Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD".

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.

The physiology, assessment, and treatment of neonatal pain.

Studies have clearly shown that development of pain receptors starts as early as 20-weeks' gestation. Despite contrary belief, the human fetus develops a similar number of receptive pain fibers as seen in adults. These receptors' maturation is based on response to sensory stimuli received after birth which makes the NICU a critical place for developing central nervous system's pain perception. In practice, the assessment of pain relies mostly on bedside staff. In this review we will discuss the various developing features of pain pathways in the neonatal brain and the modification of pain perception secondary to various interactions immediately after birth. We also discuss the various tools utilized in the NICU for pain assessment that rely on physiological and behavioral patterns. Finally, we address the management of pain in the NICU by either pharmacological or non-pharmacological intervention while highlighting potential benefits, disadvantages, and situations where one may be preferred over another.

IRF7 and UNC93B1 variants in an infant with recurrent herpes simplex virus infection.

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age. An immune workup showed an anergic PBMC cytokine response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IFN-regulatory factor 7 (IRF7) and UNC-93 homolog B1 (UNC93B1). PBMC single-cell RNA-Seq done during childhood revealed decreased expression of several innate immune genes and a repressed TLR3 pathway signature at baseline in several immune cell populations, including CD14 monocytes. Functional studies in fibroblasts and human leukemia monocytic THP1 cells showed that both variants individually suppressed TLR3-driven IRF3 transcriptional activity and the type I IFN response in vitro. Furthermore, fibroblasts expressing the IRF7 and UNC93B1 variants had higher intracellular viral titers with blunting of the type I IFN response upon HSV-1 challenge. This study reports an infant with recurrent HSV-1 disease complicated by encephalitis associated with deleterious variants in the IRF7 and UNC93B1 genes. Our results suggest that TLR3 pathway mutations may predispose neonates to recurrent, severe HSV.

Improving safe sleep practices in an urban inpatient newborn nursery and neonatal intensive care unit.

OBJECTIVE: To improve safe sleep compliance in a newborn nursery (NN) and neonatal intensive care unit (NICU) to >80% in 1 year. STUDY DESIGN: Prospective quality improvement study of infants admitted to a NN and NICU. Interventions were targeted at parent education, staff education, and system processes. RESULTS: Compliance with safe sleep improved to >80% in both units. Tracking of process measures revealed NICU parents received safe sleep education 98-100% of the time. No change was observed in the balancing measures. Transfers from the NN to the NICU for temperature instability did not increase. Parent satisfaction with discharge preparedness did not change (98.2% prior to and 99.6% after). CONCLUSION: We achieved improved compliance with safe sleep practices in our NN and NICU through education of staff and parents and improved system processes. We believe this will translate to improved safe sleep practices used by parents at home.

Outcomes following perinatal palliative care consultation: a retrospective review.

OBJECTIVE: To inform clinical practice by describing a model of perinatal palliative care delivery within a fully staffed fetal health center (FHC) inside a freestanding children's hospital. STUDY DESIGN: The team conducted a retrospective chart review of the palliative care team (PaCT) database from FHC's inception in 2010 to 31 December, 2018, and surveyed the FHC neonatologists. RESULTS: PaCT consults in the FHC increased from 1 in 2010 to 102 in 2018. PaCT met 430 mothers for prenatal consultation. Of the 390 live-born infants, 172 died; 48 received comfort care only from birth; and 19 survived to discharge home with hospice. At the time of review, PaCT still follows 109 children met prenatally. PaCT discharged 96 patients that no longer required PaCT services. CONCLUSIONS: PaCT provides an integral service within the FHC as evidenced by the increasing volume of consultations, variety of care provided and perceived value by FHC neonatologists.