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Perfluoroalkyl substances (PFASs) are persistent and bio-accumulative compounds that have been recognized as important immune hazards by animal studies. However, epidemiological studies regarding the impact on infant infections were inconsistent. We investigated the associations between prenatal exposure to PFASs and acute infectious diseases including common cold, bronchitis/pneumonia, and diarrhea in early childhood. Participating 235 mother–infant pairs were recruited from the Laizhou Wan (Bay) birth cohort (LWBC), a prospective study in Shandong, China between September 2010 and 2013. Ten selected PFASs congeners including PFOA, PFOS, PFNA, PFDA, PFUA, PFDoA, PFHxS, PFBS, PFHpA, and PFOSA were measured from maternal serum by HPLC-MS/MS. Detailed information on parent-reported frequency of acute infectious diseases was collected from questionnaires at 1-year follow-up, which was confirmed by the medical records. Logistic and Poisson regression models were used on binary health outcomes (yes/no) and the number of episodes of outcomes, which were reported as odds ratio (OR) and incidence rate-ratio (IRR), respectively. The risk of diarrhea increased by 4.99 (95% CI = 1.86, 13.39) per log-unit increase in PFOA. The frequencies of diarrhea increased by 97%–116% for each 10-fold increase in PFOA, PFNA, and PFDA. Moreover, when stratified by exclusively breastfeeding duration (at least 4 months or not), the adverse effects of PFASs exposures on diarrhea were more pronounced among the breastfed infants. There were no associations between prenatal PFASs exposure and common cold or bronchitis/pneumonia. Exposure to PFASs was associated with increased risks of diarrhea during the first year of life, and these effects were stronger among the breastfed infants. Due to the small sample size, our results should be interpreted with caution and additional studies on larger populations are needed to confirm our findings. [Display omitted] • Perfluoroalkyl substances (PFASs) are widely used in China and around the world. • We assessed the association between PFASs and acute infectious diseases in infancy. • PFASs especially PFOA was positively associated with the occurrence of diarrhea. • The adverse effects were stronger among the exclusively breastfed infants. [ABSTRACT FROM AUTHOR]