Abstract：
BACKGROUND: There is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth.
OBJECTIVE: We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA).
METHODS: We included all births in Sweden during 2012-2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture.
RESULTS: Among the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01-1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight.
CONCLUSIONS: We observed an association of the sum of PFAS4 - especially PFOS - with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.
OBJECTIVE: We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA).
METHODS: We included all births in Sweden during 2012-2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture.
RESULTS: Among the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01-1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight.
CONCLUSIONS: We observed an association of the sum of PFAS4 - especially PFOS - with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.
摘要：
背景：全氟烷基物质和多氟烷基物质（PFAS）与胎儿生长之间的关联尚无定论。
目的：我们进行了一项全国范围的基于注册的队列研究，以评估估计的孕妇暴露量与全氟辛烷磺酸（PFOS）总和（PFAS4）的相关性。全氟辛酸（PFOA），全氟壬酸（PFNA）和全氟己烷磺酸（PFHxS）具有出生体重以及小（SGA）和大胎龄（LGA）的风险。
方法：我们纳入了2012-2018年期间瑞典所有出生的母亲，这些母亲在接受市政饮用水服务的地区出生≥4年，在这些地区测量了生水和饮用水中的PFAS。使用一室毒物动力学模型，我们通过联系居住史估计了怀孕期间PFAS4的累积母体血液水平。瑞典的市政PFAS水浓度和特定年份的背景血清PFAS浓度。通过注册链接获得个体出生结果和协变量。通过线性和逻辑回归估计β系数和比值比（OR）的平均值和95％置信区间（CI），分别。进行分位数g-计算回归以评估PFAS4混合物的影响。
结果：在包括248,804名单胎新生儿中，未观察到PFAS4与出生体重或SGA的总体关联.然而,LGA有一个协会，将最高PFAS4四分位数与最低四分位数进行比较时，多变量校正OR1.08（95％CI：1.01-1.16）。这些关联仍然存在于混合效应方法中，所有PFAS，除了PFOA,贡献了积极的权重。
结论：我们观察到PFAS4（尤其是PFOS）的总和与LGA的风险增加有关，但不是SGA或出生体重。与暴露评估相关的限制在解释中仍然需要谨慎。
目的：我们进行了一项全国范围的基于注册的队列研究，以评估估计的孕妇暴露量与全氟辛烷磺酸（PFOS）总和（PFAS4）的相关性。全氟辛酸（PFOA），全氟壬酸（PFNA）和全氟己烷磺酸（PFHxS）具有出生体重以及小（SGA）和大胎龄（LGA）的风险。
方法：我们纳入了2012-2018年期间瑞典所有出生的母亲，这些母亲在接受市政饮用水服务的地区出生≥4年，在这些地区测量了生水和饮用水中的PFAS。使用一室毒物动力学模型，我们通过联系居住史估计了怀孕期间PFAS4的累积母体血液水平。瑞典的市政PFAS水浓度和特定年份的背景血清PFAS浓度。通过注册链接获得个体出生结果和协变量。通过线性和逻辑回归估计β系数和比值比（OR）的平均值和95％置信区间（CI），分别。进行分位数g-计算回归以评估PFAS4混合物的影响。
结果：在包括248,804名单胎新生儿中，未观察到PFAS4与出生体重或SGA的总体关联.然而,LGA有一个协会，将最高PFAS4四分位数与最低四分位数进行比较时，多变量校正OR1.08（95％CI：1.01-1.16）。这些关联仍然存在于混合效应方法中，所有PFAS，除了PFOA,贡献了积极的权重。
结论：我们观察到PFAS4（尤其是PFOS）的总和与LGA的风险增加有关，但不是SGA或出生体重。与暴露评估相关的限制在解释中仍然需要谨慎。
