Early Pulmonary Hypertension in Preterm Infants.

Pulmonary hypertension (PH) in preterm neonates has multifactorial pathogenesis with unique characteristics. Premature surfactant-deficient lungs are injured following exposure to positive pressure ventilation and high oxygen concentrations resulting in variable phenotypes of PH. The prevalence of early PH is variable and reported to be between 8% and 55% of extremely preterm infants. Disruption of the lung development and vascular signaling pathway could lead to abnormal pulmonary vascular transition. The management of early PH and the off-label use of selective pulmonary vasodilators continue to be controversial.

Do hematological biomarkers predict surgical necrotizing enterocolitis?

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency in preterm infants and the clinical presentation of NEC may vary with gestational age. We lack reliable biomarkers for early diagnosis of NEC limiting timely intervention. Hematological changes in NEC are actively researched for their potential role as biomarkers. The pattern and severity of hematological abnormalities have been correlated with rapid progression, the need for surgery, increased risk of mortality, and morbidity. In this issue of Pediatric Research, Chong et al. report GA-specific hematological biomarkers in preterm infants with NEC that could predict the need for surgery. Thrombocytopenia at NEC onset was an independent predictor of surgical intervention in extremely preterm infants. Persistent thrombocytopenia and lymphopenia at 72 h and elevated C-reactive protein at 48 h after NEC onset, predicted surgery in infants of 28 to <32 weeks GA. Persistent thrombocytopenia at 24 h after the onset of NEC was predictive of mortality in infants who underwent surgery. Well-designed, prospective, multi-center studies are needed to confirm the role of hematological biomarkers in early diagnosis and prognostication in NEC.

Less Invasive Surfactant Administration: A Viewpoint.

The standard of care in treating respiratory distress syndrome in preterm infants is respiratory support with nasal continuous positive airway pressure or a combination of continuous positive airway pressure and exogenous surfactant replacement. Endotracheal intubation, the conventional method for surfactant administration, is an invasive procedure associated with procedural and mechanical ventilation complications. The INSURE (intubation, surfactant administration, and extubation soon after) technique is an accepted method aimed at reducing the short-term complications and long-term morbidities related to mechanical ventilation but does not eliminate risks associated with endotracheal intubation and mechanical ventilation. Alternative methods of surfactant delivery that can overcome the problems associated with the INSURE technique are surfactant through a laryngeal mask, surfactant through a thin intratracheal catheter, and aerosolized surfactant delivered using nebulizers. The three alternative methods of surfactant delivery studied in the last two decades have advantages and limitations. More than a dozen randomized controlled trials have aimed to study the benefits of the three alternative techniques of surfactant delivery compared with INSURE as the control arm, with promising results in terms of reduction in mortality, need for mechanical ventilation, and bronchopulmonary dysplasia. The need to find a less invasive surfactant administration technique is a clinically relevant problem. Before broader adoption in routine clinical practice, the most beneficial technique among the three alternative strategies should be identified. This review aims to summarize the current evidence for using the three alternative techniques of surfactant administration in neonates, compare the three techniques, highlight the knowledge gaps, and suggest future directions. KEY POINTS: · The need to find a less invasive alternative method of surfactant delivery is a clinically relevant problem.. · Clinical trials that have studied alternative surfactant delivery methods have shown promising results but are inconclusive for broader adoption into clinical practice.. · Future studies should explore novel clinical trial methodologies and select clinically significant long term outcomes for comparison..

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.

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.

Initial Use of 100% but Not 60% or 30% Oxygen Achieved a Target Heart Rate of 100 bpm and Preductal Saturations of 80% Faster in a Bradycardic Preterm Model.

Background: Currently, 21−30% supplemental oxygen is recommended during resuscitation of preterm neonates. Recent studies have shown that 58% of infants < 32 week gestation age are born with a heart rate (HR) < 100 bpm. Prolonged bradycardia with the inability to achieve a preductal saturation (SpO2) of 80% by 5 min is associated with mortality and morbidity in preterm infants. The optimal oxygen concentration that enables the achievement of a HR ≥ 100 bpm and SpO2 of ≥80% by 5 min in preterm lambs is not known. Methods: Preterm ovine model (125−127 d, gestation equivalent to human neonates < 28 weeks) was instrumented, and asphyxia was induced by umbilical cord occlusion until bradycardia. Ventilation was initiated with 30% (OX30), 60% (OX60), and 100% (OX100) for the first 2 min and titrated proportionately to the difference from the recommended preductal SpO2. Our primary outcome was the incidence of the composite of HR ≥ 100 bpm and SpO2 ≥ 80%, by 5 min. Secondary outcomes were to evaluate the time taken to achieve the primary outcome, gas exchange, pulmonary/systemic hemodynamics, and the oxidative injury. Results: Eighteen lambs (OX30-6, OX60-5. OX100-7) had an average HR < 91 bpm with a pH of <6.92 before resuscitation. Sixty seven percent achieved the primary outcome in OX100, 40% in OX60, and none in OX30. The time taken to achieve the primary outcome was significantly shorter with OX100 (6 ± 2 min) than with OX30 (10 ± 3 min) (* p = 0.04). The preductal SpO2 was highest with OX100, while the peak pulmonary blood flow was lowest with OX30, with no difference in O2 delivery to the brain or oxidative injury by 10 min. Conclusions: The use of 30%, 60%, and 100% supplemental O2 in a bradycardic preterm ovine model did not demonstrate a significant difference in the composite primary outcome. The current recommendation to use 30% oxygen did not achieve a preductal SpO2 of 80% by 5 min in any preterm lambs. Clinical studies to optimize supplemental O2 in depressed preterm neonates not requiring chest compressions are warranted.

Laryngeal Masks in Neonatal Resuscitation-A Narrative Review of Updates 2022.

Positive pressure ventilation (PPV) is crucial to neonatal cardiopulmonary resuscitation because respiratory failure precedes cardiac failure in newborns affected by perinatal asphyxia. Prolonged ineffective PPV could lead to a need for advanced resuscitation such as intubation, chest compression, and epinephrine. Every 30 s delay in initiation of PPV increased the risk of death or morbidity by 16%. The most effective interface for providing PPV in the early phases of resuscitation is still unclear. Laryngeal masks (LMs) are supraglottic airway devices that provide less invasive and relatively stable airway access without the need for laryngoscopy which have been studied as an alternative to face masks and endotracheal tubes in the initial stages of neonatal resuscitation. A meta-analysis found that LM is a safe and more effective alternative to face mask ventilation in neonatal resuscitation. LM is recommended as an alternative secondary airway device for the resuscitation of infants > 34 weeks by the International Liaison Committee on Resuscitation. It is adopted by various national neonatal resuscitation guidelines across the globe. Recent good-quality randomized trials have enhanced our understanding of the utility of laryngeal masks in low-resource settings. Nevertheless, LM is underutilized due to its variable availability in delivery rooms, providers' limited experience, insufficient training, preference for endotracheal tube, and lack of awareness.

Staphylococcus lugdunensis Bacteremia with an Infected Aortic Thrombus in a Preterm Infant.

Staphylococcus lugdunensis is a rare cause of late-onset sepsis in preterm infants. To our best knowledge, we report the fourth case of a male preterm infant who developed fulminant late-onset sepsis due to Staphylococcus lugdunensis with persistent bacteremia secondary to an infected aortic thrombus confirmed with two positive blood cultures. Our patient was an extremely low birth weight growth-restricted infant born at 27 weeks gestation and initially required an umbilical arterial catheter for blood pressure and blood gas monitoring. The course of this neonate was complicated by severe respiratory distress syndrome that evolved into chronic lung disease along with multiple episodes of tracheitis. Hemodynamically, the infant had a significant patent ductus arteriosus, and an episode of medical necrotizing enterocolitis followed by Staphylococcus lugdunensis septicemia. He was diagnosed with an infected aortic thrombus, probably the occult focus responsible for the persistent bacteremia. After a 6-week course of intravenous antibiotics and 4-week course of anticoagulant therapy, the infant responded and recovered without complications.

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.

Proficiency of Laryngeal Mask Airway Insertion Skill in NRP Certified Providers.

OBJECTIVE: In 2015, Neonatal Resuscitation Program (NRP) recommended laryngeal mask airway (LMA) as an alternative to the endotracheal tube (ETT) in situations where the provider is "unable to intubate and unable to ventilate." LMA insertion is being taught in the NRP routinely. However, endotracheal intubation is the primary method considered as the standard of care in neonatal resuscitation. LMA insertion is a relatively simple procedure with an average insertion time of < 10 seconds. Newer generation LMA can have the added advantage of reducing the risk of aerosol generation and improving the safety of the providers. Only a few recent studies have evaluated the LMA insertion skills of neonatal resuscitation providers. We wanted to study the proficiency of NRP providers in the technique of LMA insertion. We hypothesized that NRP providers would have LMA insertion skills equivalent to the standard of care (ETT insertion). STUDY: DESIGN: A manikin-based study was done from July 2019 to December 2019. We enrolled 31 NRP providers with 1 or more years since the first certification and current valid NRP provider/instructor status. The participants were instructed to insert an ETT and LMA in the manikin. The procedures were video recorded. The time taken to insert and start ventilation with each device, including the number of attempts for successful insertion, was noted. A Likert scale questionnaire was filled by each participant indicating the level of confidence, perception of ease, and the ability to provide effective positive pressure ventilation (PPV) with each of the procedures. The paired t-test, chi-square test, and Kruskal-Wallis' test were used for the statistical analysis. RESULTS: Eight (25.8%) out of the 31 participants failed to insert any one of the devices. So, 23 providers were analyzed for the outcomes. We found that the mean duration taken to insert the ETT and LMA was not statistically different (32 vs. 36 seconds). LMA insertion had a higher failure rate compared with ETT. Providers did not perceive confidence to insert LMA when compared with ETT. They did not recognize LMA insertion as a more effortless procedure relative to endotracheal intubation. The providers felt that their ability to provide effective PPV using LMA was inferior to ETT. CONCLUSION: The NRP certified providers in this study did not demonstrate proficiency in the insertion of LMA equivalent to the endotracheal intubation. KEY POINTS: · LMA insertion skill was studied in NRP providers using a manikin.. · Providers had a higher frequency of failure in inserting LMA compared to ETT.. · Providers' perceived confidence and effectiveness of the LMA procedure were inferior to ETT..

Antenatal Bartter syndrome: a new compound heterozygous mutation in exon 2 of KCNJ1 gene.

A 30+6/7-week infant was born by vaginal delivery to a 21-year-old primigravida with pregnancy complicated by polyhydramnios. The infant developed polyuria and significant weight loss in the first 2 weeks of life despite appropriate fluid management. He developed hyponatraemia, hypochloraemia, transient hyperkalaemia and prerenal azotaemia with metabolic acidosis. On further evaluation, he had elevated plasma renin and aldosterone levels. Bartter syndrome was considered in the differential diagnosis. Bartter syndrome gene panel revealed a rare compound heterozygous mutation in exon 2 of the KCNJ1 gene (Lys186Glu/Thr71Met), suggesting antenatal Bartter syndrome (type 2). The infant developed late-onset hypokalaemia and metabolic alkalosis by week 4 of life. He regained birth weight by week 3 of life but failed to thrive (10-20 g/kg/day) despite high caloric intake (140 kcal/kg/day). His electrolyte abnormalities gradually improved, and he was discharged home without the need for electrolyte supplements or medications.

Pantoea Infections in the Neonatal Intensive Care Unit.

Pantoea is a plant pathogen infrequently reported to cause opportunistic bloodstream infections. This gram-negative bacillus is a rare cause of hospital-acquired infections in newborn infants with high mortality. Since the creation of the new genus Pantoea in 1989, the evidence base available to neonatal health care providers is limited. Most of the available literature consists of case reports and case series. This review aims to consolidate the current reported literature on Pantoea infections, focusing on newborn infants and the neonatal intensive care unit (NICU). Prematurity and the associated relative immunocompromised state are major risk factors for hospital-acquired infections due to Pantoea in newborn infants. Recent advances in molecular biology have improved our understanding of the cross-kingdom pathogenesis exhibited by Pantoea. Respiratory symptoms and association with central venous lines are the most common clinical presentation of Pantoea bacteremia in newborn infants. Early institution of appropriate antibiotic therapy against this organism could be lifesaving. Therefore, it is critical for neonatologists to understand the clinical spectrum of Pantoea infections in NICUs.

Prevalence of disability among adults using Rapid Assessment of Disability tool in a rural district of South India.

BACKGROUND: There are different estimates of disability prevalence reported in India due to the differences in definitions and methodologies. Reliable data is needed to plan effective disability inclusive strategies. OBJECTIVE: The objective of this study was to determine the prevalence and risk factors associated with disability among adults ≥18 years of age in Prakasam district of Andhra Pradesh using the Rapid Assessment of Disability (RAD) tool. METHODS: The RAD survey was conducted in 50 villages (clusters) of Ongole division of Prakasam district. A two-stage cluster random sampling was used. Within each village 80 participants were surveyed. Compact segment sampling was used to determine the houses included. A person was reported as disabled based on their responses to the functioning section of the RAD tool. RESULTS: A total of 4134 adults were included. The overall prevalence of disability was 10.4% (431 adults). The highest prevalence of functional impairment was related to mobility (4.7%) followed by vision (2.1%) and fine motor (1.8%). The prevalence of psychological distress was 2.3%. Disability was significantly more prevalent in the poor socio economic group (OR 2.8; 95% CI: 1.5; 5.0) and among unemployed (OR 3.6; 95% CI: 2.3, 5.5). The prevalence of disability was strongly associated with age where, participants aged 70 years and over were eleven times more likely to report disability than younger age groups. CONCLUSION: The high prevalence of disability in the region points to disability being of public health concern and as a health condition needing urgent attention and specific interventions.