Laryngeal mask ventilation with chest compression during neonatal resuscitation: randomized, non-inferiority trial in lambs.

BACKGROUND: Effective positive-pressure ventilation is a critical factor in newborn resuscitation. Neonatal endotracheal intubation (ETT) needs considerable training and experience, which poses a human factor challenge. Laryngeal mask airway (LMA) ventilation can be a secure and viable alternative during the initial stages of newborn resuscitation. However, there is limited evidence for its use during chest compression (CC). METHODS: Seventeen lambs were randomized into LMA or ETT ventilation post cord occlusion induced cardiac arrest. After 5 min of cardiac arrest, resuscitation was initiated as per NRP recommendations. Ventilation, oxygenation, systemic and pulmonary hemodynamic parameters were recorded till the return of spontaneous circulation (ROSC) or 20 min. RESULTS: Baseline characteristics were similar between the groups. The incidence of ROSC was 75% (6/8) in the LMA group and 56% (5/9) in the ETT group (p = 0.74). The median (IQR) time to achieve ROSC was 6.85 min (6 min-9.1 min) in the LMA group and 7.50 min (5.33 min-18 min) in the ETT group (p = 0.65). CONCLUSION: LMA ventilation during CC is feasible and non-inferior to ETT in this model. IMPACT: Laryngeal mask airway (LMA) ventilation with chest compression is feasible and non-inferior to endotracheal tube ventilation in this experimental near-term lamb model of asphyxial cardiac arrest. First translational study to evaluate the use of LMA as an airway device with chest compression. Evidence primer for clinical studies to evaluate and confirm the feasibility and efficacy of LMA ventilation with chest compression are necessary before randomized clinical trials in neonates. LMA use in neonatal cardiopulmonary resusciation (CPR) could have the potential to optimize advanced resuscitation, especially in resource-limited healthcare settings.

Placental transfusion during neonatal resuscitation in an asphyxiated preterm model.

BACKGROUND: Neonatal Resuscitation Program does not recommend placental transfusion in depressed preterm neonates. METHODS: Our objectives were to study the effect of delayed cord clamping (DCC) with ventilation for 5 min (DCCV, n-5), umbilical cord milking (UCM) without ventilation (n-6), UCM with ventilation (UCMV, n-6), early cord clamping followed by ventilation (ECCV, n-6) on red cell volume (RCV), and hemodynamic changes in asphyxiated preterm lambs. Twenty-three preterm lambs at 127-128 days gestation were randomized to DCCV, UCM, UCMV, and ECCV. We defined asphyxia as heart rate <100/min. RESULTS: The UCMV had the highest neonatal RCV as a percentage of fetoplacental volume compared to the other groups (UCMV 85.5 ± 10%, UCM 72 ± 10%, ECCV 65 ± 14%, DCCV 61 ± 10%, p < 0.01). The DCCV led to better ventilation (66 ± 1 mmHg) and higher pulmonary blood flow (75 ± 24 ml/kg/min). The carotid flow was significantly higher in UCM without ventilation. The fluctuations in carotid flow with milking were 25 ± 6% higher from baseline during UCM, compared to 6 ± 3% in UCMV (p < 0.01). CONCLUSIONS: Cord milking with ventilation led to higher RCV than other interventions. Ventilation during cord milking reduced fluctuation in carotid flow compared to UCM alone. DCCV led to better ventilation and pulmonary blood flow but did not increase RCV. IMPACT: The best practice of placental transfusion in a depressed preterm neonate remains unknown. Ventilation with an intact cord improves gas exchange and hemodynamics in an asphyxiated preterm model. Cord milking without ventilation led to lower red cell volume but higher carotid blood flow fluctuations compared to milking with ventilation. Our data can be translated to bedside and could impact preterm resuscitation.

Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension.

Optimal oxygen saturation as measured by pulse oximetry (SpO2) in neonatal lung injury, such as meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of newborn (PPHN), is not known. Our goal was to determine the SpO2 range in lambs with MAS and PPHN that results in the highest brain oxygen delivery (bDO2) and pulmonary blood flow (Qp) and the lowest pulmonary vascular resistance and oxidative stress. Meconium was instilled into endotracheal tubes in 25 near-term gestation lambs, and the umbilical cord was occluded to induce asphyxia and gasping, causing MAS and PPHN. Lambs were randomized into four groups and ventilated for 6 hours with fixed fraction of inspired oxygen (FiO2) = 1.0 irrespective of SpO2, and three groups had FiO2 titrated to keep preductal SpO2 between 85% and 89%, 90% and 94%, and 95% and 99%, respectively. Tissues were collected to measure nitric oxide synthase activity, 3-nitrotyrosine, and 8-isoprostanes. Throughout the 6-hour exposure period, lambs in the 95-99% SpO2 target group had the highest Qp, lowest pulmonary vascular resistance, and highest bDO2 but were exposed to higher FiO2 (0.5 ± 0.21 vs. 0.29 ± 0.17) with higher lung 3-nitrotyrosine (0.67 [interquartile range (IQR), 0.43-0.73] ng/mcg protein vs. 0.1 [IQR, 0.09-0.2] ng/mcg protein) and lower lung nitric oxide synthase activity (196 [IQR, 192-201] mMol nitrite/mg protein vs. 270 [IQR, 227-280] mMol nitrite/mg protein) compared with the 90-94% target group. Brain 3-nitrotyrosine was lower in the 85-89% target group, and brain/lung 8-isoprostane levels were not significantly different. In term lambs with MAS and PPHN, Qp and bDO2 through the first 6 hours are higher with target SpO2 in the 95-99% range. However, the 90-94% target range is associated with significantly lower FiO2 and lung oxidative stress. Clinical trials comparing the 90-94% versus the 95-99% SpO2 target range in term infants with PPHN are warranted.

Antibiotic Treatments and Patient Outcomes in Necrotizing Enterocolitis.

OBJECTIVE: This study aimed to examine the impact of different antibiotic treatments on necrotizing enterocolitis (NEC) outcomes. STUDY DESIGN: Patient outcomes, including total parenteral nutrition and hospitalization durations, abdominal surgeries, intestinal strictures, and mortality data, were analyzed and compared by various antibiotic groups and treatment durations for 160 NEC patients managed at the Women and Children's Hospital of Buffalo between 2008 and 2016. RESULTS: Fourteen different antibiotics were used for NEC, most commonly ampicillin, gentamicin, and metronidazole (AGM). Medical (vs. surgical) NEC patients more likely received AGM (37 vs. 6%, p < 0.001). Surgical (vs. medical) NEC patients more likely received vancomycin (80 vs. 30%, p < 0.001) and antipseudomonal agents (69 vs. 15%, p < 0.001). For medical NEC there were no outcome differences between patients receiving only AGM versus those receiving other treatments; in patients receiving AGM, there were no outcome differences in durations of ≤10 days versus longer courses. CONCLUSION: Antibiotic use for NEC varies substantially without definite outcome differences. Particularly with medical NEC, AGM for ≤10 days had comparable outcomes to other treatments. In light of growing concern for short and longer term adverse effects with early-life antibiotic exposure, narrow-spectrum and shorter course NEC treatment may be preferred.

Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model.

BACKGROUND: The Neonatal Resuscitation Program recommends initial resuscitation of preterm infants with low oxygen (O2) followed by titration to target preductal saturations (SpO2). We studied the effect of resuscitation with titrated O2 on gas exchange, pulmonary, and systemic hemodynamics. METHODOLOGY: Twenty-nine preterm lambs (127 d gestation) were randomized to resuscitation with 21% O2 (n = 7), 100% O2 (n = 6), or initiation at 21% and titrated to target SpO2 (n = 16). Seven healthy term control lambs were ventilated with 21% O2. RESULTS: Preductal SpO2 achieved by titrating O2 was within the desired range similar to term lambs in 21% O2. Resuscitation of preterm lambs with 21% and 100% O2 resulted in SpO2 below and above the target, respectively. Ventilation of preterm lambs with 100% O2 and term lambs with 21% O2 effectively decreased pulmonary vascular resistance (PVR). In contrast, preterm lambs with 21% O2 and titrated O2 demonstrated significantly higher PVR than term lambs on 21% O2. CONCLUSION(S): Initial resuscitation with 21% O2 followed by titration of O2 led to suboptimal pulmonary vascular transition at birth in preterm lambs. Ventilation with 100% O2 in preterm lambs caused hyperoxia but reduced PVR similar to term lambs on 21% O2. Studies evaluating the initiation of resuscitation at a higher O2 concentration followed by titration based on SpO2 in preterm neonates are needed.

Continuous capnography monitoring during resuscitation in a transitional large mammalian model of asphyxial cardiac arrest.

BACKGROUND: In neonates requiring chest compression (CC) during resuscitation, neonatal resuscitation program (NRP) recommends against relying on a single feedback device such as end-tidal carbon dioxide (ETCO2) or saturations (SpO2) to determine return of spontaneous circulation (ROSC) until more evidence becomes available. METHODS: We evaluated the role of monitoring ETCO2 during resuscitation in a lamb model of cardiac arrest induced by umbilical cord occlusion (n = 21). Lambs were resuscitated as per NRP guidelines. Systolic blood pressure (SBP), carotid and pulmonary blood flows along with ETCO2 and blood gases were continuously monitored. Resuscitation was continued for 20 min or until ROSC (whichever was earlier). Adequate CC was arbitrarily defined as generation of 30 mmHg SBP during resuscitation. ETCO2 thresholds to predict adequacy of CC and detect ROSC were determined. RESULTS: Significant relationship between ETCO2 and adequate CC was noted during resuscitation (AUC-0.735, P < 0.01). At ROSC (n = 12), ETCO2 rapidly increased to 57 ± 20 mmHg with a threshold of ≥32 mmHg being 100% sensitive and 97% specific to predict ROSC. CONCLUSION: In a large mammalian model of perinatal asphyxia, continuous ETCO2 monitoring predicted adequacy of CC and detected ROSC. These findings suggest ETCO2 in conjunction with other devices may be beneficial during CC and predict ROSC.

Continuous Chest Compressions During Sustained Inflations in a Perinatal Asphyxial Cardiac Arrest Lamb Model.

OBJECTIVE: Continuous chest compressions are more effective during resuscitation in adults. Sustained inflation rapidly establishes functional residual capacity in fluid-filled lungs at birth. We sought to compare the hemodynamics and success in achieving return of spontaneous circulation in an asphyxial cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs between subjects receiving continuous chest compressions during sustained inflation and those receiving conventional 3:1 compression-to-ventilation resuscitation. DESIGN: Prospective, randomized, animal model study. SETTING: An experimental laboratory. SUBJECTS: Fourteen newborn term gestation lambs. INTERVENTIONS: Lambs were randomized into two groups: 3:1 compression-to-ventilation (control) and continuous chest compressions during sustained inflation. The umbilical cord was occluded to induce asphyxia and asystole. The control group was resuscitated per NRP guidelines. In the sustained inflation + continuous chest compressions group, sustained inflation at 35 cm H2O was provided for 30 seconds with 1-second interruptions before another sustained inflation was provided. One hundred twenty chest compressions/min started after the initial sustained inflation. The first dose of IV epinephrine was given at 6 minutes if return of spontaneous circulation was not achieved and then every 3 minutes until return of spontaneous circulation or for a total of four doses. MEASUREMENT AND RESULTS: All lambs achieved return of spontaneous circulation in a comparable median time (interquartile range) of 390 seconds (225-405 s) and 345 seconds (204-465 s) in the sustained inflation + continuous chest compressions and control groups, respectively. Four of seven (sustained inflation + continuous chest compressions) and three of six (control) lambs required epinephrine to achieve return of spontaneous circulation. Diastolic blood pressures were lower in the sustained inflation + continuous chest compressions (4 ± 2 mm Hg) compared to the control group (7 ± 2 mm Hg), p < 0.05. PaCO2, PaO2, and lactate were similar between the groups during the study period. CONCLUSION: In this perinatal cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs, sustained inflation + continuous chest compressions is as effective as 3:1 compression-to-ventilation resuscitation in achieving return of spontaneous circulation. Half the lambs achieved return of spontaneous circulation without epinephrine. continuous chest compressions during sustained inflation reduced diastolic pressures but did not alter gas exchange or carotid blood flow compared to 3:1 compression-to-ventilation resuscitation.

Fetal and postnatal ovine mesenteric vascular reactivity.

BACKGROUND: Intestinal circulation and mesenteric arterial (MA) reactivity may play a role in preparing the fetus for enteral nutrition. We hypothesized that MA vasoreactivity changes with gestation and vasodilator pathways predominate in the postnatal period. METHODS: Small distal MA rings (0.5-mm diameter) were isolated from fetal (116-d, 128-d, 134-d, and 141-d gestation, term ~ 147 d) and postnatal lambs. Vasoreactivity was evaluated using vasoconstrictors (norepinephrine (NE) after pretreatment with propranolol and endothelin-1(ET-1)) and vasodilators (NO donors A23187 and s-nitrosopenicillamine (SNAP)). Protein and mRNA assays for receptors and enzymes (endothelin receptor A, alpha-adrenergic receptor 1A (ADRA1A), endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase5 (PDE5)) were performed in mesenteric arteries. RESULTS: MA constriction to NE and ET-1 peaked at 134 d. Relaxation to A23187 and SNAP was maximal after birth. Basal eNOS activity was low at 134 d. ADRA1A mRNA and protein increased significantly at 134 d and decreased postnatally. sGC and PDE5 protein increased from 134 to 141 d. CONCLUSION: Mesenteric vasoconstriction predominates in late-preterm gestation (134 d; the postconceptional age with the highest incidence of necrotizing enterocolitis (NEC)) followed by a conversion to vasodilatory influences near the time of full-term birth. Perturbations in this ontogenic mechanism, including preterm birth, may be a risk factor for NEC.

Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration.

BACKGROUND: The Neonatal Resuscitation Program (NRP) recommends upper and lower limits of preductal saturations (SpO2) extrapolated from studies in infants resuscitated in room air. These limits have not been validated in asphyxia and lung disease. METHODS: Seven control term lambs delivered by cesarean section were ventilated with 21% O2. Thirty lambs with asphyxia with meconium aspiration were randomly assigned to resuscitation with 21% O2 (n = 6), 100% O2 (n = 6), or initiation with 21% O2 followed by variable FIO2 to maintain NRP target SpO2 ranges (n = 18). Hemodynamic and ventilation parameters were recorded for 15 min. RESULTS: Control lambs maintained preductal SpO2 near the lower limit of NRP target range. Asphyxiated lambs had low SpO2 (38 ± 2%), low arterial pH (6.99 ± 0.01), and high PaCO2 (96 ± 7 mm Hg) at birth. Resuscitation with 21% O2 resulted in SpO2 values below the target range with low pulmonary blood flow (Qp) compared to variable FIO2 group. The increase in PaO2 and Qp with variable FIO2 resuscitation was similar to control lambs. CONCLUSION: Maintaining SpO2 as recommended by NRP by actively adjusting inspired O2 leads to effective oxygenation and higher Qp in asphyxiated lambs with lung disease. Our findings support the current NRP SpO2 guidelines for O2 supplementation during resuscitation of an asphyxiated neonate.

Tracheal suctioning improves gas exchange but not hemodynamics in asphyxiated lambs with meconium aspiration.

BACKGROUND: Current neonatal resuscitation guidelines recommend tracheal suctioning of nonvigorous neonates born through meconium-stained amniotic fluid. METHODS: We evaluated the effect of tracheal suctioning at birth in 29 lambs with asphyxia induced by cord occlusion and meconium aspiration during gasping. RESULTS: Tracheal suctioning at birth (n = 15) decreased amount of meconium in distal airways (53 ± 29 particles/mm(2) lung area) compared to no suction (499 ± 109 particles/mm(2); n = 14; P < 0.001). Three lambs in the suction group had cardiac arrest during suctioning, requiring chest compressions and epinephrine. Onset of ventilation was delayed in the suction group (146 ± 11 vs. 47 ± 3 s in no-suction group; P = 0.005). There was no difference in pulmonary blood flow, carotid blood flow, and pulmonary or systemic blood pressure between the two groups. Left atrial pressure was significantly higher in the suction group. Tracheal suctioning resulted in higher Pao2/FiO2 levels (122 ± 21 vs. 78 ± 10 mm Hg) and ventilator efficiency index (0.3 ± 0.05 vs.0.16 ± 0.03). Two lambs in the no-suction group required inhaled nitric oxide. Lung 3-nitrotyrosine levels were higher in the suction group (0.65 ± 0.03 ng/µg protein) compared with the no-suction group (0.47 ± 0.06). CONCLUSION: Tracheal suctioning improves oxygenation and ventilation. Suctioning does not improve pulmonary/systemic hemodynamics or oxidative stress in an ovine model of acute meconium aspiration with asphyxia.

Packed red cell transfusions alter mesenteric arterial reactivity and nitric oxide pathway in preterm lambs.

BACKGROUND: Cases of necrotizing enterocolitis occurring within 48 h of packed red blood cell (PRBC) transfusions are increasingly being described in observational studies. Transfusion-associated gut injury is speculated to result from an abnormal mesenteric vascular response to transfusion. However, the mechanism of disruption of the balance between mesenteric vasoconstriction and relaxation following transfusion is not known. METHODS: Preterm lambs (n = 16, 134 d gestation; term: 145-147 d) were delivered and ventilated for 24 h. All the lambs received orogastric feeds with colostrum. In addition, 10 of these lambs received PRBC transfusions. Vasoreactivity was evaluated in isolated mesenteric arterial rings using norepinephrine and endothelin-1 as vasoconstrictors. Endothelium-dependent (A23187, a calcium ionophore) and endothelium-independent (SNAP) nitric oxide (NO) donors were used as vasorelaxants. Mesenteric arterial endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase 5 (PDE5) mRNA analyses and protein assays were performed. RESULTS: Transfusion with PRBC significantly increased mesenteric vasoconstriction to norepinephrine and endothelin-1 and impaired relaxation to A23187 and SNAP. Mesenteric arterial eNOS protein decreased following PRBC transfusion. No significant changes were noted in sGC and PDE5 mRNA or protein assays. CONCLUSION: PRBC transfusion in enterally fed preterm lambs promotes mesenteric vasoconstriction and impairs vasorelaxation by reducing mesenteric arterial eNOS.

Viral Infections and Neonatal Necrotizing Enterocolitis: A Meta-analysis.

CONTEXT: Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting preterm infants. Studies implicate viral infections in etiopathogenesis. OBJECTIVE: To summarize the association of viral infections with NEC by systematic review and meta-analysis. DATA SOURCES: We searched Ovid-Medline, Embase, Web of Science, and Cochrane databases in November 2022. STUDY SELECTION: We included observational studies that examined the association between viral infections and NEC in newborn infants. DATA EXTRACTION: We extracted data regarding the methodology, participant characteristics, and outcome measures. RESULTS: We included 29 and 24 studies in the qualitative review and meta-analysis, respectively. The meta-analysis demonstrated a significant association between viral infections and NEC (odds ratio [OR], 3.81, 95% confidence interval: 1.99-7.30, 24 studies). The association remained significant after excluding the outliers (OR, 2.89 [1.56-5.36], 22 studies) and studies with poor methodology (OR, 3.33 [1.73-6.43], 22 studies). In subgroup analysis based on participants' birth weight, studies including very low birth weight infants only (OR, 3.62 [1.63-8.03], 8 studies) and non-very low birth weight infants only (OR, 5.28 [1.69-16.54], 6 studies) showed a significant association. In subgroup analysis based on specific viruses, infection with rotavirus (OR, 3.96 [1.12-13.95], 10 studies), cytomegalovirus (OR, 3.50 [1.60-7.65], 5 studies), norovirus (OR, 11.95 [2.05-69.84], 2 studies), and astrovirus (OR, 6.32 [2.49-16.02], 2 studies) was significantly associated with NEC. LIMITATIONS: Heterogeneity of the included studies. CONCLUSIONS: Viral infection is associated with an increased risk of NEC in newborn infants. We need methodologically sound prospective studies to assess the effect of preventing or treating viral infections on NEC incidence.

Femoral Occlusion during Neonatal Cardiopulmonary Resuscitation Improves Outcomes in an Ovine Model of Perinatal Cardiac Arrest.

BACKGROUND: The goal of chest compressions during neonatal resuscitation is to increase cerebral and coronary blood flow leading to the return of spontaneous circulation (ROSC). During chest compressions, bilateral femoral occlusion may increase afterload and promote carotid and coronary flow, an effect similar to epinephrine. Our objectives were to determine the impact of bilateral femoral occlusion during chest compressions on the incidence and timing of ROSC and hemodynamics. METHODOLOGY: In this randomized study, 19 term fetal lambs in cardiac arrest were resuscitated based on the Neonatal Resuscitation Program guidelines and randomized into two groups: femoral occlusion or controls. Bilateral femoral arteries were occluded by applying pressure using two fingers during chest compressions. RESULTS: Seventy percent (7/10) of the lambs in the femoral occlusion group achieved ROSC in 5 ± 2 min and three lambs (30%) did not receive epinephrine. ROSC was achieved in 44% (4/9) of the controls in 13 ± 6 min and all lambs received epinephrine. The femoral occlusion group had higher diastolic blood pressures, carotid and coronary blood flow. CONCLUSION: Femoral occlusion resulted in faster and higher incidence of ROSC, most likely due to attaining increased diastolic pressures, coronary and carotid flow. This is a low-tech intervention that can be easily adapted in resource limited settings, with the potential to improve survival and neurodevelopmental outcomes.

Masked Randomized Trial of Epinephrine versus Vasopressin in an Ovine Model of Perinatal Cardiac Arrest.

BACKGROUND: Current neonatal resuscitation guidelines recommend the use of epinephrine for bradycardia/arrest not responding to ventilation and chest compressions. Vasopressin is a systemic vasoconstrictor and is more effective than epinephrine in postnatal piglets with cardiac arrest. There are no studies comparing vasopressin with epinephrine in newly born animal models with cardiac arrest induced by umbilical cord occlusion. Objective: To compare the effect of epinephrine and vasopressin on the incidence and time to return of spontaneous circulation (ROSC), hemodynamics, plasma drug levels, and vasoreactivity in perinatal cardiac arrest. Design/Methods: Twenty-seven term fetal lambs in cardiac arrest induced by cord occlusion were instrumented and resuscitated following randomization to epinephrine or vasopressin through a low umbilical venous catheter. Results: Eight lambs achieved ROSC prior to medication. Epinephrine achieved ROSC in 7/10 lambs by 8 ± 2 min. Vasopressin achieved ROSC in 3/9 lambs by 13 ± 6 min. Plasma vasopressin levels in nonresponders were much lower than responders after the first dose. Vasopressin caused in vivo increased pulmonary blood flow and in vitro coronary vasoconstriction. Conclusions: Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.

Gestational Age Alters Assessment of Neonatal Abstinence Syndrome.

Neonatal abstinence syndrome (NAS) due to maternal opioid use affects both term and preterm infants; however, the relationship between gestational age and clinical symptomatology is still poorly understood. In this study, we compared the clinical features and outcomes of NAS in infants admitted to a neonatal intensive care unit (NICU) based on gestational age groups: preterm (32-36 6/7 weeks) and term (37 weeks or older). A retrospective data analysis was conducted using the medical records of infants with a diagnosis of NAS admitted to a regional perinatal center between 2014 and 2020. A modified Finnegan scoring system was used based on three different symptom categories, including Central Nervous System (CNS), Gastrointestinal (GI) and Other. In total, 166 infants with a diagnosis of NAS were included, with 52 (31%) who were preterm and 114 (69%) who were term. The highest NAS score was significantly lower for the preterm group than for the term group. Preterm infants were less likely to require first-line pharmacotherapy with morphine (52% versus 75%) and to experience GI symptoms during their hospitalization. Newer NAS assessment modalities, such as eat, sleep, console (ESC), may overcome the existing challenges of traditional scoring systems, but will require validation in preterm infants.

Non-coding RNAs in Necrotizing Enterocolitis- A New Frontier?

With the recognition that only 2% of the human genome encodes for a protein, a large part of the "non-coding" portion is now being evaluated for a regulatory role in cellular processes. These non-coding RNAs (ncRNAs) are subdivided based on the size of the nucleotide transcript into microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), but most of our attention has been focused on the role of microRNAs (miRNAs) in human health and disease. Necrotizing enterocolitis (NEC), an inflammatory bowel necrosis affecting preterm infants, has a multifactorial, unclear etiopathogenesis, and we have no specific biomarkers for diagnosis or the impact of directed therapies. The information on ncRNAs, in general, and particularly in NEC, is limited. Increasing information from other inflammatory bowel disorders suggests that these transcripts may play an important role in intestinal inflammation. Here, we review ncRNAs for definitions, classifications, and possible roles in prematurity and NEC using some preliminary information from our studies and from an extensive literature search in multiple databases including PubMed, EMBASE, and Science Direct. miRNAs will be described in another manuscript in this series, hence in this manuscript we mainly focus on lncRNAs.

Alloimmune Neutropenia in a Neonate: Case Report and Review of Literature.

Neonatal alloimmune neutropenia, variably referred to in the literature as NAIN, FNAIN or NIN, is a disorder of neutrophil destruction in newborns similar to better-known conditions such as hemolytic disease of the newborn and neonatal alloimmune thrombocytopenia (FNAIT). Infants affected by this self-limiting condition can present asymptomatically or have a wide range of symptoms, from skin manifestations and mucositis to severe infections such as sepsis and pneumonia. In our case, we report an otherwise asymptomatic term infant born with severe neutropenia to a mother affected by COVID-19 in the 3rd trimester. However, it is unclear if COVID-19 contributed to our patients' neutropenia. Diagnostic testing eventually revealed the presence of anti-neutrophil antibodies, confirming the diagnosis of alloimmune neutropenia. The infant was conservatively managed with early discharge prior to resolution of neutropenia and close post-discharge follow up.

Essentials of Neonatal-Perinatal Medicine fellowship: part 2 - clinical education and experience.

This is the second article in a seven-part series in the Journal of Perinatology that aims to critically examine the current state of Neonatal-Perinatal Medicine (NPM) fellowship training from the structure and administration of a program, to the clinical and scholarly requirements, and finally to the innovations and future careers awaiting successful graduates. This article focuses on the current clinical requirements; recent changes to the clinical environment and their effect on learning; and additional challenges and opportunities in clinical education.