The Apgar score in clinical research: for what, how and by whom it is used.

OBJECTIVES: To review how the Apgar score is used in published clinical research as well as who uses it, and how this may have changed between 1989-90 and 2018-19. METHODS: Pubmed search for English publications using MeSH Terms "apgar score" OR "apgar" AND "score" AND "humans" for epochs 1989-90 & 2018-19. The location and specialty of first author, primary purpose and how the Apgar score was used was recorded. RESULTS: There was a 61% increase in number of publications in 2018-19 compared to 1989-90, from all regions except North America. The most common purpose for using the Apgar was to assess newborn status after pregnancy/delivery interventions. There were 50 different definitions of a significant score. Definition of significance was influenced by specialty in 2018-19 and by study purpose in both epochs. CONCLUSIONS: Most studies using the Apgar score are focused on the mother. There is no consistent definition of a significant score. Development of any future newborn assessment tools should account for the multiple purposes for which the Apgar score is used.

New modes of surfactant delivery.

The provision of exogenous surfactant to premature infants with respiratory distress syndrome has revolutionized the way we care for these patients, significantly improving survival and decreasing morbidity. Currently, the Intubate-SURfactant-Extubate (INSURE) to non-invasive ventilation method remains the standard method for surfactant delivery in the United States. However, the INSURE method requires intubation via direct visualization with a laryngoscope and possible need for sedation. Both carry significant risk to the patients, prompting the development of less invasive ways of safely and efficaciously providing surfactant to newborn infants. The present article reviews and describes the benefits and limitations of several of these alternative methods, including Less Invasive Surfactant Administration (LISA), Minimally Invasive Surfactant Therapy (MIST), via aerosolization, laryngeal mask airway (LMA), and direct nasopharyngeal deposition, focusing on assessment of clinical benefits and the level/risk of invasiveness.

Covid-19 in pregnant women and babies: What pediatricians need to know.

Beginning in late 2019, a novel coronavirus labeled SARS-CoV-2 spread around the world, affecting millions. The impact of the disease on patients and on health care delivery has been unprecedented. Here, we review what is currently known about the effects of the virus and its clinical condition, Covid-19 in areas of relevance to those providing care to neonates. While aspects of pregnancy, including higher expression of the cell receptor for the virus, ACE2, could put these women at higher risk, preliminary epidemiological information does not support this. Viral carriage prevalence based on universal screening show that rates vary from 13% in "hot spots" such as New York City, to 3% in areas with lower cases. Vertical transmission risks are unknown but 3.1% of 311 babies born to mothers with Covid-19 were positive within a week of birth. The clinical description of 26 neonates <30 days of age showed no deaths and only one requiring intensive care. Risks for breast-feeding and for milk banks are discussed.

sRAGE Is Elevated in the Lungs of Premature Infants Receiving Mechanical Ventilation.

Background Soluble receptor for advanced glycation end-products (sRAGE), a soluble isoform of the RAGE receptor, is elevated in lungs from patients with acute conditions such as acute respiratory distress syndrome and bronchiolitis. This study investigated whether sRAGE is present in ventilated infants. Methods Tracheal aspirates from the first week or the fifth week of life were obtained from intubated very low birth weight subjects and analyzed by Western blot. Immunohistochemistry analysis for sRAGE was performed on paraffin-embedded lung autopsy slides from 19 other infants. Results The sRAGE band densities were similar among the seven infants who fully recovered, eight who developed bronchopulmonary dysplasia (BPD), and 5 who died (analysis of variance p = 0.797) but was higher at 4 weeks, p = 0.0324. There was minimal sRAGE staining in the autopsied lungs from previable infants (20-21 weeks) or from those who were not ventilated or had mild lung disease. In contrast, substantial staining was present in two of three with BPD, and those who received high ventilatory support. Conclusion sRAGE is present in ventilated infants. Levels are generally higher in those who receive prolonged or vigorous mechanical ventilation. Since sRAGE may have roles in inflammation and cell adherence, its role in the development of BPD may warrant study.

Cardiac Troponin Levels in Neonates Who Require ECMO for Noncardiac Indications Are Elevated in Nonsurvivors.

OBJECTIVE: The aim of the study is to determine the utility of cardiac troponin (cTnI) as a marker of mortality and morbidity in newborn infants who require extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Retrospective medical chart analysis of term or near-term newborn infants treated with ECMO from 2002 to 2012 at a single Level III neonatal intensive care unit. Data analyzed included serial serum cTnI measurements, clinical and demographic characteristics, pre-ECMO laboratory values, and ECMO laboratory values and outcomes. RESULTS: Survival (27/46) was significantly related to birth weight (3,413.9 ± 662.3 vs. 2,667.7 ± 478.3 g, p < 0.001), outborn status (22/30 vs. 5/13, p = 0.0021), and the absence of a congenital diaphragmatic hernia (22/30 vs. 5/18, p = 0.0021). Mean peak cTnI did not differ between survivors and nonsurvivors but when peak cTnI was < 2.8 ng/mL, survival was 64% compared with 22% when it was > 2.8 ng/mL (p = 0.0224; odds ratio = 0.160, 95% confidence interval = 0.0292-0.8778). By multivariate analysis, peak cTnI > 2.1 was a significant risk factor for nonsurvival, p = 0.0497. The area under the curve of a receiver-operator analysis using peak cTnI > 2.1, birth weight, and birthplace was 0.89, p < 0.001. CONCLUSION: cTnI is an independent biomarker for poor outcome in neonates who receive ECMO therapy for noncardiac generations.

Interleukins for the paediatric pulmonologist.

Interleukins are critical immune modulators and since their first description in 1977, there has been a steady increase in the recognition of their roles in many paediatric respiratory diseases. This basic and clinical knowledge is now maturing into both approved and investigational therapies aimed at blocking or modifying the interleukin response. The purpose of this review is to bring up to date what is known about interleukin function in paediatric pulmonology, focusing on nine important lung conditions. This is followed by summaries about 18 interleukins which have been associated with these paediatric pulmonary conditions. Throughout, emphasis is placed on where interventions have been tested. Over the next several years, it is likely that many more treatments based on interleukin biology and function will become available and understanding the basis for these therapies will allow the practicing paediatric pulmonologist to take appropriate advantage of them.

The contribution of low Apgar scores in identifying neonates with short-term morbidities in a large single center cohort.

OBJECTIVE: To evaluate the association and utility of low 1- and 5-min Apgar scores to identify short-term morbidities in a large newborn cohort. METHODS: 15,542 infants >22 weeks gestation from a single center were included. Clinical data and low Apgar scores were analyzed for significance to ten short-term outcomes and were used to construct Receiver Operating Characteristic Curves and the AUC calculated for ten outcomes. RESULTS: A low Apgar score related to all (1-min) or most (5-min) outcomes by univariate and multivariate logistic regression analysis. Including any of the 4 low Apgar scores only improved the clinical factor AUC by 0.9% ± 2.7% (±SD) and was significant in just 5 of the 40 score/outcome scenarios. CONCLUSION: The contribution of a low Apgar score for identifying risk of short-term morbidity does not appear to be clinically significant.

Resonance Raman Spectroscopy Tissue Oxygenation Measurements in Neonates.

INTRODUCTION: Current oxygen monitoring by pulse oximetry has limitations and cannot provide estimates of the oxygen content in the microvasculature, where oxygen is used. Resonance Raman spectroscopy (RRS) provides noninvasive microvascular oxygen measurement. The objectives of this study were to (i) measure the correlation between preductal RRS microvascular oxygen saturations (RRS-StO2) and central venous oxygen saturation (SCVO2), (ii) develop normative data for RRS-StO2 measurements in healthy preterm infants, and (iii) determine the effect of blood transfusion on RRS-StO2. METHODS: Thirty-three buccal and thenar RRS-StO2 measurements were performed in 26 subjects to correlate RRS-StO2 with SCVO2. Thirty-one measurements were performed in 28 subjects to develop normative RRS-StO2 values, and eight subjects were enrolled in the transfusion group to assess changes in RRS-StO2 with blood transfusion. RESULTS: There were good correlations for buccal (r = 0.692) and thenar (r = 0.768) RRS-StO2 versus SCVO2. The median RRS-StO2 in healthy subjects was 76% (IQR 68.7-80.8). There was a significant increase of 7.8 ± 4.6% in the thenar RRS-StO2 after blood transfusion. CONCLUSIONS: RRS appears to be a safe and noninvasive means of monitoring microvascular oxygenation. Thenar RRS-StO2 measurements are more feasible and practical to use than buccal. In healthy preterm infants, the median RRS-StO2 was calculated based on measurements across various gestational age and gender. More studies evaluating the effects of gestational age of RRS-StO2 in various critical clinical settings are needed to confirm the findings.

NAVA-synchronized compared to nonsynchronized noninvasive ventilation for apnea, bradycardia, and desaturation events in VLBW infants.

Neurally adjusted ventilatory assistance (NAVA) can overcome technical difficulties with synchronizing noninvasive ventilation breaths with the patient, a modality often used in very low birthweight infants (VLBW) with apnea of prematurity (AOP). This study is a retrospective single-center investigation into whether NAVA-synchronized noninvasive (niNAVA) ventilation is better than nonsynchronized (nasal intermittent positive pressure ventilation [nIPPV]) for symptomatic apnea in VLBW infants. Nursing records of apnea, bradycardia, and/or desaturations were abstracted from the electronic medical records of 108 VLBW infants admitted to the neonatal intensive care unit (NICU) from 2015 to 2017 who received either of the two modalities, 61 epochs of niNAVA totaling 488 days and 103 epochs of nIPPV totaling 886.5 days. niNAVA was associated with a significant reduction in the number of isolated bradycardic events/day (0.48 ± 0.14 vs 1.35 ± 0.27; P = .019) and overall bradycardias/day (2.42 ± 0.47 vs 4.02 ± 0.53; P = .042) and there were more epochs with no events with niNAVA compared with nIPPV (23.0% vs 6.8%; P = .004). These results justify a prospective trial of NAVA-synchronized noninvasive ventilation for VLBW infants with caffeine-resistant AOP.

Correction: Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

Since the publication of the above article, the authors have noted that the name of the first Item in the NRAS scoring system in Figure 1 was omitted. It is Heart Rate (C1). The authors apologise for any inconvenience caused by this error. The html and online pdf versions have now been rectified and carry the corrected Figure.

Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability.

OBJECTIVE: To test the non-inferiority of an alternative to the Apgar score. STUDY DESIGN: The Neonatal Resuscitation and Adaptation Score (NRAS) was recorded in parallel to the Apgar score by a resuscitation team at deliveries. Correlation between the systems was assessed, as well as the predictive ability of NRAS and Apgar scores for mortality or short-term morbidities. RESULTS: A total of 340 infants were in the study group. The two scores correlated strongly (r = 0.87 and 0.83 at 1 and 5 min, respectively). Those needing ventilation at 48 h of life had a 5-min NRAS < 7 in 23/26 vs Apgar < 7 (23/36, p = 0.001). A low (0-3) 1-min NRAS score was more predictive of death, 53% vs 17%, p = 0.0065. CONCLUSIONS: NRAS correlates with Apgar status assessment, and identifies newborns who die or may require further care better than the Apgar score.

Theoretical open-loop model of respiratory mechanics in the extremely preterm infant.

Non-invasive ventilation is increasingly used for respiratory support in preterm infants, and is associated with a lower risk of chronic lung disease. However, this mode is often not successful in the extremely preterm infant in part due to their markedly increased chest wall compliance that does not provide enough structure against which the forces of inhalation can generate sufficient pressure. To address the continued challenge of studying treatments in this fragile population, we developed a nonlinear lumped-parameter respiratory system mechanics model of the extremely preterm infant that incorporates nonlinear lung and chest wall compliances and lung volume parameters tuned to this population. In particular we developed a novel empirical representation of progressive volume loss based on compensatory alveolar pressure increase resulting from collapsed alveoli. The model demonstrates increased rate of volume loss related to high chest wall compliance, and simulates laryngeal braking for elevation of end-expiratory lung volume and constant positive airway pressure (CPAP). The model predicts that low chest wall compliance (chest stiffening) in addition to laryngeal braking and CPAP enhance breathing and delay lung volume loss. These results motivate future data collection strategies and investigation into treatments for chest wall stiffening.

Dexamethasone dosing, mechanical ventilation and the risk of cerebral palsy.

OBJECTIVE: Risk factors for cerebral palsy (CP) in premature infants include duration of mechanical ventilation and exposure to postnatal dexamethasone (DEX). Since DEX can reduce the duration of mechanical ventilation, limited DEX exposure could be beneficial. METHODS: This was a retrospective, cohort study of infants of less than 1500 g birth weight surviving to discharge between 1 January 1996 and 30 June 2001 who received postnatal dexamethasone. DEX administration was based only on the need for O2 and/or mechanical ventilation. CP was diagnosed at over 10 months post-conceptional age. Univariate and multivariate analyses were used to determine significant risk factors and the relative contribution of these factors to overall risk of CP. RESULTS: Of 218 eligible infants 162 were followed-up (74%). The CP rate was 27.3%. Significant risk factors for CP included gestational age, ventilator duration, DEX dose, presence of periventricular leukomalacia (PVL), seizures, diagnosis of retinopathy of prematurity (ROP) and use of vasopressors. By multiple logistic regression, ventilator duration, PVL, grade III/IV intraventricular hemorrhage (IVH) and DEX dose were significantly related to CP. By stepwise multiple regression, grade III/IV IVH and ventilator duration were the strongest risk factors, but DEX dose continued to be a significant risk factor. CONCLUSIONS: The risk of CP was significantly related to the total cumulative dose of DEX. This could be due to a smaller exposure to DEX or to a reduced need for mechanical ventilation.

Effect of dose on response to adrenocorticotropin in extremely low birth weight infants.

CONTEXT: Various cosyntropin doses are used to test adrenal function in premature infants, without consensus on appropriate dose or adequate response. OBJECTIVE: The objective of this study was to test the cortisol response of extremely low birth weight infants to different cosyntropin doses and evaluate whether these doses differentiate between groups of infants with clinical conditions previously associated with differential response to cosyntropin. DESIGN: The design was a prospective, nested study conducted within a randomized clinical trial of low-dose hydrocortisone from November 1, 2001, to April 30, 2003. SETTING: The setting was nine newborn intensive care units. PATIENTS: The patients included infants with 500-999 g birth weight. INTERVENTION: The drug used was cosyntropin, at 1.0 or 0.1 microg/kg, given between 18 and 28 d of birth. MAIN OUTCOME MEASURE: We measured the cortisol response to cosyntropin. RESULTS: Two hundred seventy-six infants were tested. Previous hydrocortisone treatment did not suppress basal or stimulated cortisol values. Cosyntropin, at 1.0 vs. 0.1 microg/kg, yielded higher cortisol values (P < 0.001) and fewer negative responses (2 vs. 21%). The higher dose, but not the lower dose, showed different responses for girls vs. boys (P = 0.02), infants receiving enteral nutrition vs. not (P < 0.001), infants exposed to chorioamnionitis vs. not (P = 0.04), and those receiving mechanical ventilation vs. not (P = 0.02), as well as a positive correlation with fetal growth (P = 0.03). A response curve for the 1.0-microg/kg dose for infants receiving enteral nutrition (proxy for clinically well infants) showed a 10th percentile of 16.96 microg/dl. Infants with responses less than the 10th percentile had more bronchopulmonary dysplasia and longer length of stay. CONCLUSIONS: A cosyntropin dose of 0.1 microg/kg did not differentiate between groups of infants with clinical conditions that affect response. We recommend 1.0 microg/kg cosyntropin to test adrenal function in these infants.