Search

ABSTRACTIntroductionAcute Respiratory Distress Syndrome (ARDS) is a heterogeneous form of lung injury with severe hypoxemia and bilateral infiltrates after an inciting event that results in diffuse lung inflammation with a high mortality rate. While research in COVID-related ARDS has resulted in several pharmacotherapeutic agents that have undergone successful investigation, non-COVID ARDS studies have not resulted in many widely accepted pharmacotherapeutic agents despite exhaustive research.Areas coveredThe aim of this review is to discuss adjuvant pharmacotherapies targeting non-COVID Acute Lung Injury (ALI)/ARDS and novel therapeutics in COVID associated ALI/ARDS. In ARDS, variable data may support selective use of neuromuscular blocking agents, corticosteroids and neutrophil elastase inhibitors, but are not yet universally used. COVID-ALI/ARDS has data supporting the use of IL-6 monoclonal antibodies, corticosteroids, and JAK inhibitor therapy.Expert opinionAlthough ALI/ARDS modifying pharmacological agents have been identified in COVID-related disease, the data in non-COVID ALI/ARDS has been less compelling. The increased use of more specific molecular phenotyping based on physiologic parameters and biomarkers, will ensure equipoise between groups, and will likely allow more precision in confirming pharmacological agent efficacy in future studies.

In extremely preterm infants, poor post-natal growth, intestinal dysbiosis and bronchopulmonary dysplasia are common, and each is associated with long-term complications. The central hypothesis that this review will address is that these three common conditions are interrelated. Challenges to studying this hypothesis include the understanding that malnutrition and poor post-natal growth are not synonymous and that there is not agreement on what constitutes a normal intestinal microbiota in this evolutionarily new population. If this hypothesis is supported, further study of whether “correcting” intestinal dysbiosis in extremely preterm infants reduces postnatal growth restriction and/or bronchopulmonary dysplasia is indicated.

Objective: Assess the quality of critical congenital heart disease (CCHD) screening data reports in California, where CCHD screening is not mandatory but reporting is. Study design: Retrospective review of California hospital-level CCHD screening data to evaluate data reliability and adherence to state screening and reporting recommendations. Data were evaluated for internal consistency and compared to two databases. Results: Over one-third of hospitals did not submit data. Only 70.7% of the Vital Records live births were reported in CCHD screening data. Only 46% of reporting hospitals submitted data with matching numbers of completed screens and results, and 22% matched their respective live births in a second database. Conclusion: CCHD data reporting in California is incomplete, which may miss 359 CCHD cases/year from non-reporting. Data inconsistencies may miss additional cases. Mandatory screening, reporting, and improvements in data reliability are urgently needed to inform screening modifications and enhance timely detection and disease surveillance.

ObjectiveTo compare death or severe neurodevelopmental impairment (NDI) at 22–26 months’ corrected age (CA) among extremely preterm infants following exposure to different forms of umbilical cord management.DesignRetrospective study.SettingEunice Kennedy ShriverNational Institute of Child Health and Human Development Neonatal Research Network registry.PatientsInfants born <27 weeks’ gestation in 2016–2018 without severe congenital anomalies who received active treatment after birth and underwent neurodevelopmental assessments between 22 and 26 months’ CA.ExposuresImmediate cord clamping (ICC), delayed cord clamping (DCC) or umbilical cord milking (UCM).Main outcomes and measurePrimary composite outcome of death or severe NDI at 22–26 months’ CA, defined as severe cerebral palsy, Bayley-III cognitive/motor composite score <70, bilateral deafness or blindness; individual components were examined as secondary outcomes. Multivariable regression examined associations, adjusting for risk factors identified a priori and potential confounders. Mediation analysis explored the effect of severe intraventricular haemorrhage (IVH) on the exposure-outcome relationship.ResultsAmong 1900 infants, 64.1% were exposed to ICC, 27.8% to DCC and 8.1% to UCM. Compared with ICC-exposed infants, DCC-exposed infants had lower odds of death or severe NDI (adjusted OR 0.64, 95% CI 0.50 to 0.83). No statistically significant differences were observed when comparing UCM with either ICC or DCC, or between secondary outcomes across groups. Association between cord management and the primary outcome was not mediated by severe IVH.ConclusionCompared with ICC, DCC exposure was associated with lower death or severe NDI at 22–26 months’ CA among extremely preterm infants, which was not mediated by severe IVH.

ObjectiveTo assess whether laryngeal mask airway (LMA) as compared with face mask (FM) or endotracheal intubation (ETT) is more effective in delivering positive pressure ventilation (PPV) during neonatal resuscitation in low-and-middle income countries (LMICs).Study designWe followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and searched Medline (PubMed interphase), Cumulative Index of Nursing and Allied Health Literature, Embase and Cochrane Registry between January 1990 and April 2022 for the studies that examined the effect of LMA in delivering PPV compared with the FM or ETT in infants during neonatal resuscitation. We included the studies conducted in LMIC only. We assessed the quality of all the included studies using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) recommendations.ResultsOur search resulted in eight randomised studies Six studies compared LMA with FM and three studies compared LMA with ETT. When used as the primary device for providing PPV, the LMA as compared with FM resulted in a significant lower failure rate (relative risk (RR) 0.23, 95% CI 0.13 to 0.43) with moderate certainty of evidence (CoE) and lesser need for intubation (RR 0.21, 95% CI 0.07 to 0.58) with low CoE. There was no difference in the incidence of encephalopathy, neonatal admission, need for advanced resuscitations or death. No differences were observed between LMA and ETT. Studies comparing LMA to ETT were limited for any conceivable conclusion.ConclusionLMA is more effective than FM in delivering PPV with less failure rates and reduced need for intubation during neonatal resuscitation in term infants and in LMIC without any difference in the incidence of encephalopathy or death. Studies comparing LMA to ETT are scarce with important methodological limitations.PROSPERO registration numberCRD42021283478.

Resuscitation guidelines are developed and revised by medical societies throughout the world. These guidelines are increasingly based on evidence from preclinical and clinical research. The International Liaison Committee on Resuscitation reviews evidence for each resuscitation practice and provides summary consensus statements that inform resuscitation guideline committees. A similar process is used for different populations including neonatal, pediatric, and adult resuscitation. The NeoHeart 2020 Conference brought together experts in resuscitation to discuss recent evidence and guidelines for resuscitation practices. This review summarizes the main focus of discussion from this symposium.

Respiratory care of premature neonates has witnessed substantial advances in the last two decades and has played a crucial role in decreasing early mortality in this population. This review outlines advances in techniques of synchronization and modes of synchronized invasive mechanical ventilation in neonates. The use of synchronized ventilation in the neonatal population was delayed as compared to adults, mainly because of technical reasons. Coordinating the infant's respiratory effort and the onset of mechanical ventilation in the neonatal population has requested high sensitivity instruments.

Persistent pulmonary hypertension of the newborn (PPHN) is a disorder of circulatory transition resulting in high pulmonary vascular resistance with extrapulmonary right-to-left shunts causing hypoxemia. There has been substantial gain in understanding of pathophysiology of PPHN over the past 2 decades, and biochemical pathways responsible for abnormal vasoconstriction of pulmonary vasculature are now better understood. Easy availability of bedside echocardiography helps in establishing early definitive diagnosis, understanding the pathophysiology and hemodynamic abnormalities, monitoring the disease process, and response to therapeutic intervention. There also has been significant advancement in specific management of PPHN targeted at deranged biochemical pathways and hemodynamic instability.

Diverse genetic developmental lung diseases can present in the neonatal period with hypoxemic respiratory failure, often associated with with pulmonary hypertension. Intractable hypoxemia and lack of sustained response to medical management should increase the suspicion of a developmental lung disorder. Genetic diagnosis and lung biopsy are helpful in establishing the diagnosis. Early diagnosis can result in optimizing management and redirecting care if needed. This article reviews normal lung development, various developmental lung disorders that can result from genetic abnormalities at each stage of lung development, their clinical presentation, management, prognosis, and differential diagnoses.

Long-term outcomes of persistent pulmonary hypertension of newborn (PPHN) depend on disease severity, duration of ventilation, and associated anomalies. Congenital diaphragmatic hernia survivors may have respiratory morbidities and developmental delay. The presence of PPHN is associated with increased mortality in hypoxic-ischemic encephalopathy, though the effects on neurodevelopment are less clear. Preterm infants can develop pulmonary hypertension (PH) early in the postnatal course or later in the setting of bronchopulmonary dysplasia (BPD). BPD-PH is associated with higher mortality, particularly within the first year. Evidence suggests that both early and late PH in preterm infants are associated with neurodevelopmental impairment.

Objective: To determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Methods: We compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, “usual care” arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18–22 months adjusted for severity of HIE, center, and RCT. Results: Among 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86–3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92–4.53), respectively. Conclusions: PPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.

The neonatal resuscitation program recommends a wide dose range of epinephrine for newborns who receive chest compressions (endotracheal tube [ET] dose of 0.05–0.1 mg/kg or intravenous [IV] dose of 0.01–0.03 mg/kg), which presents a challenge to neonatal care providers when attempting to determine the optimal initial dose. Dosing errors are common when preparing epinephrine for neonatal resuscitation. Based on animal data, we suggest preparing 0.1 mg/kg or 1 ml/kg of 1 mg/10 ml epinephrine in a 5 ml syringe for ET administration. For IV epinephrine, we suggest preparing an initial dose of 0.02 mg/kg or 0.2 ml/kg of 1 mg/10 ml epinephrine in a 1 ml syringe. A dose of 0.02 mg/kg enables use of a 1 ml syringe for a wide range of birth weights from 500 g to 5 kg. The use of a color-coded syringe may decrease errors in dose preparation.

ObjectivesNeonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.DesignForty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.ResultsTen lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

La hipertensión pulmonar persistente del neonato (PPHN) es un síndrome de alta resistencia vascular pulmonar (RVP), observado comúnmente en todo el mundo durante el periodo neonatal inmediato. Recientemente, varios reportes de casos en la India han descrito la ocurrencia de hipertensión pulmonar grave en infantes en el periodo posneonatal. Típicamente, en estos casos se presenta dificultad respiratoria en infantes de 1–6 meses de edad, amamantados por madres con una dieta basada en arroz blanco. Los factores predisponentes incluyen infecciones del tracto respiratorio, como laringotraqueobronquitis con cambio en la voz, que conducen a hipertensión pulmonar, dilatación de la aurícula y el ventrículo derechos, edema pulmonar y hepatomegalia. La mortalidad es alta si no se aplica una terapia específica. La asistencia respiratoria, tratamiento con vasodilatadores pulmonares, inotrópicos, diuréticos y la infusión de tiamina han mejorado el pronóstico de estos infantes. En esta revisión se describen cuatro pacientes típicos con hipertensión pulmonar aguda de la primera infancia, sensible a la tiamina (TRAPHEI), debida a la deficiencia de esta vitamina, y se discute su fisiopatología, sus características clínicas, sus criterios diagnósticos y las opciones terapéuticas disponibles.

In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.

Transient tachypnea of newborn (TTN) results from failure of the newborn to effectively clear the fetal lung fluid soon after birth. TTN represents the most common etiology of respiratory distress in term gestation newborns and sometimes requires admission to the neonatal intensive care unit. TTN can lead to maternal-infant separation, the need for respiratory support, extended unnecessary exposure to antibiotics and prolonged hospital stays. Recent evidence also suggests that TTN may be associated with wheezing syndromes later in childhood. New imaging modalities such as lung ultrasound can help in the diagnosis of TTN and early management with distending pressure using continuous positive airway pressure may prevent exacerbation of respiratory distress.

The initial colonization of the neonatal intestinal tract is influenced by delivery mode, feeding, the maternal microbiota, and a host of environmental factors. After birth, the composition of the infant’s microbiota undergoes a series of significant changes particularly in the first weeks and months of life ultimately developing into a more stable and diverse adult-like population in childhood. Intestinal dysbiosis is an alteration in the intestinal microbiota associated with disease and appears to be common in neonates. The consequences of intestinal dysbiosis are uncertain, but strong circumstantial evidence and limited confirmations of causality suggest that dysbiosis early in life can influence the health of the infant acutely, as well as contribute to disease susceptibility later in life.

SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients.

Background: Little is known about the perinatal aspects of COVID-19. Objective: To summarize available evidence and provide perinatologists/neonatologists with tools for managing their patients. Methods: Analysis of available literature on COVID-19 using Medline and Google scholar. Results: From scant data: vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely. Consequences of COVID-19 infection among women during early pregnancy remain unknown. We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19. Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk. Links to websites of organizations with updated COVID-19 information are provided. Infographics summarize an approach to the pregnant woman or neonate with suspected or confirmed COVID-19. Conclusions: As the pandemic continues, more data will be available that could lead to changes in current knowledge and recommendations.

Supplemental Digital Content is available in the text.

Inhaled nitric oxide is approved by FDA for the management of hypoxemic respiratory failure in term and near-term infants. However, approximately a third of patients treated with inhaled nitric oxide fail to have a sustained improvement in oxygenation. Recruitment of the lung with surfactant enables optimal delivery of nitric oxide to the alveolar space leading to effective pulmonary vasodilation.