.05）。在趾甲砷浓度高于0.46µg/g的母亲中没有发现相关性(校正OR:1.09,95%CI:0.52-2.29,p=0.82).
结论：母亲的砷暴露改变了叶酸与脊柱裂的保护性联系。加强监测和额外的预防战略，如叶酸强化和减少砷，在高砷暴露地区需要。
方法：我们在达卡的国家神经科学与医院研究所（NINS＆H）进行了一项基于医院的病例对照研究，孟加拉国,2016年12月至2022年12月。病例为一岁以下患有脊柱裂的婴儿，并由神经外科医生和影像学进一步分类。对照来自在NINS＆H和附近的DhakaShishu医院看到的儿童。母亲报告说怀孕期间使用叶酸，我们通过血清检测来评估叶酸的状态。使用石墨炉原子吸收分光光度法（GF-AAS）估算饮用水中的砷暴露量，并使用电感耦合等离子体质谱法（ICP-MS）估算脚趾甲中的砷暴露量。我们使用逻辑回归分析砷和脊柱裂之间的关系。我们使用分层模型来检查不同砷暴露水平下叶酸与脊柱裂之间的关联。
结果：我们评估了294例脊柱裂和163例对照的数据。我们没有发现母亲砷暴露对脊柱裂风险的主要影响。然而,在分层分析中，在趾甲砷浓度低于中位数0.46µg/g的女性中，使用叶酸与脊柱裂的几率较低（调整后的优势比[OR]：0.50，95％置信区间[CI]：0.25-1.00，p=0.05）。在趾甲砷浓度高于0.46µg/g的母亲中没有发现相关性(校正OR:1.09,95%CI:0.52-2.29,p=0.82).
结论：母亲的砷暴露改变了叶酸与脊柱裂的保护性联系。加强监测和额外的预防战略，如叶酸强化和减少砷，在高砷暴露地区需要。
