Optimizing Newborn Screening for Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: From First Test to Diagnostic Outcome and Follow-up

• Grant number: 23/11168-1
• Support Opportunities: Research Grants - Research in Public Policies
• Start date: February 01, 2024
• End date: January 31, 2027
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Tania Aparecida Sartori Sanchez Bachega
• Grantee: Tania Aparecida Sartori Sanchez Bachega
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Carolina Fischinger Moura de Souza ; Helena Panteliou Lima Valassi ; ROBERTO GIUGLIANI
• Associated scholarship(s): 24/17494-0 - Optimizing Congenital Adrenal Hyperplasia Diagnosis in the National Neonatal Screening Program with Molecular Confirmatory Testing., BP.MS

Abstract

Newborn screening (NBS) aims to precociously diagnose frequent and serious diseases, in the pre-symptomatic phase. APAE-SP, was a pioneer in NBS in Brazil, starting with screening for phenylketonuria in 1986. Gradually, NBS was expanded to Brazil and, in order to obtain equity, on 06/06/2001, Ordinance 822 of the Ministry of Health ( MH) creates the National Newborn Screening Program (PNTN), which provides funding for neonatal/confirmatory tests, monitoring of those affected and dispensing medications. Initially the program included the diagnosis of 4 diseases, only 10 years later the inclusion of 2 others was provided. The Endocrinology Department of Sao Paulo University (HCFMUSP) sent data on comorbidities related to the late diagnosis of its series of individuals with Congenital Adrenal Hyperplasia (CAH) to the MH, which resulted in its inclusion in the PNTN. Subsequently, Gyselle Hayashi and Prof Tânia participated in the Working Group of the São Paulo State Health Department in the creation of the CAH-NBS flow. Since then, HCFMUSP has maintained a partnership with the Jô Clemente Institute (formerly APAE-SP) to optimize the diagnosis of CAH in public NBS, which resulted in scientific publications, 1st place in the 2015 Abril Saúde Prize and a Master's degree by Giselle, manager of the IJC. In the current CAH-NBS flow in SP, newborns (NB) with the first test moderately altered, with 17OH-progestrone dosage by immunofluorimetric method, are called for a new collection. Considering that most altered tests represent false-positives result, this procedure causes stress for families and delays diagnostic elucidation. We emphasize that municipalities cannot always provide transportation for these families, which puts the affected newborns at risk of death due to the salt loss crisis.HCFMUSP has newborn screening as one of its lines of research. Thus, this project has 2 objectives, the first will be to optimize the time of the diagnosis of CAH, through the standardization of the dosage of 17OH-progesterone by LC-MS/MS in the neonatal samples initially collected, avoiding the summoning of these NBs. It is known that the LC-MS/MS methodology is the gold standard method for steroid dosage and its use in the first sample with altered results will help in the diagnostic differentiation. Additionally, FEPE (Ecumenical Foundation for the Protection of the Exceptional, in Curitiba) is another renowned laboratory, accredited by the PNTN. FEPE will participate by sending samples of those affected by CAH, in order to have a significant number of cases for analysis of positive and negative predictive values. At the same time, two master's and doctoral students will come to SP, to learn LC-MS/MS methodologies and CAH molecular diagnosis for implementation in Curitiba.On 05/26/21, Mr Antonie Daher (founder of Casa dos Raros-CDR) and Profa Tânia (president of SBTEIM), participated in a social movement to expand the number of diseases to be tracked by the PNTN, in addition to providing scientific advice for the enactment of law 14,154, which provides for the expansion of the PNTN to ~ 53 diseases. With the expansion, it becomes necessary to optimize the flow of the NBS, so that it can put into practice the expansion foreseen in the law. The second objective of this project involves the education of public managers in NBS. The NBS flow involves not only the excellence of the NBS indexes, but also depends on the involvement of managers in the organization, through: family education programs during prenatal care, availability of sample transport to laboratories, insertion of patients in tertiary networks and for dispensing medications. Bearing in mind the rotation of public managers, we identified this gap in education. We will use the expertise of CDR, which already has this education project in the RGS, and we will apply it in SP, evaluating the performance of the indicators. (AU)