Maheshwari A, Lui K, Motta M. We need to work together to save premature infants. Newborn 2024; 3(4):iv-viii. DOI: 10.5005/newborn-3-4-iv.

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Spillane NT, Guzman L, Lozy T, Michalak Z, Malik SK. Success of Expectant Observation and Needle Aspiration in Reducing the Need for Chest Tube Drainage for Management of Neonatal Pneumothoraces. Newborn 2024; 3(4):245-250. DOI: 10.5005/jp-journals-11002-0111.

 

Abstract: Aim: Expectant observation (EO), needle aspiration (NA), and chest tube drainage (CTD) were compared as definitive treatment options for neonatal pneumothoraces (PTX).
Materials and methods: This is a retrospective single-center study from 2017 to 2019 of 114 PTX. Maternal, neonatal, and PTX characteristics were examined; associations with type and efficacy of intervention and patient/PTX characteristics were assessed.
Results: For primary treatment, 20.2% of PTX were treated with chest tube drainage (CTD), 25.4% with needle aspiration (NA), and 54.4% with EO. The efficacy of primary treatment was 91.3% with CTD, 37.9% with NA, and 96.8% with EO. NA and CTD were utilized more frequently than EO for moderate PTX (59.3 vs 40.9 vs 13.1%, p < 0.001), late PTX (75.9 vs 78.3 vs 27.4%, p < 0.001), and PTX with tension (41.4 vs 39.1 vs 1.6%, p < 0.001). In multivariate analysis, NA was the only factor associated with significantly lower success [adjusted odds ratio (OR) 0.08, 95% confidence interval (CI) 0.02–0.40]. None of the infants experienced any complications.
Conclusion: EO was the most frequent treatment modality and highly successful in management of small PTX. NA was utilized in less mature neonates with more complex PTX; it was safe and avoided more invasive CTD in a significant percentage of neonates.
Clinical significance: In our experience, EO and NA were highly safe, efficacious, and definitive management strategies of small pneumothoraces, not just a temporizing procedure to stabilize these infants prior to eventual CTD. CTD, which is much more invasive, was required only in a small fraction of these patients and further study is needed to define its indications.

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Key scientific associations: Newborn, neonate, preterm, quality improvement, pneumothorax, chest tube drainage, expectant management, needle aspiration, air leak, neurodevelopmental disabilities, expectant management, tension pneumothorax, positive pressure ventilation, nurse practitioner, physician assistant, CPAP, Declaration of Helsinki, Shapiro-Wilk test, Q-Q plots, Welch’s t-test, homoscedasticity, Mantel-Haenszel test, logistic regression, hemodynamic instability, implementation science.

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Shahrour O, Narchi H, Siwji Z, Ben Ayad AE, Rahmani A, Abdullatif M. Need for Cautious Adoption of American Academy of Pediatrics Guidelines for Management of Neonatal Hyperbilirubinemia in Different Parts of the World. Newborn 2024; 3(4):251–256. DOI: 10.5005/jp-journals-11002-0114. 

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Abstract: Background: Early hospital discharge (<72 hours following birth) of healthy-term and near-term infants is favored to promote family care but may have increased hyperbilirubinemia-related hospital readmissions. In this study, we compared the 2009 and 2022 American Academy of Pediatrics (AAP) discharge guidelines in the United Arab Emirates (UAE) for the impact on hyperbilirubinemia-related readmissions.
Materials and methods: This was a retrospective cohort single-center study conducted in the UAE. We reviewed records from the period January 2021 to November 2021; the infants included those with a gestational age (GA) ≥35 weeks and a birth weight (BW) ≥2,500 gms and GA ≥36 weeks/BW ≥ 2,000 gms. Infants were classified into risk zones based on pre-discharge transcutaneous bilirubin (TcB) or total serum bilirubin (TSB) levels (AAP 2009 hyperbilirubinemia nomograms). We compared the 2009 and 2022 AAP discharge thresholds for the needs for follow-up and readmissions for hyperbilirubinemia.
Results: We studied 895 newborns; 672 (75%) were born at term with a mean (± standard deviation) GA of 38 ± 1.3 weeks. Most (75.3%) were classified as appropriate for GA and 637 (71%) attended the 1st follow-up as recommended. Based on the 2009 AAP guidelines, 13 (2.9%) out of 447 (70%) were low risk; 12 (6.6%) out of 183 (29%) were low-intermediate risk; and 3 out of 7 (42.9%) were high-intermediate risk. A total of 49 (5.5%) infants were readmitted to the hospital for phototherapy. Unlike in the United States, the 2022 guidelines would have recommended follow-up visits within 2 days in a larger number [579 (64.7%)] than the 2009 recommendations [308 (34.4%)]; the overall need for phototherapy would also have been higher. However, the frequency of severe hyperbilirubinemia requiring phototherapy would have remained similar. Our population did not have more specific risk factors such as scalp bleeds for developing severe neonatal hyperbilirubinemia. We did have a high number of missed follow-up appointments.
Conclusion: In our region, the adoption of the 2022 AAP early hospital discharge guidelines may have increased the number of follow-up visits within 2 days after discharge from the hospital and the overall need of phototherapy. These guidelines need to be specifically evaluated in different ethnic groups in various parts of the world.

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Key scientific associations: Infant, bilirubin, monitoring, nomograms, American Academy of Pediatrics, early discharge, readmission risk, retrospective cohort study, follow-up timing, kernicterus, bilirubin encephalopathy, low intermediate-risk, transcutaneous bilirubin, serum bilirubin, Middle East, pre-discharge bilirubin, Rhesus incompatibility, direct antiglobulin test, total serum bilirubin, nomograms, glucose-6-phosphate dehydrogenase, delta TSB, delta TcB, spectrophotometry, Pearson chi2 test, Fisher's exact test​.

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Thakkar P, Raju V, Raju P, et al. Pulmonary Hemorrhage Management Practices in Extremely Preterm Infants: A Global Survey. Newborn 2024; 3(4):257–262. DOI: 10.5005/jp-journals-11002-0113. 

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Abstract: Background: Pulmonary hemorrhage (PHEM) can be life-threatening in extremely premature infants, with only supportive treatment available. Little is known regarding specific management strategies for PHEM because of the rarity of its occurrence and significant associated mortality.

Materials and methods: A multi-institutional working group of physicians was created with the common goal of expanding knowledge about PHEM. We designed a 14-question survey around our experience and current controversies reported in the literature. The survey was circulated via neonatal listservs (MEDNAX neonatology forum, nicu99, Envision Physician Services, and the AAP Training and Early Career neonatologists’ group) to capture the management strategies of various neonatologists practicing under different settings and resources. The data were collected in REDCap software, and statistical analysis was conducted using SPSS version 27.
Results: There were 360 responses from 73 countries. Most neonatologists (79.2%) managed PHEM without unit-based guidelines. For the management of PHEM, there was a consensus on using endotracheal (ET) epinephrine, blood products and high-frequency oscillatory ventilation after acute PHEM. More participants responded using surfactant replacement after (55.6%) rather than during (33.1%) the management of PHEM. Post PHEM, most neonatologists obtain echocardiograms (66%) and consider treatment for patent ductus arteriosus (PDA) (65%), with the majority using acetaminophen (56.4%). Comparative analysis of practices in North America and other NICUs are also reported.
Conclusions: Our study provides a global overview of experience, and opinion-based practices used in the management of PHEM and reflects on the lack of available algorithms. Creating high-quality, evidence-based guidelines is necessary to provide appropriate care and reduce heterogeneity in the management.

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Key scientific associations: pulmonary hemorrhage, preterm, infant, risk factors, management, endotracheal epinephrine, transfusions, high-frequency oscillatory ventilation, surfactant, RedCAP, hemocoagulase, cryoprecipitate, activated recombinant factor VII, acetaminophen, pulmonary blood flow, SARS-CoV-2, cytomegalovirus, coxsackievirus, alveolar tamponade.

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Singh S, Maheshwari A. Epigenetics of Down Syndrome. Newborn 2024; 3(4):263–280. DOI: 10.5005/jp-journals-11002-0112. 

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Abstract: Down syndrome (DS) can show a wide clinical range in terms of type/severity of presentations/defects. This extensive heterogeneity/pleiotropy is surprising because DS is rooted in a fairly restricted genetic zone; nearly 95% have a freely segregating triplication of human chromosome 21 (Homo sapiens 21, Hsa21). The remaining 5% may carry translocated 21 or mosaicism of mixed clones. As in most genetic disorders, gene-dosage/copy number variations are a consideration. However, a possibility of epigenetic modifications is also being considered; this is an attractive area for study because many epigenetic marks are reversible, which might provide opportunities for therapeutic interventions aimed at prophylaxis/treatment/remission/reversal aimed at cure/rehabilitation of these patients. In this article, we have reviewed epigenetic changes in DS. Ongoing efforts show that these changes in DS might not be limited to Hsa21 but could be genome-wide; DNA methylation, post-translational histone modifications, and histone core variants have been noted. Existing data emphasize two trans-acting molecular mechanisms. The first involves enhanced expression of regulatory genes through histone modifications such as Hsa21-linked S-adenosylmethionine (SAM)-dependent methylation, and the effect of transcription factors such as Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A (DYRK1A), ETS2, high mobility group nucleosome binding domain 1 (HMGN1), Bromodomain and WD repeat domain containing 1 (BRWD1), and RUNX family transcription factor 1 (RUNX1). The second involves Hsa21q21 microRNAs (miRNAs) lethal-7c (let7c), miRNA-99a, and miRNA-125b encoded at the band q21.1; miRNA-802 at q21.12, and miRNA-155 at q21.3. Wherever possible, we focused on the protein-coding gene EURL (early undifferentiated retina and lens) as a read-out; Early undifferentiated retina and lens is the Chromosome 21 open reading frame 91 (C21ORF91) located at the centromeric boundary of the DS critical region (DSCR). We have assimilated research findings from our own laboratory with an extensive review of the literature utilizing key terms in multiple databases including PubMed, EMBASE, and Science Direct. To avoid bias in the identification of studies, keywords were short-listed a priori from anecdotal experience and PubMed’s Medical Subject Heading (MeSH) thesaurus..

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Key scientific associations: Key words- neonate, newborn, infant, epigenetics, gene dosage-effect hypothesis, HDACs, RUNX1, microRNA-Let7A, trained immunity, DNA methylation, DS-DM, differential DNA methylation,  RNA silencing, post translational modification, histones, lncRNA, ncRNA, HSA21, DNMT3L, DYRK1, CBS, PCDHG, CELSR, CPT1B, TET, REST/NRSF, NOX5, FLI1, CTCF, C/EBP, SNX-27, miRNA-155, miRNA-802, miRNA-99a, miRNA-125-b2, miRNA-138-5p, miRNA-nov1, miRNA-nov2, miR-329, miR-27b, miR-27a, APP, GATA1, gene expression, post-translational modifications, histone, cytosine, CpG dinucleotides, 5-methylcytosine, methyltransferases, DNMT3a, DNMT3b, DNMT1, writers, erasers, readers, microRNA (miRNA), gene repression, regulatory ncRNA, untranslated region, RNA interference (RNAi) processes, post-transcriptional gene silencing, acetylation, epigenetic clock, clock CPGs, epidrugs, segmental progeria, DNA methylation age, neural iPSCs, epigenetic editing, triploidy, Hsa21, S-adenosylmethionine, ETS2 [(Erythroblastosis Virus E26 Oncogene Homolog-1) Proto-Oncogene 2, Transcription Factor], HMGN1 (High Mobility Group Nucleosome Binding Domain 1), BRWD1 (Bromodomain And WD Repeat Domain Containing 1), RUNX1 [(Runt-Related Transcription Factor 1) Family Transcription Factor 1]; and (b) altered expression of microRNAs (miRNAs) let-7c, miRNA-99a, miRNA-125b, miRNA-802, miRNA-155, methyl-CpG-binding proteins, ten-eleven translocation, synaptic plasticity, DNA packaging protein histone 4, histone deacetylase (HDAC) inhibitors, differential methylation, Lysine Demethylase 2B, tuberous sclerosis protein complex 2, cystathionine β-synthase, Protocadherin Gamma Cluster, Carnitine Palmitoyltransferase 1B, Cadherin EGF LAG Seven-Pass G-Type Receptor 3, Restrictive Silencing Transcription factor, dachsous, 7-transmembrane (CELSR) cadherins, calcineurin inhibitors, H2A histone family member Z, H2B histone fam­ily member S, chromatin assembly factor 1B, hetero­chromatin protein 1, cAMP response element-binding protein-binding protein, Methyl-CpG binding protein 2, Rubinstein–Taybi syndrome, synaptic plasticity, histone H1, linker histone, zinc-finger transcription, gene expression dysregulation domains, 15-lipoxygenase, synapsin-2, complement factor H, tetraspanin-12, Nodal/Smad2 signaling, CCAAT/enhancer binding protein, Sorting nexin 27, Rett syndrome, miR-1973, miR-3196, miR-504, miR-191, miR-133b, miR-188-3p, long non-coding RNAs, NADPH oxidase 5, nicotinamide adenine dinucleotide, memory circuits, tyrosine-phosphorylated kinase, γ-protocadherins, Cadherin EGF LAG Seven-Pass G-Type Receptor 3, hypermethylated, repressor, enhancer-like activity, synaptosomal structure, cortical lamination defects, dendritic spine structural anomalies, memory suppressor genes, H3K4me3, HOXA3, HOXD3, SH3 Domain Binding Protein 2, Zinc Finger DHHC-Type Palmitoyltransferase 14, palmitoyl transferase, neuroligin-2, cytohesin-2, amigo-3, brsk-2/sad-a kinase, Krueppel-Like transcription Factor 16, Cardiomyopathy Associated 5, NudE Neurodevelopment Protein, BHLH Transcription Factor 1, Fli-1 proto-oncogene, ETS transcription factor, megakaryopoiesis, GATA1-truncating mutations, (T/A)GATA(A/G), Vault RNA 2-1, N-6 Adenine-Specific DNA Methyltransferase 1, MIS18 Kinetochore Protein A, carnitine palmitoyltransferase 1, Solute Carrier Family 19 Member 1, Superoxide Dismutase 1, Glycinamide Ribonucleotide Formyltransferase, Amyloid precursor protein, Alzheimer-like neuropathology, telomere length measurements, CpG methylation patterns, NCOR, hippocampus-dependent visuospatial memory, Morris water maze, epigallocatechin-gallate, novel object recognition test, Ts65Dn mice, TgDyrk1A mice, SWI/SNF complex, XIST transgene.

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Frydrysiak-Brzozowska A, Jape K, Athalye-Jape G, et al. Fetuses can Listen, Learn, and Remember: We Need to be Cautious about What and How We Say It! Newborn 2024; 3(4):281–291. DOI: 10.5005/jp-journals-11002-0102. 

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Abstract: The fetal auditory system becomes functional during mid-gestation or possibly even earlier. Existing data show that fetuses can respond to maternal voice and different types of music, both vocal and instrumental. The ability to receive and transmit sound waves, and then recognize and retain some memory of these auditory stimuli could possibly be one of the most important developmental sensory milestones that we need to learn about. Unfortunately, we still have limited evidence for the precise role and timing of prenatal sound simulation. There is a need for methodologically strong, randomized controlled trials with rigorously designed interventions and standardized reporting measures. We may need to compare different durations and types of musical (sound) intervention. At a minimum, these interventions can improve maternal–fetal bonding and family-centered outcomes. Any evidence of neurodevelopmental gains would be an important scientific/medical advancement. In certain conditions such as neonatal abstinence syndrome, emerging evidence suggests that early, in utero intervention with music therapy can be helpful; these findings bring hope for new therapeutic tools to enhance the neurological development of at-risk fetuses. Considering that prenatal music exposure might have positive effects on the fetus and newborn infant, we need carefully conducted studies of intrauterine neurosensory organization with long-term follow-up.

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Key scientific associations: neonates, sepsis, Point-of-care ultrasound, POCUS, meningitis, brain abscess, central nervous system, fungal infections, viral infections, ventriculitis, cerebral abscess, cerebral thrombosis, ionizing radiation, sedation, cerebral calcifications, ischemic lesions,  hematomas, late-onset neonatal sepsis, hydrocephalus, severity-of-illness, neurodevelopmental outcomes, anterior fontanel, acoustic window, Group B streptococci, Gram-negative bacilli, Listeria monocytogenes, Proteus, Citrobacter, Streptococcus, Serratia, Neisseria meningitis, Candida albicans, Candida parapsilosis, herpes simplex, parvovirus, Zika virus, rotavirus, pustular cavity, meningeal thickening, brain sulci, cerebral gyri, sulci, gyral surface, sagittal sinus, perforating vessels, extra-axial fluid collections, reactive effusions, chinking of ventricles, empyema, cerebral thrombosis, ependymitis, choroid plexitis, arachnoiditis, fibroglial elements, non-communicating hydrocephalus, ventriculomegaly, ex vacuo ventriculomegaly, ventricular index, anterior horn width, thalamo-occipital distance, occipital horn, fibrous septae, intraventricular compartmentalization, intraventricular cysts, obstructive hydrocephalus, cisternal structures, resistive index, infarction, cerebritis, vertebral arch, spinous processes, pulsatility of arterial blood flow, granulomas, micro-abscesses.

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Vereen R, Gautham K, King B, Mitra S, Malhotra A. Navigating Information Overload on Social Media: Opportunities and Misadventures for Clinicians and Professionals. Newborn 2024; 3(4):292–296. DOI: 10.5005/jp-journals-11002-0108.

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Abstract: In an age with numerous online and social media platforms where families, clinicians, and professionals rely more on the internet and social media for information finding, sharing, understanding, and analyzing medical literature is more complex than ever. Navigating social media has become increasingly difficult with misinformation and disinformation concerns and the growing number of dissemination methods. Social media plays an ever-increasingly significant role in facilitating or hindering the practice of evidence-based medicine. There are ever-growing challenges to practicing medicine in the age of social media.This article describes the benefits and risks of using social media for health professionals to stay updated with medical literature and provides best-use practices for critical appraisal, specifically for adapting essential techniques of appraisal when encountering social media. This article also describes best-use practices for understanding and collaborating with colleagues and partnering with families in information sharing.

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Key scientific associations: Pregnancy, family with young infant, critical appraisal, evidence-based medicine, health and communication, health and media, social media, misinformation, social media, critical appraisal, misinformation, evidence-based medicine, health and media, health and communication, social profile creation, social connectivity, blogging, media sharing, instant messaging, content creation, social media promotion, advertisement, crowdsourcing, health-related content, publication alerts, organizational promotion, clinician education, patient education, content generation, content consumption, clickbait, likes, reposts, shares, interaction bias, self-selection bias, sampling bias, second-order biases, social media algorithms, influencer, community of practice, Twitter, automated bots, spin in communicating results, critical appraisal, systematic appraisal, health advocacy, professional networking, time commitment, learning, spin bias, best practice, professional networking, interaction with patients and families.

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Ocampo-Chih C, Weitkamp AS, Weitkamp J-H, Gillam-Krakauer M. Intrauterine Acquired Congenital Herpes Simplex Virus Infection in a Newborn. Newborn 2024; 3(4):297–300. DOI: 10.5005/jp-journals-11002-0109.

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Abstract: ​Aim: We present a fatal case of congenital herpes simplex virus (HSV) infection following exposure of a non-immune mother by her partner during critical fetal development.
Background: Globally, neonatal HSV infection affects 1 in 10,000 births. The usual mode of transmission is perinatal through passage through the vaginal canal (85%), followed by postnatal acquisition (10%). Rarely, intrauterine infection can occur (5%) resulting in congenital HSV, presenting with a classic triad of skin desquamation, chorioretinitis and brain malformations including hydrocephaly, anencephaly, and porencephaly.
Case description: A 30-week pregnant woman with a history of flu-like illness at 18 weeks presented with decreased fetal movement and vaginal bleeding. Initial evaluation showed echogenic bowel on ultrasound. At 30 weeks, polyhydramnios and fetal brain abnormalities were noted. A C-section was performed, and the infant required resuscitation at birth. The infant’s father reported a history of genital HSV outbreaks and HSV-2 was detected in the infant’s blood. The infant had extensive skin desquamation, seizures, and succumbed to fatal brain malformations.
Conclusion: While maternal treatment with antiviral medication and cesarean section are effective in preventing perinatal HSV infection, congenital infection in the 1st/2nd trimester with devastating consequences for the fetus can occur in women without HSV immunity.
Clinical significance: Given the lack of available HSV immunization, protection of non-immune pregnant individuals from HSV exposure is currently the only preventive measure against congenital HSV disease.

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Key scientific associations: Herpes simplex virus, congenital infection, newborn, brain malformation, prevention, polyhydramnios, fetal brain abnormalities, neonatal skin desquamation, neonatal seizures, bullous pemphigoid, disseminated candidiasis, bilateral acute retinal necrosis in a newborn, corneal dendrites in a newborn, corneal abrasion in a newborn, punctate foci of echogenicity near the left vertex, cystic structure in the posterior fossa, periventricular echogenicity in a newborn, hydrocephaly, porencephaly, accelerated placental villous maturation, acute placental villous vasculitis, organizing placental intervillous hematoma, multifocal placental villous edema.

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Jha VV, Arora G, Arora V. Neonate with Bilateral Vocal Cord Palsy Presenting with Respiratory Distress and Congenital Stridor: A Diagnostic and Therapeutic Challenge. Newborn 2024; 3(4):301-305. DOI: 10.5005/jp-journals-11002-0110.

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Abstract: Objective: We recently treated a neonate with biphasic stridor secondary to bilateral vocal cord palsy (BVCP). This experience evoked considerable discussion in our unit; hence, we have outlined our approach to neonatal stridor, the importance of direct visualization using bronchoscopy, and management options in this condition.
Case presentation: A full-term male infant presented with biphasic stridor two days after birth. The pre- and peri-natal course was uneventful, but he developed respiratory distress immediately after birth and needed assistive ventilation. There was no remarkable lung disease; the radiographs were reported as normal. We were able to wean him to non-invasive respiratory support within 48 hours, but there was persistent biphasic stridor with increased work of breathing. Extensive evaluation of the airways using flexible and rigid bronchoscopy showed BVCP. There was no change in the vocal cord movement over time, and eventually, on day 38 after birth, we had to perform a tracheostomy. He was successfully discharged home after a few days. So far, after a few months, he continues to tolerate feedings and has shown good growth, but there has been no change in BVCP.
Conclusion: Vocal cord palsy should be considered as a possibility in infants who present with stridor and respiratory distress but have a noticeable cry. Transnasal fiberoptic flexible laryngoscopy is an important tool in assessing and monitoring these infants. A comprehensive evaluation should ascertain whether the laryngeal dysfunction is an isolated, primary clinical problem or part of a secondary systemic infectious/syndromic illness. The prognosis will depend on the etiology; isolated vocal cord palsy usually takes months to years to show improvement, so surgical treatment options may have to be explored. In contrast, secondary laryngeal paralysis will need more extensive systemic assessment, monitoring, and prognostication; treatment focused on cure, remission, or rehabilitation might be possible in some infants based on the specific diagnosis.

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Key scientific associations: Bronchoscopy, case report, newborn, respiratory distress, stridor, tracheostomy, stridor, bronchoscopy, tracheostomy, respiratory distress, newborn, vocal cord palsy, laryngomalacia, subclinical EBV infection, bilateral abductor porcine bronchus, recurrent laryngeal nerve branch of the vagus, Arnold Chiari malformation type 1, posterior cricoid split with cartilage grafting, anterior and posterior cricoid split with dilation and stenting.