Early prediction of mortality and morbidities in VLBW preterm neonates using machine learning.

BACKGROUND: Predicting mortality and specific morbidities before they occur may allow for interventions that may improve health trajectories. HYPOTHESIS: Integrating key maternal and postnatal infant variables in the first 2 weeks of age into machine learning (ML) algorithms will reliably predict survival and specific morbidities in VLBW preterm infants. METHODS: ML algorithms were developed to integrate 47 features for predicting mortality, bronchopulmonary dysplasia (BPD), neonatal sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP). A retrospective cohort (n = 3341) was used to train and validate the models with a repeated 10-fold cross-validation strategy. These models were then tested on a separate cohort (n = 447) to evaluate the final model performance. RESULTS: Among the seven ML algorithms employed, tree-based ensemble models, specifically Random Forest (RF) and XGBoost, had the best performance metrics. The area under the receiver operating characteristic curve (AUROC) of sepsis with or without meningitis (0.73), NEC (0.73), BPD (0.71), and mortality (0.74) exceeded 0.7, while the area under Precision-Recall curve (AUPRC) for all outcomes was greater than the prevalence, demonstrating effective risk stratification in VLBW preterm infants. CONCLUSIONS: Our study demonstrates the potential of predictive analytics leveraging ML techniques in advancing precision medicine. IMPACT: Reliable prediction of adverse outcomes before they occur has the potential to institute interventions and possibly improve health trajectories in VLBW preterm infants. We used machine learning to develop and test predictive models for mortality and five major morbidities in VLBW preterm infants. Individualized prediction of outcomes and individualized interventions will advance Precision Medicine in Neonatology.

Initial surgery for spontaneous intestinal perforation in extremely low birth weight infants is not associated with mortality or in-hospital morbidities.

OBJECTIVE: Determine short-term outcomes following peritoneal drain (PD), laparotomy (LAP) after PD (PD-LAP), and LAP in extremely low birth weight (ELBW) infants with spontaneous intestinal perforation (SIP). STUDY DESIGN: ELBW infants with SIP were identified using the Children's Hospitals Neonatal Database. Mortality and length of stay (LOS) were compared among groups. RESULTS: Of 729 SIP infants from 6/2010-12/2016, 383(53%) received PD, 61(8%) PD-LAP, and 285(39%) LAP. PD infants had lower GA at birth, at SIP diagnosis and upon admission than PD-LAP or LAP; and higher sepsis rates than LAP. Bivariate analysis and Kaplan-Meier survival estimates suggested PD had increased mortality vs. PD-LAP and LAP (27%, 11.5%, and 15.8% respectively, p < 0.001). However, surgical approach was not significantly associated with mortality in multivariable analysis accounting for GA and illness severity. LOS did not differ by surgical approach. CONCLUSIONS: In ELBW infants with SIP, mortality, and LOS are independent of the initial surgical approach.

Cholestasis is associated with a higher rate of complications in both medical and surgical necrotizing enterocolitis.

OBJECTIVE: To evaluate the relationship between cholestasis and outcomes in medical and surgical necrotizing enterocolitis (NEC). STUDY DESIGN: A retrospective analysis of prospectively collected data from 1472 infants with NEC [455 medical (mNEC) and 1017 surgical (sNEC)] from the Children's Hospital Neonatal Database. RESULTS: The prevalence of cholestasis was lower in mNEC versus sNEC (38.2% vs 70.1%, p < 0.001). In both groups, cholestasis was associated with lower birth gestational age [mNEC: OR 0.79 (95% CI 0.68-0.92); sNEC: OR 0.86 (95% CI 0.79-0.95)] and increased days of parenteral nutrition [mNEC: OR 1.08 (95% CI 1.04-1.13); sNEC: OR 1.01 (95% CI 1.01-1.02)]. For both groups, the highest direct bilirubin was associated with the composite outcome mortality or length of stay >75th percentile [mNEC: OR 1.21 (95% CI 1.06-1.38); sNEC: OR 1.06 (95% CI 1.03-1.09)]. CONCLUSION: Cholestasis with both medical NEC and surgical NEC is associated with adverse patient outcomes including increased mortality or extreme length of stay.

Optimizing clinical care and training in the neonatal intensive care unit: the relationship between front line providers and physician trainees.

Changes in neonatal intensive care unit (NICU) coverage models, restrictions in trainee work hours, and alterations to the training requirements of pediatric house staff have led to a rapid increase in utilization of front-line providers (FLPs) in the NICU. FLP describes a provider who cares for neonates and infants in the delivery room, nursery, and NICU, and includes nurse practitioners, physician assistants, and/or hospitalists. The increasing presence and responsibility of FLPs in the NICU have fundamentally changed the way patient care is provided as well as the learning environment for trainees. With these changes has come confusion over role clarity with resulting periodic conflict. While staffing changes have addressed a critical clinical gap, they have also highlighted areas for improvement amongst the teams of NICU providers. This paper describes the current landscape and summarizes improvement opportunities with a dynamic neonatal interprofessional provider team.

Current Patterns of Probiotic Use in U.S. Neonatal Intensive Care Units: A Multi-Institution Survey.

OBJECTIVE: Probiotic supplementation is associated with health benefits in preterm infants. The 2021 American Academy of Pediatrics (AAP) statement on probiotic use advised caution, citing heterogeneity and absence of federal regulation. We assessed the impact of the AAP statement and current institution-wide patterns of probiotic use across neonatal intensive care units (NICU) across the United States. STUDY DESIGN: A cross-sectional web-based institutional survey using REDCap was emailed to 430 Children's Hospital Neonatal Consortium (CHNC) and Pediatrix Medical Group institutions. The survey captured data on probiotic formulations, supplementation, initiation and cessation criteria, reasons for discontinuation, interest in initiating, and AAP statement's impact. RESULTS: Ninety-five (22.1%) hospitals, including 42/46 (91%) CHNC and 53/384 (14%) Pediatrix institutions, completed the survey. Thirty-seven (39%) currently use probiotics. Fourteen different probiotic formulations were reported. The common criteria for initiation were birth weight <1,500 g and gestational age <32 weeks. Parental consent or assent was obtained at only 30% of institutions. Five hospitals (11%) with prior probiotic use discontinued solely due to the AAP statement. Overall, 23 (24%) of hospitals indicated that the AAP statement significantly influenced their decision regarding probiotic use. Nineteen of 51 nonusers (37%) are considering initiation. CONCLUSION: Probiotic use in preterm infants is likely increasing in NICUs across the United States, but significant variability exists. The 2021 AAP statement had variable impact on NICUs' decision regarding probiotic use. The growing interest in adopting probiotics and the significant interhospital variability highlight the need for better regulation and consensus guidelines to ensure standardized use. KEY POINTS: · Probiotic use in preterm infants is likely increasing in U.S. NICUs, but clinical variability exists.. · The AAP statement on probiotic use in preterm infants had a modest impact on current practices.. · There's a need for better product regulation and consensus guidelines to ensure standardized use..

Patterns of lipid-injectable emulsion use in neonatal intensive care units across the United States: A multi-institution survey.

BACKGROUND: Lipid-injectable emulsions (ILEs) are a necessity for neonates dependent on parenteral nutrition (PN). In this manuscript, we describe the patterns of ILE use in neonatal intensive care units (NICUs) in the United States (US). METHODS: An electronic survey was sent to 488 NICUs across the US between December 2020 and March 2021. Survey fields included availability and utilization of various ILE in neonates. RESULTS: The response rate was 22% (107 out of 488). Soybean oil ILE (SO-ILE) and soybean oil, medium-chain triglycerides, olive oil, fish oil ILE (SO, MCT, OO, FO-ILE) had similar availability (87% vs 86%, respectively), and SO, MCT, OO, FO-ILE was more commonly used (SO-ILE, 71% vs SO, MCT, OO, FO-ILE, 86%). Fish oil-ILE (FO-ILE) was used by 55% of centers. SO-ILE was most frequently used with PN and needs <4 weeks without cholestasis (79%). The most common reason for SO, MCT, OO, FO-ILE use was cholestasis (71%). ILE minimization was used by 28% of SO-ILE and 22% of SO, MCT, OO, FO-ILE users; 95% of these centers restrict SO, MCT, OO, FO-ILE to doses ≤2 g/kg/day. Twenty-two percent of centers started FO-ILE at direct bilirubin of >5 mg/dl. CONCLUSION: The results of this survey reveal significant variability in ILE usage across the US. Lipid minimization with SO, MCT, OO, FO-ILE and initiation of FO-ILE for cholestasis at higher bilirubin thresholds are prevalent. Such reports are crucial for a better understanding of ILE use in the NICU and in future ILE development.

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.

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.

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..

Neonatal Use of Acute Care Services During the COVID-19 Pandemic.

OBJECTIVE: To describe changes in neonatal use of acute care services during the coronavirus disease 2019 (COVID-19) pandemic. We hypothesized neonatal visits would decrease and the degree of decline would vary by condition. METHODS: We conducted a retrospective cohort study of neonatal visits to the urgent cares, emergency departments, inpatient units, and intensive care units at a free-standing pediatric healthcare system during the COVID-19 pandemic and a comparator period. We included visits of infants presenting for acute care within the first 30 days of life. Transfers from a referring nursery, inpatient unit, or ICU were excluded. Data collected included demographics, patient characteristics, and visit characteristics. Descriptive statistics and χ2 tests were used for analyses and to determine statistically significant differences. RESULTS: We identified 4439 neonatal acute care visits, of which 2677 occurred in the prepandemic period and 1762 in the COVID-19 pandemic period, representing a 34.2% decline. Urgent cares and emergency departments experienced the greatest decline in visits for infectious conditions (49%) and the proportion of these visits also significantly decreased. Similarly, the largest clinically significant declines in hospitalizations were for infectious and respiratory diagnoses (48% and 52%, respectively) and the proportions of these hospitalizations also significantly decreased. Despite a small decline in hospitalizations for jaundice, the proportion of jaundice hospitalizations significantly increased by 5.7% (P = .02). CONCLUSIONS: The COVID-19 pandemic was associated with a significant reduction in neonatal visits across a spectrum of acute care settings. The impact on use varied by diagnosis with the most notable decline in visits for infectious conditions.

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.

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.

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.

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.

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.

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.

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.