Population newborn screening for inherited metabolic disease: Current UK perspectives

Some of the generally accepted criteria for screening programmes are inappr opriate for newborn metabolic screening as they ignore the family dimension and the importance of timely genetic information. Uncritical application o f such criteria creates special difficulties for screening by tandem mass s pectrometry, which can detect a range diseases with widely different natura l histories and responsiveness to treatment. Further difficulties arise fro m increasing demands for direct proof of the effects of screening on long-t erm morbidity and mortality. The randomized controlled trial is held to be the gold standard, but for ethical and practical reasons it will be impossi ble to achieve for such relatively rare diseases. This approach also oversi mplifies the complex matrix of costs and benefits of newborn metabolic scre ening. A more workable approach could involve Bayesian synthesis, combining quantitative performance data from carefully designed prospective pilot st udies of screening with existing experience of the natural history, diagnos is, and management of the individual disorders concerned.