Faculty Bibliography

OBJECTIVE: There are limited published data on the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from mothers to newborns through breastfeeding or from breast milk. The World Health Organization released guidelines encouraging mothers with suspected or confirmed COVID-19 to breastfeed as the benefits of breastfeeding outweighs the possible risk of transmission. The objective of this study was to determine if SARS-CoV-2 was present in the breast milk of lactating mothers who had a positive SARS-CoV-2 nasopharyngeal swab test prior to delivery, and the clinical outcomes for their newborns. STUDY DESIGN/METHODS:by two-step reverse transcription polymerase chain reaction. Additionally, the clinical characteristics of the maternal newborn dyad, results of nasopharyngeal SARS-CoV-2 testing, and neonatal follow-up data were collected. RESULTS: A total of 19 mothers were included in the study and their infants who were all fed breast milk. Breast milk samples from 18 mothers tested negative for SARS-CoV-2, and 1 was positive for SARS-CoV-2 RNA. The infant who ingested the breast milk that tested positive had a negative nasopharyngeal test for SARS-CoV-2, and had a benign clinical course. There was no evidence of significant clinical infection during the hospital stay or from outpatient neonatal follow-up data for all the infants included in this study. CONCLUSION/CONCLUSIONS: In a small cohort of SARS-CoV-2 positive lactating mothers giving birth at our institution, most of their breast milk samples (95%) contained no detectable virus, and there was no evidence of COVID-19 infection in their breast milk-fed neonates. KEY POINTS/CONCLUSIONS:· Breast milk may rarely contain detectable SARS-CoV-2 RNA and was not detected in asymptomatic mothers.. · Breast milk with detectable SARS-CoV-2 RNA from a symptomatic mother had no clinical significance for her infant.. · Breast feeding with appropriate infection control instructions appears to be safe in mother with COVID infection..

BACKGROUND:Pregnancy represents a unique challenge for the maternal-fetal immune interface, requiring a balance between immunosuppression, which is essential for the maintenance of a semi-allogeneic fetus, and pro-inflammatory host defense to protect the maternal-fetal interface from invading organisms. Adaptation to repeated inflammatory stimuli (endotoxin tolerance) may be critical in preventing inflammation-induced preterm birth resulting from exaggerated maternal inflammatory responses to mild/moderate infections that are common during pregnancy. However, the exact mechanisms contributing to the maintenance of tolerance to repeated infections are not completely understood. miRNAs play important roles in pregnancy, with several miRNAs implicated in gestational tissue function, as well as in pathologic pregnancy conditions. miRNA-519c, a member of the C19MC cluster, is a human-specific miRNA mainly expressed in the placenta. However, its role in pregnancy is largely unknown. OBJECTIVES/OBJECTIVE:To explore the role of "endotoxin tolerance" failure in the pathogenesis of an exaggerated inflammatory response often seen in inflammation-mediated preterm birth. In this study, we investigated the role of miRNA-519c, a placenta-specific miRNA, as a key regulator of endotoxin tolerance at the maternal-fetal interface. STUDY DESIGN/METHODS:-trimester placentas were treated with LPS. After 24 hours, the conditioned media was collected for analysis, and the placental explants were re-exposed to repeated doses of LPS for 3 days. The supernatant was analyzed for inflammatory markers, presence of extracellular vesicles (EVs) and microRNAs. To study the possible mechanism of action of the microRNAs, we evaluated the phosphodiesterase 3 B (PDE3B) pathway involved in TNF-α production using a miRNAs mimic and PDE3B siRNA transfection. Finally, we analyzed human placental samples from different gestational ages and from women affected by inflammation-associated pregnancies. RESULTS:Our data showed that repeated exposure of the human placenta to endotoxin challenges induced a tolerant phenotype characterized by decreased TNF-α and upregulated IL-10 levels. This reaction was mediated by the placenta-specific miRNA-519c packaged within placental EVs. LPS treatment increased the EVs that were positive for the exosome tetraspanin markers, namely CD9, CD63, and CD81, and secreted primarily by trophoblasts. Primary human trophoblast cells transfected with miR-519c mimic decreased PDE3B. While lack of PDE3B, achieved by siRNA transfection, resulted in a decreased TNF-α production. These data supported the hypothesis that the anti-inflammatory action of miRNA-519c was mediated by a downregulation of the phosphodiesterase 3 B pathway, leading to inhibition of TNF-α production. Furthermore, human placentas from normal and inflammation-associated pregnancies demonstrated that decreased placental miRNA-519c level was linked to infection-induced inflammatory pathologies during pregnancy. CONCLUSION/CONCLUSIONS:We identified miRNA-519c, a human placenta-specific miRNA, as a novel regulator of immune adaptation associated with infection-induced preterm birth at the maternal-fetal interface. Our study can serve as a basis for future experiments to explore the potential use of miRNA-519c as a biomarker for infection-induced preterm birth.

Clinical studies in preterm neonates are rarely performed due to ethical concerns and difficulties associated with trials and recruitment. Consequently, dose selection in this population is primarily empirical. Scaling neonatal doses from adult doses does not account for developmental changes and may not accurately predict drug kinetics. This is especially important for gentamicin, a narrow therapeutic index aminoglycoside antibiotic. While gentamicin's bactericidal effect is associated with its peak plasma concentration, keeping trough concentrations below 1 μg/mL prevents toxicity and also helps counteracting adaptive resistance in bacteria such as Escherichia coli. In this study, physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) modeling was used to support and/or guide dosing decisions, and to predict the antibacterial effect in preterm neonates. A gentamicin PBPK model was successfully verified in healthy adults and preterm neonates across all gestational ages. Clinical data from a neonatal intensive care unit at NYU Langone Long Island hospital was used to identify dosing regimens associated with increased incidence of elevated gentamicin trough concentrations in different preterm patient cohorts. Model predictions demonstrated that a higher dose with an extended-dosing interval (Q36h) in neonates with a postmenstrual age of 30-34 weeks and ≥ 35 weeks, with postnatal age 8-28 days and 0-7 days, respectively, were more likely to have a trough < 1 μg/mL when compared with once-daily (Q24h) dosing. PBPK-PD modeling suggested that a higher dose administered Q36h may provide effective antibacterial therapy. This article is protected by copyright. All rights reserved.

BACKGROUND:Baby-Friendly hospitals encourage rooming-in newborns with mothers. In our institution, we noticed increased incidence of hypothermia following Baby-Friendly designation. We aimed to reduce the incidence of hypothermia in the mother-baby-unit to <15% and to decrease the rate of isolated hypothermia admissions to the neonatal intensive care unit (NICU) by 20% over two years. METHODS:After a retrospective review of newborns ≥35 weeks gestation in the mother-baby-unit with hypothermia, we implemented multiple interventions such as nursing education, hypothermia algorithm, Kamishibai cards, and Key cards. RESULTS:Hypothermia incidence in the mother-baby-unit decreased from 20.9 to 14.5% (p < 0.001) and infants requiring NICU admission decreased by 71% (p < 0.001) following all interventions. Apart from nursing education, all interventions led to significant reductions in both outcomes from baseline. CONCLUSION/CONCLUSIONS:Instituting a hypothermia algorithm and utilizing K-cards and Key cards reduces the incidence of hypothermia in the mother-baby-unit and NICU admissions for isolated hypothermia.

Premature infants are at high risk for heat loss. Infants undergoing surgical procedures outside of the neonatal intensive care unit have an increased risk of hypothermia. Hypothermia can lead to delayed recovery, hypoglycemia, metabolic acidosis, sepsis, and emotional stress for the parents. We aimed to reduce the incidence of hypothermia for infants undergoing surgical procedures from a baseline of 44.4% to less than 25% over 3 years (2016-2018) with the utilization of a checklist and education.

Introduction: The assessment of dysphagia in preterm infants has been limited to clinical bedside evaluation followed by videofluoroscopic swallow study (VFSS) in selected patients. Recently, fiberoptic endoscopic evaluation of swallowing (FEES) is being described more in literature for preterm infants. However, it is unclear if one test has a better diagnostic utility than the other in this population. Furthermore, it is also unclear if performing FEES and VFSS simultaneously will increase the sensitivity and specificity of detecting dysphagia compared to either test performed independently. Objectives: The primary objective of this study is to evaluate the feasibility of performing VFSS and FEES simultaneously in preterm infants. Our secondary objective is to determine whether simultaneously performed VFSS-FEES improves the diagnostic ability in detecting dysphagia in preterm infants compared to either test done separately. Methods: In this pilot study, we describe the process involved in performing simultaneous VFSS-FEES in five preterm infants (postmenstrual age ≥36 weeks) with dysphagia. A total of 26 linked VFSS-FEES swallows were analyzed, where the same bolus during the same swallow was compared using simultaneous fluoroscopy and endoscopy. The sensitivity and specificity of detecting penetration and aspiration were evaluated in simultaneous VFSS-FEES compared with each test done independently. Results: Our results demonstrated that performing simultaneous VFSS-FEES is feasible in preterm infants with dysphagia. All patients tolerated the procedures well without any complications. Our pilot study in these five symptomatic preterm infants demonstrated a low incidence of aspiration but a high incidence of penetration. Simultaneous VFSS-FEES (26 linked swallows) improved the ability to detect penetration compared to each test done separately. Conclusion: To our knowledge, this study is the first to demonstrate the feasibility of performing VFSS and FEES simultaneously in symptomatic preterm infants with dysphagia resulting in potentially higher diagnostic yield than either procedure done separately.

OBJECTIVE:To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. STUDY DESIGN/METHODS: × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. RESULTS:and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected. CONCLUSIONS:Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov: NCT02452476.