An approach to the management of children with problematic severe asthma.

Acta Biomed. 2020 Sep 07;91(3):e2020055

Authors: Fainardi V, Saglani S

Abstract
Children with poor asthma control despite high levels of prescribed treatment are described as having problematic severe asthma. Most of these children have steroid sensitive disease which improves with adherence to daily inhaled corticosteroids and after having removed modifiable factors like poor inhalation technique, persistent adverse environmental exposures and psychosocial factors. These children are described as having "difficult-to-treat asthma" while children with persistent symptoms despite above-mentioned factors having been addressed are described as having "severe therapy-resistant asthma". In this review, we will describe the 6-step approach to the diagnosis and management of a child with problematic severe asthma adopted by The Royal Brompton Hospital (London, UK). The role of a multidisciplinary team is crucial for identification and treatment of modifiable factors and comorbidities in order to avoid invasive examinations and useless pharmacological treatments. The current knowledge on add-on therapies will be discussed.

PMID: 32921752 [PubMed - in process]

Sars-CoV-2 infection in patients with cystic fibrosis. An overwiew.

Acta Biomed. 2020 Sep 07;91(3):e2020035

Authors: Fainardi V, Longo F, Chetta A, Esposito S, Pisi G

Abstract
The novel coronavirus SARS-CoV-2 was first identified in China in December 2019 and has since spread worldwide. People with Cystic Fibrosis (CF) have reduced survival mainly because of respiratory failure due to chronic pulmonary infections. Therefore, CF patients should be considered to have an increased risk of developing severe manifestations in case of SARS-CoV-2 infection. Surprisingly, the results of recent studies concerning SARS-CoV-2 infection in patients with CF show that in these patients the infection rate was lower than that of the general population. Various factors have been considered to explain a possible protective effect of CF against SARS-CoV-2 infection.

PMID: 32921729 [PubMed - in process]

[Applications of airway clearance techniques in children].

Zhonghua Er Ke Za Zhi. 2020 Aug 02;58(8):690-693

Authors: Jiang Y, Wang YS, Tang LF, Chen ZM

PMID: 32842394 [PubMed - indexed for MEDLINE]

Integrating Mental Health Care for Medically Complex Children.

Pediatrics. 2020 08;146(2):

Authors: Canavera K, Johnson LM

PMID: 32699070 [PubMed - indexed for MEDLINE]

The Natural Product Elegaphenone Potentiates Antibiotic Effects against Pseudomonas aeruginosa.

Angew Chem Int Ed Engl. 2019 06 17;58(25):8581-8584

Authors: Zhao W, Cross AR, Crowe-McAuliffe C, Weigert-Munoz A, Csatary EE, Solinski AE, Krysiak J, Goldberg JB, Wilson DN, Medina E, Wuest WM, Sieber SA

Abstract
Natural products represent a rich source of antibiotics that address versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we applied elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity-based protein profiling (AfBPP) in Gram-positive and Gram-negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant provided unique insights into the mode of action. Elegaphenone enhanced the elimination of intracellular P. aeruginosa in macrophages exposed to sub-inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.

PMID: 30969469 [PubMed - indexed for MEDLINE]

Epidemiology of Pseudomonas aeruginosa in cystic fibrosis patients in Iran: A systematic review and meta-analysis.

Infez Med. 2020 Sep 01;28(3):314-321

Authors: Alavi Foumani A, Yaghubi Kalurazi T, Mohammadzadeh Rostami F, Sedigh Ebrahim-Saraie H, Nazari-Alam A, Halaji M

Abstract
The present study aims to investigate the prevalence of Pseudomonas aeruginosa in Iranian Cystic Fibrosis (CF) patients. We conducted a systematic search on this topic in Web of Science, PubMed, Embase, Scopus, and Google Scholar electronic databases to the end of July 2019. Then, 14 articles with eligible criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of P. aeruginosa was 40.6% (95% CI: 32.4%-49.4%) ranging from 32.4% to 49.4%. There was a significant heterogeneity among the studies (χ2 =21.02; p <0.001; I2 = 86.07%). The funnel plot for publication bias showed no evidence of asymmetry. Based on the results of Begg's and Egger's test no significant publication bias was observed. The study demonstrated a relative prevalence of P. aeruginosa among CF patients in Iran. Due to the rapid spread and infection severity of P. aeruginosa and other opportunistic pathogens, efforts are required to identify risk factors, reservoirs, transmission routes and source of infection.

PMID: 32920566 [PubMed - in process]

Exhaled volatile organic compounds analysis in clinical pediatrics: a systematic review.

Pediatr Res. 2020 Sep 12;:

Authors: Martínez RAS, Hernández JMP, Torrado ÓY, Díaz MC, Puente TD, Crevillent MV

Abstract
BACKGROUND: Measured exhaled volatile organic compounds (VOCs) in-breath also referred to as exhaled volatilome have been long claimed as a potential source of non-invasive and clinically applicable biomarkers. However, the feasibility of using exhaled volatilome in clinical practice remains to be demonstrated, particularly in pediatrics where the need for improved non-invasive diagnostic and monitoring methods is most urgent. This work presents the first formal evidence-based judgment of the clinical potential of breath volatilome in the pediatric population.
METHODS: A rigorous systematic review across Web of Science, SCOPUS, and PubMed databases following the PRISMA statement guidelines. A narrative synthesis of the evidence was conducted and QUADAS-2 was used to assess the quality of selected studies.
RESULTS: Two independent reviewers deemed 22 out of the 229 records initially found to satisfy inclusion criteria. A summary of breath VOCs found to be relevant for several respiratory, infectious, and metabolic pathologies was conducted. In addition, we assessed their associated metabolism coverage through a functional characterization analysis.
CONCLUSION: Our results indicate that current research remains stagnant in a preclinical exploratory setting. Designing exploratory experiments in compliance with metabolomics practice should drive forward the clinical translation of VOCs breath analysis.
IMPACT: What is the key message of your article?Metabolomics practice could help to achieve the clinical utility of exhaled volatilome analysis.What does it add to the existing literature?This work is the first systematic review focused on disease status discrimination using analysis of exhaled breath in the pediatric population. A summary of the reported exhaled volatile organic compounds is conducted together with a functional characterization analysis.What is the impact?Having noted challenges preventing the clinical translation, we summary metabolomics practices and the experimental designs that are closer to clinical practice to create a framework to guide future trials.Fig. 1Flow diagram of PRISMA-oriented systematic search and literature records selection.Fig. 2VOCS DISCRIMINANT PROFILE SUMMARIZED ACROSS THE STUDIES INCLUDED IN THE QUALITATIVE SYNTHESIS.: a Asthma or allergic asthma patients vs. healthy controls (HCTR). b Asthma with exacerbations vs. stable patients. c Cystic fibrosis (CF) vs. HCTR.Fig. 3QUALITY ASSESSMENT OF THE INCLUDED STUDIES IN THE QUALITATIVE SYNTHESIS THROUGH QUADAS-2 SCORING SYSTEM.: a Summary for individual studies. Display of b risk of bias and c applicability concerns across different domains.

PMID: 32919397 [PubMed - as supplied by publisher]

Genomics-driven discovery of a novel glutarimide antibiotic from Burkholderia gladioli reveals an unusual polyketide synthase chain release mechanism.

Angew Chem Int Ed Engl. 2020 Sep 12;:

Authors: Challis G, Nakou IT, Jenner M, Dashti Y, Romero-Canelón I, Masschelein J, Mahenthiralingam E

Abstract
A gene cluster encoding a cryptic trans -acyl transferase polyketide synthase (PKS) was identified in the genomes of Burkholderia gladioli BCC0238 and BCC1622, both isolated from the lungs of cystic fibrosis patients. Bioinfomatics analyses indicated the PKS assembles a novel member of the glutarimide class of antibiotics, hitherto only isolated from Streptomyces species. Screening of a range of growth parameters enabled gladiostatin, the metabolic product of the PKS, to be identified. NMR spectroscopic analysis revealed that gladiostatin, which has promising activity against several human cancer cell lines and inhibits tumor cell migration, contains an unusual 2-acyl-4-hydroxy-3-methylbutenolide in addition to the glutarimide pharmacophore. An AfsA-like domain at the C-terminus of the PKS was shown to catalyze condensation of 3-ketothioesters with dihydroxyacetone phosphate, indicating it plays a key role in polyketide chain release and butenolide formation.

PMID: 32918852 [PubMed - as supplied by publisher]

Living and dying with cystic fibrosis.

BMJ Support Palliat Care. 2020 Sep 11;:

Authors: Miller M

PMID: 32917651 [PubMed - as supplied by publisher]

Baseline Cystic fibrosis disease severity has an adverse impact on pregnancy and infant outcomes, but does not impact disease progression.

J Cyst Fibros. 2020 Sep 08;:

Authors: Cohen-Cymberknoh M, Gindi Reiss B, Reiter J, Lechtzin N, Melo J, Pérez G, Blau H, Mussaffi H, Levine H, Bentur L, Gur M, Livnat G, Perez Miranda J, Polverino E, Blasi F, Aliberti S, Aviram M, Golan Tripto I, Picard E, Novoselsky M, Amsalem H, Hochner Celnikier D, Kerem E, Shteinberg M

Abstract
BACKGROUND: With increasing longevity and quality of life in adults with Cystic fibrosis (CF), growing maternity rates are reported. Women with severe CF are becoming pregnant, with unpredictable maternal and fetal outcomes.
AIM: To determine how baseline disease severity, pancreatic insufficiency (PI) and Pseudomonas aeruginosa (PA) infection affect fertility, the pregnancy course, delivery, neonatal outcome, and subsequent disease progression.
METHODS: A multicenter-retrospective cohort study. Data on patients that had been pregnant between 1986-2018 was collected from ten CF centers worldwide. Disease severity [mild or moderate-severe (mod-sev)] was defined according to forced expiratory volume % predicted in 1 second (FEV1) and body mass index (BMI). Three time periods were compared, 12 months prior to conception, the pregnancy itself and the 12 months thereafter.
RESULTS: Data was available on 171 pregnancies in 128 patients aged 18-45 years; 55.1% with mod-sev disease, 43.1% with PI and 40.3% with PA. Women with mod-sev disease had more CF-related complications during and after pregnancy and delivered more preterm newborns. However, FEV1 and BMI decline were no different between the mild and mod-sev groups. A more rapid decline in FEV1 was observed during pregnancy in PI and PA infected patients, though stabilizing thereafter. PI was associated with increased risk for small for gestational age infants.
CONCLUSION: Baseline disease severity, PA infection and PI have an adverse impact on infant outcomes, but do not impact significantly on disease progression during and after pregnancy. Consequently, pregnancies in severe CF patients can have a good prognosis.

PMID: 32917549 [PubMed - as supplied by publisher]

Lumacaftor/ivacaftor therapy fails to increase insulin secretion in F508del/F508del CF patients.

J Cyst Fibros. 2020 Sep 08;:

Authors: Moheet A, Beisang D, Zhang L, Sagel SD, VanDalfsen JM, Heltshe SL, Frederick C, Mann M, Antos N, Billings J, Rowe SM, Moran A, PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network

Abstract
BACKGROUND: Glucose tolerance abnormalities including cystic fibrosis related diabetes (CFRD) are common in patients with cystic fibrosis (CF). The underlying pathophysiology is not fully understood. Emerging evidence suggests that CFTR dysfunction may directly or indirectly impact β-cell function, offering the potential for improvement with CFTR modulator therapy. In small pilot studies, treatment with ivacaftor improved insulin secretion in patients with the G551D CFTR mutation. In the current study, we examined the impact of lumacaftor/ivacaftor therapy on glucose tolerance and insulin secretion in patients with CF who were homozygous for the F508del mutation.
METHODS: 39 subjects from the PROSPECT Part B study who had been prescribed lumacaftor/ivacaftor by their CF care team at a CF Foundation's Therapeutic Development Network center were recruited. Subjects underwent 2-hour oral glucose tolerance tests (OGTTs) at baseline prior to first dose of lumacaftor/ivacaftor, and at 3, 6 and 12 months on therapy. OGTT glucose, insulin and c-peptide parameters were compared.
RESULTS: Compared to baseline, OGTT fasting and 2 hour glucose levels, glucose area under the curve, insulin area under the curve and time to peak insulin level were not significantly different at 3, 6 and 12 months on lumacaftor/ivacaftor therapy. Similarly, C-peptide levels were no different.
CONCLUSIONS: Lumacaftor/ivacaftor therapy did not improve insulin secretion or glucose tolerance in patients with CF who were homozygous for the F508del mutation.

PMID: 32917547 [PubMed - as supplied by publisher]

A systematic cochrane review of probiotics for people with cystic fibrosis.

Paediatr Respir Rev. 2020 Aug 13;:

Authors: Coffey MJ, Garg M, Homaira N, Jaffe A, Ooi CY

PMID: 32917517 [PubMed - as supplied by publisher]

Transition to adult care in cystic fibrosis: The challenges and the structure.

Paediatr Respir Rev. 2020 Aug 02;:

Authors: Singh J, Towns S, Jayasuriya G, Hunt S, Simonds S, Boyton C, Middleton A, Kench A, Pandit C, Keatley LR, Chien J, Bishop J, Song Y, Robinson P, Selvadurai H, Middleton PG, Fitzgerald DA

Abstract
In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

PMID: 32917516 [PubMed - as supplied by publisher]

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children.

BMC Med Res Methodol. 2020 Sep 11;20(1):228

Authors: Lima R, Gootkind EF, De la Flor D, Yockey LJ, Bordt EA, D'Avino P, Ning S, Heath K, Harding K, Zois J, Park G, Hardcastle M, Grinke KA, Grimmel S, Davidson SP, Forde PJ, Hall KE, Neilan AM, Matute JD, Lerou PH, Fasano A, Shui JE, Edlow AG, Yonker LM

Abstract
BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions.
METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic.
RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens.
CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

PMID: 32917141 [PubMed - as supplied by publisher]

A New Model of Chronic Mycobacterium abscessus Lung Infection in Immunocompetent Mice.

Int J Mol Sci. 2020 Sep 09;21(18):

Authors: Riva C, Tortoli E, Cugnata F, Sanvito F, Esposito A, Rossi M, Colarieti A, Canu T, Cigana C, Bragonzi A, Loré NI, Miotto P, Cirillo DM

Abstract
Pulmonary infections caused by Mycobacterium abscessus (MA) have increased over recent decades, affecting individuals with underlying pathologies such as chronic obstructive pulmonary disease, bronchiectasis and, especially, cystic fibrosis. The lack of a representative and standardized model of chronic infection in mice has limited steps forward in the field of MA pulmonary infection. To overcome this challenge, we refined the method of agar beads to establish MA chronic infection in immunocompetent mice. We evaluated bacterial count, lung pathology and markers of inflammation and we performed longitudinal studies with magnetic resonance imaging (MRI) up to three months after MA infection. In this model, MA was able to establish a persistent lung infection for up to two months and with minimal systemic spread. Lung histopathological analysis revealed granulomatous inflammation around bronchi characterized by the presence of lymphocytes, aggregates of vacuolated histiocytes and a few neutrophils, mimicking the damage observed in humans. Furthermore, MA lung lesions were successfully monitored for the first time by MRI. The availability of this murine model and the introduction of the successfully longitudinal monitoring of the murine lung lesions with MRI pave the way for further investigations on the impact of MA pathogenesis and the efficacy of novel treatments.

PMID: 32916885 [PubMed - as supplied by publisher]

The dark side of gamma-glutamyltransferase (GGT): Pathogenic effects of an 'antioxidant' enzyme.

Free Radic Biol Med. 2020 Sep 08;:

Authors: Corti A, Belcastro E, Dominici S, Maellaro E, Pompella A

Abstract
Having long been regarded as just a member in the cellular antioxidant systems, as well as a clinical biomarker of hepatobiliary diseases and alcohol abuse, gamma-glutamyltransferase (GGT) enzyme activity has been highlighted by more recent research as a critical factor in modulation of redox equilibria within the cell and in its surroundings. Moreover, due to the prooxidant reactions which can originate during its metabolic function in selected conditions, experimental and clinical studies are increasingly involving GGT in the pathogenesis of several important disease conditions, such as atherosclerosis, cardiovascular diseases, cancer, lung inflammation, neuroinflammation and bone disorders. The present article is an overview of the laboratory findings that have prompted an evolution in interpretation of the significance of GGT in human pathophysiology.

PMID: 32916278 [PubMed - as supplied by publisher]

An in vitro model for assessing drug transport in cystic fibrosis treatment: Characterisation of the CuFi-1 cell line.

Eur J Pharm Biopharm. 2020 Sep 08;:

Authors: Sheikh Z, Bradbury P, Pozzoli M, Young PM, Xin Ong H, Traini D

Abstract
Cystic fibrosis (CF) is a disease that most commonly affects the lungs and is characterized by mucus retention and a continuous cycle of bacterial infection and inflammation. Current CF treatment strategies are focused on targeted drug delivery to the lungs. Novel inhalable drug therapies require an in vitro CF model that appropriately mimics the in vivo CF lung environment to better understand drug delivery and transport across the CF epithelium, and predict drug therapeutic efficacy. Therefore, the aim of this research was to determine the appropriate air-liquid interface (ALI) culture method of the CuFi-1 (CF cell line) compared to the NuLi-1 (healthy cell line) cells to be used as in vitro models of CF airway epithelia. Furthermore, drug transport on both CuFi-1 and NuLi-1 was investigated to determine whether these cell lines could be used to study transport of drugs used in CF treatment using Ibuprofen (the only anti-inflammatory drug currently approved for CF) as a model drug. Differentiating characteristics specific to airway epithelia such as mucus production, inflammatory response and tight junction formation at two seeding densities (Low and High) were assessed throughout an 8-week ALI culture period. This study demonstrated that both the NuLi-1 and CuFi-1 cell lines fully differentiate in ALI culture with significant mucus secretion, IL-6 and IL-8 production, and functional tight junctions at week 8. Additionally, the High seeding density was found to alter the phenotype of the NuLi-1 cell line. For the first time, this study identifies that ibuprofen is transported via the paracellular pathway in ALI models of NuLi-1 and CuFi-1 cell lines. Overall, these findings highlight that NuLi-1 and CuFi-1 as promising in vitro ALI models to investigate the transport properties of novel inhalable drug therapies for CF treatment.

PMID: 32916267 [PubMed - as supplied by publisher]

Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

PLoS One. 2020;15(9):e0238524

Authors: Nielsen BU, Kolpen M, Jensen PØ, Katzenstein T, Pressler T, Ritz C, Mathiesen IHM, Faurholt-Jepsen D

Abstract
BACKGROUND: Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated.
METHODS: We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose.
RESULTS: No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02).
CONCLUSIONS: In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.

PMID: 32915806 [PubMed - as supplied by publisher]

Motile cilia genetics and cell biology: big results from little mice.

Cell Mol Life Sci. 2020 Sep 11;:

Authors: Lee L, Ostrowski LE

Abstract
Our understanding of motile cilia and their role in disease has increased tremendously over the last two decades, with critical information and insight coming from the analysis of mouse models. Motile cilia form on specific epithelial cell types and typically beat in a coordinated, whip-like manner to facilitate the flow and clearance of fluids along the cell surface. Defects in formation and function of motile cilia result in primary ciliary dyskinesia (PCD), a genetically heterogeneous disorder with a well-characterized phenotype but no effective treatment. A number of model systems, ranging from unicellular eukaryotes to mammals, have provided information about the genetics, biochemistry, and structure of motile cilia. However, with remarkable resources available for genetic manipulation and developmental, pathological, and physiological analysis of phenotype, the mouse has risen to the forefront of understanding mammalian motile cilia and modeling PCD. This is evidenced by a large number of relevant mouse lines and an extensive body of genetic and phenotypic data. More recently, application of innovative cell biological techniques to these models has enabled substantial advancement in elucidating the molecular and cellular mechanisms underlying the biogenesis and function of mammalian motile cilia. In this article, we will review genetic and cell biological studies of motile cilia in mouse models and their contributions to our understanding of motile cilia and PCD pathogenesis.

PMID: 32915243 [PubMed - as supplied by publisher]

Infants with Congenital Disorders Identified Through Newborn Screening - United States, 2015-2017.

MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1265-1268

Authors: Sontag MK, Yusuf C, Grosse SD, Edelman S, Miller JI, McKasson S, Kellar-Guenther Y, Gaffney M, Hinton CF, Cuthbert C, Singh S, Ojodu J, Shapira SK

Abstract
Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens. Numbers of cases for 33 disorders on the RUSP (32 DBS disorders and HL) reported by 50 U.S. state programs were tabulated. The three subtypes of sickle cell disease (SCD) listed as separate disorders on the RUSP (S,S disease; S,beta-thalassemia; and S,C disease) were combined for the current analysis, and the frequencies of the resulting disorders were calculated relative to annual births. During 2015-2017, the overall prevalence was 34.0 per 10,000 live births. Applying that frequency to 3,791,712 live births in 2018,† approximately 12,900 infants are expected to be identified each year with one of the disorders included in the study. The most prevalent disorder is HL (16.5 per 10,000), and the most prevalent DBS disorders are primary congenital hypothyroidism (CH) (6.0 per 10,000), SCD (4.9 per 10,000), and cystic fibrosis (CF) (1.8 per 10,000). Notable changes in prevalence for each of these disorders have occurred since the previous estimates based on 2006 births (2). The number of infants identified at a national level highlights the effect that NBS programs are having on infant health through early detection, intervention, and potential improved health, regardless of geographic, racial/ethnic, or socioeconomic differences.

PMID: 32915168 [PubMed - as supplied by publisher]