Situs Inversus Totalis in a Newborn With Primary Ciliary Dyskinesia.

Respiratory distress in the newborn is associated with numerous etiologies, some common and some rare. When respiratory distress is accompanied by laterality defects, namely, situs inversus (SI), the index of suspicion for comorbid primary ciliary dyskinesia (PCD) should be raised. Primary ciliary dyskinesia is characterized by ciliary dysmotility and the accumulation of thick secretions in the airways that obstruct air and gas exchange. Neonatal clinicians should know that while PCD is definitively diagnosed in infancy or early childhood, findings suspicious for PCD should be communicated to primary care providers at discharge from the hospital to facilitate timely subspecialty involvement, diagnosis, and treatment. This article will present a case report of a term newborn with SI totalis who was later diagnosed with PCD. We will discuss epidemiology, pathophysiology, clinical manifestations, and diagnostics, followed by management strategies. Additionally, we discuss the outpatient needs and lifespan implications.

Congenital glottic stenosis as a clinical manifestation of FREM1-associated disorders in a neonate with respiratory distress and aphonia.

A female infant born at 38 weeks and 2 days via induced vaginal delivery was admitted to the neonatal intensive care unit for respiratory distress soon after birth. Noted to have aphonia on examination, the patient underwent direct laryngoscopy and was diagnosed with an anterior glottic web and subglottic stenosis. The patient underwent a genetic workup including whole exome sequencing which resulted in a diagnosis of a FREM1-associated disorder. Congenital glottic webs and subglottic stenoses have not been previously described as clinical manifestations of FREM1-associated disorders.

The role of chest X-ray in the diagnosis of neonatal respiratory distress syndrome: a systematic review concerning low-resource birth scenarios.

BACKGROUND: Access to diagnostic tools like chest radiography (CXR) is challenging in resource-limited areas. Despite reduced reliance on CXR due to the need for quick clinical decisions, its usage remains prevalent in the approach to neonatal respiratory distress syndrome (NRDS). OBJECTIVES: To assess CXR's role in diagnosing and grading NRDS severity compared to current clinical features and laboratory standards. METHODS: A review of studies with NRDS diagnostic criteria was conducted across six databases (MEDLINE, EMBASE, BVS, Scopus-Elsevier, Web of Science, Cochrane) up to 3 March 2023. Independent reviewers selected studies, with discrepancies resolved by a senior reviewer. Data were organised into descriptive tables to highlight the use of CXR and clinical indicators of NRDS. RESULTS: Out of 1,686 studies screened, 23 were selected, involving a total of 2,245 newborns. All selected studies used CXR to diagnose NRDS, and 21 (91%) applied it to assess disease severity. While seven reports (30%) indicated that CXR is irreplaceable by other diagnostic tools for NRDS diagnosis, 10 studies (43%) found that alternative methods surpassed CXR in several respects, such as severity assessment, monitoring progress, predicting the need for surfactant therapy, foreseeing Continuous Positive Airway Pressure failure, anticipating intubation requirements, and aiding in differential diagnosis. CONCLUSION: CXR remains an important diagnostic tool for NRDS. Despite its continued use in scientific reports, the findings suggest that the study's outcomes may not fully reflect the current global clinical practices, especially in low-resource settings where the early NRDS approach remains a challenge for neonatal survival.Trial registration: PROSPERO number CRD42022336480.

Main findings: Access to diagnostic tools like chest radiography is challenging in resource-limited areas, yet its usage persists in the management of neonatal respiratory distress syndrome despite a decreased dependency due to the imperative for swift clinical decisions.Added knowledge: Despite its continued significance in scientific literature, the usage of chest radiography as a diagnostic tool for neonatal respiratory distress syndrome may not entirely reflect current global clinical practices, particularly in low-resource settings where early management of neonatal respiratory distress syndrome poses a challenge for neonatal survival.Global health impact for policy and action: The results underscore the necessity of guidelines for the utilisation of chest radiography to minimise unnecessary ionising radiation exposure while ensuring timely access to critical clinical information for appropriate newborn care.

Towards quantifying biomarkers for respiratory distress in preterm infants: Machine learning on mid infrared spectroscopy of lipid mixtures.

Neonatal respiratory distress syndrome (nRDS) is a challenging condition to diagnose which can lead to delays in receiving appropriate treatment. Mid infrared (IR) spectroscopy is capable of measuring the concentrations of two diagnostic nRDS biomarkers, lecithin (L) and sphingomyelin (S) with the potential for point of care (POC) diagnosis and monitoring. The effects of varying other lipid species present in lung surfactant on the mid IR spectra used to train machine learning models are explored. This study presents a lung lipid model of five lipids present in lung surfactant and varies each in a systematic approach to evaluate the ability of machine learning models to predict the lipid concentrations, the L/S ratio and to quantify the uncertainty in the predictions using the jackknife + -after-bootstrap and variant bootstrap methods. We establish the L/S ratio can be determined with an uncertainty of approximately ±0.3 mol/mol and we further identify the 5 most prominent wavenumbers associated with each machine learning model.

ABCA3 mutation-induced congenital pulmonary surfactant deficiency: A case report.

INTRODUCTION: Congenital surfactant deficiency, often caused by mutations in genes involved in surfactant biosynthesis such as ABCA3, presents a significant challenge in neonatal care due to its severe respiratory manifestations. This study aims to analyze the clinical data of a newborn male diagnosed with pulmonary surfactant metabolism dysfunction type 3 resulting from ABCA3 gene mutations to provide insights into the management of this condition. PATIENT CONCERNS: A newly born male child aged 1 day and 3 hours was referred to our department due to poor crying and shortness of breath. DIAGNOSIS: Primary diagnoses by the duty physicians were: neonatal pneumonia, neonatal respiratory failure, persistent neonatal pulmonary hypertension, birth asphyxia, myocardial damage, and arteriovenous catheterization. Genetic test revealed a compound heterozygous variant in the ABCA3 gene. One allele may be exon variant c.4561C>T, the second allele may be intron variant c.1896 + 2_1896 + 17del. The associated disease included pulmonary surfactant metabolism dysfunction type 3. INTERVENTIONS: He was initially treated with an antiinfective therapeutic regimen. OUTCOMES: The family was informed of this condition and signed off, and the child died. CONCLUSION: Hereditary pulmonary surfactant deficiency is a rare and untreatable disease. The case highlights the challenges in managing congenital surfactant deficiencies and emphasizes the need for heightened awareness of this rare cause of infant respiratory failure.

Acinar Dysplasia in a Full-Term Newborn with a NKX2.1 Variant.

Acinar dysplasia (AcDys) is one of the three main diffuse developmental disorders of the lung. The transcription factor NK2 homeobox 1 (NKX2.1) partly controls the synthesis of surfactant proteins by type 2 alveolar epithelial cells (AEC2), and germline mutations are known to be associated with brain-lung thyroid syndrome. We report the case of a full-term neonate who developed refractory respiratory failure with pulmonary hypertension requiring venoarterial extracorporeal membrane oxygenation. Histological examination of the lung biopsy specimen was consistent with the diagnosis of AcDys. Molecular analyses led to the identification of the missense heterozygous variant in NKX2.1 (NM_001079668) c.731A>G p.(Tyr244Cys), which is predicted to be pathogenic. After 5 weeks, because AcDys is a fatal disorder and the patient's status worsened, life-sustaining therapies were withdrawn, and she died after a few hours. This study is the first to extend the phenotype of NKX2.1 pathogenic variant, to a fatal form of AcDys.

Global, Regional and National Trends in the Burden of Neonatal Respiratory Failure and essentials of its diagnosis and management from 1992 to 2022: a scoping review.

Neonatal respiratory failure (NRF) is an emergency which has not been examined extensively. We critically synthesized the contemporary in-hospital prevalence, mortality rate, predictors, aetiologies, diagnosis and management of NRF to better formulate measures to curb its burden. We searched MEDLINE and Google Scholar from 01/01/1992 to 31/12/2022 for relevant publications. We identified 237 papers from 58 high-income and low-and middle-income countries (LMICs). NRF prevalence ranged from 0.64 to 88.4% with some heterogeneity. The prevalence was highest in Africa, the Middle East and Asia. Globally as well as in Asia and the Americas, respiratory distress syndrome (RDS) was the leading aetiology of NRF. Neonatal sepsis was first aetiology in Africa, whereas in both Europe and the Middle East it was transient tachypnoea of the newborn. Independent predictors of NRF were prematurity, male gender, ethnicity, low/high birth weight, young/advanced maternal age, primiparity/multiparity, maternal smoking, pregestational/gestational diabetes mellitus, infectious anamneses, antepartum haemorrhage, gestational hypertensive disorders, multiple pregnancy, caesarean delivery, antenatal drugs, foetal distress, APGAR score, meconium-stained amniotic fluid and poor pregnancy follow-up. The NRF-related in-hospital mortality rate was 0.21-57.3%, highest in Africa, Asia and the Middle East. This death toll was primarily due to RDS globally and in all regions. Clinical evaluation using the Silverman-Anderson score was widely used and reliable. Initial resuscitation followed by specific management was the common clinical practice. CONCLUSION: NRF has a high burden globally, driven by RDS, especially in LIMCs where more aggressive treatment and innovations, preferably subsidized, are warranted to curb its alarming burden. WHAT IS KNOWN: • Neonatal respiratory failure is a frequent emergency associated with a significant morbidity and mortality, yet there is no comprehensive research paper summarizing its global burden. • Neonatal respiratory failure needs prompt diagnosis and treatment geared at improving neonatal survival. WHAT IS NEW: • Neonatal respiratory failure has an alarmingly high global burden largely attributed to Respiratory distress syndrome. Low resource settings are disproportionately affected by the burden of neonatal respiratory failure. • Independent preditors of neonatal respiratory failure are several but can be classified into foetal, maternal and obstetrical factors. An illustrative pedagogical algorithm is provided to facilitate diagnosis and management of neonatal respiratory failure by healthcare providers.

Prevalência e desfechos materno-fetais de pacientes internadas por amniorrexe prematura no pré-termo no Hospital Universitário da Faculdade de Medicina de Jundiaí nos anos de 2020 e 2021 / Prevalence and maternal-fetal outcomes in patients hospitalized with preterm premature rupture of membranes at the University Hospital of Jundiaí's Medical School in the years 2020 and 2021

Objetivo: Atualizar a estatística do serviço, reconhecendo a prevalência de amnior- rexe prematura no pré-termo e seus principais desfechos materno-fetais. Méto- dos: Estudo transversal realizado pela análise de prontuários médicos de pacien- tes internadas devido a amniorrexe prematura no pré-termo e de seus respectivos conceptos no Hospital Universitário da Faculdade de Medicina de Jundiaí durante o período de janeiro de 2020 a dezembro de 2021. Resultados: Participaram da pesquisa 161 pacientes e 166 conceptos, resultando em uma prevalência de 2,12% no período estudado, com intervalo de confiança de 95% (1,80-2,47). Entre os des- fechos maternos, 2,5% das gestantes compunham critérios para near miss mater- no; enquanto entre os desfechos fetais, o resultado foi de 54,8% dos conceptos apresentando complicações, sendo as mais prevalentes a síndrome do desconfor- to respiratório (36,3%), icterícia (39,5%), baixo peso (27,5%) e hipoglicemia (24,2%). Além disso, 40,4% necessitaram de internação na unidade de terapia intensiva, 22,9% foram classificados como near miss neonatal e 4,4% foram a óbito. Conclu- são: Os resultados seguiram os padrões nacionais e internacionais esperados para prevalência de amniorrexe prematura no pré-termo e seus desfechos materno-fe- tais, com alta porcentagem de internações e complicações neonatais e baixa taxa de complicações maternas.

Objective: To update service statistics, recognizing the preva- lence of the pathology and its main outcomes. Methods: Cros- s-sectional study carried out through the analysis of medical records of patients hospitalized due to preterm premature rup- ture of membranes and their respective fetuses at the Univer- sity Hospital of Jundiaí's Medical School during the period from January 2020 to December 2021. Results: A total of 161 patients and 166 fetuses participated in the research, resulting in a pre- valence of 2.12% in the period studied with 95% confidence in- terval (1.80-2.47). About the outcomes, 2.5% of the pregnant wo- men composed the criteria for maternal near miss; as for the fetus, complications evolved in 54.8% of the fetuses, the most prevalent being respiratory distress syndrome (36.3%), jaundice (39.5%), low birth weight (27.5%) and hypoglycemia (24.2%). In addition, 40.4% required admission to the intensive care unit, 22.9% were neonatal near miss and 4.4% died. Conclusion: The results followed the expected national and international standards for the prevalence of preterm premature rupture of membranes and its maternal and fetal outcomes, with a high percentage of hospitalizations and neonatal complications, and a low rate of maternal complications.

Surfactant status assessment and personalized therapy for surfactant deficiency or dysfunction.

Surfactant is a pivotal neonatal drug used both for respiratory distress syndrome due to surfactant deficiency and for more complex surfactant dysfunctions (such as in case of neonatal acute respiratory distress syndrome). Despite its importance, indications for surfactant therapy are often based on oversimplified criteria. Lung biology and modern monitoring provide several diagnostic tools to assess the patient surfactant status and they can be used for a personalized surfactant therapy. This is desirable to improve the efficacy of surfactant treatment and reduce associated costs and side effects. In this review we will discuss these diagnostic tools from a pathophysiological and multi-disciplinary perspective, focusing on the quantitative or qualitative surfactant assays, lung mechanics or aeration measurements, and gas exchange metrics. Their biological and technical characteristics are described with practical information for clinicians. Finally, available evidence-based data are reviewed, and the diagnostic accuracy of the different tools is compared. Lung ultrasound seems the most suitable tool for assessing the surfactant status, while some other promising tests require further research and/or development.

High-flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP) vs nasal intermittent positive pressure ventilation as primary respiratory support in infants of ≥ 32 weeks gestational age (GA): study protocol for a three-arm multi-center randomized controlled trial.

BACKGROUND: Health problems in neonates with gestational age (GA) ≥ 32 weeks remain a major medical concern. Respiratory distress (RD) is one of the common reasons for admission of neonates with GA ≥ 32 weeks. Noninvasive ventilation (NIV) represents a crucial approach to treat RD, and currently, the most used NIV modes in neonatal intensive care unit include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and nasal intermittent positive pressure ventilation. Although extensive evidence supports the use of NIPPV in neonates with a GA < 32 weeks, limited data exist regarding its effectiveness in neonates with GA ≥ 32 weeks. Therefore, the aim of this study is to compare the clinical efficacy of HFNC, CPAP, and NIPPV as primary NIV in neonates with GA ≥ 32 weeks who experience RD. METHODS: This trial is designed as an assessor-blinded, three-arm, multi-center, parallel, randomized controlled trial, conducted in neonates ≥ 32 weeks' GA requiring primary NIV in the first 24 h of life. The neonates will be randomly assigned to one of three groups: HFNC, CPAP or NIPPV group. The effectiveness, safety and comfort of NIV will be evaluated. The primary outcome is the occurrence of treatment failure within 72 h after enrollment. Secondary outcomes include death before discharge, surfactant treatment within 72 h after randomization, duration of both noninvasive and invasive mechanical ventilation, duration of oxygen therapy, bronchopulmonary dysplasia, time to achieve full enteral nutrition, necrotizing enterocolitis, duration of admission, cost of admission, air leak syndrome, nasal trauma, and comfort score. DISCUSSION: Currently, there is a paucity of data regarding the utilization of NIPPV in neonates with GA ≥ 32 weeks. This study will provide clinical evidence for the development of respiratory treatment strategies in neonates at GA ≥ 32 weeks with RD, with the aim of minimizing the incidence of tracheal intubation and reducing the complications associated with NIV. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2300069192. Registered on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=171491 .