Inhaled nitric oxide use in neonates: Balancing what is evidence-based and what is physiologically sound.

Inhaled nitric oxide is a powerful therapeutic used in neonatology. Its use is evidenced-based for term and near-term infants with persistent pulmonary hypertension; however, it is frequently used off-label both in term and preterm babies. This article reviews the off-label uses of iNO in infants. Rationale is discussed for a selective application of iNO based on physiologically guided principles, and new research avenues are considered.

Preventing Continuous Positive Airway Pressure Failure: Evidence-Based and Physiologically Sound Practices from Delivery Room to the Neonatal Intensive Care Unit.

Routine use of continuous positive airway pressure (CPAP) to support preterm infants with respiratory distress is an evidenced-based strategy to decrease incidence of bronchopulmonary dysplasia. However, rates of CPAP failure remain unacceptably high in very premature neonates, who are at high risk for developing bronchopulmonary dysplasia. Using the GRADE framework to assess the quality of available evidence, this article reviews strategies aimed at decreasing CPAP failure, starting with delivery room interventions and followed through to system-based efforts in the neonatal intensive care unit. Despite best efforts, some very premature neonates fail CPAP. Also reviewed are predictors of CPAP failure in this vulnerable population.

Redistribution of Extracellular Superoxide Dismutase Causes Neonatal Pulmonary Vascular Remodeling and PH but Protects Against Experimental Bronchopulmonary Dysplasia.

BACKGROUND: A naturally occurring single nucleotide polymorphism (SNP), (R213G), in extracellular superoxide dismutase (SOD3), decreases SOD3 matrix binding affinity. Humans and mature mice expressing the R213G SNP exhibit increased cardiovascular disease but decreased lung disease. The impact of this SNP on the neonatal lung at baseline or with injury is unknown. METHODS: Wild type and homozygous R213G mice were injected with intraperitoneal bleomycin or phosphate buffered saline (PBS) three times weekly for three weeks and tissue harvested at 22 days of life. Vascular and alveolar development were evaluated by morphometric analysis and immunostaining of lung sections. Pulmonary hypertension (PH) was assessed by right ventricular hypertrophy (RVH). Lung protein expression for superoxide dismutase (SOD) isoforms, catalase, vascular endothelial growth factor receptor 2 (VEGFR2), endothelial nitric oxide synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GTPCH-1) was evaluated by western blot. SOD activity and SOD3 expression were measured in serum. RESULTS: In R213G mice, SOD3 lung protein expression decreased, serum SOD3 protein expression and SOD serum activity increased compared to wild type (WT) mice. Under control conditions, R213G mice developed pulmonary vascular remodeling (decreased vessel density and increased medial wall thickness) and PH; alveolar development was similar between strains. After bleomycin injury, in contrast to WT, R213G mice were protected from impaired alveolar development and their vascular abnormalities and PH did not worsen. Bleomycin decreased VEGFR2 and GTPCH-1 only in WT mice. CONCLUSION: R213G neonatal mice demonstrate impaired vascular development and PH at baseline without alveolar simplification, yet are protected from bleomycin induced lung injury and worsening of pulmonary vascular remodeling and PH. These results show that vessel bound SOD3 is essential in normal pulmonary vascular development, and increased serum SOD3 expression and SOD activity prevent lung injury in experimental bronchopulmonary dysplasia (BPD) and PH.

Effects of different complementary feeding regimens on iron status and enteric microbiota in breastfed infants.

OBJECTIVE: To compare iron status in breastfed infants randomized to groups receiving complementary feeding regimens that provided iron from fortified infant cereals or meats, and to examine the development of the enteric microbiota in these groups. STUDY DESIGN: Forty-five exclusively breastfed 5-month-old infants were randomized to 1 of 3 feeding groups (FGs)-commercially available pureed meats, iron- and zinc-fortified infant cereals, or iron-only fortified infant cereals-as the first and primary complementary food through 9-10 months of age. Dietary iron was determined by monthly 3-day diet records. Iron status was assessed at the end of the study by measurements of hemoglobin, serum ferritin, and soluble transferrin receptor levels. In a subsample of 14 infants, enteric microbiota were profiled in monthly stool samples (5-9 months) by 16S ribosomal RNA gene pyrosequencing. RESULTS: Infants in the 2 cereal FGs had 2- to 3-fold greater daily iron intakes versus the meat FG (P < .0001). More than one-quarter (27%) of the infants had a low serum ferritin level, and 36% were mildly anemic, with no significant differences by FG; more infants in the meat FG had a high soluble transferrin receptor value (P = .03). Sequence analysis identified differences by time and FG in the abundances of several bacterial groups, including significantly more abundant butyrate-producing Clostridium group XIVa in the meat FG (P = .01) CONCLUSION: A high percentage of healthy infants who were breastfed-only were iron-deficient, and complementary feeding, including iron exposure, influenced the development of the enteric microbiota. If these findings are confirmed, then reconsideration of strategies to both meet infants' iron requirements and optimize the developing microbiome may be warranted.