A premature male infant was delivered at 32 weeks gestation due to category-2 fetal tracing after preterm labor. The physical exam showed shortened and bowed long bones, with calvarium felt in small area of the head. Serum alkaline phosphatase was very low on admission. Extensive metaphyseal abnormalities, bowing of long bones, and poor ossification of all bones were noted on skeletal survey (radiography). Based on ultrasound evidence of bowing and long bone fractures at 26 weeks, amniocentesis was performed that later diagnosed hypophosphatasia by genetic testing while ruling out osteogenesis imperfecta. Although ventilated initially, the infant gradually improved with enzyme replacement therapy (ERT) and was extubated to noninvasive ventilation for 6 weeks. Following clinical deterioration with hypoxic respiratory failure secondary to sepsis at 4 months of age, he succumbed to severe pulmonary hypertension, likely secondary to chronic lung disease and prolonged ventilation. Early diagnosis allowed timely initiation of appropriate therapy. Radiological improvement with the therapy showed promising results in this rare disease. Despite specific novel therapy being available, variability in presentation dictates prognosis in this previously universally fatal condition. The potential unknown effects of ERT on pulmonary vascular remodeling need further investigation.

Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO₂) in the alveolus (PAO₂) and pulmonary artery (PaO₂) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO₂) and a target range of 91-95% are recommended during acute PPHN management. However, for a given SpO₂, there is wide variability in arterial PaO₂, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO₂, and SpO₂ in the management of PPHN. Translational and clinical studies suggest maintaining a PaO₂ of 50-80 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO₂ or PO₂. Also, most critically ill patients have umbilical arterial catheters and postductal PaO₂ may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO₂ and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO₂/SpO₂ target ranges for the management of PPHN and compare outcomes.

A premature male infant was delivered at 32 weeks' gestation due to category-2 fetal tracing after preterm labor. The physical exam showed shortened and bowed long bones, with calvarium felt in small area of the head. Serum alkaline phosphatase was very low on admission. Extensive metaphyseal abnormalities, bowing of long bones, and poor ossification of all bones were noted on skeletal survey (radiography). Based on ultrasound evidence of "bowing" and long bone fractures at 26 weeks, amniocentesis was performed that later diagnosed hypophosphatasia by genetic testing while ruling out osteogenesis imperfecta. Although ventilated initially, the infant gradually improved with enzyme replacement therapy (ERT) and was extubated to noninvasive ventilation for 6 weeks. Following clinical deterioration with hypoxic respiratory failure secondary to sepsis at 4 months of age, he succumbed to severe pulmonary hypertension, likely secondary to chronic lung disease and prolonged ventilation. Early diagnosis allowed timely initiation of appropriate therapy. Radiological improvement with the therapy showed promising results in this rare disease. Despite specific novel therapy being available, variability in presentation dictates prognosis in this previously universally fatal condition. The potential unknown effects of ERT on pulmonary vascular remodeling need further investigation.

Oxidative stress can be associated with hyperoxia and hypoxia and is characterized by an increase in reactive oxygen (ROS) and nitrogen (RNS) species generated by an underlying disease process or by supplemental oxygen that exceeds the neutralization capacity of the organ system. ROS and RNS acting as free radicals can inactive several enzymes and vasodilators in the nitric oxide pathway promoting pulmonary vasoconstriction resulting in persistent pulmonary hypertension of the newborn (PPHN). Studies in animal models of PPHN have shown high ROS/RNS that is further increased by hyperoxic ventilation. In addition, antioxidant therapy increased PaO2 in these models, but clinical trials are lacking. We recommend targeting preductal SpO2 between 90 and 97%, PaO2 between 55 and 80 mmHg and avoiding FiO2 > 0.6-0.8 if possible during PPHN management. This review highlights the role of oxidative and nitrosative stress markers on PPHN and potential therapeutic interventions that may alleviate the consequences of increased oxidant stress during ventilation with supplemental oxygen.

BACKGROUND AND OBJECTIVES: Oxygen (O2) use during neonatal cardiopulmonary resuscitation (CPR) remains a subject of controversy. The inspired O2 concentration during neonatal CPR, that hastens return of spontaneous circulation (ROSC), allows adequate cerebral and myocardial O2 delivery, and enhances survival to discharge, is not known. The optimal FiO2 during CPR should decrease incidence of hypoxia but also avoid hyperoxia, and ultimately lead to improved neurodevelopmental outcomes. Due to infrequent need for extensive resuscitation, and emergent circumstances surrounding neonatal CPR, conducting randomized clinical trials continues to be a challenge. The goal of this study was to review the evolution of oxygen use during neonatal CPR, the evidence from animal and clinical studies on oxygen use during neonatal CPR and after ROSC, the pertinent physiology including myocardial oxygen consumption and cerebral oxygen delivery during CPR, and outcomes following CPR in the DR and in the neonatal intensive care unit. METHODS: This narrative review is based on recent and historic English literature in PubMed and Google scholar over the past 35 years (January 1, 1985 - May 1, 2021). KEY CONTENT AND FINDINGS: Several studies in animal models have compared ventilation with different inspired O2 concentrations (mostly 21% and 100%) during chest compressions and after ROSC. These studies reported no difference in short-term outcomes, even with as low as 18% O2. However, in lamb models of cardiac arrest and CPR, 100% O2 during chest compressions is associated with better oxygen delivery to the brain compared to 21% O2. Abrupt weaning to 21% O2 following ROSC followed by titration to achieve preductal SpO2 of 85-95% minimizes systemic hyperoxia and oxidative stress compared to slow weaning from 100% O2 following ROSC. CONCLUSIONS: Clinical research is needed to arrive at the best strategy for assessment of oxygenation and choice of FiO2 during neonatal CPR that lead to improved survival and outcomes. In this article, we have reviewed the literature on evidence behind O2 use during neonatal advanced CPR and after ROSC.

Epinephrine is the only medication recommended by the International Liaison Committee on Resuscitation for use in newborn resuscitation. Strong evidence from large clinical trials is lacking owing to the infrequent use of epinephrine during neonatal resuscitation. Current recommendations are weak as they are extrapolated from animal models or pediatric and adult studies that do not adequately depict the transitioning circulation and fluid-filled lungs of the newborn in the delivery room. Many gaps in knowledge including the optimal dosing, best route and timing of epinephrine administration warrant further studies. Experiments on a well-established ovine model of perinatal asphyxial cardiac arrest closely mimicking the newborn infant provide important information that can guide future clinical trials.

One hundred years after the 1918 influenza pandemic, we now face another pandemic with the severe acute respiratory syndrome-novel coronavirus-2 (SARS-CoV-2). There is considerable variability in the incidence of infection and severe disease following exposure to SARS-CoV-2. Data from China and the United States suggest a low prevalence of neonates, infants, and children, with those affected not suffering from severe disease. In this article, we speculate different theories why this novel agent is sparing neonates, infants, and young children. The low severity of SARS-CoV-2 infection in this population is associated with a high incidence of asymptomatic or mildly symptomatic infection making them efficient carriers. KEY POINTS: · There is a low prevalence of novel coronavirus disease in neonates, infants, and children.. · The fetal hemoglobin may play a protective role against coronavirus in neonates.. · Immature angiotensin converting enzyme (ACE2) interferes with coronavirus entry into the cells..

Newborn infants with risk factors may require intravenous (IV) dextrose for asymptomatic hypoglycemia. Administration of IV dextrose and transfer to the neonatal intensive care unit (NICU) may interfere with parent-infant bonding. To study the effect of implementing dextrose gel supplement with feeds in late preterm/term infants affected by asymptomatic hypoglycemia on reducing IV dextrose therapy. A retrospective study was conducted before and after dextrose gel use: 05/01/2014 to 10/31/2014 and 11/01/2014 to 04/30/2015, respectively. Asymptomatic hypoglycemic (blood glucose level <45 mg/dl) infants in the newborn nursery (NBN) were given a maximum of 3 doses of dextrose gel (200 mg/kg of 40% dextrose) along with feeds. Transfer to the NICU for IV dextrose was considered treatment failure. Dextrose gel with feeds increased the blood glucose level in 184/250 (74%) of asymptomatic hypoglycemic infants compared to 144/248 (58%) with feeds only (p < 0.01). Transfer from the NBN to the NICU for IV dextrose decreased from 35/1,000 to 25/1,000 live births (p < 0.01). Exclusive breastfeeding improved from 19 to 28% (p = 0.03). Use of dextrose gel with feeds reduced the need for IV fluids, avoided separation from the mother and promoted breastfeeding. Neonates who failed dextrose gel therapy were more likely to be large for gestational age, delivered by cesarean section and had lower baseline blood glucose levels.

Birth asphyxia accounts for nearly one million deaths worldwide each year, and is one of the primary causes of early neonatal morbidity and mortality. Many aspects of the current neonatal resuscitation guidelines remain controversial given the difficulties in conducting randomized clinical trials owing to the infrequent and often unpredictable need for extensive resuscitation. Most studies on neonatal resuscitation stem from manikin models that fail to truly reflect physiologic changes or piglet models that have cleared their lung fluid and that have completed the transition from fetal to neonatal circulation. The present protocol provides a detailed step-by-step description on how to create a perinatal asphyxiated fetal lamb model. The proposed model has a transitioning circulation and fluid-filled lungs, which mimics human newborns following delivery, and is, therefore, an excellent animal model to study newborn physiology. An important limitation to lamb experiments is the higher associated cost.

Congenital Diaphragmatic hernia (CDH) is a condition characterized by a defect in the diaphragm leading to protrusion of abdominal contents into the thoracic cavity interfering with normal development of the lungs. The defect may range from a small aperture in the posterior muscle rim to complete absence of diaphragm. The pathophysiology of CDH is a combination of lung hypoplasia and immaturity associated with persistent pulmonary hypertension of newborn (PPHN) and cardiac dysfunction. Prenatal assessment of lung to head ratio (LHR) and position of the liver by ultrasound are used to diagnose and predict outcomes. Delivery of infants with CDH is recommended close to term gestation. Immediate management at birth includes bowel decompression, avoidance of mask ventilation and endotracheal tube placement if required. The main focus of management includes gentle ventilation, hemodynamic monitoring and treatment of pulmonary hypertension followed by surgery. Although inhaled nitric oxide is not approved by FDA for the treatment of PPHN induced by CDH, it is commonly used. Extracorporeal membrane oxygenation (ECMO) is typically considered after failure of conventional medical management for infants ≥ 34 weeks' gestation or with weight >2 kg with CDH and no associated major lethal anomalies. Multiple factors such as prematurity, associated abnormalities, severity of PPHN, type of repair and need for ECMO can affect the survival of an infant with CDH. With advances in the management of CDH, the overall survival has improved and has been reported to be 70-90% in non-ECMO infants and up to 50% in infants who undergo ECMO.