Noninvasive Respiratory Severity Indices Predict Adverse Outcomes in Bronchopulmonary Dysplasia.

OBJECTIVE: To test the hypothesis that elevated respiratory severity indices will identify patients with severe bronchopulmonary dysplasia (BPD) at the greatest risk for adverse in-hospital outcomes. STUDY DESIGN: This was a retrospective cohort study. A modified respiratory severity score (mean airway pressure × fraction of inspired oxygen) and a modified pulmonary score (respiratory support score × fraction of inspired oxygen + sum of medication scores) were calculated in a consecutive cohort of patients ≥36 weeks of postmenstrual age with severe BPD admitted to a referral center between 2010 and 2018. The association between each score and the primary composite outcome of death/prolonged length of stay (>75th percentile for cohort) was assessed using area under the receiver operator characteristic curve (AUROC) analysis and logistic regression. Death and the composite outcome death/tracheostomy were analyzed as secondary outcomes. RESULTS: In 303 patients, elevated scores were significantly associated with increased adjusted odds of death/prolonged length of stay: aOR 1.5 (95% CI 1.3-1.7) for the modified respiratory severity score and aOR 11.5 (95% CI 5.5-24.1) for the modified pulmonary score. The modified pulmonary score had slightly better discrimination of death/prolonged length of stay when compared with the modified respiratory severity score, AUROC 0.90 (95% CI 0.85-0.94) vs 0.88 (95% CI 0.84-0.93), P = .03. AUROCs for death and death/tracheostomy did not differ significantly when comparing the modified respiratory severity score with the modified pulmonary score. CONCLUSIONS: In our referral center, the modified respiratory severity score or the modified pulmonary score identified patients with established severe BPD at the greatest risk for death/prolonged length of stay, death, and death/tracheostomy.

Use of a Quality Scorecard to Enhance Quality and Safety in Community Hospital Newborn Nurseries.

OBJECTIVE: To implement a quality improvement (QI) scorecard as a tool for enhancing quality and safety efforts in level 1 and 2 community hospital nurseries affiliated with Nationwide Children's Hospital. STUDY DESIGN: A QI scorecard was developed for data collection, analytics, and reporting of neonatal quality metrics and cross-sector collaboration. Newborn characteristics were included for risk stratification, as were clinical and process measures associated with neonatal morbidity and mortality. Quality and safety activities took place in community hospital newborn nurseries in Ohio, and education was provided in both online and in-person collaborations, followed by local team sessions at partner institutions. Baseline (first 12 months) and postbaseline comparisons of clinical and process measures were analyzed by logistic regression, adjusting for potential confounders. RESULTS: In logistic regression models, at least 1 center documented improvements in each of the 4 process measures, and 3 of the 4 centers documented improvements in compliance with glucose checks obtained within 90 minutes of birth among at-risk infants. CONCLUSION: Collaborative QI projects led to improvements in perinatal metrics associated with important outcomes. Formation of a center-driven QI scorecard is feasible and provides community hospitals with a framework for collecting, analyzing, and reporting neonatal QI metrics.

Changes, Challenges, and Variations in Neonatal-Perinatal Medicine Fellowship: A View from the Program Directors.

OBJECTIVE: Neonatal-perinatal medicine (NPM) fellowship programs in the United States support >800 learners annually. Understanding variations in the programmatic structure, challenges, and needs is essential to optimize the educational environment and ensure the specialty's future. STUDY DESIGN: NPM fellowship program directors (PDs) and associate program directors (APDs) were invited to complete an electronic survey on their program administration, recruitment, clinical training, assessment methods, scholarly program, and career pathways. Each participant identified individual programmatic strengths, challenges, opportunities, and threats to the field. RESULTS: Representatives from 59 NPM fellowships provided data (response rate 59/96 = 61%). In total, 30% of PDs received less than the Accreditation Council for Graduate Medical Education -recommended protected time for administrative duties, and 44% of APDs received no protected time. Fellow clinical service assignments varied widely from 13 to 18 months and 90 to 175 call nights over 3 years. Recruitment practices varied across programs; 59% of respondents raised concerns over the pipeline of applicants. Conflicts between fellows and advanced practice providers were identified by 61% of responders. Programs varied in their scholarly offerings, with 44% of NPM fellowships interested in adding broader research opportunities. CONCLUSIONS: NPM fellowship leaders identified a need for improved programmatic support, enhanced measures to assess competency, opportunities to strengthen scholarly programs, shared curricular resources, and strategies to balance education with clinical demands. PDs and APDs identified threats to the future of NPM training programs including the diminishing pipeline of applicants into neonatology, challenges with clinical exposure and competence, inadequate support for the educational mission, issues supporting high-quality scholarship, and fewer graduates pursuing physician-investigator pathways. National organizations and academic institutions should take action to address these challenges so that fellowships can optimally prepare graduates to meet their patients' needs. KEY POINTS: · Numerous challenges exist for current program directors in NPM including balancing clinical work with scholarly activities, accurately assessing competency, optimizing the culture of the learning environment, and ensuring that fellows are adequately prepared for a range of postgraduate positions.. · Significant variation exists across NPM fellowship programs in clinical service/calls assigned over 3 years of fellowship training, as well as opportunities to pursue scholarly activities across a variety of areas.. · Challenges exist related to ensuring an adequate number of future applicants into the specialty, including those from backgrounds traditionally underrepresented in medicine, as well as those seeking to pursue careers as physician-investigators..

Nutritional Practices and Growth in Premature Infants After Surgical Necrotizing Enterocolitis.

OBJECTIVE: The aim of the study was to describe the nutritional provisions received by infants with surgical necrotizing enterocolitis (NEC) and the associated effects on short-term growth. METHODS: Through the Children's Hospitals Neonatal Database, we identified infants born ≤32 weeks' gestation with surgical NEC from 5 regional neonatal intensive care units for 4 years. Excluded infants had isolated intestinal perforation and died <14 days postoperatively. Infants were stratified by their median parenteral protein dose (low [LP] or high [HP] protein) for the first postoperative week. The primary outcome was postoperative weight growth velocity. Growth (weight, length, and head circumference [HC]) was measured and the effects related to protein dose were estimated using multivariable analyses. RESULTS: There were 103 infants included; the median parenteral protein dose received was 3.27 g ·â€Škg ·â€Šday (LP: 2.80 g ·â€Škg ·â€Šday; HP: 3.87 g ·â€Škg ·â€Šday). Postoperative weight (11.5 ±â€Š6.5 g ·â€Škg ·â€Šday) and linear growth (0.9 ±â€Š0.2 cm/wk) were similar regardless of dose (P > 0.3 between groups for weight and length). Unadjusted and independent associations were identified with HC changes and HP dose (ß = 0.1 cm/wk, P = 0.03) after adjusting for gestational age, the presence of severe bronchopulmonary dysplasia, short bowel syndrome, blood stream infection, severe intraventricular hemorrhage, small for gestational age, and calorie intake. Eventual nonsurvivors received 18% less protein and 14% fewer calories over the first postoperative month. CONCLUSIONS: Postoperative protein doses in infants with surgical NEC appear related to increases in HC. The influence of postoperative nutritional support on risk of adverse outcomes deserves further attention.

Apgar Score at 5 Minutes Is Associated with Mortality in Extremely Preterm Infants Even after Transfer to an All Referral NICU.

OBJECTIVE: The Apgar score has been shown to have utility in predicting mortality in the extremely preterm infant in delivery hospital populations, where most mortality occurs within 12 hours of birth. We tested the hypothesis that the 5 minute Apgar score would remain associated with mortality in extremely preterm infants after transfer from the delivery hospital to an all referral neonatal intensive care unit at an average age of 10 days. STUDY DESIGN: A retrospective analysis of 454 infants born at < 27 weeks gestation. RESULTS: The median Apgar score was 3 at 1 minute (interquartile range [IQR] 2-6) and 6 at 5 minutes (IQR 4-7). The Apgar score increased from 1 to 5 minutes by 2.0 ± 1.7 (p < 0.001). In logistic regression modeling, an Apgar score of < 5 at 5 minutes was associated with an increased mortality (odds ratio 1.76 [95% confidence interval 1.06-2.94], p < 0.05), but not morbidities. CONCLUSION: Infants born at < 27 weeks gestation admitted to an all referral children's hospital at a mean age of 10 days with a 5 minute Apgar < 5 are at an increased risk of mortality. Our findings continue to support the importance of the Apgar score given at delivery even in the extremely preterm infant referred to a nondelivery children's hospital.

Postnatal weight gain in preterm infants with severe bronchopulmonary dysplasia.

OBJECTIVES: To characterize postnatal growth failure (PGF), defined as weight < 10th percentile for postmenstrual age (PMA) in preterm (≤ 27 weeks' gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others. STUDY DESIGN: Retrospective review of data from the multicenter Children's Hospital Neonatal Database (CHND). RESULTS: Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks' PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to > 70% and parenteral nutrition to a third of infants between 36 and 44 weeks' PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p < 0.01). CONCLUSIONS: Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population.

A pivotal moment in the evolution of neonatal care.

While extraordinary advances have been made in the medical care of critically ill newborns, understanding the need of even the smallest of these infants for early, extensive, intimate human contact and facilitating the family's role in the care of their baby has been much slower and inconsistent. There is abundant evidence for the essential role of nurturing parent-infant connections (bonding/attachment) for development of optimal physical, cognitive, and emotional health of all babies. It is time to leave behind the tradition of sensory deprivation and social isolation common in the care of high-risk infants. A paradigm shift is needed in neonatal care to acknowledge the critical importance of infant and family-centered developmental care and to remove any remaining constraints on a family's ability to become full partners in the nurture of their NICU newborn.

Development of a small baby unit to improve outcomes for the extremely premature infant.

Survival and outcomes for extremely premature (EP) infants have improved and even infants born at 23 and 24 weeks that were previously considered non-viable are now routinely surviving. This review describes our particular institution's basis for and process of creating and sustaining a small baby program for a quaternary, referral-based neonatal intensive care unit. Through multi-disciplinary collaboration, small baby guidelines were developed that established uniform care and optimized evidence-based practice for the care of this unique patient population. A focus on parent-centered care while removing noxious stimuli for the patient has improved neurodevelopmental outcomes. Data collection, quality improvement, and ongoing research are incorporated in the small baby program to establish and sustain best practices and outcomes for the EP patient. Through the establishment of a small baby unit, we have improved survival, decreased short-term morbidities, and improved neurodevelopmental outcomes for the EP infant in our region.

Essentials of Neonatal-Perinatal Medicine fellowship: an overview.

Neonatal-Perinatal Medicine (NPM) fellowship programs have undergone constant evolution since their first appearance in the 1960s. This article is the first in a seven-part series (Table 1) that critically evaluates the essentials of neonatology fellowship clinical and research education, performance assessment, and administrative support necessary to support NPM fellowship programs. This overview article will provide background on the history of NPM fellowship programs and provide a framework for the article series. Table 1 Essentials of NPM fellowship article series. Essentials of NPM fellowship Part 1: Overview of NPM fellowship Description of the evolution of NPM Fellowship Part 2: Clinical education and experience Strengths, weaknesses, opportunities, and threats of clinical education in NPM fellowship Part 3: Scholarship opportunities and threats Scholarship requirements during NPM fellowship Part 4: Innovations in medical education Critical analysis of current educational practices and andragogical innovations in NPM fellowship Part 5: Evaluation of competence and proficiency using milestones Assessment of NPM fellows during training using competency-based medical education principles Part 6: Program administration Administrative infrastructure and stakeholders necessary to run a NPM fellowship program Part 7: Careers in NPM Career preparation and opportunities for NPM fellowship graduates.

Perspectives on developing and sustaining a small baby program.

The Small Baby Program at Nationwide Children's Hospital was launched in 2004 in response to a need for better care for infants born extremely preterm. Standardization of care, decreased variability, multidisciplinary support, and robust research and quality improvement have allowed us to greatly improve our outcomes. In addition to the numerous medical and technological advances during this time, a strong commitment to kangaroo care and family-centered care have been integral to the growth and success of our program. The following review of the program aims to highlight the above areas while detailing the specific processes that have contributed to its ongoing success. Key areas of focus have been on respiratory management, neurodevelopmental care, and nutritional optimization. The implementation and continued refinement of the Small Baby Program has allowed us to improve the survival of extremely preterm infants, decrease certain morbidities, and improve long-term neurodevelopmental outcomes.

Variability in antibiotic duration for necrotizing enterocolitis and outcomes in a large multicenter cohort.

OBJECTIVES: To evaluate variability in antibiotic duration for necrotizing enterocolitis (NEC) and associated clinical outcomes. STUDY DESIGN: Five-hundred ninety-one infants with NEC (315 medical; 276 surgical) were included from 22 centers participating in Children's Hospitals Neonatal Consortium (CHNC). Multivariable analyses were used to determine predictors of variability in time to full feeds (TFF) and length of stay (LOS). RESULTS: Median (IQR) antibiotic duration was 12 (9, 17) days for medical and 17 (14, 21) days for surgical NEC. Wide variability in antibiotic use existed both within and among centers. Duration of antibiotic therapy was associated with longer TFF in both medical (OR 1.04, 95% CI [1.01, 1.05], p < 0.001) and surgical NEC (OR 1.02 [1, 1.03] p = 0.046); and with longer LOS in medical (OR 1.03 [1.02, 1.04], p < 0.001) and surgical NEC (OR 1.01 [1.01, 1.02], p = 0.002). CONCLUSION: Antibiotic duration for both medical and surgical NEC remains variable within and among high level NICUs.

Probiotics and prebiotics for the prevention of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) continues to be a major cause of morbidity and mortality in premature infants. Although the pathogenesis of NEC remains unclear, abnormal bacterial colonization has been postulated as playing a central role. Various factors impact bacterial colonization following delivery. Compared to term infants, the bacterial colonization pattern in prematurely born infants is markedly different, with a greater predilection for colonization with pathogenic bacteria. Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment, favoring the growth of commensal bacteria. Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC. These preliminary studies support the need for a large, randomized, controlled trial to further investigate the role of probiotics in the prevention of NEC.

In-hospital outcomes of late referrals for established bronchopulmonary dysplasia.

OBJECTIVE: To determine the in-hospital outcomes for patients with established bronchopulmonary dysplasia (BPD) referred late for severe disease. STUDY DESIGN: Retrospective cohort study of patients with established BPD referred to our center after 36 weeks PMA. RESULT: Among 71 patients with BPD referred to our center after 36 weeks PMA between 2010 and 2018, the median PMA was 47 weeks (IQR, 42, 53) and the median respiratory severity score was 8.1 (IQR 4.5, 11.0) on admission. Survival in this cohort was 92%. Most survivors were discharged home without the need for positive pressure respiratory support (77%) or pulmonary vasodilators (89%). For survivors, we observed a significant improvement in median z-scores for length (-6.7 vs -3.3, p < 0.0001) between admission and discharge. CONCLUSION: Despite presenting relatively late with a high degree of illness severity, nearly all patients in this cohort survived to hospital discharge with improvement in comorbidities.

Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.

Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1ß, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.

Prenatal lipopolysaccharide increases postnatal intestinal injury in a rat model of necrotizing enterocolitis.

BACKGROUND: An increased incidence of necrotizing enterocolitis (NEC) has been noted in infants who are born to mothers with chorioamnionitis. HYPOTHESIS: Our objective was to test the hypothesis that newborn rat pups born to mothers exposed to prenatal lipopolysaccharide during pregnancy would be more susceptible to intestinal injury in a rat model of NEC and that the increased intestinal injury is mediated by dysregulation of inducible nitric oxide synthase. METHODS: Time-dated pregnant Sprague-Dawley dams were given an intraperitoneal injection of either 2 mg/kg of lipopolysaccharide or vehicle. Rat pups from each group of dams were delivered at term and placed in a rat NEC model. A subset of pups was given either vehicle or aminoguanidine. Intestines were harvested and graded for degree of intestinal injury. RESULTS: Maternal prenatal lipopolysaccharide exposure increased the frequency and severity of intestinal injury in the neonatal rat NEC model. Treatment with aminoguanidine significantly decreased plasma nitric oxide levels. Additionally, aminoguanidine significantly decreased intestinal injury. CONCLUSIONS: Intestinal injury observed may be mediated via nitric oxide synthase dysregulation.

Does the initial surgery for necrotizing enterocolitis matter? Comparative outcomes for laparotomy vs. peritoneal drain as initial surgery for necrotizing enterocolitis in infants <1000 g birth weight.

PURPOSE: Quantify short-term outcomes associated with initial surgery [laparotomy (LAP) vs. peritoneal drain (PD)] for necrotizing enterocolitis (NEC) in extremely-low-birth-weight (ELBW) infants. METHODS: Using the Children's Hospitals Neonatal Database, we identified ELBW infants <32 weeks' gestation with surgical NEC (sNEC). Unadjusted and multivariable regression analyses were used to estimate the associations between LAP (or PD) and death/short bowel syndrome (SBS) and length of stay (LOS). RESULTS: LAP was the more common initial procedure for sNEC (n = 359/528, 68%). Infants receiving LAP were older and heavier. Initial procedure was unrelated to death/SBS in both bivariate (LAP: 43% vs PD: 46%, p = 0.573) and multivariable analyses (OR = 0.89, 95% CI = 0.57, 1.38, p = 0.6). LAP was inversely related to mortality (29% vs. 41%, p < 0.007) in bivariate analysis, but not significant in multivariable analysis accounting for markers of preoperative illness severity. However, the association between LAP and SBS (14% vs. 5%, p = 0.012) remained significant in multivariable analyses (adjusted OR = 2.25, p = 0.039). LOS among survivors was unrelated to the first surgical procedure in multivariable analysis. CONCLUSION: ELBW infants who undergo LAP as the initial operative procedure for sNEC may be at higher risk for SBS without a clear in-hospital survival advantage or shorter hospitalization. LEVEL OF EVIDENCE: Level II.

The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis.

Based on the demonstration of coagulation necrosis, it is clear that intestinal ischemia plays a role in the pathogenesis of necrotizing enterocolitis (NEC). Intestinal vascular resistance is determined by a dynamic balance between vasoconstrictive and vasodilatory inputs. In the newborn, this balance heavily favors vasodilation secondary to the copious production of endothelium-derived nitric oxide (NO), a circumstance which serves to ensure adequate blood flow and thus oxygen delivery to the rapidly growing intestine. Endothelial cell injury could shift this balance in favor of endothelin (ET)-1-mediated vasoconstriction, leading to intestinal ischemia and tissue injury. Evidence obtained from animal models and from human tissue collected from infants with NEC implicates NO and ET-1 dysregulation in the pathogenesis of NEC. Strategies focused on maintaining the delicate balance favoring vasodilation in the newborn intestinal circulation may prove to be useful in the prevention and treatment of NEC.

Factors associated with long-term mechanical ventilation in extremely preterm infants.

BACKGROUND: The objective of this study was to determine factors associated with long-term intermittent positive pressure ventilation (IPPV) in extremely preterm infants. METHODS: Study setting was a ten bed pod (SBP) part of the Level IV all referral NICU, dedicated to the care of infants born at <27 weeks and which utilizes a protocol-driven approach to care. All admissions to the SBP from 2005 to 2011 were included if admitted in the first week of life and alive at 56 days of age. RESULTS: There were 210 patients and 35% were on IPPV for ≥56 days (for the purposes of this study defined as long-term IPPV). Long-term IPPV patients were born earlier, had lower birth weight, were admitted later, and more likely to come from a level III NICU. LTV patients were more likely to have a PDA ligation, receive dopamine, receive TPN longer, and receive supplemental oxygen at 36 weeks PMA. In logistic regression modeling transfer from another Level III NICU (OR 3.7, 95% CI 1.5-9.2, p = 0.006) and recieveing dopamine (OR 3.1, 95% CI 1.5-6.3, p = 0.002) were associated with long-term IPPV. CONCLUSIONS: In this cohort of infants born at <27 weeks gestation 35% were on long term IPPV. There are identifiable factors known on admission and occurring during the NICU stay that are associated with long-term IPPV.

Endothelial nitric oxide synthase in human intestine resected for necrotizing enterocolitis.

OBJECTIVE: To determine the expression and function of endothelial nitric oxide synthase (eNOS) in submucosal arterioles harvested from human intestine resected for necrotizing enterocolitis (NEC) or congenital bowel disease. STUDY DESIGN: eNOS expression was determined by using immunohistochemistry. The arteriolar diameter was measured in vitro at pressures of 10 to 40 mm Hg and also in response to the eNOS agonist acetylcholine (ACh), the exogenous nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine, and the smooth muscle relaxant papaverine. Arteriolar release of NO in response to ACh was determined with a Sievers NOAnalyzer. Hemodynamics were also determined at flow rates of 50 and 100 microL/min. RESULTS: eNOS was present in microvessels from both groups, but NEC arterioles failed to demonstrate physiological evidence of eNOS function: they constricted in response to pressure, failed to dilate or generate NO in response to ACh, and failed to dilate in response to flow. However, they dilated in response to exogenous NO and papaverine, indicating functional vascular smooth muscle and vasodilator reserve. CONCLUSION: eNOS-derived NO, a vasodilator in the newborn intestine, did not contribute to vasoregulation in arterioles harvested from intestine resected for NEC. These vessels were constricted; lack of eNOS-derived NO may contribute to this vasoconstriction.