产前暴露于全氟和多氟烷基物质 (PFAS) 与儿童期哮喘和喘息发病率的关系：一项在瑞典罗讷比进行的基于登记的队列研究
2026/04/28
摘要
背景：生命早期暴露于全氟和多氟烷基物质 (PFAS) 可能会影响发育中的肺部和免疫系统，并增加儿童哮喘的风险，但尚未在高暴露人群中进行过相关研究。本研究旨在评估瑞典布莱金厄省（Blekinge County）产前 PFAS 暴露与儿童期哮喘和喘息发病率之间的关联。在该省罗讷比市（Ronneby），一部分居民因饮用水被水成膜泡沫 (AFFF) 污染而暴露于 PFAS。
方法：我们建立了一个基于登记的开放队列，包含 11,488 名 2006 年至 2013 年间出生于布莱金厄省的儿童，并对每个人从出生起随访至 12 岁或 2022 年 12 月 31 日。我们将母亲的居住地址记录与供水记录相链接，以创建一个分类代理变量，用于反映因饮用水导致的产前 PFAS 暴露情况。我们从行政健康档案中确定了喘息和哮喘的新发病例，并使用 Cox 比例风险模型估算了风险比 (HR），该模型针对个体层面的混杂因素进行了调整，包括母亲孕早期吸烟、分娩时母亲年龄、产次、儿童性别、父母哮喘史以及社会经济因素。作为次要分析，我们应用鲁宾因果模型 (RCM) 分析，通过使用在已测量的混杂因素上达到平衡的极高暴露个体和背景暴露个体的匹配数据集，来评估产前 PFAS 暴露对极高暴露人群中喘息和哮喘的平均边际效应。
结果：总体而言，在随访期间，18% 的儿童被诊断为喘息，17% 的儿童被诊断为哮喘。极高的产前 PFAS 暴露与哮喘发病率相关（HR：1.44，95% 置信区间 [1.08, 1.92]），而在高暴露或中度暴露组中，以及对于喘息而言，均未观察到相关性。在 RCM 分析中，背景暴露组的哮喘估计累积发病率为 16.1%，极高暴露组为 26.7%（Fisher 精确检验 p < 0.001）。本研究的局限性包括依赖基于地址的分类代理变量来评估产前 PFAS 暴露，这可能会导致非差异性暴露错分，并限制了区分产前暴露和儿童早期暴露影响的能力。
结论：在本研究中，极高的产前 PFAS 暴露与较高的儿童期哮喘发病率相关。尽管这些结果仍需进一步验证，但它们表明与 AFFF 相关的 PFAS 污染对公共卫生具有重要的影响。
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and incidence of asthma and wheeze in childhood: A register-based cohort study in Ronneby, Sweden
Blomberg AJ, Nielsen C, Borgström Bolmsjö B, Bind MA, Hartman L, Saxne Jöud A
Abstract
BACKGROUND:Early-life exposure to per- and polyfluoroalkyl substances (PFAS) may impact the developing lungs and immune system and increase the risk of childhood asthma, but no studies have been conducted in a high-exposed population. The objective of this study was to estimate associations between prenatal PFAS exposure and childhood incidence of asthma and wheeze in Blekinge County, Sweden, where a subset of residents in the city of Ronneby was exposed to PFAS from drinking water contaminated by aqueous film-forming foam (AFFF).
METHODS:We constructed a register-based open cohort of 11,488 children born in Blekinge county between 2006 and 2013 and followed each individual from birth until age 12 or December 31, 2022. Maternal address history was linked to water distribution records to create a categorical proxy variable for prenatal PFAS exposure from drinking water. We identified incident cases of wheeze and asthma from administrative health records and estimated hazard ratios (HRs) using Cox proportional hazards models adjusted for individual-level confounders, including maternal smoking in early pregnancy, maternal age at delivery, parity, child sex, parental asthma, and socioeconomic factors. As a secondary analysis, we applied a Rubin Causal Model (RCM) analysis to estimate the average marginal effect of prenatal PFAS exposure on wheeze and asthma among the very highly-exposed population, using a matched dataset of very-high and background-exposed individuals balanced on measured confounders.
RESULTS:Overall, 18% of children were diagnosed with wheeze and 17% with asthma during follow-up. Very high prenatal PFAS exposure was associated with incidence of asthma (HR: 1.44, 95% CI [1.08, 1.92]), whereas no associations were observed for the high or intermediate exposure groups or for wheeze. In the RCM analysis, the estimated cumulative incidence of asthma was 16.1% in the background-exposed group and 26.7% in the very highly exposed group (Fisherian p < 0.001). Study limitations include reliance on an address-based categorical proxy for prenatal PFAS exposure, which likely results in non-differential exposure misclassification and limits the ability to distinguish prenatal from early-childhood exposure effects.
CONCLUSION:In this study, very high prenatal PFAS exposure was associated with a higher incidence of childhood asthma. Although these results should be replicated, they suggest an important public health impact of AFFF-associated PFAS contamination.
背景：生命早期暴露于全氟和多氟烷基物质 (PFAS) 可能会影响发育中的肺部和免疫系统，并增加儿童哮喘的风险，但尚未在高暴露人群中进行过相关研究。本研究旨在评估瑞典布莱金厄省（Blekinge County）产前 PFAS 暴露与儿童期哮喘和喘息发病率之间的关联。在该省罗讷比市（Ronneby），一部分居民因饮用水被水成膜泡沫 (AFFF) 污染而暴露于 PFAS。
方法：我们建立了一个基于登记的开放队列，包含 11,488 名 2006 年至 2013 年间出生于布莱金厄省的儿童，并对每个人从出生起随访至 12 岁或 2022 年 12 月 31 日。我们将母亲的居住地址记录与供水记录相链接，以创建一个分类代理变量，用于反映因饮用水导致的产前 PFAS 暴露情况。我们从行政健康档案中确定了喘息和哮喘的新发病例，并使用 Cox 比例风险模型估算了风险比 (HR），该模型针对个体层面的混杂因素进行了调整，包括母亲孕早期吸烟、分娩时母亲年龄、产次、儿童性别、父母哮喘史以及社会经济因素。作为次要分析，我们应用鲁宾因果模型 (RCM) 分析，通过使用在已测量的混杂因素上达到平衡的极高暴露个体和背景暴露个体的匹配数据集，来评估产前 PFAS 暴露对极高暴露人群中喘息和哮喘的平均边际效应。
结果：总体而言，在随访期间，18% 的儿童被诊断为喘息，17% 的儿童被诊断为哮喘。极高的产前 PFAS 暴露与哮喘发病率相关（HR：1.44，95% 置信区间 [1.08, 1.92]），而在高暴露或中度暴露组中，以及对于喘息而言，均未观察到相关性。在 RCM 分析中，背景暴露组的哮喘估计累积发病率为 16.1%，极高暴露组为 26.7%（Fisher 精确检验 p < 0.001）。本研究的局限性包括依赖基于地址的分类代理变量来评估产前 PFAS 暴露，这可能会导致非差异性暴露错分，并限制了区分产前暴露和儿童早期暴露影响的能力。
结论：在本研究中，极高的产前 PFAS 暴露与较高的儿童期哮喘发病率相关。尽管这些结果仍需进一步验证，但它们表明与 AFFF 相关的 PFAS 污染对公共卫生具有重要的影响。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（PLoS Med. 2026 Apr 9; DOI: 10.1371/journal.pmed.1004659）
（PLoS Med. 2026 Apr 9; DOI: 10.1371/journal.pmed.1004659）
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and incidence of asthma and wheeze in childhood: A register-based cohort study in Ronneby, Sweden
Blomberg AJ, Nielsen C, Borgström Bolmsjö B, Bind MA, Hartman L, Saxne Jöud A
Abstract
BACKGROUND:Early-life exposure to per- and polyfluoroalkyl substances (PFAS) may impact the developing lungs and immune system and increase the risk of childhood asthma, but no studies have been conducted in a high-exposed population. The objective of this study was to estimate associations between prenatal PFAS exposure and childhood incidence of asthma and wheeze in Blekinge County, Sweden, where a subset of residents in the city of Ronneby was exposed to PFAS from drinking water contaminated by aqueous film-forming foam (AFFF).
METHODS:We constructed a register-based open cohort of 11,488 children born in Blekinge county between 2006 and 2013 and followed each individual from birth until age 12 or December 31, 2022. Maternal address history was linked to water distribution records to create a categorical proxy variable for prenatal PFAS exposure from drinking water. We identified incident cases of wheeze and asthma from administrative health records and estimated hazard ratios (HRs) using Cox proportional hazards models adjusted for individual-level confounders, including maternal smoking in early pregnancy, maternal age at delivery, parity, child sex, parental asthma, and socioeconomic factors. As a secondary analysis, we applied a Rubin Causal Model (RCM) analysis to estimate the average marginal effect of prenatal PFAS exposure on wheeze and asthma among the very highly-exposed population, using a matched dataset of very-high and background-exposed individuals balanced on measured confounders.
RESULTS:Overall, 18% of children were diagnosed with wheeze and 17% with asthma during follow-up. Very high prenatal PFAS exposure was associated with incidence of asthma (HR: 1.44, 95% CI [1.08, 1.92]), whereas no associations were observed for the high or intermediate exposure groups or for wheeze. In the RCM analysis, the estimated cumulative incidence of asthma was 16.1% in the background-exposed group and 26.7% in the very highly exposed group (Fisherian p < 0.001). Study limitations include reliance on an address-based categorical proxy for prenatal PFAS exposure, which likely results in non-differential exposure misclassification and limits the ability to distinguish prenatal from early-childhood exposure effects.
CONCLUSION:In this study, very high prenatal PFAS exposure was associated with a higher incidence of childhood asthma. Although these results should be replicated, they suggest an important public health impact of AFFF-associated PFAS contamination.
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