Our study has demonstrated a profile of extracellular vesicle (EVs) in women with Hb Bart’s fetalis fetuses. Specifically, women with Bart’s fetuses have smaller EVs particle size but higher placental alkaline phosphatase (PLAP)-EV level than those with normal pregnancies. Several proteomics EV proteins are differentially expressed in women with Bart’s fetuses and these proteins involves in zymogen activation, fibrinogen complex, vesicles in cellular component, fibrin clot formation and integrin signaling. We envision that the non-invasive liquid biopsy could provide information in relation to placental health in women with Bart’s fetuses. In this report, the liquid biopsy based on an examination of placenta-derived EVs in maternal blood for the identification of Hb Bart’s fetuses is feasible and this may ultimately reduce the rate of unnecessary invasive prenatal diagnosis testing inthe future.