Search

The reader will come to appreciate: • An analysis of the characteristics of CFSPID individuals who evolve into CF. • That the presence of one CF-causing CFTR variant, an initial sweat chloride (SC) ≥ 40 mmol/L or an increase of SC > 2.5 mmol/L/year could allow identification of subjects at risk of progression to CF. • That CFSPID individuals with a CF causing variant/VVCC genotype and first SC in the higher borderline range may require more frequent and prolonged clinical follow-up. Aim of this study was to identify risk factors for a progression to cystic fibrosis (CF) in individuals detected as CF Screening Positive, Inconclusive Diagnosis (CFSPID). This is a systematic review through literature databases (2015–2023). Blood immunoreactive trypsinogen (b-IRT) values, CFTR genotype, sweat chloride (SC) values, isolation of Pseudomonas aeruginosa (Pa) from respiratory samples, Lung Clearance Index (LCI) values in CFSPIDs who converted to CF (CFSPID > CF) and age at CF transition were assessed. Percentage of CFSPID > CF varies from 5.3 % to 44 %. Presence of one CF-causing CFTR variant in trans with a variant with variable clinical consequences (VVCC), an initial SC ≥ 40 mmol/L, an increase of SC > 2.5 mmol/L/year and recurrent isolation of pseudomonas aeruginosa (Pa) from airway samples could allow identification of subjects at risk of progression to CF. CFSPIDs with CF causing variant/VVCC genotype and first SC in the higher borderline range may require more frequent and prolonged clinical follow-up. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the level of knowledge of healthcare professionals involved in newborn heel prick tests. The study was conducted between 10.02.2021–10.03.2021 with 147 healthcare workers working in heel prick screening in health institutions where heel prick blood samples were collected in a province and districts in the Central Anatolia region of Turkey. As a data collection tool, a questionnaire prepared by the researcher in line with the literature was used. The data were evaluated by number, percentage, mean and standard deviation analysis and chi-square analysis was performed in IBM SPSS for Windows 29.0v programme. The majority of healthcare professionals gave correct answers to the questions regarding the collection, storage and transfer of heel prick. It has been observed that healthcare professionals do not have sufficient information regarding the definition of Congenital Metabolic Diseases, their findings and where to refer patients whose results are suspicious.The most significance was found in the distribution of answers regarding the symptoms of the screened diseases according to occupational groups. In diseases that can be controlled with treatment and nutrition if detected early, errors in the collection, storage and transport of the sample can affect the test result and delay the diagnosis. Healthcare professionals have important responsibilities issues from genetic counseling before marriage, taking heel blood, from informing the family to caring for the diagnosed baby. This study will provide valuable information to health professionals involved in newborn screening and to future studies in this field. • The knowledge levels of healthcare professionals involved in newborn heel blood screening were investigated. • It was observed that the healthcare professionals participating in the research did not have sufficient knowledge on the subject. • It is important to know the subject well for early diagnosis and treatment of congenital metabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Fatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations and outcome. Early detection by systematic neonatal screening may improve their prognosis. Long-term outcome studies of these disorders in the Middle East and North Africa region are limited. The purpose of this study is to report the diagnostic challenges and outcome of fatty acid oxidation defects in a major tertiary care center in Lebanon, a resource-constrained country in the Middle East. Methods: A retrospective review of charts of all fatty acid oxidation defects sequential patients diagnosed and followed at our center was conducted. Collected data included: parental consanguinity, age at diagnosis, clinical presentation, biochemical profile, confirmatory diagnosis, treatment and outcome. A genotype–phenotype correlation was also performed, when available. Results: Seven types of fatty acid oxidation defects were identified in a total of 34 patients from 21 families. Most families (79%) were consanguineous (first-degree cousins). The majority were diagnosed when clinically symptomatic (78%), at various ages between 10 days and 19 years (average: 2 years). Follow-up duration spanned between 2 months and 15 years (average: 5 years). The remainder of the patients were detected while still asymptomatic by systematic neonatal screening (9%) or due to positive family history (9%). The most common defect was carnitine transporter deficiency (50%) with an exclusive cardiac presentation related to a founder variant c.981C > T, (p.Arg254*) in the SLC22A5 gene. Medium chain acyl-CoA dehydrogenase deficiency was found in 13% only, which could be explained by the absence of systematic neonatal screening. Rare gene variants were detected in very long chain and multiple acyl-CoA dehydrogenase deficiency. The worse prognosis was observed in very long chain acyl-CoA dehydrogenase deficiency. The overall survival at last follow-up reached 75% with a complete reversal of symptoms with treatment in most patients (63%), despite their late diagnosis. Conclusions: Our experience highlights the diagnostic challenges and outcome of fatty acid oxidation defects in a resource-constrained country with high consanguinity rates. Physicians' awareness and systematic neonatal screening are key for diagnosis. Larger genotype–phenotype studies are still needed to understand the natural history of these rare diseases and possibly improve their outcome. [ABSTRACT FROM AUTHOR]

Introduction: Early identification of developmental dysplasia of the hip (DDH) is necessary to minimize its negative effects. Ultrasound screening is useful for detecting DDH in hospitals. Awareness about community-based screening systems is low in Japan. Despite established nationwide home visiting services and child health checkups in the country, more than 10% of DDH patients are diagnosed at the age of ≥1 year. This review aimed to clarify the status of universal ultrasound screening for DDH among infants in community settings in Japan. Methods: The electronic databases of Igaku Chuo Zasshi, MEDLINE, CHINAL, ERIC, and APA PsycInfo were searched for articles published between 2002 and 2022. Articles were evaluated with the reach, effectiveness, adoption, implementation, and maintenance framework. Results: In total, 148 articles were identified. Two articles were manually added, and 67 articles were excluded through abstract reviews, of which 20 were duplicates. Finally, 18 articles were included in the analysis. There are two types of universal ultrasound screening in community settings: municipality-led and hospital-led. Since 1992, municipality-led screening has been conducted during public infant health checkups in five municipalities. Six hospitals implemented ultrasound screening. The participation rate was around 90%. The Graf method is typically used for this purpose. The prevalence of abnormal hips was 3.6%–16.6%. Owing to limited human resources and skills in ultrasound, all studies mentioned the necessity of a universal screening system for the early detection of DDH. Conclusion: Embedding universal ultrasound screening in community health checkup systems enables collaboration between healthcare professionals and caregivers to improve health inequities and ensure early detection of DDH cases. [ABSTRACT FROM AUTHOR]

Cytomegalovirus causes the most common congenital infection worldwide. With most infants asymptomatic at birth, the few affected may present with variable clinical scenarios, from isolated hearing loss to severe neurologic impairment. Public health interventions include all actions at the health system, community, and individual levels that aim at reducing the burden of congenital Cytomegalovirus. This review examines the literature on maternal and neonatal screening programs in light of current evidence for treatment and the development of vaccines against Cytomegalovirus. Potential biases and benefits of these interventions are outlined, with the objective of increasing awareness about the problem and providing readers with data and critical tools to participate in this ongoing debate. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy and the postpartum period is a difficult time for women living with HIV (WLWH) and postpartum engagement with HIV care is often reduced, with implications for health and well-being. We aimed to explore the postpartum health experiences of WLWH in relation to engagement in HIV care. Methods: The NESTOR (iNvESTigating the pregnancy and pOst-paRtum health experience of women living with HIV) study was a UK based qualitative semi-structured interview study. 61 eligible women were identified. We used a purposive sampling technique to recruit women with differing levels of engagement in HIV care. Interviews were conducted via telephone or video call. Interviews were audio recorded and fully transcribed. We used a thematic approach for data analysis, and two researchers independently coded the data and established the key themes. Results: 11 of 61 (18%) eligible women participated in the interviews, and the three main themes were 'infant feeding decisions', 'managing the risk of mother to child transmission', and 'managing the knowledge of their HIV status'. These themes offer detailed insights into the significant psychological and emotional challenges these women had experienced, and the practical support from healthcare professionals in both HIV and maternity services that had enabled them to navigate those challenges. Discussion: There have been life-changing developments in the treatment and care for people living with HIV. However, even in the U = U (undetectable = untransmittable) era, traditional concerns about breastfeeding, risk of transmission to the infant and stigma continue to shape the postpartum experience of WLWH. As these impact on their emotional and psychological wellbeing, support in these areas needs to be prioritised. Significance: Studies report that postpartum retention in HIV care and viral load suppression are suboptimal for women living with HIV, where an important reason is the financial cost and access to healthcare. However, there is a relative scarcity of evidence describing the problems faced by women accessing HIV and maternity services within socialised healthcare systems, such as those in the UK. Women living with HIV face unanticipated challenges when becoming new mothers relating to disclosure of their HIV status, fears of vertical transmission and perceived perceptions of others deeming them inadequate mothers. Importantly, our analysis illustrates potential opportunities where intervention might mitigate the emotional and physical impact of these issues on their wellbeing throughout pregnancy and postpartum. [ABSTRACT FROM AUTHOR]

Purpose: Developmental hip dysplasia is a prevalent pediatric musculoskeletal condition that lacks international standardized screening. We sought to characterize developmental hip dysplasia screening practices in countries with the top global health indices. We also explored diverse definitions in reported epidemiologic rates of this condition. Methods: We performed a scoping review of developmental hip dysplasia screening protocols utilizing countries ranked in the top 25 of the Bloomberg Global Health Index using a protocolized search strategy, progressing from academic to layperson sources. A reference was eligible for inclusion if it mentioned the countries' screening program and developmental hip dysplasia was the pathology of concern. Incidence rates, when present, were also recorded. The United States Census Bureau's International Database tool provided countries' populations. We compiled the data and performed descriptive statistics and appropriate validation methods. Results: Twenty countries (80%) had searchable screening programs. Clinical screening with selective universal screening was the most commonly observed (n = 16). Four countries had universal ultrasound screening: Switzerland, Austria, Germany, and Slovenia. Five countries did not have searchable programs. No countries employed radiographic screening. Incidence rates were expressly stated in the literature for nine countries; however, the cohort of interest varied from developmental hip dysplasia versus severity of developmental hip dysplasia versus miscellaneous (e.g. requiring hospitalization). Conclusion: The findings of this investigation highlight international inconsistencies regarding developmental hip dysplasia screening and epidemiologic data. Screening variations exist despite consensus statements calling for uniformity. We agree with prior literature advocating for increasing consistency in developmental hip dysplasia management or, at a minimum, increasing transparency regarding how we manage these young patients. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. Methods: PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. Results: After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P < 0.001). Furthermore, the result of the meta-analysis showed that the frequency of the variant with c.1400C > G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P < 0.05). Conclusions: This study systematically analyzed PCD prevalence and identified common SLC22A5 gene variants in the Chinese population. The findings provide valuable epidemiological insights and guidance for future PCD screening effects in newborns. [ABSTRACT FROM AUTHOR]

The current German newborn screening (NBS) panel includes 13 inherited metabolic diseases (IMDs). In addition, a NBS pilot study in Southwest Germany identifies individuals with propionic acidemia (PA), methylmalonic acidemia (MMA), combined and isolated remethylation disorders (e.g., cobalamin [cbl] C and methylenetetrahydrofolate reductase [MTHFR] deficiency), cystathionine β‐synthase (CBS) deficiency, and neonatal cbl deficiency through one multiple‐tier algorithm. The long‐term health benefits of screened individuals are evaluated in a multicenter observational study. Twenty seven screened individuals with IMDs (PA [N = 13], MMA [N = 6], cblC deficiency [N = 5], MTHFR deficiency [N = 2] and CBS deficiency [N = 1]), and 42 with neonatal cbl deficiency were followed for a median of 3.6 years. Seventeen screened IMD patients (63%) experienced at least one metabolic decompensation, 14 of them neonatally and six even before the NBS report (PA, cbl‐nonresponsive MMA). Three PA patients died despite NBS and immediate treatment. Fifteen individuals (79%) with PA or MMA and all with cblC deficiency developed permanent, mostly neurological symptoms, while individuals with MTHFR, CBS, and neonatal cbl deficiency had a favorable clinical outcome. Utilizing a combined multiple‐tier algorithm, we demonstrate that NBS and specialized metabolic care result in substantial benefits for individuals with MTHFR deficiency, CBS deficiency, neonatal cbl deficiency, and to some extent, cbl‐responsive MMA and cblC deficiency. However, its advantage is less evident for individuals with PA and cbl‐nonresponsive MMA. Synopsis: Early detection through newborn screening and subsequent specialized metabolic care improve clinical outcomes and survival in individuals with MTHFR deficiency and cystathionine‐β‐synthase deficiency, and to some extent in cobalamin‐responsive methylmalonic acidemia (MMA) and cblC deficiency while the benefit for individuals with propionic acidemia and cobalamin‐nonresponsive MMA is less evident due to the high (neonatal) decompensation rate, mortality, and long‐term complications. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Fatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations and outcome. Early detection by systematic neonatal screening may improve their prognosis. Long-term outcome studies of these disorders in the Middle East and North Africa region are limited. The purpose of this study is to report the diagnostic challenges and outcome of fatty acid oxidation defects in a major tertiary care center in Lebanon, a resource-constrained country in the Middle East. Methods A retrospective review of charts of all fatty acid oxidation defects sequential patients diagnosed and followed at our center was conducted. Collected data included: parental consanguinity, age at diagnosis, clinical presentation, biochemical profile, confirmatory diagnosis, treatment and outcome. A genotype–phenotype correlation was also performed, when available. Results Seven types of fatty acid oxidation defects were identified in a total of 34 patients from 21 families. Most families (79%) were consanguineous (first-degree cousins). The majority were diagnosed when clinically symptomatic (78%), at various ages between 10 days and 19 years (average: 2 years). Follow-up duration spanned between 2 months and 15 years (average: 5 years). The remainder of the patients were detected while still asymptomatic by systematic neonatal screening (9%) or due to positive family history (9%). The most common defect was carnitine transporter deficiency (50%) with an exclusive cardiac presentation related to a founder variant c.981C > T, (p.Arg254*) in the SLC22A5 gene. Medium chain acyl-CoA dehydrogenase deficiency was found in 13% only, which could be explained by the absence of systematic neonatal screening. Rare gene variants were detected in very long chain and multiple acyl-CoA dehydrogenase deficiency. The worse prognosis was observed in very long chain acyl-CoA dehydrogenase deficiency. The overall survival at last follow-up reached 75% with a complete reversal of symptoms with treatment in most patients (63%), despite their late diagnosis. Conclusions Our experience highlights the diagnostic challenges and outcome of fatty acid oxidation defects in a resource-constrained country with high consanguinity rates. Physicians’ awareness and systematic neonatal screening are key for diagnosis. Larger genotype–phenotype studies are still needed to understand the natural history of these rare diseases and possibly improve their outcome.

Abstract Background Primary carnitine deficiency (PCD) is a rare autosomal recessive fatty acid oxidation disorder caused by variants in SLC22A5, with its prevalence and SLC22A5 gene mutation spectrum varying across races and regions. This study aimed to systematically analyze the incidence of PCD in China and delineate regional differences in the prevalence of PCD and SLC22A5 gene variants. Methods PubMed, Embase, Web of Science, and Chinese databases were searched up to November 2023. Following quality assessment and data extraction, a meta-analysis was performed on screening results for PCD among Chinese newborns. Results After reviewing 1,889 articles, 22 studies involving 9,958,380 newborns and 476 PCD cases were included. Of the 476 patients with PCD, 469 underwent genetic diagnosis, revealing 890 variants of 934 alleles of SLC22A5, among which 107 different variants were detected. The meta-analysis showed that the prevalence of PCD in China was 0.05‰ [95%CI, (0.04‰, 0.06‰)] or 1/20 000 [95%CI, (1/16 667, 1/25 000)]. Subgroup analyses revealed a higher incidence in southern China [0.07‰, 95%CI, (0.05‰, 0.08‰)] than in northern China [0.02‰, 95%CI, (0.02‰, 0.03‰)] (P G, c.51C > G, c.760C > T, c.338G > A, and c.428C > T were 45% [95%CI, (34%, 59%)], 26% [95%CI, (22%, 31%)], 14% [95%CI, (10%, 20%)], 6% [95%CI, (4%, 8%)], and 5% [95%CI, (4%, 8%)], respectively. Among the subgroup analyses, the variant frequency of c.1400C > G in southern China [39%, 95%CI, (29%, 53%)] was significantly lower than that in northern China [79‰, 95%CI, (47‰, 135‰)] (P

Background: Neonatal electrocardiogram (ECG) screening can potentially identify congenital long QT syndrome and other heart diseases. Early identification is likely to reduce mortality. A barrier is the difficulty in obtaining a 12-lead ECG in an infant. We aimed to assess the feasibility of using a single lead ECG recorded with a handheld device (Eko DUO) in neonates. Methods: This cross-sectional study included neonates in the first 3 days of life. We recorded a single-lead ECG using the Eko DUO. Time from the beginning of recording until a satisfactory recording was measured with a stopwatch and reported as mean and standard deviation. We reported the ratio of interpretable recordings and the proportion of those with any abnormalities. Results: The mean time for recording was 198.1 ± 94.7 s. The total number of interpretable recordings was 63% (n = 63). Of the interpretable recordings, one neonate was found to have tachycardia (1.6%). Conclusions: Neonatal ECG screening using Eko DUO is feasible. However, the fidelity of the recorded ECG is suboptimal. While most of the ECGs were interpretable for rate and rhythm, QT interval measurement was not possible in most neonates.

Abstract A universal newborn screening program for sickle cell disease (uNS‐SCD) was implemented in the province of Québec (Qc) in November 2013, close in time to the recommendation of early initiation of hydroxyurea (HU) therapy for children. This retrospective cohort study evaluated the impact of such a program on children first seen between January 2000 and December 2019. Cohorts pre‐SCD‐uNS in Qc (pre‐QcNS) (n = 253) and post‐QcNS (n = 157) for patients seen prior to or after Nov 2013 were compared. Kaplan‐Meier curves, Poisson regression, and logistic regressions were used for statistical analysis, using Software R version 4.2.1. Median age at first visit decreased significantly from 14.4 [interquartile range: 2.4–72.0] to 1.2 months [1.2–57.6] (p

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20–40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Abstract Background Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inborn error of mitochondrial fatty acid metabolism with autosomal recessive pattern of inheritance. Its phenotype is highly variable (neonatal, infantile, and adult onset) on the base of mutations of the CPT II gene. In affected subjects, long-chain acylcarnitines cannot be subdivided into carnitine and acyl-CoA, leading to their toxic accumulation in different organs. Neonatal form is the most severe, and all the reported patients died within a few days to 6 months after birth. Hereby, we report on a male late-preterm newborn who presented refractory cardiac arrhythmias and acute multiorgan (hepatic, renal, muscular) injury, leading to cerebral hemorrhage, hydrocephalus, cardiovascular failure and early (day 5 of life) to death. Subsequently, extended metabolic screening and target next generation sequencing (NGS) analysis allowed the CPT II deficiency diagnosis. Case presentation The male proband was born at 36+ 4 weeks of gestation by spontaneous vaginal delivery. Parents were healthy and nonconsanguineous, although both coming from Nigeria. Family history was unremarkable. Apgar score was 9/9. At birth, anthropometric measures were as follows: weight 2850 g (47th centile, -0.07 standard deviations, SD), length 50 cm (81st centile, + 0.89 SD) and occipitofrontal circumference (OFC) 35 cm (87th centile, + 1.14 SD). On day 2 of life our newborn showed bradycardia (heart rate around 80 bpm) and hypotonia, and was then transferred to the Neonatal Intensive Care Unit (NICU). There, he subsequently manifested many episodes of ventricular tachycardia, which were treated with pharmacological (magnesium sulfate) and electrical cardioversion. Due to the critical conditions of the baby (hepatic, renal and cardiac dysfunctions) and to guarantee optimal management of the arrythmias, he was transferred to the Pediatric Cardiology Reference Center of our region (Sicily, Italy), where he died 2 days later. Thereafter, the carnitines profile evidenced by the extended metabolic screening resulted compatible with a fatty acid oxidation defect (increased levels of acylcarnitines C16 and C18, and low of C2); afterwards, the targeted next generation sequencing (NGS) analysis revealed the known c.680 C > T p. (Pro227Leu) homozygous missense mutation of the CPTII gene, for diagnosis of CPT II deficiency. Genetic investigations have been, then, extended to the baby’s parents, who were identified as heterozygous carriers of the same variant. When we meet again the parents for genetic counseling, the mother was within the first trimester of her second pregnancy. Therefore, we offered to the couple and performed the prenatal target NGS analysis on chorionic villi sample, which did not detect any alterations, excluding thus the CPT II deficiency in their second child. Conclusions CPTII deficiency may be suspected in newborns showing cardiac arrhythmias, associated or not with hypertrophic cardiomyopathy, polycystic kidneys, brain malformations, hepatomegaly. Its diagnosis should be even more suspected and investigated in cases of increased plasmatic levels of creatine phosphokinase and acylcarnitines in addition to kidney, heart and liver dysfunctions, as occurred in the present patient. Accurate family history, extended metabolic screening, and multidisciplinary approach are necessary for diagnosis and adequate management of affected subjects. Next generation sequencing (NGS) techniques allow the identification of the CPTII gene mutation, essential to confirm the diagnosis before or after birth, as well as to calculate the recurrence risk for family members. Our report broads the knowledge of the genetic and molecular bases of such rare disease, improving its clinical characterization, and provides useful indications for the treatment of patients.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20–40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals. [ABSTRACT FROM AUTHOR]

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, prenatal, neonatal and later in life. Screening should only be offered if the advantages outweigh the disadvantages. Technical innovations in testing and treatment are driving changes in the field of prenatal and neonatal screening, where many jurisdictions have organized population-based screening programs. As a result, a greater number and wider range of conditions are being added to the programs, which can benefit couples' reproductive autonomy (preconception and prenatal screening) and improve early diagnosis to prevent irreversible health damage in children (neonatal screening) and in adults (cancer and cascade screening). While many developments in screening are technology-driven, citizens may also express a demand for innovation in screening, as was the case with non-invasive prenatal testing. Relatively new emerging issues for genetic screening, especially if testing is performed using DNA sequencing, relate to organization, data storage and interpretation, benefit–harm ratio and distributive justice, information provision and follow-up, all connected to acceptability in current healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inborn error of mitochondrial fatty acid metabolism with autosomal recessive pattern of inheritance. Its phenotype is highly variable (neonatal, infantile, and adult onset) on the base of mutations of the CPT II gene. In affected subjects, long-chain acylcarnitines cannot be subdivided into carnitine and acyl-CoA, leading to their toxic accumulation in different organs. Neonatal form is the most severe, and all the reported patients died within a few days to 6 months after birth. Hereby, we report on a male late-preterm newborn who presented refractory cardiac arrhythmias and acute multiorgan (hepatic, renal, muscular) injury, leading to cerebral hemorrhage, hydrocephalus, cardiovascular failure and early (day 5 of life) to death. Subsequently, extended metabolic screening and target next generation sequencing (NGS) analysis allowed the CPT II deficiency diagnosis. Case presentation: The male proband was born at 36+ 4 weeks of gestation by spontaneous vaginal delivery. Parents were healthy and nonconsanguineous, although both coming from Nigeria. Family history was unremarkable. Apgar score was 9/9. At birth, anthropometric measures were as follows: weight 2850 g (47th centile, -0.07 standard deviations, SD), length 50 cm (81st centile, + 0.89 SD) and occipitofrontal circumference (OFC) 35 cm (87th centile, + 1.14 SD). On day 2 of life our newborn showed bradycardia (heart rate around 80 bpm) and hypotonia, and was then transferred to the Neonatal Intensive Care Unit (NICU). There, he subsequently manifested many episodes of ventricular tachycardia, which were treated with pharmacological (magnesium sulfate) and electrical cardioversion. Due to the critical conditions of the baby (hepatic, renal and cardiac dysfunctions) and to guarantee optimal management of the arrythmias, he was transferred to the Pediatric Cardiology Reference Center of our region (Sicily, Italy), where he died 2 days later. Thereafter, the carnitines profile evidenced by the extended metabolic screening resulted compatible with a fatty acid oxidation defect (increased levels of acylcarnitines C16 and C18, and low of C2); afterwards, the targeted next generation sequencing (NGS) analysis revealed the known c.680 C > T p. (Pro227Leu) homozygous missense mutation of the CPTII gene, for diagnosis of CPT II deficiency. Genetic investigations have been, then, extended to the baby's parents, who were identified as heterozygous carriers of the same variant. When we meet again the parents for genetic counseling, the mother was within the first trimester of her second pregnancy. Therefore, we offered to the couple and performed the prenatal target NGS analysis on chorionic villi sample, which did not detect any alterations, excluding thus the CPT II deficiency in their second child. Conclusions: CPTII deficiency may be suspected in newborns showing cardiac arrhythmias, associated or not with hypertrophic cardiomyopathy, polycystic kidneys, brain malformations, hepatomegaly. Its diagnosis should be even more suspected and investigated in cases of increased plasmatic levels of creatine phosphokinase and acylcarnitines in addition to kidney, heart and liver dysfunctions, as occurred in the present patient. Accurate family history, extended metabolic screening, and multidisciplinary approach are necessary for diagnosis and adequate management of affected subjects. Next generation sequencing (NGS) techniques allow the identification of the CPTII gene mutation, essential to confirm the diagnosis before or after birth, as well as to calculate the recurrence risk for family members. Our report broads the knowledge of the genetic and molecular bases of such rare disease, improving its clinical characterization, and provides useful indications for the treatment of patients. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a chronic and potentially life-threatening condition, wherein timely diagnosis assumes paramount significance for the prompt initiation of therapeutic interventions, thereby ameliorating pulmonary function, addressing nutritional deficits, averting complications, mitigating morbidity, and ultimately enhancing the quality of life and extending longevity. This review aims to amalgamate existing knowledge to provide a comprehensive appraisal of contemporary diagnostic modalities pertinent to CF in the 21st century. Deliberations encompass discrete delineations of each diagnostic modality and the elucidation of potential diagnostic quandaries encountered in select instances, as well as the delineation of genotype–phenotype correlations germane to genetic counseling endeavors. The synthesis underscores that, notwithstanding the availability and strides in diagnostic methodologies, including genetic assays, the sweat test (ST) retains its position as the preeminent diagnostic standard for CF, serving as a robust surrogate for CFTR functionality. Prospective clinical investigations in the realm of CF should be orchestrated with the objective of discerning novel diagnostic modalities endowed with heightened specificity and sensitivity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: The Brazilian Unified National Health System (SUS) has incorporated newborn screening for cystic fibrosis since 2001. The protocol involves two samples of immunoreactive trypsinogen (IRT1/IRT2). This study aims to analyze fixed and floating values at the first and second IRT (IRT1/IRT2) cutoff points and assess the accuracy of the IRT/IRT methodology in a population from Northeastern Brazil. Descriptive, individual-level data from the newborn screening reference service data system (2013-2017) were used in this observational population study. The sensitivity, specificity, and positive predictive values (PPV) for the protocol were calculated. The best cutoff point was determined using the Youden’s index. The previous year’s cut-off values for the IRT1 and IRT2 99.4-, 99.5-, 99.6-, and 99.7-percentiles were utilized for the floating cutoff. During the studied period, 840,832 newborns underwent screening for cystic fibrosis, obtaining 49 cystic fibrosis diagnoses: 39 by newborn screening (79.6%) and 10 (20.4%) by clinical suspicion (false negative). The sensitivity, specificity, and PPV of the protocol totaled 79.6%, 99.9%, and 6.1%, respectively. No proposed cutoff for IRT1 performed better than the current one. IRT2 performed similarly to the current protocol at a cutoff point of 90ng/mL, showing the appropriate sensitivity and specificity while reducing the frequency of false positives. The protocol to screen newborns for cystic fibrosis had low sensitivity, a predictive positive value, and a high number of false positives and negatives. A floating cut point for IRT1 or IRT2 seems to constitute no viable option. However, changing the IRT2 cut point from 70ng/mL to 90ng/mL seems to have advantages and should undergo consideration.

Abstract Aims To thoroughly evaluate the quality of the entire process of neonatal screening (NBS) in China. Methods We collected survey questionnaires from 54.4% (135/248) of NBS institutions in China and conducted on-site visits to 20 of these facilities to validate the data. The quality performance of the institutions was evaluated, and differences across various factors were analysed. Results Merely 62.5% of the provinces had acceptable performance in neonatal screening. Institutions with limited staff were more prone to organizational management shortcomings. Institutions in provinces with a per capita GDP below 10,000 USD exhibited lower quality control levels than those with a per capita GDP between 10,000 and 15,000 USD. Obstetrics departments have a lower awareness of quality control compared to other blood collection facilities. Conclusions A nationwide, comprehensive quality control system for continuous enhancements in quality management, screening, diagnosis, and treatment is imperative to ensure prompt diagnosis and intervention.

Developmental hip dysplasia or developmental dysplasia of the hip (DDH) includes a wide range of deformities of the hip, such as congenital dysplasia, subluxation, and dislocation. It is usually identified through neonatal screening during the first 6–8 weeks of life. The incidence of DDH ranges from 1–7% in neonates among some populations, but this may vary among different ethnicities and countries. A consensus about the ideal age for screening has not been reached to date. The aim of this study is to summarize the existing data regarding the incidence of congenital hip dysplasia and screening tests among European countries. The authors conducted a systematic search in PubMed/Medline and Scopus and collected original studies published in English, French or German. The incidence of DDH presents fluctuations, not only among European countries, but also within the same country. There is no unanimity regarding the screening methods of DDH; in some countries, universal ultrasound is proposed as the basic screening method for neonates for DDH; in other countries screening is performed only in high-risk cases. More robust data are needed to conclude which screening approach is associated with improved long-term outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: High blood lead levels (BLLs) in pregnant women are associated with poor outcome in neonates. One of the newest non-occupational sources of lead contamination is opium consumption. Accordingly, this study aimed to assess BLLs in mothers addicted to opium and their neonates in Kerman. Methods: This cross-sectional was conducted in Afzalipour hospital in Kerman, from February 2019 to February 2020. The BLLs were measured in 100 opium-addicted and non-addicted mothers and their newborns, and the lead levels higher than 5 μg/dL were considered contamination. Then, the demographic and anthropometric data were compared. Findings: Based on the results of the present study, the BLLs of opium-addicted mothers (33.40 ± 9.22 μg/dL vs 3.2 ± 1.5 μg/dL) and their neonates (13.46 ± 4.86 vs 1.1 ± 0.9) were significantly higher (P = 0.001) than those of non-addicts. Moreover, the average birth weight of the newborns in the addicted group was significantly lower than in the non-addicted group (2572.8 ± 77.49 vs 2946 ± 46.87) (P = 0.001). Besides, there was a significant relationship between the average birth weight and the BLL of the mother and baby, and the average weight of the babies was significantly lower at higher levels of lead. However, no correlation was observed regarding the average height and head circumference of the neonates (P > 0.05). Conclusion: It seems that the serum level of lead in neonates of opium-addicted mothers contaminated with lead is significantly higher than that of non-addicts, but their anthropometric characteristics at birth were not different from those of the nonaddicted group. [ABSTRACT FROM AUTHOR]

The identification of cystic fibrosis screening-positive, inconclusive diagnosis (CFSPID) in infants is a controversial outcome of newborn screening for cystic fibrosis (CF). Today, despite improvements in the knowledge of CFSPID and the description of several cohorts, little data are available on cohorts with a follow-up period of more than 6 years. In this study, we report the outcomes of an Italian cohort of CFSPID individuals with CFSPID or formerly CFTR-related disorders (CFTR-RD) (CFSPID > CFTR-RD) or diagnosed with CF (CFSPID > CF). This was an observational and multicentre Italian study collecting clinical data on CFSPID born between the period January 1, 2011, and December 13, 2019. A total of 268 participants were included: 243 with persistent CFSPID, 7 with CFSPID > CFTR-RD, and 18 with CFSPID > CF. The trend of sweat chloride (SC) values, percentage of definitive diagnoses, lung function in school-aged children, and development of CF-related complications were evaluated. At the end of the observation period, almost 80% of the individuals with CFSPID did not have a conclusive diagnosis. A total of 29 children (10.8%) transitioned to a diagnosis of CF for pathological SC values (≥ 60 mmol/L) or multi-organ involvement, and 18 (6.7%) to CFTR-RD. Children who were followed up for > 6 years (median age, 7.5 years; range, 6.04–10.5) had normal lung function and were pancreatic sufficient, and the evolution in CF was only present in two cases. Conclusion: Most Italian preschool and school-aged children with CFSPID did not have a conclusive diagnosis, and progression to CF was unlikely in children > 6 years of age. An annual follow-up could be indicated to identify early evolution in clinical features consistent with a CFTR-RD. What is Known: • Cystic Fibrosis newborn screening identifies also subjects with an inconclusive diagnosis (CFSPID). • Over time a variable percentage of CFSPIDs will be diagnosed as CF. • Little data is available on CFSPIDs with a follow-up period of more than six years. What is New: • 80% of Italian preschool and school-age CFSPIDs not have a conclusive diagnosis. • Italian preschool and school-age CFSPIDs have normal lung function and are pancreatic sufficient. • Annual follow-up after 6 years is recommended in CFSPID with abnormal LCI2.5 or with a CF-causing variant in trans with a VVCC. [ABSTRACT FROM AUTHOR]

Aims: To thoroughly evaluate the quality of the entire process of neonatal screening (NBS) in China. Methods: We collected survey questionnaires from 54.4% (135/248) of NBS institutions in China and conducted on-site visits to 20 of these facilities to validate the data. The quality performance of the institutions was evaluated, and differences across various factors were analysed. Results: Merely 62.5% of the provinces had acceptable performance in neonatal screening. Institutions with limited staff were more prone to organizational management shortcomings. Institutions in provinces with a per capita GDP below 10,000 USD exhibited lower quality control levels than those with a per capita GDP between 10,000 and 15,000 USD. Obstetrics departments have a lower awareness of quality control compared to other blood collection facilities. Conclusions: A nationwide, comprehensive quality control system for continuous enhancements in quality management, screening, diagnosis, and treatment is imperative to ensure prompt diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Copyright of Revista Médica de Rosario is the property of Circulo Medico de Rosario and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Neonatal electrocardiogram (ECG) screening can potentially identify congenital long QT syndrome and other heart diseases. Early identification is likely to reduce mortality. A barrier is the difficulty in obtaining a 12‑lead ECG in an infant. We aimed to assess the feasibility of using a single lead ECG recorded with a handheld device (Eko DUO) in neonates. Methods: This cross‑sectional study included neonates in the first 3 days of life. We recorded a single‑lead ECG using the Eko DUO. Time from the beginning of recording until a satisfactory recording was measured with a stopwatch and reported as mean and standard deviation. We reported the ratio of interpretable recordings and the proportion of those with any abnormalities. Results: The mean time for recording was 198.1 ± 94.7 s. The total number of interpretable recordings was 63% (n = 63). Of the interpretable recordings, one neonate was found to have tachycardia (1.6%). Conclusions: Neonatal ECG screening using Eko DUO is feasible. However, the fidelity of the recorded ECG is suboptimal. While most of the ECGs were interpretable for rate and rhythm, QT interval measurement was not possible in most neonates. [ABSTRACT FROM AUTHOR]

Abstract Primary carnitine deficiency (PCD) can be lethal. Carnitine is essential for the transfer of long‐chain fatty acids across the inner mitochondrial membrane for β‐oxidation. The reported prevalence of PCD in the Faroe Islands of 1:300 is the highest in the world. The Faroese PCD patient cohort has been closely monitored and we now report results from a 10‐year follow‐up study of 139 PCD patients. Four patients have died of natural causes since diagnosis. There were no signs of cardiac complications related to PCD. 70.5% reported an effect of L‐carnitine treatment. 33.7% reported current symptoms with fatigue and low stamina being the most common. 65.1% had experienced side effects during L‐carnitine treatment. Most common side effects were fish odor, abdominal pain, and diarrhea. The overall mean L‐carnitine dosage was 66.3 mg/kg/day. Free p‐carnitine was similar between male and female patients on L‐carnitine—18.6 and 18.8 μmol/L, respectively. L‐carnitine supplementation seems to be a safe and effective treatment when suffering from PCD. PCD patients in the Faroe Islands are alive and doing well more than 10 years after diagnosis.

The use of dried blood spots (DBS) obtained from the heels of infants has many advantages over the collection of whole blood samples. DNA extracted from DBS can be used to detect genetic diseases by PCR, which has contributed to the development of population-based newborn screening worldwide. Since January 2023, the list of identified diseases includes a group of primary immunodeficiencies (PIDs), associated with the absence or decrease in the levels of T and/or B lymphocytes, determined as part of screening by the levels of TREC and KREC molecules in peripheral blood, respectively. Quantitative analysis requires special attention to biological material. The aim is to evaluate the impact of the preanalytical step on the quantitative analysis of TREC/KREC levels in peripheral blood.The material included 5219 DBS obtained from infants on days 3-4 of life, as well as DBS prepared from the whole blood of 100 apparently healthy individuals aged 18 to 29 years. A comparative analysis of the TREC/KREC molecules number in correctly and incorrectly collected DBS from newborns and adults, as well as depending on the volume of applied blood, was carried out by RT-PCR using test systems to assess the levels of TREC and KREC in peripheral blood. DBS quality was assessed visually.In the first months of the project, a significant number of incorrectly taken samples were identified – over a third of all DNA maps received for each corresponding month. As a result of additional training of medical staff, the amount of incorrectly collected material decreased to a level not exceeding 1% of all monthly samples collected. When using DNA extracted from DBS with application errors, the majority of samples (64% for newborns, 78% for adults) failed to obtain a result. In the remaining cases, the results obtained were significantly lower than the normal levels of TREC/KREC determined in the same samples with correct DBS collection (all p < 0.0001, 95% CI). The volume of blood used when correctly applied to Guthrie cards did not affect the results obtained, TREC and KREC levels were comparable; when comparing the medians calculated for each group of samples, no significant differences were identified (p > 0.05).When quantitatively analyzing TREC/KREC levels in peripheral blood, correctly taken material is fundamental importance to obtain reliable indicators, primarily to exclude false-positive results. To minimize errors in the preanalytical stage, additional training of medical personnel is necessary to control and/or correct errors.

Neonatal screening is a mandatory newborn screening procedure that detects the presence of genetic diseases. Dry blood stains are used for mass screening of children. This technology is the most affordable and convenient for the transportation and storage of biological material. DNA extraction is one of the important steps in molecular diagnostics, the accuracy of which is particularly important in genetic analysis. Different DNA extraction kits offer different protocols and reagents, which may vary in efficiency and quality of extraction.The aim of our work was to perform a comparative analysis of reagent kits for DNA extraction from dried blood spots.The materials were dried blood drop samples on Guthrie cards obtained from healthy preterm infants on day 3-4 of life as part of a newborn screening program.The study methods included spectrophotometric analysis to determine the concentration and purity of DNA, the simplicity of protocols, the duration of isolation, and the possibility of automating the process were also evaluated. The efficiency of DNA isolation using different reagent kits was additionally monitored by real-time PCR results using a test system to assess the level of TREC and KREC in peripheral blood, since quantitative analysis requires more attention to the material under study.In assessing the purity of the nucleic acid extracted using four kits analyzed, successful deproteinization of DNA samples and relative purity could be observed. The average DNA purity for the “Extra-DNA-Bio” set was 2.2±0.23, for “EXTRA-prep PS” – 1.89±0.23, for “MagnoPrime UNI” with manual and automatic isolation – 2.31±0.21 and 2.85±0.09, respectively. The average DNA concentration for the Extra-DNA-Bio kit was 15.28 μg/mL, for the EXTRA-Prep PS kit it was 16.26 μg/mL, and for the MagnoPrime UNI for manual and automated isolation it was 62.5 μg/mL and 102.28 μg/mL, respectively. According to the applied Kraskell-Wallis criterion and Dunn’s test, significant differences in both TREC and KREC parameters are present between the group of DNA samples extracted using the “MagnoPrime UNI” reagent kit for manual extraction and the groups of samples extracted by other methods (“MagnoPrime UNI” for automatic extraction) or “Extra-DNA-Bio” and “EXTRA-Prep PS” kits.In the course of the present study, four comparable reagent sets demonstrated a high level of convergence of the obtained data, satisfying all the necessary parameters for further molecular genetic analysis, can be used for neonatal screening and in other areas of research requiring DNA extraction from a dried blood spots.

Congenital adrenal hyperplasia (CAH) occurs due to enzyme defects in adrenal steroidogenesis. The 21-hydroxylase deficiency accounts for 90–95% of cases, triggering accumulation of 17-hydroxyprogesterone (17-OHP). Early diagnosis through neonatal screening allows adequate treatment and reduced mortality. The purpose of the study was to determine 17-OHP cutoffs for the diagnosis of CAH in a public newborn screening program in Southern Brazil. A retrospective, descriptive, cross-sectional study was conducted to analyze 17-OHP levels in dried blood samples collected on filter paper of 317,745 newborns screened at a public newborn screening center from May 2014 to April 2017. Neonatal 17-OHP was measured in DBS samples using a time-resolved fluoroimmunoassay (GSP® kit 3305-0010; PerkinElmer). Different cutoffs were determined and stratified by birth weight. The incidence of CAH was 1:15,88 7 live births in the state of Rio Grande do Sul, with 20 cases of classical CAH diagnosed during the study period. Most newborns (80.73%) were white, and the prematurity rate was 9.8% in the study population. The combination of different percentiles, 98.5th for birth weight 2001–2500 g and 99.8th for the other birth weight groups, decreased false-positive results and increased specificity compared with current reference values to identify classical CAH cases. The local 17-OHP cutoffs determined were higher than those currently used by this screening program for all birth weight groups. The calculation of reference values from local population data and the combination of percentiles proved to be a valuable tool for proper diagnosis of CAH and reduction in the number of false positives.

Cytomegalovirus causes the most common congenital infection worldwide. With most infants asymptomatic at birth, the few affected may present with variable clinical scenarios, from isolated hearing loss to severe neurologic impairment. Public health interventions include all actions at the health system, community, and individual levels that aim at reducing the burden of congenital Cytomegalovirus. This review examines the literature on maternal and neonatal screening programs in light of current evidence for treatment and the development of vaccines against Cytomegalovirus. Potential biases and benefits of these interventions are outlined, with the objective of increasing awareness about the problem and providing readers with data and critical tools to participate in this ongoing debate.

Context: Subtle cognitive impairments have been described in children with congenital hypothyroidism (CH) detected by neonatal screening (NS), even with early and adequate treatment. Patients with CH may present with brain cortical thickness (CT) abnormalities, which may be associated with neurocognitive impairments. Objective: This work aimed to evaluate the CT in adolescents with CH detected by the NS Program (Paraná, Brazil), and to correlate possible abnormalities with cognitive level and variables of neurocognitive prognosis. Methods: A review was conducted of medical records followed by psychometric evaluation of adolescents with CH. Brain magnetic resonance imaging with analysis of 33 brain areas of each hemisphere was performed in 41 patients (29 girls) and in a control group of 20 healthy adolescents. CT values were correlated with Full-scale Intelligence Quotient (FSIQ) scores, age at start of treatment, pretreatment thyroxine levels, and maternal schooling. Results: No significant difference in CT between patients and controls were found. However, there was a trend toward thinning in the right lateral orbitofrontal cortex among patients and in the right postcentral gyrus cortex among controls. CT correlated significantly with FSIQ scores and with age at start of treatment in 1 area, and with hypothyroidism severity in 5 brain areas. Maternal schooling level did not correlate with CT but was significantly correlated with FSIQ. Cognitive level was within average in 44.7% of patients (13.2% had intellectual deficiency). Conclusion: There was a trend toward morphometric alterations in the cerebral cortex of adolescents with CH compared with healthy controls. The correlations between CT and variables of neurocognitive prognosis emphasize the influence of hypothyroidism on cortical development. Socioeconomic status exerts a limiting factor on cognitive outcome. [ABSTRACT FROM AUTHOR]

This study was planned to determine maternal attitudes and knowledge about newborn screening. The universe of the descriptive study consisted of postpartum mothers living in the centers of three provinces in the north and east of Turkey. The sample included mothers who were older than 18 years of age, who could read and write Turkish, whose babies were in the 24th and 72nd hour after birth, and who volunteered to take part in the study. The study was completed with 407 mothers. The data were collected with the face-to-face interview method by the researchers using the "Descriptive Information Form" and the "Maternal Attitudes and Knowledge Survey about Newborn Screening." The results showed that 40.3% of the mothers were between the ages of 25 and 30 years, 52.8% received information about newborn screening, 61.1% received this information during pregnancy (27.3% in the first trimester and 33.8% in the last trimester), and most of the information was provided by a healthcare professional (77.8%). Mothers with only one child (p =.001) and those with nuclear families (p =.024) were found to have lower maternal attitudes and knowledge about newborn screening. The study showed that the level of knowledge of Turkish mothers about newborn screening is inadequate in general. In particular, the knowledge and attitudes of mothers with nuclear families, those with one child, and those not having regular check-ups during pregnancy are inadequate. Improving mothers' understanding of screening tests will lead to more successful screening program implementation and earlier detection and care of newborns with a disease. [ABSTRACT FROM AUTHOR]

Introduction: congenital metabolic diseases (CMD) are a group of disorders caused by a genetic mutation that leads to specific enzymatic dysfunction and can mostly be diagnosed through neonatal screening. Objective: to determine the prevalence of CMD identified by neonatal screening in newborns care for in a Family Medicine Unit in Oaxaca City, Mexico. Material and methods: cross-sectional study carried out with newborns treated in the period 2019 to 2022. The neonatal screening was performed with the Guthrie card and the confirmation of a CME was made by specific diagnostic tests. Prevalence rates are presented in cases per 1,000 newborns. Results: during the study period, 1,859 newborns underwent neonatal screening. Eightyfive newborns had a positive result on the screening, resulting in a prevalence of 45.7 per 1,000 newborns, with hypothyroidism being the most frequent (rate 16.7). Of the 85 with a positive screening, diagnostic confirmation was obtained only in nine patients: seven with adrenal hyperplasia and two with congenital hypothyroidism. Conclusions: in this study, the prevalence of congenital adrenal hyperplasia and congenital hypothyroidism is higher than that previously reported in Mexico, at the national level. [ABSTRACT FROM AUTHOR]

Background: The standard treatment for congenital adrenal hyperplasia (CAH) in children is still hydrocortisone. Improved strategies for timing of the dose during the day and the dose per square meter body surface area used in children of different ages and developmental phases have improved the situation and outcome for the patients. Neonatal screening enables an earlier diagnosis and initiation of treatment, prevents from adrenal crisis, and improves growth and development also for children with the less severe forms of CAH. Summary: This review describes the current treatment strategies for children with CAH and discusses some potential treatment options that have been developed with the primary aim to decrease the adrenal androgen production. Novel modified release glucocorticoid therapies are also discussed. Key Messages: The long-term effects of the new adjunct therapies are unknown, and some are not suitable for use in children and adolescents. The effects of the new therapies on bone mineral density, gonadal functions, and long-term cognitive development are yet to be assessed. It is not known what levels of adrenal androgens are optimal for normal growth, puberty, and bone health. The basis of using glucocorticoids and mineralocorticoids in the treatment of CAH remains, and in some individuals, it may be beneficial to add therapies to reduce the androgen load during certain life stages. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Newborn screening (NBS) allows early identification of individuals with rare disease, such as isovaleric aciduria (IVA). Reliable early prediction of disease severity of positively screened individuals with IVA is needed to guide therapeutic decision, prevent life‐threatening neonatal disease manifestation in classic IVA and over‐medicalization in attenuated IVA that may remain asymptomatic. We analyzed 84 individuals (median age at last study visit 8.5 years) with confirmed IVA identified by NBS between 1998 and 2018 who participated in the national, observational, multicenter study. Screening results, additional metabolic parameters, genotypes, and clinical phenotypic data were included. Individuals with metabolic decompensation showed a higher median isovalerylcarnitine (C5) concentration in the first NBS sample (10.6 vs. 2.7 μmol/L; p < 0.0001) and initial urinary isovalerylglycine concentration (1750 vs. 180 mmol/mol creatinine; p = 0.0003) than those who remained asymptomatic. C5 was in trend inversely correlated with full IQ (R = −0.255; slope = −0.869; p = 0.0870) and was lower for the "attenuated" variants compared to classic genotypes [median (IQR; range): 2.6 μmol/L (2.1–4.0; 0.7–6.4) versus 10.3 μmol/L (7.4–13.1; 4.3–21.7); N = 73]. In‐silico prediction scores (M‐CAP, MetaSVM, and MetaLR) correlated highly with isovalerylglycine and ratios of C5 to free carnitine and acetylcarnitine, but not sufficiently with clinical endpoints. The results of the first NBS sample and biochemical confirmatory testing are reliable early predictors of the clinical course of IVA, facilitating case definition (attenuated versus classic IVA). Prediction of attenuated IVA is supported by the genotype. On this basis, a reasonable algorithm has been established for neonates with a positive NBS result for IVA, with the aim of providing the necessary treatment immediately, but whenever possible, adjusting the treatment to the individual severity of the disease. [ABSTRACT FROM AUTHOR]