PFAS as silent programmers of human health: Prenatal exposure, low-dose effects, and intergenerational risk

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants. Due to their chemical stability, bioaccumulative potential, and use in industrial and consumer products, human exposure to PFAS has become unavoidable. The prenatal period represents a sensitive developmental window, during which even low-level exposure to endocrine-disrupting chemicals may interfere with fetal programming and contribute to long-term health outcomes. PFAS are of particular concern because they can cross the placental barrier. Prenatal exposure has been associated with disturbances in endocrine, metabolic, immune, and developmental pathways, with consequences that may become evident later in life. The concept of PFAS as “silent programmers” of human health reflects their capacity to alter biological processes during critical stages of development, often without immediate clinical manifestations. Lowdose effects, non-monotonic dose–response relationships, and combined exposure to chemical mixtures further complicate toxicological risk assessment. Human biomonitoring studies based on paired maternal and umbilical cord blood samples, placental tissue, and early-life biomarkers are essential for understanding maternal–fetal transfer and early biological responses. Regional mother–child cohort studies, including TOXMOM and PrenTox, contribute to evidence on prenatal exposure to PFAS and other endocrine-disrupting chemicals, particularly in populations with limited biomonitoring data. Prenatal PFAS exposure represents an important issue at the intersection of environmental toxicology, reproductive health, child development, and public health prevention. Improved exposure assessment, early preventive strategies, and communication among researchers, healthcare professionals, pharmacists, policymakers, and the public are needed to reduce risks for future generations.