Newborn screening of congenital errors of metabolism using tandem mass spectrometry

Full title: Cost-effectiveness of the newborn screening of congenital errors of metabolism using tandem mass spectrometry

Authors: Ramos Goñi JM, Serrano Aguilar PG, Espada Sáenz-Torres M, Posada de la Paz M.

Contact person: Juan Manuel Ramos Goñi (



Congenital errors of metabolism (ECM) are inherited basic biochemistry metabolic diseases. Some ECM meets the required criteria to be included in newborn screening programs by means of minimally invasive and low costly tests. The tandem mass spectrometry (MS/MS) introduction in neonatal screening is an effective and potentially cost–effective alternative for ECM screening. An Avalia-t recent report confirms the MS/MS effectiveness for henylketonuria (PKU) and deficit acyl-CoA dehydrogenase medium chain (MCADD) screening. PKU is an ECM that originates from deficits of the liver enzyme phenylalanine hydroxylase. The incidence of the disease in Spain is about 7.87 cases/100.000 infants. MCADD is another low frequency ECM that affects the -oxidative metabolism of fatty acids. The incidence in Spain is 5-6 cases/100.000 infants.


The objective of this study is to determine the cost-effectiveness ratio of the MS/MS introduction for PKU and MCADD screening, in ECM neonatal screening programs of Spanish Communities.


A decision tree model composed by two main branches was developed. One of these represents a scenario where MS/MS has been implanted for PKU and MCADD screening, while the another branch represents a scenario without MS/MS technology, so in this case, the screening program doesn’t cover MCADD. The analysis was performed by the NHS perspective and the time horizon is the lifetime of infants. The parameters of the model were obtained from one Spanish newborn screening program, scientific literature, and recommendations from experts in the clinical monitoring of these pathologies. The selected effectiveness measure in this study has been years of life gained (LYG). The applied discount rate was 3%. We performed a stochastic and multivariate sensitivity analysis through Monte Carlo method, so acceptability curves, net health benefit and expected value of perfect information could be calculated.


The incremental cost-effectiveness ratio (ICER) for screening program in Spain with a single screening centre is € 5,757 /LYG, with a confidence interval (CI) [€ 5,707 /LYG; € 5,808 /LYG]. In case of decentralized screening programs along Autonomous Communities, with a number of annual births around 90,000-100,000; the ICER is € 5,936 /LYG and CI is[€ 5,866 /LYG; € 5,986 /LYG]. However, for communities with a number of births around 5,000 /year or less, the ICER is € 30,554 /LYG and CI is [€ 30,236 /LYG; € 30,877 /LYG]. For a willingness to pay € 30,000 /LYG, the probabilities of right decision in each scenario listed above are 100%, 100% and 43.28% respectively.


The MS/MS introduction for neonatal ECM screening offers a favourable cost-effectiveness ratio when it is used to early detection of PKU and MCADD. When you have evidence on MS/MS screening effectiveness for other ECM, the introduction of this ECM in MS/MS screening program will contribute to improve the cost-effectiveness ratio. The cost-effectiveness ratio becomes more and more favourable when larger is the annual volume of neonatal samples to be processed with the MS/MS, remaining more or less constant for a number superior to 30-40 thousand infants per year. The findings of this report support the introduction of this technology for ECM screening in the Spanish Autonomous Communities, when the number of alive newborns is superior to 5,000 per year. Neonatal screening programs based on MS/MS, in territorial areas with less than 5 thousand infants per year, do not reach favourable costeffectiveness ratios.


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