Jennifer L Ames, Vanshika Sharma, Kristen Lyall

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals with many modern applications, leading to widespread contamination and universal human exposure. PFAS exposure during early life is of particular concern, given susceptibility of the developing fetal and infant brain to toxic exposures. This review aims to synthesize current evidence, discuss methodological challenges, and highlight research gaps to guide future studies on the impact of PFAS on neurodevelopment. Sixty-one studies in total were published from 2008 to March 2024, with 35 in the last five years. Findings primarily link early life PFAS exposure to reduced cognitive, motor, and language development in infancy and increased behavioral issues like hyperactivity in childhood. Large studies have shown mixed results concerning child cognition, executive function, autism, and ADHD, with some indicating no association or unexpected protective findings. Sex-specific associations have been observed, but not consistently. Most research has addressed low-level exposure, suggesting subtle but potentially significant population-wide neurodevelopmental effects. Recent research also highlights concerns about newer, alternative PFAS, suggesting they too might affect neurodevelopment.  The effects of early-life PFAS exposure on neurodevelopment merit further study, particularly the cumulative effects of prenatal and postnatal exposures. Research has not fully explored sensitive subgroups or potential mitigating factors such as breastfeeding and nutrient intake, which will require larger, more diverse samples. Future directions include deeper study of PFAS mixtures, interactions with other neurotoxic environmental chemicals, and effects of newer PFAS types. There is also a need to focus on neuropsychological functioning in later childhood, using direct assessments for more reliable evaluations.