Systematic review and meta-analysis of epidemiologic data on infectious disease in relation to exposure to twelve perfluoroalkyl substances (PFAS)

Abstract

Background

While some per- and polyfluoroalkyl substances (PFAS) are immunosuppressants, whether they have an adverse effect on infectious disease morbidity is unclear. We conducted a systematic review and meta-analysis of epidemiologic data on the association between an incremental increase in serum concentration of any of 12 PFAS and the risk or rate of infectious disease (ID).

Methods

From 25 reports representing 18 unique study populations, we conducted meta-analyses stratified on exposure type (log-transformed or absolute scale) and outcome type (risk or rate). To synthesize data that could not be combined with meta-analysis due to different exposure or outcome types, we additionally conducted vote counting and calculated combined p-values.

Results

A small positive association between PFAS exposure and ID risk or rate was more frequently reported than not, though in the synthesized data statistical significance was present only in a few instances. The meta-analyses and combined p-value analyses had many similar findings. In the combined p-value analyses, statistically significant positive associations were noted between Perfluorononanoic acid and lower respiratory tract infection (LRTI) event rates, Perfluorooctanesulfonamide and LRTI event rates and LRTI risk and rates combined, Perfluorooctanoic acid and Perfluorodecanoic acid with all ID risk and rates combined, and Perfluoroundecanoic acid with all ID risk.

Conclusion

We identified moderate evidence of positive associations that were of variable size but usually small; the certainty of evidence was, however, generally low or very low and diminished by the possible influences of multiple testing and covariance among results not accounted for in the analyses.

Prospero registration

CRD42024551990.