Respiratory Severity Score and Oxygen Saturation Index during the First 2 Hours of Life as Predictors for Noninvasive Respiratory Support Failure in Respiratory Distress Syndrome.

OBJECTIVE: Noninvasive respiratory support (NRS) failure is common in preterm infants with respiratory distress syndrome (RDS). We evaluated the utility of respiratory severity score (RSS) and oxygen saturation index (OSI) during the first 2 hours of life (HOL) as predictors for NRS failure in moderate preterm infants. STUDY DESIGN: We conducted a retrospective cohort study of infants born between 280/7 and 336/7 weeks with RDS. Univariate and multivariable logistic regression analyses were used to assess whether the RSS and OSI summary measures were associated with NRS failure. RESULTS: A total of 282 infants were included in the study. Median gestational age and birth weights were 32 weeks and 1.7 kg, respectively. Fifty-eight infants (21%) developed NRS failure at the median age of 10.5 hours. RSS and OSI summary measures in the first 2 HOL were associated with NRS failure within 72 HOL. CONCLUSION: RSS and OSI during the first 2 HOL can predict NRS failure. Optimal RSS and OSI cutoffs for the prediction of NRS failure need to be determined in large cohort studies. KEY POINTS: · Nearly one in five moderate preterm infants on NRS at 2 hours of life developed NRS failure.. · RSS and OSI during the first 2 HOL can predict NRS failure.. · Optimal RSS and OSI cutoffs for the prediction of NRS failure need to be determined..

Surfactant delivery by aerosol inhalation - past, present, and future.

Surfactant replacement therapy (SRT) by nebulization to spontaneously breathing patients has been regarded as the Holy Grail since surfactant deficiency was first identified as the cause for neonatal respiratory distress syndrome. It avoids neonatal endotracheal intubation, a procedure that is often difficult and occasionally harmful. Unapproved alternatives to endotracheal tube placement for liquid surfactant instillation, such as LISA (thin catheter intubation) and SALSA (supraglottic airway insertion) have significant merit but are still invasive, leaving nebulized SRT as the only truly non-invasive method. In the past 60 years, we have learned much about the potential - and limitations - of nebulized SRT. In this review, we examine the promises and pitfalls of nebulized SRT, discuss what we know about neonatal aerosol drug delivery and recap some of the most recent randomized clinical trials of nebulized SRT. We conclude with a discussion of what is known and the next steps needed if this type of SRT is to become a regular part of clinical care.

Incidence and types of congenital heart disease at a referral hospital in Jordan: retrospective study from a tertiary center.

Background: Congenital heart disease (CHD) is the most common birth defect and accounts for significant global morbidity and mortality. Relatively little is known about the epidemiology of CHD in Jordan or the manner in which CHD is identified. Methods: A retrospective medical record review was conducted for all neonates who had an abnormal echocardiogram performed at a tertiary referral hospital. All included neonates had echocardiography performed by the same pediatric cardiologist at the discretion of the treatment team. Descriptive statistics were used to describe CHD incidence, types of CHD identified, and mechanism of identification. Results: The incidence of congenital heart disease was 17.8 per 1,000 live births. This rose to 24.6 per 1,000 if patent ductus arteriosus in preterm infants was included. The most common identified abnormalities were PDA, atrial septal defects, persistent pulmonary hypertension, septal hypertrophy, and ventricular septal defects. Most children were evaluated either for a murmur heard on exam or as a part of screening due to other comorbidities or risk factors. Less than 1% of children had a prenatal diagnosis. There was a higher rate of persistent pulmonary hypertension during the COVID-19 pandemic than before (p < 0.001). Conclusions: There is a high incidence of CHD in Jordan. Increased prenatal and perinatal screening for CHD may allow for earlier detection.

Respiratory Severity Score during the First 3 Hours of Life as a Predictor for Failure of Noninvasive Respiratory Support and Need for Late Rescue Surfactant Administration.

OBJECTIVE: Preterm infants often develop failure of noninvasive respiratory support. These infants miss the advantages of early rescue surfactant therapy. In this study, we evaluate the utility of respiratory severity score (RSS) during the first 3 hours of life (HOL) as a predictor for failure of noninvasive respiratory support. STUDY DESIGN: We conducted a post hoc analysis of infants between 23 and 40 weeks' gestational age who received usual care in the AERO-02 clinical trial. Univariate and multivariable logistic regression analysis were used to assess whether the RSS summary measures were associated with the odds of surfactant administration. RESULTS: Study involved 146 infants. Sixty-four infants (45%) received surfactant within the first 72 hours. Administration of surfactant was associated with the mean RSS (p < 0.01) and the linear trend (p < 0.01). CONCLUSION: We demonstrated that RSS during the first 3 HOL can predict failure of noninvasive respiratory support and need for late rescue surfactant administration. Optimal RSS cutoffs for early rescue surfactant therapy need to be determined in large cohort studies. KEY POINTS: · Early recognition of infants at risk of failure of noninvasive ventilation is important to prevent complications.. · It is desirable to identify patients who would benefit from early rescue surfactant treatment.. · RSS in first 3 hours can be used as a predictor of failure of noninvasive respiratory support..

Predictors of successful treatment of respiratory distress with aerosolized calfactant.

INTRODUCTION: Predictors for successful aerosolized surfactant treatment are not well defined. OBJECTIVE: To identify predictors for successful treatment in the AERO-02 trial and the AERO-03 expanded access program. METHODS: Neonates receiving nasal continuous positive airway pressure (NCPAP) at the time of first aerosolized calfactant administration were included in this analysis. Associations between demographic and clinical predictors to need for intubation were examined using univariate testing and multivariate logistic regression analyses. RESULTS: Three hundred and eighty infants were included in the study. Overall, 24% required rescue by intubation. Multivariate modeling revealed that the predictors of successful treatment were a gestational age ≥31 weeks, a respiratory severity score (RSS) of <1.9, and <2 previous aerosol treatments. CONCLUSION: Gestational age, number of aerosols, and RSS are predictive of successful treatment. These criteria will help select patients most likely to benefit from aerosolized surfactant.

Response to aerosolized calfactant in infants with respiratory distress syndrome; a post-hoc analysis of AERO-02 trial.

BACKGROUND: The aerosolized calfactant decreased the need for intubation in neonates with respiratory distress syndrome (AERO-02 trial). OBJECTIVE: To determine the oxygenation response to aerosolized calfactant among infants born 28 0/7-36 6/7 weeks with RDS in the AERO-02 trial. METHODS: Trends in hourly fraction of oxygen (FiO2), mean airway pressure (MAP) and respiratory severity score (RSS) were compared between the aerosolized calfactant (AC) and usual care (UC) groups from time of randomization for 72 h. RESULTS: A total of 353 subjects were included in the study. FiO2, MAP, and RSS were lower in the UC group. FiO2 decrease was seen after the first aerosolized calfactant dose. CONCLUSION: FiO2, MAP, and RSS were lower in the UC group. This is likely due to early and higher rate of liquid surfactant administration in the UC group. Decrease in FiO2 was noted in the AC group after the first aerosolization.

Implementation of Surfactant Administration through Laryngeal or Supraglottic Airways (SALSA): A Jordanian NICU's Journey to Improve Surfactant Administration.

Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. Surfactant administration through laryngeal or supraglottic airways (SALSA) is a simplified procedure for delivery of surfactant that is less invasive and better tolerated. The Al Bashir Maternity and Children's Hospital NICU in Amman, Jordan, implemented SALSA as a potentially better practice in 2019 with the objective to effectively and efficiently deliver surfactant in a minimally invasive way and to decrease the adverse events associated with intubation−surfactant−extubation (InSurE) and laryngoscopy. The quality improvement initiative was conducted from March 2019 to December 2019. All infants who weighed 750 g or more who required surfactant were eligible. As physicians were trained in the technique and use expanded, we were able to use plan−do−study−act cycles to observe differences between SALSA and InSurE. The primary aim was the optimization of non-invasive ventilation by the effective and efficient delivery of surfactant. Balancing measures included episodes of bradycardia while receiving surfactant or the need for a second dose of surfactant. We evaluated 220 infants who received surfactant by SALSA or InSurE with a mean gestational age of 32 weeks and a mean birth weight of 1.8 kg. The Respiratory Severity Score (RSS) prior to surfactant administration was 2.7 in the SALSA group compared to 2.9 in the InSurE group (p = 0.024). Those in the InSurE group had a lower mean heart rate during the procedure (p =< 0.0001) and were more likely to need a second dose of surfactant (p = 0.026) or require intubation for mechanical ventilation (p = 0.022). Both groups were effectively delivered surfactant as evidenced by improvement in their RSS over an 8 h period. SALSA was a more time efficient surfactant delivery method (93 vs. 111 secs, p =< 0.0001). Implementation of SALSA into the Al Bashir NICU was successful. We found that it was equally effective to InSurE, but was a more efficient method of delivery. Infants who received surfactant by this method tolerated it well.

Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA): A Viable Method for Low-Income and Middle-Income Countries.

Administration of liquid surfactant through an endotracheal tube for the treatment of respiratory distress syndrome has been the standard of care for decades. A skilled health care provider is needed to perform this procedure. In lower-income and middle-income countries (LMICs), healthcare resources are often limited, leading to increased mortality of premature infants, many of whom would benefit from surfactant administration. Therefore, having a simplified procedure for delivery of surfactant without the need for advanced skills could be life-saving, potentially diminish gaps in care, and help ensure more equitable global neonatal survival rates. Modifications to the standard approach of surfactant administration have been put into practice and these include: INtubation-SURfactant-Extubation (INSURE), thin catheter surfactant administration (TCA), aerosolized surfactant, and surfactant administration through laryngeal or supraglottic airways (SALSA). Although there is a need for larger studies to evaluate the comparative effectiveness of these newer methods, these methods are being embraced by the global community and being implemented in various settings throughout the world. Because the SALSA technique does not require laryngoscopy, a provider skilled in laryngoscopy is not required for the procedure. Therefore, because of the ease of use and safety profile, the SALSA technique should be strongly considered as a viable method of delivering surfactant in LMICs.

Factors associated with initial tidal volume selection during neonatal volume-targeted ventilation in two NICUs: a retrospective cohort study.

OBJECTIVE: To quantify initial tidal volume (VT) during neonatal volume-targeted ventilation (VTV) and to characterize the agreement of initial VT with the limited-evidence available. STUDY DESIGN: We performed a multi-center retrospective observational cohort study in two Neonatal Intensive Care Units evaluating 313 infants who received VTV as the initial ventilation modality prior to postnatal day 14. We generated descriptive statistics and performed multivariable logistic regression analysis to determine factors associated with initial VT use that agreed with available literature. RESULTS: 154 (49%) infants received an initial VT of 5.0 mL/kg (median 5.0 mL/kg, IQR 5.0-5.1). 45 (14%) infants received an initial VT that was congruent with available literature. A birth weight of 700 -<1250 g was significantly associated with an initial VT in agreement with VT literature (aOR 9.4, 95% CI 1.7-50.4). CONCLUSIONS: Most infants receive an initial VT of 5.0 mL/kg.

Surfactant Administration Through Laryngeal or Supraglottic Airways.

Noninvasive ventilation is frequently used in the treatment of infants with respiratory distress syndrome. This practice is often effective in higher gestational age neonates, but can be difficult in those with lower gestational ages as surfactant deficiency can be severe. While noninvasive ventilation avoids the negative effects of intubation and ventilator-induced lung injury, failure of this mode of support does occur with relative frequency and is primarily caused by the poorly compliant, surfactant-deficient lung. Because of the potential problems associated with laryngoscopy and intubation, neonatologists have developed various methods to deliver surfactant in minimally invasive ways with the aim of improving the success of noninvasive ventilation. Methods of minimally invasive surfactant administration include various thin catheter techniques, aerosolization/nebulization, and the use of a laryngeal mask airway/supraglottic airway device. The clinician should recognize that currently the only US Food and Drug Administration-approved device to deliver surfactant is an endotracheal tube and all methods reviewed here are considered off-label use. This review will focus primarily on surfactant administration through laryngeal or supraglottic airways, providing a review of the history of this technique, animal and human trials, and comparison with other minimally invasive techniques. In addition, this review provides a step-by-step instruction guide on how to perform this procedure, including a multimedia tutorial to facilitate learning.

Association of time of day and extubation success in very low birthweight infants: a multicenter cohort study.

OBJECTIVE: To determine the association of overnight extubation (OE) with extubation success. STUDY DESIGN: Retrospective cohort study in three NICUs from 2016 to 2020. Infants without congenital anomalies, less than 1500 grams at birth, who were ventilated and received an extubation attempt were included. Primary exposure was OE (7:00 pm-6:59 am) and outcome was extubation success defined as no mechanical ventilation for at least 7 days after extubation. RESULTS: A total of 76/379 (20%) infants received OE. Infants extubated during the daytime were older and had higher illness severity markers. Extubation success rates did not differ for overnight (57/76, 75%) versus daytime extubations (231/303, 76%) after adjusting for confounders (adjusted relative risk 0.95, 95% CI 0.82-1.11). CONCLUSION: Though infants in our cohort undergoing daytime and OE were dissimilar, extubation success rates did not differ. Larger multicenter studies are needed to test our findings and identify markers of extubation readiness in preterm infants.

Alternative Methods of Surfactant Administration in Preterm Infants with Respiratory Distress Syndrome: State of the Art.

For preterm infants with respiratory distress syndrome, delivery of surfactant via brief intubation (INtubate, SURfactant, Extubate; InSurE) has been the standard technique of surfactant administration. However, this method requires intubation and positive pressure ventilation. It is thought that even the short exposure to positive pressure inflations may be enough to initiate the cascade of events that lead to lung injury in the smallest neonates. In an effort to avoid tracheal intubation and positive pressure ventilation, several alternative and less invasive techniques of exogenous surfactant administration have been developed over the years. These have been investigated in clinical studies, including randomized clinical trials, and have demonstrated advantages such as a decrease in the need for mechanical ventilation and incidence of bronchopulmonary dysplasia. These newer techniques of surfactant delivery also have the benefit of being easier to perform. Surfactant delivery via pharyngeal instillation, laryngeal mask, aerosolization, and placement of a thin catheter are being actively pursued in research. We present a contemporary review of surfactant administration for respiratory distress syndrome via these alternative methods in the hope of guiding physicians in their choices for surfactant application in the neonatal intensive care unit.

Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

BACKGROUND: Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis. AIMS: To define the transcriptomic and inflammatory protein response in peripheral blood among infants with exposure to histologic chorioamnionitis. STUDY DESIGN: Prospective, observational study. SUBJECTS: Uninfected preterm neonates retrospectively categorized based on placental pathology with no HCA exposure (n=18) or HCA exposure (n=15). OUTCOMES MEASURES: We measured the transcriptomic and inflammatory mediator response in prospectively collected whole blood. RESULTS: We found 488 significant (p<0.001), differentially expressed genes in whole blood samples among uninfected neonates with HCA exposure that collectively represented activated innate and adaptive immune cellular pathways and revealed a potential regulatory role for the pleotropic microRNA molecule miR-155. Differentially secreted plasma cytokines in patients with HCA exposure compared to patients without HCA included MCP-1, MPO, and MMP-9 (p<0.05). CONCLUSIONS: Exposure to HCA distinctively activates the neonatal immune system in utero with potentially long-term health consequences.

Neonatal ventricular fibrillation and an elusive ALCAPA: things are not always as they seem.

An anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital cardiac condition that typically presents with poor feeding and failure to thrive from progressive myocardial ischaemia. Previous reports of ALCAPA presenting with ventricular fibrillation (VF) have suggested a causative relationship. In this case, we present a neonate with VF without apparent cause after an extensive evaluation. Following implantable cardioverter-defibrillator placement for presumed idiopathic VF, at which time she also underwent surgical ligation of a patent ductus arteriosus (PDA), the neonate developed haemodynamic instability that ultimately was found to be due to ALCAPA. Numerous echocardiograms had missed the ALCAPA in the setting of mildly elevated pulmonary artery pressure. We discuss the limitations of current ultrasound technology in diagnosing ALCAPA in the setting of pulmonary hypertension and explain why the relationship between this patient's diagnosis of ALCAPA and her episode of VF is not clearly causative.

Postnatal Age Is a Critical Determinant of the Neonatal Host Response to Sepsis.

Neonates manifest a unique host response to sepsis even among other children. Preterm neonates may experience sepsis soon after birth or during often-protracted birth hospitalizations as they attain physiologic maturity. We examined the transcriptome using genome-wide expression profiling on prospectively collected peripheral blood samples from infants evaluated for sepsis within 24 h after clinical presentation. Simultaneous plasma samples were examined for alterations in inflammatory mediators. Group designation (sepsis or uninfected) was determined retrospectively on the basis of clinical exam and laboratory results over the next 72 h from the time of evaluation. Unsupervised analysis showed the major node of separation between groups was timing of sepsis episode relative to birth (early, <3 d, or late, ≥3 d). Principal component analyses revealed significant differences between patients with early or late sepsis despite the presence of similar key immunologic pathway aberrations in both groups. Unique to neonates, the uninfected state and host response to sepsis is significantly affected by timing relative to birth. Future therapeutic approaches may need to be tailored to the timing of the infectious event based on postnatal age.

A crossover analysis of mandatory minute ventilation compared to synchronized intermittent mandatory ventilation in neonates.

BACKGROUND: Mandatory minute ventilation (MMV) is a novel ventilator mode that combines synchronized intermittent mandatory ventilation (SIMV) breaths with pressure-supported spontaneous breaths to maintain a desired minute volume. The SIMV rate is automatically adjusted to maintain minute ventilation. OBJECTIVE: To evaluate MMV in a cohort of infants without parenchymal lung disease alternately ventilated by MMV and SIMV. DESIGN/METHODS: Neonates >33 weeks' gestational age and electively intubated for medical or surgical procedures were enrolled. Exclusionary criteria included: nonintact respiratory drive or active pulmonary disease. Infants were randomized to receive 2 hours of either SIMV or MMV and then crossed over to the other mode for 2 hours. Ventilator parameters and end-tidal CO(2) (etCO(2)) were measured via inline, mainstream monitoring and recorded every minute. RESULTS: In total, 20 infants were evaluated. No statistically significant differences were found for overall means between etCO(2), minute volumes, peak inspiratory pressure (PIP), or positive end expiratory pressure (PEEP). However, there was a significant difference in the type of ventilator breaths given and in the mean airway pressure. Additionally, there was a statistically significant negative trend in MMV over time compared to SIMV, although this was subtle and could have been due to extreme cases. CONCLUSIONS: Neonates with an intact respiratory drive can be successfully managed with MMV without an increase in etCO(2). While this mode generates similar PIP and PEEP, the decrease in mechanical breaths and the mean airway pressure generated with MMV may reduce the risk of some of the long-term complications associated with mechanical ventilation.

An infant with Kasabach-Merritt syndrome with associated renal hematoma and intussusception.

A neonate that had a forearm hemangioma, gross hematuria, and a renal parenchymal hematoma was found to have Kasabach-Merritt syndrome. He subsequently returned to our hospital and was found to have an intussusception secondary to an intestinal hemangioma.

Initial dosing of inhaled nitric oxide in infants with hypoxic respiratory failure.

BACKGROUND: Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator that decreases pulmonary resistance, and improves ventilation-perfusion matching, thereby improving oxygenation and reducing the need for more invasive therapies. Despite the efficacy of iNO at reducing the use of extracorporeal membrane oxygenation, significant concern remains over the potential toxicity from oxidative derivatives and methemoglobinemia. At present, there is no universal agreement on the lowest effective starting dose. Reported initial doses in the neonatal literature have ranged from 1 to 80 ppm. PURPOSE: To determine if the initial dose of iNO altered the incidence of adverse outcome. METHODS: A cohort of neonates who received iNO for treatment of hypoxic respiratory failure and were entered into the Duke Neonatal Nitric Oxide Registry were evaluated. Neonates with congenital anomalies were excluded. This registry collects data from 36 centers that voluntarily report their experiences with iNO. From this database, the starting dose was recorded and the clinical course was followed. Adverse outcomes were prospectively defined and monitored in the database and included: methemoglobinemia, chronic lung disease, treatment with extracorporeal membrane oxygenation, or death. RESULTS: Data on 476 patients were analyzed. Based on starting doses, records were sorted into three groups: a low-dose group (LDG; <18 ppm, n=57), a mid-dose group (MDG; 18 to 22 ppm, n=320), and a high-dose group (HDG; >22 ppm, n=99). ANOVA showed no statistically significant differences among the groups except for PaO(2)/FiO(2) (p<0.05). Neonates in the high starting dose group were more often classified as treatment failures (21% in the LDG, 27% in the MDG, and 38% in the HDG, p=0.04) and treated with extracorporeal membrane oxygenation (19% in the LDG, 23% in the MDG, and 34% in the HDG, p=0.05) compared to the lower dose groups. In addition, survival without the need for oxygen at 30 days or at discharge was higher in the lower dose groups (93% in the LDG, 84% in the MDG, and 76% in the HDG, p=0.03). Logistic regression, however, showed that the starting dose of iNO did not significantly influence these outcomes when corrected for the degree of hypoxemia (PaO(2)/FiO(2)) at the start of therapy (p>0.1). High initial doses of iNO (>22 ppm) were associated with higher levels of methemoglobin (p< 0.05). There were no differences in mortality or length of hospital stay between the groups. CONCLUSIONS: There is significant variation in the starting dose of iNO between centers. Our retrospective study shows no evidence that higher doses improve outcome. A low concentration of iNO (<18 ppm) should be considered to minimize the potential toxicity of methemoglobin. Furthermore, a well-designed, prospective trial should be undertaken to further define the optimal starting dose.

Necrotizing enterocolitis among neonates in the United States.

BACKGROUND: Prior studies have identified individual risk factors that are associated with necrotizing enterocolitis (NEC); however, the small sample sizes of these previous studies have not allowed the analysis of potential interaction between multiple variables and NEC. Our purpose was to describe the incidence and risk factors for NEC in premature neonates admitted for intensive care. METHODS: We identified neonates as having NEC if they met accepted diagnostic criterion for necrotizing enterocolitis. Using a national database, we assessed the association between NEC and a battery of risk factors previously reported in peer-reviewed literature. RESULTS: There were 15,072 neonates that met inclusion criteria; 14,682 did not have NEC, while 390 (2.6%) met criterion for NEC. Multivariate analysis showed that low birth weight was the most important risk factor for NEC. Other factors that were associated with an increased risk of NEC were exposure to antenatal glucocorticoids, vaginal delivery, need for mechanical ventilator support, exposure to both glucocorticoids and indomethacin during the first week of life, absence of an umbilical arterial catheter, and low Apgar score at 5 minutes. Length of hospital stay and mortality were higher in neonates with NEC than in neonates without NEC. CONCLUSIONS: NEC remains an important cause of morbidity and mortality in prematurely born neonates. In contrast to previous studies, we found that exposure to antenatal glucocorticoids was associated with an increased risk for NEC independent of birth weight.

Alexander's disease in a neurologically normal child: a case report.

We report the clinical and MRI findings of symmetric hyperintensity involving the deep and subcortical white matter of the frontal lobes in a neurologically normal child with macrocephaly. In this patient, a serum test for mutations in glial fibrillary acidic protein, used to diagnose Alexander's disease (AD), was positive. This case indicates an extraordinarily mild or early form of juvenile-onset AD.