By operating an antineutrino detector of simple design during several fuel cycles, we have observed long term changes in antineutrino flux that result from the isotopic evolution of a commercial Pressurized Water Reactor (PWR). Measurements made with simple antineutrino detectors of this kind offer an alternative means for verifying fissile inventories at reactors, as part of International Atomic Energy Agency (IAEA) and other reactor safeguards regimes.