Newborn screening using tandem mass spectrometry: A systematic review

Objectives: To evaluate the evidence for the clinical effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS).

Study design: Systematic review of published research.

Data sources: Studies were identified by searching 12 electronic bibliographic databases; conference proceedings and experts consulted.

Results: Six studies were selected for inclusion in the review. The evidence of neonatal screening for PKU and MCAD deficiency using tandem MS was primarily from observational data of large-scale prospective newborn screening programmes and systematic screening studies from Australia, Germany and the USA. Tandem MS based newborn screening of dried blood spots for PKU and/or MCAD deficiency was shown to be highly sensitive (>93.220%) and highly specific (>99.971%). The false positive rate for PKU screening was less than 0.046% and for MCAD deficiency the false positive rate was less than 0.023%. The positive predictive values ranged from 20 to 32% and 19 to 100%, respectively.

Conclusions: This review suggests that neonatal screening of dried blood spots using a single analytical technique (tandem MS) is highly sensitive and specific for detecting cases of PKU and MCAD deficiency, and provides a basis for modelling of the clinical benefits and potential costeffectiveness.