Grandjean Philippe, Heilmann Carsten, Weihe Pal, Nielsen Flemming, Mogensen Ulla B, Timmermann Amalie, Budtz-Jørgensen Esben
a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
b Department of Environmental Medicine , University of Southern Denmark , Odense , Denmark.
J Immunotoxicol. 2017 Dec;14(1):188-195. doi: 10.1080/1547691X.2017.1360968.
Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19-29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.
全氟烷基化物（PFASs）具有高度持久性，可能会引起免疫毒性效应。与PFAS相关的儿童疫苗抗体反应减弱可能受到婴儿期PFAS暴露的影响，而母乳喂养会增加PFAS暴露。在法罗群岛出生队列的490名成员中，275名和349名分别在18个月和5岁时参加了临床检查并提供了血样。在出生时和临床检查时测量了PFAS浓度。利用母乳喂养持续时间的信息，估计了婴儿期血清PFAS浓度曲线。作为结果，在5岁时测定了破伤风和白喉疫苗抗体的血清浓度。可获得八年前出生的前一个队列的数据用于汇总分析。产前暴露与五年后的抗体浓度呈负相关，每暴露量增加一倍，抗体浓度下降高达约20%，而18个月和5岁时血清浓度的相关性较弱。血清PFAS浓度模型显示18个月时的水平与测量值相似。估计的3个月和6个月时的浓度与5岁时的抗体浓度呈最强的负相关，尤其是破伤风抗体。联合分析显示，婴儿早期PFAS暴露每增加一倍，5岁时破伤风抗体浓度在统计学上显著下降19%-29%。这些发现支持了这样一种观点，即发育中的适应性免疫系统在婴儿期特别容易受到免疫毒性的影响。这种易感性在出生后的前6个月似乎最为明显，此时PFAS暴露受到母乳喂养的影响。
