Nine is the New Ten of Apgar Scores: An Observational Retrospective Cohort Study.

Apgar scores of 10 were once common but are now rare. We aggregated scores from US term infants from 1978 to 2021. We found that scores of 10 decreased by logarithmic decay independent of demographic changes. We hypothesize that this trend was driven by improved appreciation of transitional physiology.

Neonatal sepsis definitions from randomised clinical trials.

INTRODUCTION: Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised controlled trials (RCTs). METHOD: A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis. Definitions were sub-divided into five primary criteria for infection (culture, laboratory findings, clinical signs, radiological evidence and risk factors) and stratified by qualifiers (early/late-onset and likelihood of sepsis). RESULTS: Of 668 papers screened, 80 RCTs were included and 128 individual definitions identified. The single most common definition was neonatal sepsis defined by blood culture alone (n = 35), followed by culture and clinical signs (n = 29), and then laboratory tests/clinical signs (n = 25). Blood culture featured in 83 definitions, laboratory testing featured in 48 definitions while clinical signs and radiology featured in 80 and 8 definitions, respectively. DISCUSSION: A diverse range of definitions of neonatal sepsis are used and based on microbiological culture, laboratory tests and clinical signs in contrast to adult and paediatric sepsis which use organ dysfunction. An international consensus-based definition of neonatal sepsis could allow meta-analysis and translate results to improve outcomes.

Sequential organ failure assessment scores to predict outcomes: from adults to neonates.

PURPOSE OF REVIEW: Organ dysfunction severity scores (sequential organ failure assessment or SOFA) are commonly used in the adult and pediatric populations when assessing risk of mortality and adverse outcomes from sepsis. In contrast to sepsis definition in adults and children, clinical and laboratory criteria for defining neonatal sepsis have been inconclusive. More recently, studies have attempted to better understand the clinical progression of neonatal sepsis and associated mortality. This data has guided the development of a neonatal SOFA (nSOFA) score, based on common patterns of organ dysfunction observed in this population. RECENT FINDINGS: Although SOFA scores in the adult and pediatric populations have their limitations with moderate sensitivities and specificities depending on the clinical setting, the nSOFA score has been validated in predicting sepsis attributable mortality in very low birth weight (VLBW) infants across several patient cohorts. Furthermore, the nSOFA score has been adapted for use in neonatal disease states, other than sepsis, with similar prognostic utility. SUMMARY: Utilizing an nSOFA scoring system for prediction of sepsis attributable mortality in preterm infants allows for targeted interventions based on risk stratification, as well as better delineation of neonatal sepsis with subsequent improvements in research and patient safety outcomes.

Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials.

BACKGROUND: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered. RESULTS: Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain. CONCLUSIONS: This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation. IMPACT: This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

Routine Early Antibiotic Use in SymptOmatic Preterm Neonates: A Pilot Randomized Controlled Trial.

We enrolled 98 infants (gestational age <33 weeks) in a pilot randomized trial of antibiotics vs no antibiotics; 55 were randomized (lower maternal infectious risk; symptoms expected for gestation). Adverse events did not differ significantly between the randomization arms. This trial establishes a framework for a larger multicentered trial.

A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants.

BACKGROUND: An operational definition of organ dysfunction applicable to neonates that predicts mortality in the setting of infection is lacking. We determined the utility of an objective, electronic health record (EHR)-automated, neonatal sequential organ failure assessment (nSOFA) score to predict mortality from late-onset sepsis (LOS) in premature, very low birth weight (VLBW) infants. METHODS: Retrospective, single-center study of bacteremic preterm VLBW newborns admitted between 2012 and 2016. nSOFA scores were derived for patients with LOS at multiple time points surrounding the sepsis evaluation. RESULTS: nSOFA scores at evaluation and at all points measured after evaluation were different between survivors and non-survivors. Among patients with an nSOFA score of >4, mortality was higher at evaluation (13% vs 67%, p < 0.001), +6 h (15% vs 64%, p = 0.002), and +12 h (7% vs 71%, p < 0.001) as compared to patients with a score of ≤4. Receiver operating characteristics area under the curve was 0.77 at evaluation (95% CI 0.62-0.92; p = 0.001), 0.78 at +6 h (0.66-0.92; p < 0.001), and 0.93 at +12 h (0.86-0.997; p < 0.001). CONCLUSIONS: The nSOFA scoring system predicted mortality in VLBW infants with LOS and this automated system was integrated into our EHR. Prediction of LOS mortality is a critical step toward improvements in neonatal sepsis outcomes.

Chorioamnionitis: time for a new approach.

PURPOSE OF REVIEW: The association between maternal chorioamnionitis and early-onset sepsis in the newborn has long been recognized, and established guidelines recommend treating all exposed infants with broad-spectrum antibiotics until infection can be ruled out. However, recent data suggest that close observation of well appearing term and late-preterm newborns may be a preferable alternative. The present review addresses the evidence in favor of newly proposed changes to the diagnosis and management of women and newborns following a maternal diagnosis of chorioamnionitis. Potential implications of these new practice guidelines will also be discussed. RECENT FINDINGS: A panel of experts assembled in 2015 to provide updated, evidence-based guidelines for the diagnosis and management of women and newborns following a maternal diagnosis of chorioamnionitis. Revised terminology and diagnostic criteria were proposed as well as changes in the management of newborns of mothers with suspected intrauterine infection, most notably a recommendation to observe (rather than treat) well appearing term and late-preterm newborns. SUMMARY: A management strategy consisting of close observation of well appearing term and late-preterm infants exposed to suspected intrauterine infection is preferable to empiric antimicrobial therapy. Large prospective epidemiologic studies will be needed to ascertain the impact of these new practice guidelines on the outcomes of infants exposed to intrauterine infection and/or inflammation. Improved precision in the clinical diagnosis of intrauterine infection should improve both the quality and reproducibility of data generated from future studies.

Time for a neonatal-specific consensus definition for sepsis.

OBJECTIVE: To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. STUDY SELECTION: The review focused primarily on pediatric literature relevant to the topic of interest. CONCLUSIONS: Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.

Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus.

OBJECTIVE: To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive "trophic" (15 mL/kg/d) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus. STUDY DESIGN: Infants were eligible for the study if they were 23(1/7)-30(6/7) weeks' gestation, weighed 401-1250 g at birth, received maximum enteral volumes ≤60 mL/kg/d, and were about to be treated with indomethacin or ibuprofen. A standardized "feeding advance regimen" and guidelines for managing feeding intolerance were followed at each site (N = 13). RESULTS: Infants (N = 177, 26.3 ± 1.9 weeks' mean ± SD gestation) were randomized at 6.5 ± 3.9 days to receive "trophic" feeds ("feeding" group, n = 81: indomethacin 80%, ibuprofen 20%) or no feeds ("fasting [nil per os]" group, n = 96: indomethacin 75%, ibuprofen 25%) during the drug administration period. Maximum daily enteral volumes before study entry were 14 ± 15 mL/kg/d. After drug treatment, infants randomized to the "feeding" arm required fewer days to reach the study's feeding volume end point (120 mL/kg/d). Although the enteral feeding end point was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the 2 groups. There were no differences between the 2 groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation, or other neonatal morbidities. CONCLUSION: Infants required less time to reach the feeding volume end point if they were given "trophic" enteral feedings when they received indomethacin or ibuprofen treatments.

A physiological approach to applying CPAP in the preterm infant.

Nasal continuous positive airway pressure (CPAP) is increasingly used for respiratory support in preterm infants with respiratory distress syndrome at birth and after extubation from mechanical ventilation. Controversies with CPAP use still exists due to non-uniformity of devices and interfaces used, equivalence of testing conditions for different CPAP systems, differences in study designs, and short study periods that may be insufficient to detect important and relevant clinical outcomes. Compared with ventilator-derived constant-pressure flow-opposition CPAP, variable fluidic flow-opposition CPAP systems may be advantageous and offer some clinical benefits. The distinction between constant-flow fluid-sealed bubble CPAP and variable-flow fluidic flow-opposition systems is less clear. Appropriately designed randomized clinical trials that separately address the controversies with CPAP use in various clinical settings, are necessary to determine which CPAP system results in best outcomes.

What's new in the management of neonatal early-onset sepsis?

The expert guidelines highlighted in this review provide an evidence-based framework for approaching at-risk infants and allow for a more limited and standardised approach to antibiotic use. While these guidelines have significantly reduced antibiotic utilisation worldwide, optimally each unit would individualise their approach to early onset sepsis (EOS) based on the neonatal population they serve and available resources. As advancements in EOS research continue and limitations with sepsis prediction tools are addressed, it is inevitable that our risk stratification and management guidelines will become more precise.

Protocol for the development of a core outcome set for neonatal sepsis (NESCOS).

Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients' parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.

Infection prevention for extremely low birth weight infants in the NICU.

Extremely preterm infants are particularly vulnerable to systemic infections secondary to their immature immune defenses, prolonged hospitalizations, delays in enteral feeding, early antibiotic exposure, and need for life-sustaining invasive interventions. There have been several evidence-based practices for infection prevention in this population, such as human milk feedings, utilization of "bundle checklists" and decolonization of pathogenic organisms. Other practices, such as the use of probiotics, human milk-derived fortifiers, and antifungal prophylaxis are more controversial and require further investigation regarding the risks and benefits of such interventions. This chapter examines the susceptibility of the preterm newborn infant to invasive infections and describes several strategies for infection prevention, along with the associated limitations of such practices. It also addresses the various gaps in our understanding of preventing infections in this population, and the need for additional large multi-center randomized controlled trials. Additionally, the role of the SARs-CoV-2 global pandemic and associated strategies for infection prevention in the NICU are discussed.

Double Jeopardy: Prematurity and Congenital Heart Disease-What's Known and Why It's Important.

This article is based on a composite of talks presented during the Double Jeopardy: Prematurity and Congenital Heart Disease Plenary Session at NeoHeart 2020, a global virtual conference.Prematurity and low weight remain significant risk factors for mortality after neonatal cardiac surgery despite a steady increase in survival. Newer and lower weight thresholds for operability are constantly generated as surgeons gather proficiency, technical mastery, and experience in performing complex procedures on extremely small infants. The relationship between birth weight and survival after cardiac surgery is nonlinear with 2 kilograms (kg) being an inflection point below which marked decline in survival occurs.The prevalence of congenital heart disease (CHD) in premature infants is more than twice that in term born infants. Increased risk of preterm birth in infants with CHD is most commonly due to spontaneous preterm birth and remains poorly understood.Advances in Neonatal-Perinatal medicine have led to a marked improvement in survival of neonates born prematurely over the last several decades. However, the risk of severe morbidities including retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia and necrotizing enterocolitis remains significant in extremely low birth weight infants. Premature infants with CHD are at a greater risk of prematurity related morbidities than premature infants without CHD. Interventions that have been successful in decreasing the risk of these morbidities are addressed.

The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants.

BACKGROUND: Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants. METHODS: The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity. DISCUSSION: The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery. TRIAL REGISTRATION: Trial registration data: June 25, 2019  NCT03997266 .