Säve-Söderbergh Melle, Gyllenhammar Irina, Schillemans Tessa, Lindfeldt Emelie, Vogs Carolina, Donat-Vargas Carolina, Helte Emilie, Ankarberg Emma, Glynn Anders, Ahrens Lutz, Åkesson Agneta
Science Division, Swedish Food Agency, Uppsala, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Science Division, Swedish Food Agency, Uppsala, Sweden; Department of Animal Biosciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
Environ Int. 2025 Apr;198:109415. doi: 10.1016/j.envint.2025.109415. Epub 2025 Mar 26.
There is inconclusive evidence of associations between exposure to per- and polyfluoroalkyl substances (PFAS) and diabetes and hypertensive disorders during pregnancy.
We conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal drinking water exposure to the sum of four major PFAS (PFAS4; perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA) and perfluorohexanoate (PFHxS)) with gestational diabetes mellitus (GDM), hypertension and preeclampsia.
We included nulliparous women giving birth in Sweden during 2012-2018 in large 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 considering residential history, municipal PFAS water concentration and year-specific maternal PFAS background serum levels. The outcomes and individual covariates were ascertained via register linkage. Mean values and 95% Confidence Intervals (CI) of Odds Ratios (OR) were estimated by logistic regression.
Among the 109,031 nulliparous women included, with an estimated average 7.8 ng PFAS4/mL serum (standard deviation: 2.0 ng/mL), there were indications of a non-monotonic inverse association for PFAS4 and GDM, corresponding to multivariable-adjusted OR 0.72 (95 % CI: 0.61-0.84) when comparing extreme quartiles. An inverse association were also seen for each PFAS individually. No clear associations were seen for hypertension or preeclampsia, although individual PFAS indicated significant associations, both inverse (PFAS and PFHxS) and direct (PFOS and PFNA) for hypertension.
In the present study, we observed indications of inverse, non-monotonic associations for PFAS4 and GDM. Some individual PFAS were also associated with hypertension, both direct and inverse. The limitations linked to the exposure assessment still require caution in the interpretation.
关于接触全氟和多氟烷基物质（PFAS）与孕期糖尿病及高血压疾病之间的关联，证据尚无定论。
我们开展了一项基于全国登记系统的队列研究，以评估估计的孕妇饮用水中四种主要PFAS（PFAS4；全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟壬酸（PFNA）和全氟己酸（PFHxS））总和暴露量与妊娠期糖尿病（GDM）、高血压和先兆子痫之间的关联。
我们纳入了2012年至2018年期间在瑞典由市政饮用水供应的大地区分娩的初产妇，这些地区的原水和饮用水中测量了PFAS。使用单室毒物动力学模型，我们根据居住史、市政PFAS水浓度和特定年份的孕妇PFAS背景血清水平，估计了孕期孕妇PFAS4的累积血液水平。通过登记链接确定结局和个体协变量。通过逻辑回归估计比值比（OR）的平均值和95%置信区间（CI）。
在纳入的109,031名初产妇中，估计平均血清PFAS4水平为7.8 ng/mL（标准差：2.0 ng/mL），有迹象表明PFAS4与GDM呈非单调负相关，比较极端四分位数时，多变量调整后的OR为0.72（95%CI：0.61 - 0.84）。每种PFAS单独分析时也观察到负相关。对于高血压或先兆子痫，未发现明确关联，尽管个别PFAS显示出显著关联，对于高血压，既有负相关（PFHxS）也有正相关（PFOS和PFNA）。
在本研究中，我们观察到PFAS4与GDM呈负相关、非单调关联的迹象。一些个别PFAS也与高血压有关，既有正相关也有负相关。与暴露评估相关的局限性在解释结果时仍需谨慎。
