[Sickle cell disease in French Guiana: assessing 30 years of neonatal screening (1992-2021)]. / La drépanocytose en Guyane : bilan de 30 années de dépistage néonatal (1992-2021).

Background: Sickle cell disease is one of the most common genetic diseases in France. In French Guiana, neonatal screening was introduced in 1992, at the same time as other screening programs for childhood diseases. The aim of this study is to describe the organization of newborn screening for sickle cell disease in French Guiana. Materials and methods: We used several data sources: data collected from hospital records since 2005, activity reports from the national neonatal screening program and data from screening campaigns organized by the Drepaguyane association between 2010 and 2021 on 1,300 subjects. Blood samples from newborns are collected by capillary or venous sampling and absorbed on blotting paper (Guthrie) at the same time as those for other neonatal screenings. The dried papers are sent to the inter-regional laboratory in Lille, for further processing. In Saint-Laurent-du-Maroni, in order to reduce the proportion of people lost to follow-up, a double screening is carried out and the results are returned before discharge from the maternity hospital. All data were entered into an anonymous Excel file. The data were analyzed using STATA software. Results: Among the 175,593 screened neonates between 1992 and 2021, screening detected 823 infants with sickle cell disease and 17,950 heterozygotes. Sickle cell genotypes include 493 SS (60%), 302 SC (37%) and 28 S-Beta-thalassemia (3%). The incidence of sickle cell disease was 1/213, 95% CI [1/236-1/204], and that of heterozygotes 1/10, IC 95% [1/12-1/8]. The majority of these children (52%) were from the Maroni region. The delay between screening and test results was 7 days. Only pathological results (homozygous, heterozygous) were communicated to parents and/or the attending physician by post. These data confirm the upward trend in the number of children screened for sickle cell disease in French Guiana. Data from screening campaigns organized by the Drepaguyane association have enabled to describe the distribution of the various abnormal hemoglobin fractions, and to confirm that HbS is more frequent in Western French Guiana. In Cayenne, in 2021, the active file comprised 699 patients, including 266 children under 18 years old. Discussion and conclusion: This study provides valuable data on 30 years of neonatal screening for sickle cell disease in French Guiana, and on the evolution of sickle cell disease patients. It confirms that French Guiana is the French territory with the highest incidence of sickle cell disease. This incidence continues to rise over time. The study reveals the improvement in the organization of sickle cell disease management in French Guiana between 1992, when screening was introduced, and the present day. It highlights the role of patient associations in the fight against this disease, by organizing awareness and screening campaigns. These data will be used to guide public health policies in the pursuit of improved care and primary prevention.

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.

Machine Learning-Based Critical Congenital Heart Disease Screening Using Dual-Site Pulse Oximetry Measurements.

BACKGROUND: Oxygen saturation (Spo2) screening has not led to earlier detection of critical congenital heart disease (CCHD). Adding pulse oximetry features (ie, perfusion data and radiofemoral pulse delay) may improve CCHD detection, especially coarctation of the aorta (CoA). We developed and tested a machine learning (ML) pulse oximetry algorithm to enhance CCHD detection. METHODS AND RESULTS: Six sites prospectively enrolled newborns with and without CCHD and recorded simultaneous pre- and postductal pulse oximetry. We focused on models at 1 versus 2 time points and with/without pulse delay for our ML algorithms. The sensitivity, specificity, and area under the receiver operating characteristic curve were compared between the Spo2-alone and ML algorithms. A total of 523 newborns were enrolled (no CHD, 317; CHD, 74; CCHD, 132, of whom 21 had isolated CoA). When applying the Spo2-alone algorithm to all patients, 26.2% of CCHD would be missed. We narrowed the sample to patients with both 2 time point measurements and pulse-delay data (no CHD, 65; CCHD, 14) to compare ML performance. Among these patients, sensitivity for CCHD detection increased with both the addition of pulse delay and a second time point. All ML models had 100% specificity. With a 2-time-points+pulse-delay model, CCHD sensitivity increased to 92.86% (P=0.25) compared with Spo2 alone (71.43%), and CoA increased to 66.67% (P=0.5) from 0. The area under the receiver operating characteristic curve for CCHD and CoA detection significantly improved (0.96 versus 0.83 for CCHD, 0.83 versus 0.48 for CoA; both P=0.03) using the 2-time-points+pulse-delay model compared with Spo2 alone. CONCLUSIONS: ML pulse oximetry that combines oxygenation, perfusion data, and pulse delay at 2 time points may improve detection of CCHD and CoA within 48 hours after birth. REGISTRATION: URL: https://www.clinicaltrials.gov/study/NCT04056104?term=NCT04056104&rank=1; Unique identifier: NCT04056104.

Effects of Natural Delivery and Cesarean Section on the Result of First Hearing Screening of Newborns.

BACKGROUND: Early detection and intervention of hearing issues in newborns are crucial for their auditory and speech development, necessitating newborn hearing screenings. This study aimed to investigate the impact of delivery methods, specifically natural delivery and cesarean section, on newborn hearing screening outcomes. METHODS AND MATERIAL: A retrospective analysis was conducted on data from 600 newborns delivered at The First Affiliated Hospital of Shaoyang University between January 2020 and January 2023. The initial hearing screenings used the AccuScreen otoacoustic emission instrument. The study examined the influence of delivery method on the pass rates of newborns' first hearing screenings within and beyond 48 h postbirth. RESULTS: The pass rates for the initial hearing screenings, conducted within and after 48 h of birth, were significantly higher in the natural delivery group compared to the cesarean section group (P < 0.05). Furthermore, multivariate analysis identified the delivery method as a significant factor influencing the pass rates of newborns' first hearing screenings. CONCLUSIONS: The mode of delivery appears to affect the results of the initial hearing screenings of newborns, though further research is needed to validate these findings.

Newborn Screening for High-Risk Congenital Heart Disease by Dried Blood Spot Biomarker Analysis.

Importance: Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally. Objectives: Assessing the performance of 2 diagnostic tests using minimal amounts of dried blood spots (DBS) to identify high-risk CHD compared with controls in a Swedish cohort of neonates. Design, Setting, and Participants: This diagnostic study took place in Sweden between 2019 and 2023 and enrolled full-term babies born between 2005 and 2023. All cases were identified through centralized pediatric cardiothoracic surgical services in Lund and Gothenburg, Sweden. Controls were followed up for 1 year to ensure no late presentations of high-risk CHD occurred. Cases were verified through surgical records and echocardiography. Exposure: High-risk CHD, defined as cases requiring cardiac surgical management during infancy due to evolving signs of heart failure or types in which the postnatal circulation depends on patency of the arterial duct. Using 3-µL DBS samples, automated quantitative tests for NT-proBNP and interleukin 1 receptor-like 1 (IL-1 RL1; formerly known as soluble ST2) were compared against established CHD screening methods. Main Outcomes and Measures: Performance of DBS tests to detect high-risk CHD using receiver operating characteristic curves; Bland-Altman and Pearson correlation analyses to compare IL-1 RL1 DBS with plasma blood levels. Results: A total of 313 newborns were included (mean [SD] gestational age, 39.4 [1.3] weeks; 181 [57.8%] male). Mean (SD) birthweight was 3495 (483) grams. Analyzed DBS samples included 217 CHD cases and 96 controls. Among the CHD cases, 188 participants (89.3%) were high-risk types, of which 73 (38.8%) were suspected prenatally. Of the 188 high-risk cases, 94 (50.0%) passed pulse oximetry screening and 36 (19.1%) were initially discharged after birth without diagnoses. Combining NT-proBNP and IL-1 RL1 tests performed well in comparison with existing screening methods and enabled additional identification of asymptomatic babies with receiver operating characteristic area under the curve 0.95 (95% CI, 0.93-0.98). Conclusions and relevance: In this diagnostic study, NT-proBNP and IL-1 RL1 DBS assays identified high-risk CHD in a timely manner, including in asymptomatic newborns, and improved overall screening performance in this cohort from Sweden. Prospective evaluation of this novel approach is warranted.

Procedural elements of the complete examination and screening of the healthy term neonate: a protocol for a scoping review and evidence map.

INTRODUCTION: All newborns undergo a Complete Examination and Screening of the Neonate (CESoN) to verify the general health and well-being of the neonate and to screen for signs and symptoms of illness and significant congenital disorders, typically within 72 hours of birth. For healthy, term gestation neonates, this examination is usually performed by a qualified healthcare practitioner that is, a midwife, nurse or physician just prior to discharge from the maternity services. As a precursor to modifying and adapting an instrument that measures the quality of performance of the CESoN by healthcare professionals, this review aims to identify, evaluate, synthesise and map the evidence and theory underpinning current practice and the procedural elements of the CESoN. METHODS AND ANALYSIS: This review will be guided by the Joanna Briggs Institute methodology for scoping reviews and also the recommendations of the Campbell Collaboration for systematic evidence mapping. Based on the research question, the Person, Concept, Context framework will be used to develop eligibility criteria for inclusion in the review. Eligible information shall be sourced by searching electronic databases including PubMed, Cumulative Index of Nursing and Allied Health Literature, and Scopus, and the published guidance from expert bodies on newborn examination and screening (eg, National Institute for Health and Care Excellence, American Academy of Pediatrics, Royal College of Paediatrics and Child Health) and the grey literature. This study will include primary and secondary research papers, evidence-based guidelines, and expert text and opinions published in English from 2013 to September 2023. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review and systematic evidence mapping. The results from this study will be disseminated through peer-reviewed format, that is, conference proceedings and peer-reviewed healthcare journals.

Genomic sequencing for newborn screening: current perspectives and challenges.

Traditional newborn screening (NBS) serves as a critical tool in identifying conditions that may impact a child's health from an early stage. Newborn sequencing (NBSeq), the comprehensive analysis of an infant's genome, holds immense promise for revolutionizing health care throughout the lifespan. NBSeq allows for early detection of genetic disease risk and precision personalized medicine. The rapid evolution of DNA sequencing technologies and increasing affordability have spurred numerous endeavors to explore the potential of whole-genome sequencing in newborn screening. However, this transformative potential cannot be realized without challenges. Ethical aspects must be carefully navigated to safeguard individual rights and maintain public trust. Moreover, genomic data interpretation poses complex challenges due to its amount, the presence of variants of uncertain significance, and the dynamic nature of our understanding of genetics. Implementation hurdles, including cost, infrastructure, and specialized expertise, also present barriers to the widespread adoption of NBSeq. Addressing these challenges requires collaboration among clinicians, researchers, policymakers, ethicists, and stakeholders across various sectors. Robust frameworks for informed consent, data protection, and governance are essential. Advances in bioinformatics, machine learning, and genomic interpretation are crucial for translation into actionable clinical insights. Scalability and improving downstream health care access are vital for equitability, particularly in underserved communities. By fostering interdisciplinary collaboration, advancing technology and infrastructure, and upholding ethical principles, we can unlock the full potential of NBSeq as a tool for precision medicine and pave the way toward a future where every child has the opportunity for a healthier, genomics-informed start to life.

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.

Detection of α-Galactosidase A Reaction in Samples Extracted from Dried Blood Spots Using Ion-Sensitive Field Effect Transistors.

Fabry disease is a lysosomal storage disorder caused by a significant decrease in the activity or absence of the enzyme α-galactosidase A. The diagnostics of Fabry disease during newborn screening are reasonable, due to the availability of enzyme replacement therapy. This paper presents an electrochemical method using complementary metal-oxide semiconductor (CMOS)-compatible ion-sensitive field effect transistors (ISFETs) with hafnium oxide-sensitive surfaces for the detection of α-galactosidase A activity in dried blood spot extracts. The capability of ISFETs to detect the reaction catalyzed by α-galactosidase A was demonstrated. The buffer composition was optimized to provide suitable conditions for both enzyme and ISFET performance. The use of ISFET structures as sensor elements allowed for the label-free detection of enzymatic reactions with melibiose, a natural substrate of α-galactosidase A, instead of a synthetic fluorogenic one. ISFET chips were packaged with printed circuit boards and microfluidic reaction chambers to enable long-term signal measurement using a custom device. The packaged sensors were demonstrated to discriminate between normal and inhibited GLA activity in dried blood spots extracts. The described method offers a promising solution for increasing the widespread distribution of newborn screening of Fabry disease.

Exploratory Untargeted Metabolomics of Dried Blood Spot Samples from Newborns with Maple Syrup Urine Disease.

Currently, tandem mass spectrometry-based newborn screening (NBS), which examines targeted biomarkers, is the first approach used for the early detection of maple syrup urine disease (MSUD) in newborns, followed by confirmatory genetic mutation tests. However, these diagnostic approaches have limitations, demanding the development of additional tools for the diagnosis/screening of MUSD. Recently, untargeted metabolomics has been used to explore metabolic profiling and discover the potential biomarkers/pathways of inherited metabolic diseases. Thus, we aimed to discover a distinctive metabolic profile and biomarkers/pathways for MSUD newborns using untargeted metabolomics. Herein, untargeted metabolomics was used to analyze dried blood spot (DBS) samples from 22 MSUD and 22 healthy control newborns. Our data identified 210 altered endogenous metabolites in MSUD newborns and new potential MSUD biomarkers, particularly L-alloisoleucine, methionine, and lysoPI. In addition, the most impacted pathways in MSUD newborns were the ascorbate and aldarate pathways and pentose and glucuronate interconversions, suggesting that oxidative and detoxification events may occur in early life. Our approach leads to the identification of new potential biomarkers/pathways that could be used for the early diagnosis/screening of MSUD newborns but require further validation studies. Our untargeted metabolomics findings have undoubtedly added new insights to our understanding of the pathogenicity of MSUD, which helps us select the appropriate early treatments for better health outcomes.

Rapid detection of common variants and deletions of CYP21A2 using MALDI-TOF MS.

Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) based on hormonal testing is successfully implemented in many countries. However, this method cannot detect non-classic CAH and has high false positive rates. We have developed a novel MALDI-TOF MS assay that can identify common variants and deletions of CYP21A2 in the Chinese population. Thirty-seven clinical patients with CAH confirmed by Sanger sequencing and MLPA analysis were detected by MALDI-TOF MS assay. Two CYP21A2 variants were detected in 30 patients and one CYP21A2 variant was detected in 7 patients. The MALDI-TOF MS assay detected 67 mutant alleles in 37 patients with a detection rate of 90.5%. Sanger sequencing revealed that three variants in seven patients were not included in the designed panel. Eleven distinct CYP21A2 variants were identified, including five missense variants, two nonsense variants, two large gene deletions, one splice variant, and one frameshift variant. The most frequent variant was c.293-13C > G (37.84%), followed by c.518T > A (21.62%) and exon 1-7 deletion (17.57%). The high-throughput MALDI-TOF MS assay that can simultaneously detect common variants and deletions of CYP21A2. This assay can be used for population-based genetic screening and rapid detection of suspected patients, and is expected to be a valuable complement to biochemical-based testing for the detection of CAH.

Distribution and reference values of peripheral perfusion index in neonates from population-wide screening.

BACKGROUND: Peripheral perfusion index (PPI) is useful in a variety of neonatal settings. Currently, available reference values are from small numbers and highly variable. METHODS: We sought to generate reference values of PPI by analysing previously collected data from newborns who underwent mandated universal pulse oximetry and PPI screening from 2018 to 2021 using uniform protocol and equipment. Q-Q plots and boxplots were used to visualise distributions. Kernel density estimation for heaped and rounded data was used to estimate percentiles of the distributions. RESULTS: Data from 388 205 newborns who underwent universal pulse oximetry screening in the first week of life were used for this analysis. Pre and postductal values showed a non-normal distribution and skewed to the left, the former had a thicker tail with more extreme values. Minor, but statistically significant differences were seen in the PPI values from day 1 to 7. Median preductal PPI (2.77, IQR:1.83-3.93) was significantly higher than postductal (2.38 IQR: 1.41-3.55) (p<0.01). PPI values increased with weight and boys had higher PPI. Kernel estimates of the percentiles in the overall sample and subgroups for gender and weight have been provided for preductal and post-ductal values. CONCLUSION: This study, based on the largest available dataset, provides reference values for PPI in newborns. A significant influence of gender and birth weight on PPI values in newborns has been identified. Future research on understanding the influence of age, sex, birth weight, gestational age, ambient temperature and genetic factors on PPI is recommended.

Newborn Screening for 6 Lysosomal Storage Disorders in China.

Importance: Newborn screening (NBS) for lysosomal storage disorders (LSDs) is becoming an increasing concern in public health. However, the birth prevalence of these disorders is rarely reported in the Chinese population, and subclinical forms of diseases among patients identified by NBS have not been evaluated. Objective: To evaluate the birth prevalence of the 6 LSDs in the Shanghai population and determine subclinical forms based on clinical, biochemical, and genetic characteristics. Design, Setting, and Participants: This cohort study included 50 108 newborns recruited from 41 hospitals in Shanghai between January and December 2021 who were screened for 6 LSDs using tandem mass spectrometry (MS/MS). Participants with screen-positive results underwent molecular and biochemical tests and clinical assessments. Data were analyzed from January 2021 through October 2022. Exposures: All participants were screened for Gaucher, acid sphingomyelinase deficiency (ASMD), Krabbe, mucopolysaccharidosis type I, Fabry, and Pompe diseases using dried blood spots. Main Outcomes and Measures: Primary outcomes were the birth prevalence and subclinical forms of the 6 LSDs in the Shanghai population. Disease biomarker measurements, genetic testing, and clinical analysis were used to assess clinical forms of LSDs screened. Results: Among 50 108 newborns (26 036 male [52.0%]; mean [SD] gestational age, 38.8 [1.6] weeks), the mean (SD) birth weight was 3257 (487) g. The MS/MS-based NBS identified 353 newborns who were positive. Of these, 27 newborns (7.7%) were diagnosed with 1 of 6 LSDs screened, including 2 newborns with Gaucher, 5 newborns with ASMD, 9 newborns with Krabbe, 8 newborns with Fabry, and 3 newborns with Pompe disease. The combined birth prevalence of LSDs in Shanghai was 1 diagnosis in 1856 live births, with Krabbe disease the most common (1 diagnosis/5568 live births), followed by Fabry disease (1 diagnosis/6264 live births), and ASMD (1 diagnosis/10 022 live births). Biochemical, molecular, and clinical analysis showed that early-onset clinical forms accounted for 3 newborns with positive results (11.1%), while later-onset forms represented nearly 90% of diagnoses (24 newborns [88.9%]). Conclusions and Relevance: In this study, the combined birth prevalence of the 6 LSDs in Shanghai was remarkably high. MS/MS-based newborn screening, combined with biochemical and molecular genetic analysis, successfully identified and characterized newborns who were screen-positive, which may assist with parental counseling and management decisions.

Identifying Metabolic Diseases That Precipitate Neonatal Seizures.

Although a rare cause of neonatal seizures, inborn errors of metabolism (IEMs) remain an essential component of a comprehensive differential diagnosis for poorly controlled neonatal epilepsy. Diagnosing neonatal-onset metabolic conditions proves a difficult task for clinicians; however, routine state newborn screening panels now include many IEMs. Three in particular-pyridoxine-dependent epilepsy, maple syrup urine disease, and Zellweger spectrum disorders-are highly associated with neonatal epilepsy and neurocognitive injury yet are often misdiagnosed. As research surrounding biomarkers for these conditions is emerging and gene sequencing technologies are advancing, clinicians are beginning to better establish early identification strategies for these diseases. In this literature review, the authors aim to present clinicians with an innovative clinical guide highlighting IEMs associated with neonatal-onset seizures, with the goal of promoting quality care and safety.

It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Validation of postnatal growth and retinopathy of prematurity (G-ROP) screening guidelines in a tertiary care hospital of Pakistan: A report from low-middle income country.

Retinopathy of Prematurity (ROP) significantly contributes to childhood blindness globally, with a disproportionately high burden in low- and middle-income countries (LMICs) due to improved neonatal care alongside inadequate ROP screening and treatment facilities. This study aims to validate the performance of Postnatal Growth and Retinopathy of Prematurity (G-ROP) screening criteria in a cohort of premature infants presenting at a tertiary care setting in Pakistan. This cross-sectional study utilized retrospective chart review of neonates admitted to the neonatal intensive care unit (NICU) at The Aga Khan University Hospital, Pakistan from January 2018 to February 2022. The complete G-ROP criteria were applied as prediction tool for infants with type 1 ROP, type 2 ROP, and no ROP outcomes. Out of the 166 cases, 125 cases were included in the final analysis, and remaining cases were excluded due to incomplete data. ROP of any stage developed in 83 infants (66.4%), of whom 55 (44%) developed type 1 ROP, 28 (22.4%) developed type 2 ROP, and 19 (15.2%) were treated for ROP. The median BW was 1060 gm (IQR = 910 to 1240 gm) and the median gestational age was 29 wk (IQR = 27 to 30 wk). The G-ROP criteria demonstrated a sensitivity of 98.18% (95% CI: 90.28-99.95%) for triggering an alarm for type 1 ROP. The G-ROP criteria achieved 100% sensitivity (95% CI: 87.66 to 100%) for type 2 ROP. The overall sensitivity of G-ROP criteria to trigger an alarm for any type of ROP was 98.8% (95% CI: 93.47 to 99.97%). Thus, the G-ROP screening model is highly sensitive in detecting at-risk infants for ROP in a Pakistani tertiary care setting, supporting its use in LMICs where standard screening criteria may not suffice.

Neonatal screening of ABO/RhD blood group and direct antiglobulin Coombs test. Experience of a single institution.

BACKGROUND: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth. METHODS: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR). RESULTS: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95% CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1). DISCUSSION: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination.

INTRODUCCIÓN: La determinación del grupo sanguíneo ABO/RhD y la prueba directa de Coombs (PDC) al nacimiento son una práctica recomendada, pero existe variabilidad en su implementación universal. Se presentan los resultados de la determinación al nacimiento del grupo ABO/RhD y la PDC en una cohorte institucional. MÉTODOS: Se incluyeron los recién nacidos entre 2017 y 2020 en un hospital de atención a embarazos de alto riesgo. Se determinó el grupo ABO/RhD y se realizó la PDC en muestras de cordón umbilical o en las primeras 24 horas de vida. Se registraron las variables demográficas, maternas y neonatales. Se estimó la asociación entre las variables mediante la razón de probabilidad (OR). RESULTADOS: Se incluyeron 8721 binomios. La PDC fue positiva en 239 recién nacidos (2.7%), siendo las variables asociadas a la PDC positiva la edad materna > 40 años (OR: 1.5;IC95%: 1.0-2.3), el nacimiento por vía cesárea (1.4; 1.1-2.0), la madre del grupo O (6.4; 3.8-11.8), la prematuridad (3.6; 2.6-5.0); el peso al nacer < 2500 g (2.1; 1.6-2.8); el neonato del grupo A (15.7; 10.7-23.1) o del grupo B (17.6; 11.4-27.2), la hemoglobina al nacer < 13.5 g/dl (4.5; 2.8-7.1) y la reticulocitosis > 9% (1.9; 1.2 a 3.1). DISCUSIÓN: La frecuencia de PDC positiva neonatal es del 2.7%, con asociación significativa la incompatibilidad materna/neonatal al grupo ABO y RhD, con impacto significativo en diversas variables neonatales. Estos resultados apoyan la política de implementación universal al nacimiento de la determinación de ABO/RhD y PDC.

Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

BACKGROUND: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. METHODS: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. RESULTS: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22-0.84), with significantly higher rates (2.1%, 95% CI 0.58-5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31-4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23-37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). CONCLUSIONS: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

Quantification of N-acetyl-l-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease.

BACKGROUND: Canavan disease is a devastating neurometabolic disorder caused by accumulation of N acetylaspartate in brain and body fluids due to genetic defects in the aspartoacylase gene (ASPA). New gene therapies are on the horizon but will require early presymptomatic diagnosis to be fully effective. METHODS: We therefore developed a fast and highly sensitive liquid chromatography mass spectrometry (LC-MS/MS)-based method for quantification of N-acetylaspartate in dried blood spots and established reference ranges for neonates and older controls. With this test, we investigated 45 samples of 25 Canavan patients including 8 with a neonatal sample. RESULTS: Measuring N-acetylaspartate concentration in dried blood with this novel test, all Canavan patients (with variable severity) were well separated from the control group (median; range: 5.7; 1.6-13.6 µmol/L [n = 45] vs 0.44; 0.24-0.99 µmol/L [n = 59] (p < 0.05)). There was also no overlap when comparing neonatal samples of Canavan patients (7.3; 5.1-9.9 µmol/L [n = 8]) and neonatal controls (0.93; 0.4-1.8 µmol/L [n = 784]) (p < 0.05). CONCLUSIONS: We have developed a new LC-MS/MS-based screening test for early postnatal diagnosis of Canavan disease that should be further evaluated in a population-based study once a promising treatment becomes available. The method meets the general requirements of newborn screening and should be appropriate for multiplexing with other screening approaches that combine chromatographic and mass spectrometry techniques.

Comparative analysis of the quantitative point-of-care CareSTART™ total bilirubin with central laboratory total bilirubin assays in neonatal blood samples.

This study aimed to assess and compare the accuracy of point-of-care CareSTART™ S1 Total Bilirubin test with a central laboratory total bilirubin assay using neonatal samples. This study was conducted using 152 paired measurements obtained from 122 neonates admitted to the neonatal intensive care unit. Total serum bilirubin (TSB) levels assayed with the central laboratory assay, laboratory bilirubinomter, trancutaneous bliribubin (TcB) instrument and CareSTART were compared using Bland-Altman analysis. The mean difference between the CareSTART and TSB values was -1.43 mg/dL and the 95% limit of agreement (LoA) was -4.25 to 1.39 mg/dL. CareSTART tended to underestimate total bilirubin concentrations compared with TcB, however, the LoA was narrower due to the smaller SD of mean difference for CareSTART. The CareSTART Total Bilirubin test provides an accurate alternative to TcB for total serum bilirubin measurement. Given its low-cost, ease-of-use, and portability, the use of CareSTART is expected to provide point-of-care measurements, especially in low-resource settings.