Authors' objectives:

The purpose of this report is to assess the efficacy of an expanded newborn screening through mass spectrometry in the detection of congenital metabolic errors.

Authors' results and conclusions: There are no randomized studies assessing the efficacy of mass spectrometry (MS/MS). The prevalence and incidence of each metabolic disorder separately are very low, however, when the combined frequency of disorders is taken into account it is possible to determine that about 1 out of 3,500-4,000 live newborns will present one of them. The method's sensitivity and specificity are suitable (95 and 99.65%, respectively), though some studies point out how difficult it is to extrapolate data based on cutting points and the best time to take the sample. The rate of false negative results is low (0.33%) and similar to that obtained with conventional testing of phenylketonuria. Despite the good diagnostic performance of MS/MS, only 11.31% of the positive results identify a real metabolic disorder (Positive predictive value or PPV), that is why all cases require additional testing to confirm diagnosis. This problem is common to all the newborn screening methods and the PPV reported for conventional testing with FEI [Fundacion Endocrinologica Infantil (Child endocrinology foundation)] is 0.5%-6. With MS/MS, the PPV is the highest observed in amino acidemias (20.12%), followed by alterations in the fatty acid oxidation (8.57%) and organic acidemias (5.09%). In March, 2004, a British technology assessment on MS/MS testing identified the medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD) as the only one eligible for the new MS/MS testing program and considered that the evidence for the remaining disorders was limited. Replacement of phenylketonuria testing with the current MS/MS method, only for this disease is not justifiable but, if MCAD testing were included, it would be more cost-effective in this country.

Authors' recommendations: The MS/MS sensitivity and specificity are adequate. There is nowadays, however, a worldwide controversy over which are the remaining conditions to be covered by newborn screening or not. This is due to the low prevalence of some of them and, in many cases, lack of specific treatment proving to modify their prognosis. Also to be considered are the possible negative consequences of the screening, for example false negative results, social stigmatization, employment and health insurance system discrimination and parental attribution. On the other hand, the inclusion of new pathologies to the newborn screening should be accompanied with a program assuring access to full diagnostic, treatment and follow up services. Out of the diseases screened by the MS/MS only some of them (such as MCAD and glutaric acidemia type I) have proved to clearly benefit from the treatment and are those most widely accepted to be included in the screening expansion. However, they have not been included in most of the countries and there is not enough information about their potential significance in our country, where the conventional screening is not extensively carried out. Still more evidence is required to determine the natural history of these diseases and the economic impact of their screening in our setting. Major studies should focus on treatment and adverse effects compared to conventional screening.

Authors' methods: Overview

Project Status: Completed

URL for project: http://www.iecs.org.ar/

Year Published: 2005

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Argentina

Organisation Name: Institute for Clinical Effectiveness and Health Policy

Contact Address: Dr. Emilio Ravignani 2024, Buenos Aires - Argentina, C1414 CABA

Contact Name: info@iecs.org.ar

Contact Email: info@iecs.org.ar

Copyright: Institute for Clinical Effectiveness and Health Policy (IECS)