Background: Per- and polyfluoroalkyl substances (PFAS) are a class of endocrine-disrupting compounds. Prenatal exposure to PFAS has been linked to adverse cardiovascular health in offspring, though the underlying mechanisms remain unclear. Objectives: This study aimed to examine the association between maternal PFAS exposure during pregnancy and offspring cardiovascular development, and to investigate potential metabolic mechanisms using newborn screening data. Methods: Within the Shanghai Birth Cohort (n=1,024), nine PFAS were measured in maternal plasma during the first trimester, and metabolites were analyzed from neonatal dried blood spots. Cardiovascular development was assessed by echocardiography at age 4. Associations among PFAS, cardiac outcomes, and neonatal metabolites were evaluated using metabolome-wide association studies (MWAS), a meet-in-the-middle approach, multivariable regression, and mediation analysis. Results: Higher maternal PFAS concentrations were significantly associated with impaired cardiac structural development— including reduced ventricular wall thickness and mass—and diastolic dysfunction in offspring. PFDoA, PFBS, and PFHpA showed the most pronounced effects. Through the meet-in-the-middle analysis, five overlapping amino acids (glutamate, ornithine, aspartate, alanine, and pipecolic acid) were identified in the MWAS for maternal PFAS (PFDoA, PFOA, PFHpA, PFBS) and the MWAS for cardiovascular outcomes. Mediation analysis further indicated that the glutamate metabolism pathway plays a key role in this association. Conclusions: Maternal PFAS exposure is associated with impaired cardiovascular development in offspring, potentially mediated through perturbations in amino acid metabolism, particularly the glutamate pathway . These findings highlight the role of metabolic dysregulation in PFAS-related developmental cardiotoxicity .