Background

Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs.

Methods

A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables.

Results

Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood.

Conclusion

These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.

中文翻译：

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妊娠期暴露于全氟烷基物质和先天性心脏缺陷：巢式病例对照试验研究

背景

越来越多的证据表明，环境污染物可能会导致先天性心脏缺陷（CHD）的发生。但是，以前没有研究评估持久性环境污染物全氟烷基物质（PFAS）对冠心病的影响。这项探索性研究旨在得出妊娠PFAS与冠心病风险之间相关性的可检验假设。

方法

一项嵌套病例对照研究在11578名新生儿中进行。比较了在同一家医院分娩的158例CHD病例和158例非畸形对照者的暴露几率，分别与产妇年龄（±5岁）和同等年龄相匹配。使用超高效液相色谱-质谱联用技术，在分娩前和分娩期间收集的孕妇外周血和脐带血浆中测定了27种PFAS（包括线性和分支异构体）的浓度。条件logistic回归用于评估各个PFAS与冠心病风险之间的关联，并根据混杂变量进行了调整。

结果

孕产妇在高支链全氟辛烷磺酸（PFOS）异构体6-三氟甲基全氟庚烷磺酸钾[6 m-PFOS，校正比值比（aOR）（95％CI）= 2.47（1.05,5.83）]和全氟癸酸[PFDA，aOR（95 ％CI）= 2.33（1.00,5.45）]与间隔缺损几率的增加具有统计学意义，而线性PFOS [aOR（95％CI）= 3.65（1.09,12.16）]和全氟正十二酸[PFDoA ，aOR（95％CI）= 6.82（1.75，26.61）]与圆锥角膜缺损相关。效果评估还表明，较高的孕妇6 m-PFOS和PFDA浓度与室间隔缺损相关。但是，我们在脐带血中未观察到这些关联。

结论

这些探索性发现表明，大多数PFAS，尤其是线性PFOS，6 m-PFOS，PFDA和PFDoA的妊娠暴露与中隔和锥周缺损的更大风险相关。但是，需要进行更大范围的，有足够能力的研究来证实我们的发现，并更全面地研究其他最近引入的PFAS的潜在致畸作用，以及与个别CHD亚型的关联。