Invasive and non-invasive ventilatory strategies for early and evolving bronchopulmonary dysplasia.

In the age of surfactant and antenatal steroids, neonatal care has improved outcomes of preterm infants dramatically. Since the early 2000's neonatologists have strived to decrease bronchopulmonary dysplasia (BPD) by decreasing ventilator-associated lung injury and utilizing many novel modes of non-invasive respiratory support. After the initial success with nasal continuous positive airway pressure, it was established that discontinuing invasive ventilation early in favor of non-invasive respiratory support is the most effective way to reduce the incidence of BPD. In this review, we discuss the management of the preterm lung from the time of delivery, through the phases of respiratory distress syndrome (early BPD) and then evolving BPD. The goal remains to optimize respiratory support of the preterm lung while minimizing ventilator-associated lung injury and oxygen toxicity. A multidisciplinary approach involving the medical team and family is quintessential in reaching this goal and involves adequate respiratory support, optimizing nutrition and fluid balance as well as preventing infections.

Patho-mechanisms of the origins of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) continues to be one of the most common complications of prematurity, despite significant advancement in neonatology over the last couple of decades. The new BPD is characterized histopathologically by impaired lung alveolarization and dysregulated vascularization. With the increased survival of extremely preterm infants, the risk for the development of BPD remains high, emphasizing the continued need to understand the patho-mechanisms that play a role in the development of this disease. This brief review summarizes recent advances in our understanding of the maldevelopment of the premature lung, highlighting recent research in pathways of oxidative stress-related lung injury, the role of placental insufficiency, growth factor signaling, the extracellular matrix, and microRNAs.

Use of Propranolol in the Treatment of Chylous Effusions in Infants.

Chylothorax and chyloperitoneum are rare in infants and challenging to definitively diagnose by using current criteria extrapolated from the adult population. They can be of primary or secondary etiologies, including congenital lymphatic malformations and postoperatively, after cardiothoracic or abdominal surgery. Current first-line management consists of bowel rest, parenteral nutrition, and a modified diet of medium-chain triglycerides but can often take weeks to be effective. Off-label use of octreotide has been reported in numerous case studies for the management of chylous effusions. However, there are no definitive neonatal data available regarding dosing, safety, and efficacy; moreover, octreotide has a side effect profile that been linked to serious morbidities, such as pulmonary hypertension and necrotizing enterocolitis. Propranolol, commonly used for the treatment of infantile hemangiomas, is currently gaining interest as a novel therapy for chylous effusions. In this case series review, we describe the use of propranolol in 4 infants with presumed chylous effusions: 1 with congenital pleural effusions and 3 infants who developed postoperative chylothorax and/or chylous ascites. Clinical improvement was noted within a few days of initiating oral propranolol, and the maximum dose used in our cases was 6 mg/kg per day. In previous case reports, researchers describe the use of oral propranolol in infants with chylous effusions, with the dose used ranging from 0.5 to 4 mg/kg per day. However, this is the first case series in which researchers report its use exclusively in infants with chylothorax and chyloperitoneum. Although further research is needed to establish safety and efficacy, our experiences suggest that propranolol could be an acceptable treatment option for chylous effusions in infants.

Effect of 24/7 attending coverage in the neonatal intensive care unit on fellow education.

BACKGROUND: There is a current change in type of attending coverage in the Neonatal Intensive Care Unit (NICU) from home calls to 24/7 in house coverage. Effects of this increased attending physician presence on education of NICU fellows has not been studied. The objective of this study is to evaluate the fellows' perception of in house attending coverage on their education and evaluate its effect on their perceived autonomy. METHODS: A secure, anonymous, web-based survey was designed using RedCap. The web-based survey was sent via the section of Neonatal Perinatal Medicine of the American Academy of Pediatrics, to all members of Training & Early Career Neonatologists. Questions were focused on perception of IH attending coverage on fellows' educational experience including the respondent's perceived ability to make independent decisions (autonomy). Chi-square tests were used to compare responses between groups, with Fisher Exact tests used when the expected cell frequencies were small. RESULTS: One hundred and twenty-three surveys were analyzed, that included responses from 82 fellows & 41 early career neonatologists. 52% reported having 24/7 attending in-house (IH) coverage. Thirty of the 123 respondents experienced a change in model of attending coverage during their training. Among these 30, only 26.6% preferred the model of attending IH coverage. The respondents currently working in IH models, when compared to those in non-IH coverage models felt IH attending coverage was beneficial for fellow education (p < 0.05) but was less likely to give fellows autonomy for decision making (p = 0.02). CONCLUSION: In our survey respondents with in house attending, had a more favorable view of its benefit on fellow education. Institutions practicing or considering IH attending coverage should consider use of adequate measures to balance fellow supervision and education.

Novel biomarkers of bronchopulmonary dysplasia and bronchopulmonary dysplasia-associated pulmonary hypertension.

OBJECTIVE: To quantify and compare levels of potential biomarkers in neonates with (i) Bronchopulmonary dysplasia (BPD); (ii) BPD-associated pulmonary hypertension (BPD-PH); (iii) PH without BPD; and (iv) neonates without lung disease at ~36 weeks postmenstrual age. STUDY DESIGN: Multiple potential biomarkers were measured in plasma samples of 90 patients using a multi-spot enzyme-linked immunosorbent assay. Statistical tests done included one-way ANOVA to compare levels of biomarkers between different groups. RESULTS: Higher levels of ICAM-1 were present in infants with BPD and correlated with its severity. Infants with BPD have significantly higher levels of ANG-2 and lower levels of ANG-1. Infants with PH have higher levels of: IL-6, IL-8, IL-10, and TNF-α. Infants with BPD-PH have significantly lower levels of MCP-1 and higher levels of IL-1ß than infants with PH without BPD. CONCLUSION: ICAM-1 may be used as a specific biomarker for diagnosis of BPD and its severity.

Recent advances in understanding and management of bronchopulmonary dysplasia.

In the current era, the survival of extremely low-birth-weight infants has increased considerably because of new advances in technology; however, these infants often develop chronic dysfunction of the lung, which is called bronchopulmonary dysplasia (BPD). BPD remains an important cause of neonatal mortality and morbidity despite newer and gentler modes of ventilation. BPD results from the exposure of immature lungs to various antenatal and postnatal factors that lead to an impairment in lung development and aberrant growth of lung parenchyma and vasculature. However, we still struggle with a uniform definition for BPD that can help predict various short- and long-term pulmonary outcomes. With new research, our understanding of the pathobiology of this disease has evolved, and many new mechanisms of lung injury and repair are now known. By utilizing the novel 'omic' approaches in BPD, we have now identified various factors in the disease process that may act as novel therapeutic targets in the future. New investigational agents being explored for the management and prevention of BPD include mesenchymal stem cell therapy and insulin-like growth factor 1. Despite this, many questions remain unanswered and require further research to improve the outcomes of premature infants with BPD.

Severe Thrombocytosis in a Newborn with Subcutaneous Fat Necrosis and Maternal Chorioamnionitis.

BACKGROUND: Subcutaneous fat necrosis (SFN) is a form of transient panniculitis that presents commonly in infants with a history of perinatal insult, particularly hypothermia. It is characterized by subcutaneous nodules and plaques that appear over bony prominences on cheeks, shoulders, buttock, and thighs. SFN is usually associated with various complications including hypercalcemia, thrombocytopenia, hypertriglyceridemia, and hyperglycemia. Case Presentation. We present a unique case of a female infant with a history of maternal chorioamnionitis who presented with SFN at 11 days of life with thrombocytosis. The platelet count decreased during the hospital stay, and thrombocytosis resolved over the course of the next two weeks. She did not have any other hematological or metabolic abnormalities associated with SFN. CONCLUSION: Infants with perinatal stress are at increased risk of developing SFN during the first month of life. Infants with a diagnosis of SFN should be monitored closely for various hematological and metabolic abnormalities that can have serious consequences.

Management of Late Preterm and Term Neonates exposed to maternal Chorioamnionitis.

BACKGROUND: Chorioamnionitis is a significant risk factor for early-onset neonatal sepsis. However, empiric antibiotic treatment is unnecessary for most asymptomatic newborns exposed to maternal chorioamnionitis (MC). The purpose of this study is to report the outcomes of asymptomatic neonates ≥35 weeks gestational age (GA) exposed to MC, who were managed without routine antibiotic administration and were clinically monitored while following complete blood cell counts (CBCs). METHODS: A retrospective chart review was performed on neonates with GA ≥ 35 weeks with MC during calendar year 2013. IT ratio (immature: total neutrophils) was considered suspicious if ≥0.3. The data were analyzed using independent sample T-tests. RESULTS: Among the 275 neonates with MC, 36 received antibiotics for possible sepsis. Twenty-one were treated with antibiotics for > 48 h for clinical signs of infection; only one infant had a positive blood culture. All 21 became symptomatic prior to initiating antibiotics. Six showed worsening of IT ratio. Thus empiric antibiotic administration was safely avoided in 87% of neonates with MC. 81.5% of the neonates had follow-up appointments within a few days and at two weeks of age within the hospital system. There were no readmissions for suspected sepsis. CONCLUSIONS: In our patient population, using CBC indices and clinical observation to predict sepsis in neonates with MC appears safe and avoids the unnecessary use of antibiotics.

Newborn Infant With Mothball Toxicity Due to Maternal Ingestion.

Naphthalene poisoning due to exposure to mothballs is a common cause of toxicity in children worldwide. Naphthalene toxicity is known to cause hemolytic anemia, methemoglobinemia, and hepatic and renal injury. Neonates are more susceptible to the effects of oxidative stress from naphthalene because of their low glutathione stores and immaturity of hepatic enzymes. However, there are no reported cases of chronic fetal exposure to naphthalene during pregnancy. We report a novel case of chronic fetal exposure to naphthalene-containing mothballs that occurred from the second trimester through the third trimester of pregnancy. Our patient presented with hyperbilirubinemia, requiring exchange transfusion, severe hemolytic anemia, pulmonary hypertension, respiratory failure, and renal failure and progressed to develop "bronze baby" syndrome. Pregnant mothers should be diligently screened for such exposures and if found should receive psychiatric evaluation and counseling to prevent such devastating effects in neonates.

Sustained Neuromuscular Blockade after Vecuronium Use in a Premature Infant.

Background Prolonged use of neuromuscular blocking agents (NMBAs) is very common in critically ill children both in pediatric and neonatal intensive care units. There are no guidelines available for use of NMBAs in children or neonates in the US, and the data for their safety in this age group is limited. Case Description Our case describes prolonged neuromuscular blockade following concurrent use of a NMBA along with aminoglycosides and steroids in the setting of renal failure in a premature infant. Conclusion Prolonged use of NMBAs in preterm infants should be avoided if possible or should be restricted to the shortest possible duration and the smallest possible physiologically effective dose. Concurrent use of NMBAs with aminoglycoside and steroids should be avoided, especially in the setting of renal failure.