Insurance Reimbursement for Special Foods and Phenylalanine Levels in Patients With PKU in China.

Importance: Recent changes in China's social medical insurance reimbursement policy have impacted the financial burden of patients with phenylketonuria (PKU) for special foods. However, whether this policy change is associated with their blood phenylalanine (PHE) concentration is unclear. Objective: To investigate the association between the reimbursement policy and blood PHE concentration in patients with PKU. Design, Setting, and Participants: This cohort study measured the blood PHE concentrations of 167 patients with PKU across 4 newborn screening centers in China from January 2018 to December 2021. The reimbursement policy for special foods for patients with PKU at 2 centers was canceled in 2019 and restored from 2020 onwards. In contrast, the other 2 centers consistently implemented the policy. Data were analyzed from September 10 to December 6, 2023. Exposures: The implementation and cancelation of the reimbursement policy for special foods of patients with PKU. Main Outcomes and Measures: The blood PHE concentration was regularly measured from 2018 to 2021. A 1-sided Z test was used to compare the mean of the blood PHE concentration between different years. Results: Among 167 patients with PKU (mean [SD] age, 84.4 [48.3] months; 87 males [52.1%]), a total of 4285 measurements of their blood PHE concentration were collected from 2018 to 2021. For patients at the center that canceled the reimbursement policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (5.73) mg/dL, significantly higher than 4.84 (4.11) mg/dL in 2018 (P < .001), 5.06 (5.21) mg/dL in 2020 (P = .006), and 4.77 (4.04) mg/dL in 2021 (P < .001). Similarly, for patients at the other center that canceled the policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (3.43) mg/dL, significantly higher than 5.34 (3.45) mg/dL in 2018 (P = .03), 5.13 (3.15) mg/dL in 2020 (P = .003), and 5.39 (3.46) mg/dL in 2021 (P = .03). On the contrary, no significant difference was observed between any of the years for patients at the 2 centers that consistently implemented the policy. Conclusions and Relevance: In this cohort study of patients with PKU from multiple centers, the implementation of the reimbursement policy for special foods was associated with controlling the blood PHE concentration. Special foods expenditure for patients with PKU should be included in the scope of long-term social medical insurance reimbursement.

Prevalence of neonatal screening and associated factors in Brazil: a comparison of the 2013 and 2019 National Health Surveys. / Prevalência e fatores associados à realização dos exames de triagem neonatal no Brasil: comparação da PNS 2013 e 2019.

This study analyzed the prevalence of complete neonatal screening (CNS) of children aged under 2 years in Brazil and associated factors using data from the 2013 (n=4,442) and 2019 (n=5,643) national health surveys. We conducted a cross-sectional study to compare prevalence of CNS (eye, ear and heel prick tests) adopting 95% confidence intervals (95%CI) and a 5% significance level. Crude and adjusted Poisson regression was performed to estimate prevalence ratios (PR) and 95%CI to assess the association between socioeconomic, demographic and health variables and CNS. There was a statistically significant increase in CNS prevalence, from 49.2% (95%CI: 47.1-51.3) in 2013 to 67.4% (95%CI: 65.5-69.3) in 2019. However, large disparities persist across states and between sociodemographic groups. In both years, CNS prevalence was lowest among brown and black children, those from families in the three lowest income quintiles, children without health insurance, those from families registered in the Family Health Strategy and children living in the North, cities outside the state capital/metropolitan regions and rural areas. Despite the increase in prevalence of CNS, deep individual and contextual inequalities persist, posing challenges for health policies.

Analisou-se a prevalência e fatores associados à realização da Triagem Neonatal Completa (TNC) entre crianças (<2 anos de idade) no Brasil incluídas na Pesquisa Nacional Saúde 2013 (n=4.442) e 2019 (n=5.643). Estudo transversal comparou as estimativas de prevalência e intervalos de confiança de 95% (IC95%) da TNC (testes do olhinho, orelhinha e pezinho). Diferenças foram consideradas estatisticamente significante ao nível de 5%. Regressões de Poisson bruta e ajustada foram realizadas para estimar Razões de Prevalência (RP) e IC95% para a associação das variáveis socioeconômicas, demográficas e de saúde com a TNC. Verificou-se aumento estatisticamente significante da TNC: 67,4% (IC95%: 65,5-69,3) em 2019, ante 49,2% (IC95%: 47,1-51,3) em 2013. Porém, ainda existem desigualdades e defasagens entre os estados da federação e variáveis sociodemográficas. Entre os anos, a TNC foi menor nas crianças de cor/raça parda e preta, dos três piores quintis de renda, sem plano de saúde, cadastradas na Estratégia de Saúde da Família, da região norte, de cidades do interior e da zona rural do Brasil. Apesar de o aumento da prevalência de TNC, desigualdades e defasagens individuais e contextuais permaneceram, indicando os desafios das políticas de saúde.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Who performs neonatal hip assessment: is there a cause for concern?

OBJECTIVE: The UK falls behind other European countries in the early detection of developmental dysplasia of the hip (DDH) and screening strategies differ for early detection. Clinical detection of DDH is challenging and recognised to be dependent on examiner experience. No studies exist assessing the number of personnel currently involved in such assessments.Our objective was to review the current screening procedure by studying a cohort of newborn babies in one teaching hospital and assess the number of health professionals involved in neonatal hip assessment and the number of examinations undertaken during one period by each individual. METHODS: This was a retrospective observational study assessing all babies born consecutively over a 14-week period in 2020. Record of each initial baby check was obtained from BadgerNet. Follow-up data on ultrasound or orthopaedic outpatient referrals were obtained from clinical records. RESULTS: 1037 babies were examined by 65 individual examiners representing 9 different healthcare professional groups. The range of examinations conducted per examiner was 1-97 with a median of 5.5 examinations per person. 49% of individuals examined 5 or less babies across the 14 weeks, with 18% only performing 1 examination. Of the six babies (0.48%) treated for DDH, one was picked up on neonatal assessment. CONCLUSION: In a system where so many examiners are involved in neonatal hip assessment, the experience is limited for most examiners. Currently high rates of late presentation of DDH are observed locally, which are in accordance with published national experience. The potential association merits further investigation.

A Mathematical Algorithm for Dried Blood Spot Quality Assessment and Results concerning Quality from a Newborn Screening Program.

BACKGROUND: In addition to newborn screening, dried blood spots (DBSs) are used for a wide variety of analytes for clinical, epidemiological, and research purposes. Guidelines on DBS collection, storage, and transport are available, but it is suggested that each laboratory should establish its own acceptance criteria. METHODS: An optical scanning device was developed to assess the quality of DBSs received in the newborn screening laboratory from 11 maternity wards between 2013 and 2018. The algorithm was adjusted to agree with the visual examination consensus of experienced laboratory personnel. Once validated, the algorithm was used to categorize DBS specimens as either proper or improper. Improper DBS specimens were further divided based on 4 types of specimen defects. RESULTS: In total, 27 301 DBSs were analyzed. Compared with an annual DBS rejection rate of about 1%, automated scanning rejected 26.96% of the specimens as having at least one defect. The most common specimen defect was multi-spotting (ragged DBS, 19.13%). Among maternity wards, improper specimen rates varied greatly between 5.70% and 49.92%. CONCLUSIONS: Improper specimen rates, as well as the dominant type of defect(s), are mainly institution-dependent, with various maternity wards consistently showing specific patterns of both parameters over time. Although validated in agreement with experienced laboratory personnel consensus, automated analysis rejects significantly more specimens. While continuous staff training, specimen quality monitoring, and problem-reporting to maternities is recommended, a thorough quality assessment strategy should also be implemented by every newborn screening laboratory. An important role in this regard may be played by automation in the form of optical scanning devices.

Cost-effectiveness of newborn screening for sickle cell disease: a systematic review protocol.

OBJECTIVE: The purpose of this systematic review is to assess the cost-effectiveness of targeted/selective newborn screening compared with universal screening for sickle cell disease across various countries and settings. INTRODUCTION: The incidence of sickle cell disease is a widespread and potentially fatal hematologic disorder that affects thousands of newborns worldwide. The cost of newborn screening creates a burden on households and the economy. INCLUSION CRITERIA: Studies will be eligible for inclusion in the review if they focus on the cost-effectiveness of newborn screening for sickle cell disease, comparing targeted/selective screening with universal screening. METHODS: A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as sickle cell disease, newborn , and economic evaluations . Two reviewers will screen the titles, abstracts, and full text independently against the inclusion criteria. Disagreements will be resolved by discussion or with a third reviewer. To assess methodological quality, the JBI checklist for economic evaluation will be used. Data will be extracted by 2 reviewers using a modified JBI data extraction form. The JBI dominance ranking matrix for economic evaluations will be used to summarize and compare the results. Cost-effectiveness will be measured on the basis of cost per test/case detected, quality-adjusted life years gained, or disability-adjusted life years averted. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment will be conducted to evaluate the certainty of economic evidence, such as use of resources and expenditures, and to incorporate the results into the decision-making process. REVIEW REGISTRATION: PROSPERO CRD42017057963.

A computer vision approach to the assessment of dried blood spot size and quality in newborn screening.

BACKGROUND: Dried blood spot (DBS) size and quality affect newborn screening (NBS) test results. Visual assessment of DBS quality is subjective. METHODS: We developed and validated a computer vision (CV) algorithm to measure DBS diameter and identify incorrectly applied blood in images from the Panthera DBS puncher. We used CV to assess historical trends in DBS quality and correlate DBS diameter to NBS analyte concentrations in 130,620 specimens. RESULTS: CV estimates of DBS diameter were precise (percentage coefficient of variation < 1.3%) and demonstrated excellent agreement with digital calipers with a mean (standard deviation) difference of 0.23 mm (0.18 mm). An optimised logistic regression model showed a sensitivity of 94.3% and specificity of 96.8% for detecting incorrectly applied blood. In a validation set of images (n = 40), CV agreed with an expert panel in all acceptable specimens and identified all specimens rejected by the expert panel due to incorrect blood application or DBS diameter > 14 mm. CV identified a reduction in unsuitable NBS specimens from 25.5% in 2015 to 2% in 2021. Each mm decrease in DBS diameter decreased analyte concentrations by up to 4.3%. CONCLUSIONS: CV can aid assessment of DBS size and quality to harmonize specimen rejection both within and between laboratories.

Determinación de valores de corte de 17 hidroxiprogesterona ajustados por edad gestacional para la pesquisa neonatal de la hiperplasia suprarrenal congénita / Assessment of gestational age-adjusted 17-hydroxyprogesterone cut-off values for neonatal screening of congenital adrenal hyperplasia

La pesquisa neonatal de hiperplasia suprarrenal congénita se realiza mediante la determinación de 17 hidroxiprogesterona (17OHP) en gotas de sangre seca en papel de filtro. Los bebés prematuros presentan valores más elevados que los bebés de término, siendo de utilidad contar con límites de corte apropiados. Nuestro objetivo fue actualizar los valores de corte de 17OHP ajustados por edad gestacional para la metodología en uso a nivel nacional por las jurisdicciones asistidas por el "Programa Nacional de Fortalecimiento de la Detección Precoz de Enfermedades Congénitas". La 17OHP se determinó utilizando el kit comercial de enzimo-inmunoanálisis (ELISA competitivo), Elizen Neonatal 17OHP Screening (Zentech, Bélgica). Se obtuvieron límites de corte utilizando percentiles de la distribución de los valores de 17OHP para cada edad gestacional. La sensibilidad obtenida fue 100%, especificidad 98,76 %, tasa de falsos positivos 1,24 % y el valor predictivo positivo 1,12 %. Destacamos la importancia de disponer de límites de corte adecuados a la población. La armonización de los mismos permitirá resultados comparables entre los programas regionales de pesquisa neonatal (AU)

Newborn screening for congenital adrenal hyperplasia is performed by the measurement of 17-hydroxyprogesterone (17OHP) in dried blood spots on filter paper. Premature infants have higher values than full-term infants, and appropriate cutoff values are useful. Our aim was to update the cut-off values of 17OHP adjusted for gestational age for the methodology used at a national level in regions assisted by the "National Program for Strengthening the Early Detection of Congenital Diseases". 17OHP was determined using the commercial enzyme-linked immunosorbent assay (competitive ELISA) kit, Elizen Newborn 17OHP Screening (Zentech, Belgium). Cut-off values were obtained using percentiles of the distribution of 17OHP values for each gestational age. Sensitivity was 100%, specificity 98.76%, false positive rate 1.24%, and positive predictive value 1.12%. It is important to have cut-off values that are adjusted to the population. Harmonization will allow for the comparison of results among regional newborn screening programs (AU)

The cost-effectiveness of targeted screening for congenital cytomegalovirus in newborns compared to clinical diagnosis in the US.

OBJECTIVE: Congenital cytomegalovirus (cCMV) is the leading environmental cause of hearing loss (HL) among children, affecting four in one thousand newborns. cCMV testing in the US is currently based on clinical diagnosis which does not consistently identify cCMV cases and precludes early intervention to prevent and reduce the severity of HL. We estimated the cost-effectiveness of targeted newborn screening and cCMV testing among newborns compared to clinical diagnosis. METHODS: We use a decision-analytic model to estimate the costs of preventing HL progression, of additional cases of severe HL, of identifying a case of HL one year earlier, and of identifying an additional case of cCMV, through targeted screening and cCMV testing for infants failing two newborn hearing screens with follow-up to age five. We also estimate the costs of nationwide implementation of a newborn screening and testing program. Model pathways were based on best practices for screening, testing, and treatment. Probabilities were drawn from the published literature; costs were estimated based on Medicare reimbursement rates. Probabilistic and scenario analyses were conducted to determine the robustness of results. RESULTS: Targeted testing and cCMV screening, compared to standard of care, cost an additional $2.96 (±2.26) per infant screened and identified 0.00038 (±0.00022) cases of HL, 3.8 in 10000 children, at a cost of $8197 (±4217) per case of HL identified. Implementing targeted screening for all children in the US was estimated to cost $193,229. CONCLUSIONS: Although cases numbers are small, our model shows that targeted newborn screening and cCMV testing reduced cases of HL progression. Adoption of newborn targeted screening as standard of care should be considered given it may prevent disability at very low cost.

A cost-minimisation analysis comparing alternative telemedicine screening approaches for retinopathy of prematurity.

INTRODUCTION: Screening for retinopathy of prematurity (ROP) is an important procedure in the prevention of blindness in high-risk preterm infants. In the regionalised healthcare system of Queensland (Australia), outside of the major centres, some preterm infants are cared for in special care nurseries (SCNs). When necessary, infants in these nurseries who are at risk of ROP are transferred to a tertiary hospital for screening by paediatric ophthalmologists. The transport of preterm infants for eye examinations adds risk and incurs significant costs to the health system. Using a cost-minimisation approach, we aimed to compare the costs of the current ROP screening practice with two alternative telemedicine approaches. METHODS: We constructed a decision analytic model to estimate costs from a health service perspective with a five-year analysis horizon; activity data from a tertiary ROP screening service were used to inform the models. The three models assessed were: (a) a digital retinal photography (DRP)-equipped travelling nurse, (b) equipping SCNs with DRP, and providing training to local nurses, and (c) current practice of infant transfer. In all cases, the tertiary centre provides specialist ophthalmologic review. RESULTS: Of the three models, we estimated the most expensive option to be equipping SCNs with DRP and providing training to local nurses (AUD$4114/infant). We found that the current practice of transferring infants was the second most expensive (AUD$1021/infant). The most economical model was the specialist nurse travelling to each SCN with a portable DRP (AUD$363/infant). A sensitivity analysis, which assessed uncertainty and variability around the cost estimates, found that the ranking for the expected costs of the alternative models of care did not change. DISCUSSION: This is the first economic and cost-minimisation analysis in Australia to compare the costs of the current screening programme with two alternative telemedicine approaches for screening ROP. Telemedicine programmes that facilitate non-physician screening may improve the cost efficiency of the health system while maintaining the health outcomes for children, and reducing the risk associated with infant transport.

Cost-effectiveness analysis on implementing newborn hearing screening programmes in a low- to middle-income country.

OBJECTIVE: To analyse the cost-effectiveness (CE) of implementing different newborn hearing screening protocols in a low- to middle-income country. DESIGN: A decision analytical model with a 78-year time horizon. STUDY SAMPLE: Direct medical, direct non-medical and indirect costs were collected from 126 subjects in southern Thailand. Various protocols involving universal newborn hearing screening (UNHS) and targeted newborn hearing screening (TNHS), using two technologies, namely automated otoacoustic emissions (aOAEs) and automated auditory brainstem responses (aABRs), were evaluated. Incremental cost-effectiveness ratios (ICERs) were calculated for all protocols in United States dollars (US$)/quality-adjusted life year (QALY) gained. Also, probabilistic sensitivity analyses with 1000 trials for each specific protocol were performed. RESULTS: The ICERs of UNHS with aOAE, UNHS with aABR, TNHS with aABR and UNHS with optimised baseline parameters were 3702, 3545, 1545 and 2483 US$/QALY gained, respectively. With the CE threshold of 5000 US$/QALY gained, the chances of ICERs to be cost-effective for UNHS with aOAE, UNHS with aABR, TNHS with aABR and UNHS with optimised baseline parameters were 72, 77, 93 and 94%, respectively. CONCLUSIONS: All screening protocols were considered as cost-effective, and a very high chance of being cost-effective for UNHS could be achieved when certain baseline parameters were optimised.

Cost-Effectiveness of Newborn Screening for Phenylketonuria and Congenital Hypothyroidism.

OBJECTIVE: To evaluate the long-term costs and health effects of the Swedish newborn screening program for classic phenylketonuria (PKU) alone and in combination with congenital hypothyroidism compared with no screening. STUDY DESIGN: A decision-analytic model was developed to estimate and compare the long-term (80 years) costs and health effects of newborn screening for PKU and congenital hypothyroidism. Data were obtained from the literature and translated to Swedish conditions. A societal perspective was taken, including costs falling on health care providers, municipal care and services, as well as production loss due to morbidity. RESULTS: Screening 100 000 newborns for PKU resulted in 73 gained quality-adjusted life-years (QALYs) compared with no screening. When adding congenital hypothyroidism, the number of gained QALYs was 232 compared with PKU alone, adding up to a total of 305 QALYs gained. Corresponding cost estimates were $80.8, $70.3, and $10.05 million USD for no screening, PKU screening, and PKU plus congenital hypothyroidism screening, respectively, indicating that screening for PKU plus congenital hypothyroidism was more effective and less costly compared with the other strategies. The majority of cost savings with PKU plus congenital hypothyroidism screening was due to reductions in productivity losses and municipal care and services costs. CONCLUSION: The Swedish newborn screening program for PKU and congenital hypothyroidism saves substantial costs for society while generating additional QALYs, emphasizing the importance of public investments in early diagnosis and treatment.

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting. STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty. RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening. CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

Coste-efectividad del cribado neonatal de la tirosinemia tipo I (actualización) / Cost-effectiveness of newborn screening for tyrosinemia type I (update)

INTRODUCCIÓN La tirosinemia tipo I (TH1) es una enfermedad autosómica recesiva caracterizada por el déficit de la enzima fumaril acetoacetato hidrolasa. Los síntomas clínicos son variables e incluyen fallo hepático agudo, cirrosis, carcinoma hepatocelular (CHC), síndrome renal de Fanconi y neuropatía periférica. La TH1 es una enfermedad rara, de la que se calcula una frecuencia no mayor de 1 caso cada 100.000 recién nacidos vivos en la población mundial. La TH1, si no se trata, tiene pronóstico fatal, tanto en su forma aguda como crónica. Tradicionalmente el tratamiento ha consistido en una dieta con restricción de aminoácidos, fenilalanina y tirosina, y en el trasplante hepático. Actualmente existe un tratamiento farmacológico, la nitisinona, capaz de prevenir la degradación de la tirosina y la formación de metabolitos tóxicos. La introducción de la nitisinona como tratamiento de la TH1 se ha acompañado de un descenso considerable de la tasa de mortalidad. Actualmente, en España la TH1 no está incluida dentro del programa de cribado neonatal (PCN) de la cartera común de servicios del SNS. OBJETIVOS Evaluar y actualizar el coste-efectividad de la inclusión de la detección precoz de la TH1 mediante MS/MS en un PCN. • Estimar el impacto presupuestario que supondría para el SNS la inclusión de la detección precoz de la TH1 mediante MS/MS en el PCN actual. METODOLOGÍA Se realizó una revisión sistemática de la evidencia científica sobre el coste-efectividad del cribado neonatal de la TH1 para lo que se elaboró una estrategia de búsqueda en las bases de datos electrónicas: MEDLINE, EMBASE, Web of Science (WOS) y Cochrane desde 2013 hasta abril de 2021. Se ha desarrollado un modelo de coste-efectividad que compara dos alternativas: implantar el cribado neonatal de la tirosinemia tipo I o realizar la detección clínica de esta enfermedad. La perspectiva del análisis fue la del SNS, teniendo en cuenta los costes directos, expresados en euros de 2021. De manera adicional se tiene en cuenta la perspectiva social incluyendo los costes debidos a posibles pérdidas de productividad. La efectividad se midió empleando la medida Años de Vida Ajustados por Calidad (AVAC). Tanto los costes como la efectividad se descontaron al 3%. Por último, se realizó un análisis de impacto presupuestario para informar del coste que supondría la inclusión de la TH1 en el PCN del SNS. RESULTADOS Revisión sistemática de coste-efectividad Únicamente se pudo considerar un informe del Institute of Health Economics de Alberta (Canadá), localizado mediante búsqueda manual, publicado en 2016; cuyo objetivo fue evaluar la efectividad, seguridad y coste-efectividad de añadir siete condiciones al programa de cribado neonatal canadiense (incluyendo la TH1), mediante modelización tipo Markov. La calidad metodológica de la evaluación económica es alta. La perspectiva empleada es la del tercer pagador incluyendo exclusivamente los costes directos sanitarios; informando de un coste por niño cribado de 28,40 $CAD (21,20 € de 2021) frente a los 26,50 $CAD (19,78 € de 2021) por niño no cribado. La diferencia en años de vida entre ambas estrategias es de 0,00006 lo que resulta en una RCEI de 31.723,53 $CAD/AV (aproximadamente 23.666,66 €/AV en 2021). Aunque los autores no hacen mención al umbral coste-efectividad de referencia (y, por tanto, no especifican si la alternativa se considera coste-efectiva o no), declaran que, dado que la detección de una sola afección o una combinación de ellas produce un beneficio adicional para la salud, con costes adicionales para el sistema, su adopción depende de la disponibilidad de fondos. Análisis económico El análisis coste-efectividad muestra que el coste promedio por niño no cribado asciende a 33,03 €, mientras que el coste por niño cribado es de 35 €. Tanto los AVG como los AVAC promedio son más elevados con la estrategia de cribado neonatal lo que resulta en una RCEI de 30.034,32 €/AVAC desde la perspectiva del SNS y de 28.017,90 €/AVAC desde la perspectiva social. Ambos valores se encuentran por encima pero cercanos al umbral de coste-efectividad estimado para España en 25.000 €/AVAC. Al analizar diferentes escenarios variando los parámetros sobre los que existe mayor incertidumbre, se obtiene que la incorporación de la TH1 al programa de cribado neonatal sería una alternativa coste-efectiva si el precio del reactivo adicional para la detección de la TH1 mediante MS/MS no supera los 0,20 €/reactivo. El análisis de impacto presupuestario muestra que el coste incremental por niño cribado en el primer año se sitúa en torno a los 0,37 €, que equivale a 123.801 € para el conjunto de neonatos nacidos en España. CONCLUSIONES Existe muy escasa evidencia en la literatura científica sobre el coste-efectividad de un programa de cribado neonatal de la TH1 mediante MS/MS. Sólo se ha localizado un informe de ETS que concluye que la incorporación de la TH1 a un programa de cribado neonatal debe valorarse en función de la disponibilidad presupuestaria. • El análisis de coste-efectividad de novo realizado en este informe con datos actualizados de España concluye que la implantación del cribado neonatal de la TH1 no sería una opción coste-efectiva desde la perspectiva del SNS, ni desde la perspectiva social teniendo en cuenta una DAP de 25.000 €/AVAC. Sin embargo, si el coste del reactivo adicional necesario para la detección de la TH1 mediante MS/MS no supera los 0,20 €/reactivo, la inclusión de esta enfermedad dentro del programa de cribado neonatal mediante MS/MS sí sería una alternativa coste-efectiva. • De acuerdo al análisis de impacto presupuestario, cribar la TH1 tendría un coste incremental por neonato bajo, de aproximadamente 0,37 € el primer año.

INTRODUCTION Tyrosinemia type I (TH1) is an autosomal recessive disease characterized by a deficiency of the enzyme fumaril acetoacetate hydrolase. Clinical symptoms are variable and include acute liver failure, cirrhosis, hepatocellular carcinoma (HCC), Fanconi renal syndrome, and peripheral neuropathy. TH1 is a rare disease, with an estimated frequency of not more than 1 case per 100,000 live newborns in the world population. If untreated, TH1 has a fatal prognosis, both in its acute and chronic forms. Traditionally, treatment has consisted of a diet with restriction of amino acids, phenylalanine and tyrosine, and liver transplantation. Currently there is a pharmacological treatment, nitisinone, capable of preventing the degradation of tyrosine and the formation of toxic metabolites. The introduction of nitisinone as a treatment for TH1 has been accompanied by a considerable decrease in the mortality rate. Currently, in Spain TH1 is not included in the newborn screening programme of the portfolio of common services of the National Health System (NHS). OBJECTIVES To evaluate the cost-effectiveness of newborn screening for TH1. • To determine the cost-effectiveness of including early detection of TH1 by MS/MS in a newborn screening programme. • To estimate the budget impact of implementation of early detection of TH1 through MS/MS in NHS. METHODS A systematic review of the scientific evidence on the cost-effectiveness of newborn screening for TH1 was carried out, for which a search strategy was developed in electronic databases: MEDLINE, EMBASE, Web of Science (WOS) and Cochrane since 2013 until April 2021. A cost-effectiveness model has been developed that compares two alternatives: implement newborn screening for type I tyrosinemia or carry out clinical detection of this disease. The perspective of the analysis was that of the SNS, taking into account direct healthcare costs, expressed in 2021 euros. Effectiveness was measured using the Quality-Adjusted Life Years (QALY) measure. Both costs and effectiveness were discounted at 3%. Finally, a budget impact analysis was carried out to report the cost of including newborn screening of TH1 in the NHS. RESULTS Cost-effectiveness systematic review Only a HTA-report from the Institute of Health Economics of Alberta (Canada), located by manual search and published in 2016, could be considered. The objective of this report was to evaluate the effectiveness, safety and cost-effectiveness of adding seven conditions (including TH1), to the Canadian newborn screening program using Markov-type modeling. The methodological quality of the economic evaluation was high. The perspective used is that of the third payer, including exclusively direct healthcare costs. The authors reported a cost per child screened of CAD $ 28.40 (€ 21.20 from 2021) compared to CAD $ 26.50 (€ 19.78 from 2021) per child not screened. The difference in life years between both strategies is 0.00006, which results in an ICER of CAD $ 31,723.53/LYs (approximately € 23,666.66/LYs in 2021). Although the authors do not mention a country willigness to pay (WTP) reference (and, therefore, do not specify whether the alternative is considered cost-effective or not), they declare that, since the detection of a single condition or a combination of them produces an additional benefit for health with additional costs for the system, its adoption depends on the availability of funds. Economic analysis The cost-effectiveness analysis shows that the mean cost per child not screened is € 33.03, while the cost per child screened is € 35. Both the LYs and QALYs are higher with the newborn screening strategy, which results in an ICER of 30,034.32 €/QALY from the NHS perspective and 28,017.90 €/LY from societal perspective. Both values are close to the cost-effectiveness threshold estimated for Spain at €25,000/QALY. When analyzing different scenarios varying the parameters about which there is greater uncertainty, it is obtained that the incorporation of TH1 to the neonatal screening program would be a cost-effective alternative if the price of the additional reagent used for the detection of TH1 by MS/MS does not exceeds €0.20/reagent. The budget impact analysis shows that the incremental cost per child screened in the first year is around € 0.37, which is equivalent to € 123,801 for all newborns born in Spain. CONCLUSIONS There is limited scientific literature evidence on the cost effectiveness of TH1 newborn screening using MS/MS. Only one HTA report has been located that concludes that the incorporation of TH1 into a newborn screening program should be assessed based on budget availability. • The cost-effectiveness analysis carried out in this report with updated data from Spain concludes that the implementation of TH1 newborn screening would be a cost-effective option from the NHS perspective if the price of the reagent used to detect the disease does not exceed €0.20/reagent. • According to the budget impact analysis, screening TH1 would have a low incremental cost per newborn, of approximately € 0.37 the first year.

Better assessment of neonatal jaundice at home (BEAT Jaundice @home): protocol for a prospective, multicentre diagnostic study.

INTRODUCTION: Severe neonatal hyperbilirubinaemia can place a neonate at risk for acute bilirubin encephalopathy and kernicterus spectrum disorder. Early diagnosis is essential to prevent these deleterious sequelae. Currently, screening by visual inspection followed by laboratory-based bilirubin (LBB) quantification is used to identify hyperbilirubinaemia in neonates cared for at home in the Netherlands. However, the reliability of visual inspection is limited. We aim to evaluate the effectiveness of universal transcutaneous bilirubin (TcB) screening as compared with visual inspection to: (1) increase the detection of hyperbilirubinaemia necessitating treatment, and (2) reduce the need for heel pricks to quantify bilirubin levels. In parallel, we will evaluate a smartphone app (Picterus), and a point-of-care device for quantifying total bilirubin (Bilistick) as compared with LBB. METHODS AND ANALYSIS: We will undertake a multicentre prospective cohort study in nine midwifery practices across the Netherlands. Neonates born at a gestational age of 35 weeks or more are eligible if they: (1) are at home at any time between days 2 and 8 of life; (2) have their first midwife visit prior to postnatal day 6 and (3) did not previously receive phototherapy. TcB and the Picterus app will be used after visual inspection. When LBB is deemed necessary based on visual inspection and/or TcB reading, Bilistick will be used in parallel. The coprimary endpoints of the study are: (1) hyperbilirubinaemia necessitating treatment; (2) the number of heel pricks performed to quantify LBB. We aim to include 2310 neonates in a 2-year period. Using a decision tree model, a cost-effectiveness analysis will be performed. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethical Committee of the Erasmus MC Rotterdam, Netherlands (MEC-2020-0618). Parents will provide written informed consent. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NL9545).

Triagem neonatal por espectrometria de massas em tandem (MS/MS) para detecção da deficiência de acil-CoA desidrogenase de cadeia média (MCADD) / Neonatal screening by tandem mass spectrometry (MS/MS) for detection of medium-chain acyl-CoA dehydrogenase deficiency (MCADD)

INTRODUÇÃO: A MCADD é o distúrbio mais frequente da beta-oxidação mitocondrial dos ácidos graxos. No Brasil, a comparação de estudos epidemiológicos nacionais com dados da experiência do Distrito Federal com a triagem neonatal por MS/MS para MCADD sugerem um subdiagnóstico dessa condição no Brasil. A MCADD é uma doença grave, cujas manifestações clínicas geralmente iniciam no primeiro ano de vida. Os sintomas mais comuns incluem hipoglicemia hipocetótica recorrente, letargia, vômitos, disfunção hepática aguda, episódios semelhantes à síndrome de Reye, convulsões, coma e morte súbita. O seu diagnóstico precoce, possibilitado pela triagem neonatal por MS/MS, representa uma estratégia importante para a realização do tratamento oportuno e prevenção de óbitos e sequelas. TECNOLOGIA: Triagem neonatal por espectrometria de massas em tandem (MS/MS) em sangue seco, colhido em papelfiltro. PERGUNTA DE PESQUISA: A triagem neonatal (em sangue seco, colhido em papel-filtro) por MS/MS, para a detecção da MCADD, em recém-nascidos assintomáticos, é custo-efetiva e reduz a mortalidade e as complicações de curto e longo prazo naqueles recém-nascidos nos quais a doença é detectada, em comparação ao diagnóstico dessa doença em indivíduos com suspeita clínica ou manifestações clínicas? EVIDÊNCIAS CLINICAS: Em uma revisão sistemática da literatura, realizada em 26 de abril de 2022, foram encontradas 1037 referências, das quais 7 atendiam aos critérios de inclusão deste relatório (6 avaliaram desfechos primários e 1 avaliou desfechos secundários). Considerando os 4 desfechos primários avaliados, não foram encontrados estudos sobre apenas um deles (qualidade de vida). Os estudos incluídos descrevem maior frequência de morte súbita ou por complicações da doença, e de internações hospitalares decorrentes da doença ou de suas complicações no grupo comparador (indivíduos com suspeita clínica ou com manifestações clínicas de MCADD). Com relação à incidência de complicações ou condições resultantes da doença, independente da necessidade de admissão hospitalar, também há uniformidade entre os resultados dos estudos incluídos, indicando a eficácia/eficiência da intervenção. AVALIAÇÃO ECONÔMICA (AE) propôs-se uma análise de custo-utilidade construída com base nas diretrizes metodológicas publicadas pelo Ministério da Saúde, na perspectiva do SUS, tendo como população alvo todos os recém-nascidos no país. De acordo com a análise empreendida, o custo da triagem por MS/MS para MCADD foi de R$ 1.952,88, havendo um incremento em custos de cerca de R$ 1.949,00 em comparação à não-realização da triagem neonatal para esta doença. No entanto, a efetividade comparada da triagem por MS/MS foi superior à estratégia de não triar esta doença, mais do que o dobro daquela associada à não-triagem, havendo um incremento de cerca de 78 pontos nesta. Por fim, a Razão de Custo-efetividade Incremental (RCEI) encontrada foi de R$ 24,99/QALY. ANÁLISE DE IMPACTO ORÇAMENTÁRIO (AIO): foi feita uma avaliação do impacto orçamentário da possível incorporação do referido teste (MS/MS) ao longo de 5 anos, junto com a substituição da testagem para fenilcetonúria (PKU) pelo método de imunofluorimetria (o atualmente usado) pela mesma metodologia (MS/MS), conforme as Diretrizes Metodológicas de análise de Impacto Orçamentário do Ministério da Saúde. A realidade atual de inexistência de testagem de MCADD gera um custo anual em teste de triagem de zero. No entanto, a não identificação de indivíduos com MCADD, gera, por sua vez, custos de internação. Sendo assim, no primeiro caso o custo anual e em 5 anos seria zero. Porém se fossem considerados os custos gerados a partir dos pacientes sem diagnóstico neonatal que evoluíram a sintomas e internação no primeiro ano de vida, a estimativa em cinco anos seria de um gasto de pouco mais de R$ 100 mil. A triagem para MCADD por MS/MS descontados apenas os custos das internações evitadas com a identificação precoce daqueles com esta doença pela triagem, ficaria em cerca de R$ 288 milhões ao longo de 5 anos, sendo a média anual aproximadamente R$ 57 milhões. No entanto, considerando que a triagem por fenilcetonúria (PKU), hoje realizada por imunofluorimetria, com a adoção da triagem por MS/MS, poderia ser feita por esta última metodologia, sem que com isso houvesse acréscimo no gasto do exame realizado para MCADD (ou seja, o mesmo teste, triaria ao mesmo tempo MCADD e PKU) haveria uma economia adicional advinda dos custos salvos pela não realização da imunofluorimetria para PKU. Assim, ao considerar-se a triagem neonatal por MS/MS para MCADD e PKU ao longo de 5 anos, com todos os custos evitados (possíveis internações por sintomas da doença no primeiro ano de vida e utilização da imunofluorimetria como método da triagem para a fenilcetonúria), este valor seria cerca de R$ 222 milhões, resultando num dispêndio anual médio de cerca de R$ 44 milhões, ou seja, uma economia média anual adicional de 13 milhões apenas com a inclusão da triagem de PKU na mesma metodologia utilizada para triagem de MCADD. CONSIDERAÇÕES FINAIS: os resultados sugerem que os indivíduos com MCADD são beneficiados com a inclusão da triagem neonatal para a detecção dessa doença. A avaliação econômica mostra que a efetividade da triagem neonatal por MS/MS é de cerca de 153, sendo este valor mais que o dobro da efetividade associada à não-triagem (cerca de 75); a efetividade incremental é de 78. Já a RCEI encontrada foi de R$ 24,99/QALY. Esta análise indica ganhos evidentes da estratégia de adoção de triagem neonatal por MS/MS para MCADD. Em relação ao impacto econômico, ao longo de 5 anos, com todos os custos evitados (referentes às possíveis internações por sintomas da doença nos primeiros anos de vida e testagem conjunta de MCADD e PKU por MS/MS), este valor seria cerca de R$ 222 milhões, um dispêndio anual médio de cerca de R$ 44 milhões, uma economia média anual adicional de 13 milhões apenas com a inclusão da triagem de PKU na mesma metodologia utilizada para triagem de MCADD. RECOMENDAÇÃO PRELIMINAR DA CONITEC: na 113ª Reunião Ordinária da Conitec, realizada em 05 de outubro de 2022, os membros presentes no Plenário deliberaram por unanimidade que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à incorporação da triagem neonatal por espectrometria de massas em tandem (MS/MS), para a detecção da deficiência de MCADD. Para essa recomendação, a Conitec considerou que a detecção precoce por triagem neonatal da MCADD é eficaz, segura e custo-efetiva, estando de acordo com os critérios estabelecidos na Lei Nº 14.154, de 26 de maio de 2021, que dispõe sobre a ampliação do Programa Nacional de Triagem Neonatal (PNTN). CONSULTA PÚBLICA: : a consulta pública n° 70 ficou vigente no período entre 25/10/2022 e 14/11/2022. Foram recebidas 10 contribuições, sendo 4 da categoria técnico-científicas e 6 de experiência ou opinião. Todos os participantes estiveram de acordo com a recomendação preliminar da Conitec de incorporar a triagem neonatal por espectrometria de massas em tandem (MS/MS) para detecção da deficiência de acil-CoA desidrogenase de cadeia média (MCADD) no SUS. A consulta pública não adicionou elementos que alterassem o conteúdo deste relatório de recomendação. RECOMENDAÇÃO FINAL DA CONITEC: os membros do Plenário da Conitec, presentes em sua 12ª Reunião Extraordinária, realizada no dia 29 de novembro de 2022, deliberaram por unanimidade, recomendar a incorporação da triagem neonatal por espectrometria de massas em tandem (MS/MS) para detecção da deficiência de acilCoA desidrogenase de cadeia média (MCADD). Foi assinado o Registro de Deliberação nº 789/2022. DECISÃO: Incorporar, no âmbito do Sistema Único de Saúde - SUS, a triagem neonatal por espectrometria de massas em tandem (MS/MS) para detecção da deficiência de acilCoA desidrogenase de cadeia média (MCADD), conforme protocolo estabelecido pelo Ministério da Saúde, conforme a Portaria nº 179, publicada no Diário Oficial da União nº 244, seção 1, página 304, em 28 de dezembro de 2022.

Cost-effectiveness analysis of newborn screening by tandem mass spectrometry in Shenzhen, China: value and affordability of new screening technology.

BACKGROUND: Newborn screening (NBS) can prevent inborn errors of metabolism (IEMs), which may cause long-term disability and even death in newborns. However, in China, tandem mass spectrometry (MS/MS) screening has just started. This study aimed to assess the cost-effectiveness of NBS using MS/MS in Shenzhen under the nationally recommended program, as well as evaluate the value and affordability of introducing this new screening technology. METHODS: A Markov model was built to estimate the cost and quality-adjusted life-years (QALYs) of different screening programs. We compared PKU screening using traditional immunofluorescence (IF) with the other 11 IEMs not screened and all 12 IEMs screened using MS/MS, and the programs detecting different numbers of IEMs chosen from the national recommended program were also compared. A sensitivity analysis and budget impact analysis (BIA) were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) of detecting all 12 IEMs in the national program is 277,823 RMB per QALY, below three times per capita GDP in Shenzhen. MS/MS screening in Shenzhen can be cost-effective only if at least three diseases (PKU, PCD and MMA) are covered and when the screening program covers five diseases (PKU, PCD, MMA, MSUD, IVA), the ICER closely approaches its critical threshold. The BIA indicated the implementation cost of the national program to be around 490 million RMB over 10 years and showed no difference in budget between programs detecting different numbers of IEMs. CONCLUSIONS: We conclude that the newborn screening using MS/MS in Shenzhen is cost-effective, and the budget affordable for the Shenzhen government. Two concepts for selecting the IEMs to be detected are also presented. One is to choose the most cost-effective screening programs detecting highest number of IEMs to achieve a minimal ICER. The other considers the curability and affordability of the disease as the basis of healthcare decisions to screen suitable IEMs, achieving an ICER under the threshold and close to the minimum value.

Cost-Effectiveness of Newborn Screening for Spinal Muscular Atrophy in The Netherlands.

OBJECTIVES: Spinal muscular atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness and paralysis. In its most common and severe form, the majority of untreated infants die before 2 years of age. Early detection and treatment, ideally before symptom onset, maximize survival and achievement of age-appropriate motor milestones, with potentially substantial impact on health-related quality of life. Therefore, SMA is an ideal candidate for inclusion in newborn screening (NBS) programs. We evaluated the cost-effectiveness of including SMA in the NBS program in The Netherlands. METHODS: We developed a cost-utility model to estimate lifetime health effects and costs of NBS for SMA and subsequent treatment versus a treatment pathway without NBS (ie, diagnosis and treatment after presentation with overt symptoms). Model inputs were based on literature, local data, and expert opinion. Sensitivity and scenario analyses were conducted to assess model robustness and validity of results. RESULTS: After detection of SMA by NBS in 17 patients, the number of quality-adjusted life-years gained per annual birth cohort was estimated at 320 with NBS followed by treatment compared with treatment after clinical SMA diagnosis. Total healthcare costs, including screening, diagnostics, treatment, and other healthcare resource use, were estimated to be €12 014 949 lower for patients identified by NBS. CONCLUSIONS: NBS for early identification and treatment of SMA versus later symptomatic treatment after clinical diagnosis improves health outcomes and is less costly and, therefore, is a cost-effective use of resources. Results were robust in sensitivity and scenario analyses.

Incidence of Neonatal Developmental Dysplasia of the Hip and Late Detection Rates Based on Screening Strategy: A Systematic Review and Meta-analysis.

Importance: Universal ultrasonographic screening for developmental dysplasia of the hip (DDH) has gained increasing popularity despite the lack of benefit in terms of reducing the rates of late-detected cases (age ≥12 weeks) in randomized clinical trials. Objective: To report the reported incidence of DDH in the English scientific literature and compare rates of late-detected cases in settings with different DDH screening strategies. Data Sources: PubMed, Scopus, and Web of Science databases were searched on November 25 and 27, 2021. No time filters were used in the search. Study Selection: All observational studies reporting the incidence of early-detected or late-detected (age ≥12 weeks) DDH were included. Non-English reports were excluded if the abstract did not include enough information to be included for analysis. Data Extraction and Synthesis: The number of newborns screened and the detection rates were extracted. Meta-analysis calculated the pooled incidence of DDH per 1000 newborns with 95% CIs using a random- or fixed-effects model. This study is reported according to the PRISMA and MOOSE guidelines. Main Outcomes and Measures: The main outcome measures were early detection, early treatment, late detection, and operative treatment incidences. Results: A total of 1899 studies were identified, 203 full texts were assessed, and 76 studies with 16 901 079 infants were included in final analyses. The early detection rate was 8.4 (95% CI, 4.8-14.8) infants with DDH per 1000 newborns with clinical screening, 4.4 (95% CI, 2.4-8.0) infants with DDH per 1000 newborns with selective ultrasonographic screening, and 23.0 (95% CI, 15.7-33.4) infants with DDH per 1000 newborns with universal ultrasonographic screening. Rates for nonoperative treatment were 5.5 (95% CI, 2.1-14) treatments per 1000 newborns with clinical screening, 3.1 (95% CI, 2.0-4.8) treatments per 1000 newborns with selective ultrasonographic screening, and 9.8 (95% CI, 6.7-14.4) treatments per 1000 newborns with universal ultrasonographic screening. The incidence of late-detected DDH was 0.5 (95% CI, 0.2-1.5) infants with DDH per 1000 newborns with clinical screening, 0.6 (95% CI, 0.3-1.3) infants with DDH per 1000 newborns with selective ultrasonographic screening, and 0.2 (95% CI, 0.0-0.8) infants with DDH per 1000 newborns with universal ultrasonographic screening. The corresponding incidences of operative treatment were 0.2 (95% CI, 0.0-0.9) operations per 1000 newborns with clinical screening, 0.5 (95% CI, 0.4-0.7) operations per 1000 newborns with selective ultrasonographic screening, and 0.4 (95% CI, 0.2-0.7) operations per 1000 newborns with universal ultrasonographic screening. Conclusions and Relevance: This meta-analysis found that early detection rates and nonoperative treatments were higher with universal screening. The late detection and operative treatment rates with universal screening were similar to those among selectively and clinically screened newborns. Based on these results, universal screening may cause initial overtreatment without reducing the rates of late detection and operative treatment.