RESUMO
Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening assay, collaboration with patient organizations and medical professionals, a feasibility study, and negotiation with public health representatives. Over 12,000 newborns were tested during the 17-month feasibility study, revealing two unrelated SMA infants and one older sibling. All three children received therapeutic interventions during the presymptomatic phase and have shown no signs of SMA. No false-negative results were found among the negative test results. As frontrunners in this field in Serbia, we established screening and diagnostic algorithms and follow-up protocols and raised awareness among stakeholders about the importance of early disease detection, leading to the incorporation of NBS for SMA into the national program on 15 September 2023. Since then, 54,393 newborns have been tested, identifying six SMA cases and enabling timely treatment. Our study demonstrates that effective collaborations between academia, non-profit organizations, and industry are crucial in bringing innovative healthcare initiatives to fruition, and highlights the potential of NBS to revolutionize healthcare outcomes for presymptomatic SMA infants and their families.
RESUMO
BACKGROUND: The aim of this meta-analysis was to analyze all available data from studies investigating associations between polymorphisms in genes responsible for innate immunity and neonatal sepsis development. METHODS: A comprehensive literature search, reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-S guidelines, was performed with no language restriction. Studies derived using the PICO (population, intervention, comparison and outcomes) strategy, with data on the genotype distribution for innate immunity gene polymorphisms in newborns with and without sepsis. Data were analyzed using Review Manager. The Cochran-Mantel-Haenszel test was used to calculate odds ratios with 95% confidence intervals. Heterogeneity was tested using the I2 index. RESULTS: From a total of 9428 possibly relevant articles, 33 qualified for inclusion in this systematic review. According to the STrengthening the REporting of Genetic Association Studies, 23 studies were found to be of moderate quality, while 10 were of low quality. The results showed an association of the mannose-binding lectin (MBL) exon 1 genetic polymorphism with the risk of culture-proven sepsis. Toll-like receptor (TLR) 4 rs4986791 genotype distribution suggests its association with the increased risk of culture-proven sepsis. The certainty of evidence per GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) varied from very low to low. Publication bias was not detected. CONCLUSIONS: Out of the 11 investigated single-nucleotide polymorphisms, this meta-analysis found a possible association between the risk for culture-proven sepsis and MBL exon 1 and TLR4 rs4986791 polymorphisms. There is an evident need for larger well-designed, multicentric observational studies investigating inflammatory gene polymorphisms in neonatal sepsis.