Congenital continuous retrograde basilar flow suggests type B interrupted aortic arch in a neonate: A case report.

Reversed flow in the basilar artery can be acquired or congenital. Acquired reversed flow in the basilar artery can result from acute thrombosis of the basilar artery or retrograde vertebral artery flow. Congenital continuous retrograde basilar artery flow has not been described. We report a 2-day-old male presenting with hypocalcemic seizures which led us to obtain a Duplex echoencephalogram. An echocardiogram was subsequently ordered. In the coronal plane through the anterior fontanelle, retrograde flow was seen in the basilar artery and the right vertebral artery. In the axial plane through the temporal window, the flow was anteroposterior in both posterior communicating arteries. In the posterior cerebral arteries, the flow was retrograde in the P1 segment and anterograde in the P2 and P3 segments. An interrupted aortic arch was suspected. The echocardiogram showed a large perimembranous ventricular septal defect with bidirectional shunting, a hypoplastic and bicuspid aortic valve, an aortic arch interrupted between the left common carotid artery and the left subclavian artery (type B interrupted aortic arch), and a 5 mm patent ductus arteriosus with predominant right to left flow. Because of the patency of the large patent ductus arteriosus, our patient showed no sign of posterior circulation insufficiency. Prostaglandin E1 therapy was initiated immediately. Diagnosis of DiGeorge syndrome was proven. The infant underwent interrupted aortic arch repair and anterograde flow was established in the basilar artery. We conclude that congenital asymptomatic continuous retrograde flow in the basilar artery and left vertebral artery is a medical emergency as it implies the presence of type B interrupted aortic arch with large patent ductus arteriosus in a neonate.

Intratracheal Instillation of Budesonide-Surfactant for Prevention of Bronchopulmonary Dysplasia in Extremely Premature Infants.

OBJECTIVE: This study aimed to determine the effect of intratracheal instillation of a budesonide-surfactant combination on the incidence of bronchopulmonary dysplasia (BPD) or death compared with surfactant alone in extremely preterm infants. STUDY DESIGN: In this retrospective, single-center study, we included extremely preterm infants (<28 weeks' gestation) who received surfactant for respiratory distress in the first 3 days of life. We compared infants who received budesonide-surfactant combination (intervention group: infants born between February 2016 and October 2021) with surfactant alone (control group: infants born from January 2010 through January 2016). The primary outcome was a composite of BPD grade 2 or 3 (as defined by Jensen et al, 2019) or death before 36 weeks' postmenstrual age (PMA). RESULTS: We included 966 extremely preterm infants (528 in the control group and 438 in the intervention group). While the incidence of death/BPD grade 2 or 3 at 36 weeks of PMA was not different between the two groups (66% in the intervention group vs. 63% in the control group; adjusted relative risk [aRR], 0.99; 95% confidence interval [CI], 0.90-1.07; p-value = 0.69), budesonide was associated with a reduction in the primary outcome only in a subgroup of infants with birth weight ≥ 750 grams (36.8 vs. 43.5%, respectively; aRR 0.75; 95% CI, 0.57-0.98). Primary and secondary outcomes did not differ between the two groups within the subgroup of infants weighing <750 grams. CONCLUSION: In extremely preterm infants, the budesonide-surfactant combination therapy reduced the rates of BPD or death in infants weighing ≥750 grams; however, this beneficial effect was not seen in infants weighing <750 grams. Further investigation of this treatment may be indicated before it is considered a standard approach to management. KEY POINTS: · Intratracheal budesonide-surfactant therapy reduces BPD in preterm infants weighing ≥750 grams.. · Intratracheal budesonide-surfactant therapy does not affect BPD in preterm infants weighing <750 grams.. · Intratracheal budesonide-surfactant therapy does not affect the mortality rate in preterm infants..

Optimizing the hospital discharge process to facilitate family-centered care for well newborns.

BACKGROUND: The perceptions of discharge readiness differ among caregivers and providers. An efficient planning process ensures timely attainment of discharge readiness. Our aim was to increase the percentage of discharge orders placed by 10 a.m. from 0.5% to 10% within 6 months thereby improving discharge readiness. METHODS: We conducted a quality improvement initiative in the newborn nursery between March 2021 and June 2022 (n = 2307). We implemented a physician-led early discharge huddle and standardized the newborn screen (NBS) and circumcision process. RESULTS: By 10 a.m., our primary outcome measure, discharge orders, improved from 0.5 to 19%. Our process measures also increased. NBS specimens collected improved from 56 % to 98 % and circumcision rates increased from 66 to 88%. Balancing measure of postpartum hospital days remained stable. CONCLUSIONS: Optimizing family-centered discharge processes by addressing key drivers is essential and can be achieved without an increase in postpartum hospital days.

A Quality Improvement Bundle to Improve Outcomes in Extremely Preterm Infants in the First Week.

OBJECTIVES: Our objective with this quality improvement initiative was to reduce rates of severe intracranial hemorrhage (ICH) or death in the first week after birth among extremely preterm infants. METHODS: The quality improvement initiative was conducted from April 2014 to September 2020 at the University of Alabama at Birmingham's NICU. All actively treated inborn extremely preterm infants without congenital anomalies from 22 + 0/7 to 27 + 6/7 weeks' gestation with a birth weight ≥400 g were included. The primary outcome was severe ICH or death in the first 7 days after birth. Balancing measures included rates of acute kidney injury and spontaneous intestinal perforation. Outcome and process measure data were analyzed by using p-charts. RESULTS: We studied 820 infants with a mean gestational age of 25 + 3/7 weeks and median birth weight of 744 g. The rate of severe ICH or death in the first week after birth decreased from the baseline rate of 27.4% to 15.0%. The rate of severe ICH decreased from a baseline rate of 16.4% to 10.0%. Special cause variation in the rate of severe ICH or death in the first week after birth was observed corresponding with improvement in carbon dioxide and pH targeting, compliance with delayed cord clamping, and expanded use of indomethacin prophylaxis. CONCLUSIONS: Implementation of a bundle of evidence-based potentially better practices by using specific electronic order sets was associated with a lower rate of severe ICH or death in the first week among extremely preterm infants.

Neonatal Myocardial Ischemia-Reperfusion Injury: A Proposed Pathogenic Sequence in the Context of Maternal/Fetal Vascular Malperfusion and Paradoxical Embolism.

BACKGROUND: Neonatal myocardial infarction (MI) in a structurally normal heart is frequently an obscure event that remains undiagnosed until autopsy. Causal attributions usually cite underlying maternal or fetal conditions. Refinement in understanding of pathogenic mechanisms underlying neonatal MI is key to advancements in diagnosis, prevention, treatments and prognosis. OBJECTIVE: This study presents a 36-week gestational age female with perinatal asphyxia, congenital hemolytic anemia and umbilical vein thrombosis who sustained catastrophic MI with reperfusion injury; and it reviews pertinent literature. RESULTS: We propose a pathogenic sequence that links maternal vascular malperfusion, fetal vascular malperfusion, hemolytic anemia, umbilical venous thrombosis, and paradoxical thromboemboli. CONCLUSION: This case highlights the importance of placental examination in connecting complex neonatal events with adverse maternal/placental conditions. A high index of suspicion is essential for early diagnosis of neonatal MI.

Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD.

Emerging evidence indicates that early life events can increase the risk for developing chronic obstructive pulmonary disease (COPD). Using an inducible transgenic mouse model for NF-κB activation in the airway epithelium, we found that a brief period of inflammation during the saccular stage (P3-P5) but not alveolar stage (P10-P12) of lung development disrupted elastic fiber assembly, resulting in permanent reduction in lung function and development of a COPD-like lung phenotype that progressed through 24 months of age. Neutrophil depletion prevented disruption of elastic fiber assembly and restored normal lung development. Mechanistic studies uncovered a role for neutrophil elastase (NE) in downregulating expression of critical elastic fiber assembly components, particularly fibulin-5 and elastin. Further, purified human NE and NE-containing exosomes from tracheal aspirates of premature infants with lung inflammation downregulated elastin and fibulin-5 expression by saccular-stage mouse lung fibroblasts. Together, our studies define a critical developmental window for assembling the elastin scaffold in the distal lung, which is required to support lung structure and function throughout the lifespan. Although neutrophils play a well-recognized role in COPD development in adults, neutrophilic inflammation may also contribute to early-life predisposition to COPD.

Effects of hyperoxia on alveolar and pulmonary vascular development in germ-free mice.

Airway microbial dysbiosis is associated with subsequent bronchopulmonary dysplasia (BPD) development in very preterm infants. However, the relationship of airway microbiome in normal pulmonary development has not been defined. To better understand the role of the airway microbiome, we compared normal and abnormal alveolar and pulmonary vascular development in mice with or without a microbiome. We hypothesized that the lungs of germ-free (GF) mice would have an exaggerated phenotypic response to hyperoxia compared with non-germ-free (NGF) mice. With the use of a novel gnotobiotic hyperoxia chamber, GF and NGF mice were exposed to either normoxia or hyperoxia. Alveolar morphometry, pulmonary mechanics, echocardiograms, inflammatory markers, and measures of pulmonary hypertension were studied. GF and NGF mice in normoxia showed no difference, whereas GF mice in hyperoxia showed protected lung structure and mechanics and decreased markers of inflammation compared with NGF mice. We speculate that an increase in abundance of pathogenic bacteria in NGF mice may play a role in BPD pathogenesis by regulating the proinflammatory signaling and neutrophilic inflammation in lungs. Manipulation of the airway microbiome may be a potential therapeutic intervention in BPD and other lung diseases.

Early-Onset Neonatal Sepsis with Extended Spectrum Beta-Lactamase Producing Escherichia Coli in Infants Born to South and South East Asian Immigrants: A Case Series.

Extended-spectrum ß -lactamase (ESBL)-producing Enterobacteriaceae represent a major worldwide threat. We present three cases of early onset ESBL Escherichia coli sepsis in infants born to families from South and Southeast Asia to inform the practitioner community about this emerging threat. Infants with suspected sepsis, whose mother is from Asia or Southeast Asia, should be suspected of having an infection with an ESBL-producing organism, and practitioners should strongly consider adding a carbapenem to their usual initial antibiotic regimen.

Early airway microbial metagenomic and metabolomic signatures are associated with development of severe bronchopulmonary dysplasia.

The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We previously identified differences in the airway microbiome at birth between preterm infants who were BPD predisposed versus those who were BPD resistant. In this study, we attempted to identify mechanisms by which the airway microbiome could modify the risk for BPD. We used a software-based method to predict the metagenome of the tracheal aspirate (TA) microbiome from 16S rRNA sequencing data in preterm infants and to identify functional ortholog genes that were differentially abundant in BPD-predisposed and BPD-resistant infants. We also identified metabolites that were differentially enriched in these samples by use of untargeted mass spectrometry and mummichog to identify the metabolic pathways involved. Microbial metagenome analysis identified specific pathways that were less abundant in the functional metagenome of the microbiota of BPD-predisposed infants compared with BPD-resistant infants. The airway metabolome of BPD-predisposed infants was enriched for metabolites involved in fatty acid activation and androgen and estrogen biosynthesis compared with BPD-resistant infants. These findings suggest that in extremely preterm infants the early airway microbiome may alter the metabolome, thereby modifying the risk of BPD. The differential enrichment of sex steroid metabolic pathways supports previous studies suggesting a role for sexual dimorphism in BPD risk. This study also suggests a role for metabolomic and metagenomic profiles to serve as early biomarkers of BPD risk.

Exosomal microRNA predicts and protects against severe bronchopulmonary dysplasia in extremely premature infants.

Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls. Similarly, bronchoalveolar lavage fluid from hyperoxia-exposed mice (an animal model of BPD) and supernatants from hyperoxia-exposed human bronchial epithelial cells (in vitro model of BPD) had increased exosomes compared with air controls. Next, in a prospective cohort study of tracheal aspirates obtained at birth from extremely preterm infants, utilizing independent discovery and validation cohorts, we identified unbiased exosomal miRNA signatures predictive of severe BPD. The strongest signal of reduced miR-876-3p in BPD-susceptible compared with BPD-resistant infants was confirmed in the animal model and in vitro models of BPD. In addition, based on our recent discovery of increased Proteobacteria in the airway microbiome being associated with BPD, we developed potentially novel in vivo and in vitro models for BPD combining Proteobacterial LPS and hyperoxia exposure. Addition of LPS led to a larger reduction in exosomal miR 876-3p in both hyperoxia and normoxia compared with hyperoxia alone, thus indicating a potential mechanism by which alterations in microbiota can suppress miR 876-3p. Gain of function of miR 876-3p improved the alveolar architecture in the in vivo BPD model, demonstrating a causal link between miR 876-3p and BPD. In summary, we provide evidence for the strong predictive biomarker potential of miR 876-3p in severe BPD. We also provide insights on the pathogenesis of neonatal lung disease, as modulated by hyperoxia and microbial product-induced changes in exosomal miRNA 876-3p, which could be targeted for future therapeutic development.

Nonsurgical Management of Persistent and Hemodynamically Significant Patent Ductus Arteriosus among Extremely Low Birth Weight Infants: A Propensity Score Matched Analysis.

OBJECTIVE: The objective of this study was to evaluate the impact of a nonsurgical approach (with the incorporation of late postnatal hydrocortisone treatment to facilitate extubation) in comparison to the surgical approach for the management of persistent hemodynamically significant patent ductus arteriosus (hsPDA) among chronically ventilator-dependent extremely low birth weight (ELBW) infants. METHODS: In this retrospective study, ELBW infants with a diagnosis of hsPDA (diagnosed based on the echocardiographic criteria and chronic ventilator dependence) that were persistent beyond 14 days of postnatal age despite adequate medical treatment were included. RESULTS: Out of 127 infants (surgical approach group, n = 67 and nonsurgical approach group, n = 60), 72 infants were matched based on the propensity scores. In the matched cohort, in comparison to infants managed with the surgical approach (control group, n = 36), infants in the nonsurgical approach group (treatment group, n = 36) had a lower rate of surgical ligation (14 vs. 100%, p = < 0.001), but there were no differences in both primary outcome (death or bronchopulmonary dysplasia) and secondary outcome measures. CONCLUSION: For chronically ventilator-dependent ELBW infants with persistent hsPDA, a nonsurgical management approach is associated with a reduced rate of surgical ligation of PDA, but not associated with increased risk of adverse major short-term neonatal outcomes.

Is there a need for "triple therapy"? Role of anticoagulation with dual antiplatelet therapy in acute coronary syndromes (ATLAS Study & TRAP Study).

In the past two decades there has been a succession of advances in the development of anticoagulant and antiplatelet therapies to be used in the treatment of ACS. Despite optimal dual antiplatelet therapy, nearly 10-12 % of patients still face a risk of death or myocardial infarction one year following PCI. This large residual risk provides the impetus for the development of more effective strategies. Dual pathway regimens that combine antiplatelets (aspirin and a thienopyridine), along with an anticoagulant such as rivaroxaban may prove to be a therapeutic option in patients with ACS.