The Landscape of Resource Utilization After Resuscitation of 22-, 23-, and 24-Weeks' Gestation Infants.

OBJECTIVE: To compare estimated healthcare resources needed to care for 22 through 24 weeks' gestation infants. STUDY DESIGN: This multicenter, retrospective cohort study included 1505 live in-born and out-born infants 22 through 24 weeks' gestational age at delivery from 6 pediatric tertiary care hospitals from 2011 through 2020. Median neonatal intensive care unit (NICU) length of stay (LOS) for each gestational age was used as a proxy for hospital resource utilization, and the number of comorbidities and medical technology use for each infant were used as estimates of future medical care needs. Data were analyzed using Kruskal-Wallis with Nemenyi's posthoc test and Fisher's exact test. RESULTS: Of the identified newborns, 22-week infants had shorter median LOS than their 23- and 24-week counterparts due to low survival rates. There was no significant difference in LOS for surviving 22-week infants compared with surviving 23-week infants. Surviving 22-week infants had similar proportions of comorbidities and medical technology use as 23-week infants. CONCLUSIONS: Compared with 23- and 24-week infants, 22-week infants did not use a disproportionate amount of hospital resources. Twenty-two-week infants should not be excluded from resuscitation based on concern for increased hospital care and medical technology requirements. As overall resuscitation efforts and survival rates increase for 22-week infants, future research will be needed to assess the evolution of these results.

Microbiome function and neurodevelopment in Black infants: vitamin B12 emerges as a key factor.

The early life gut microbiome affects the developing brain, and therefore may serve as a target to support neurodevelopment of children living in stressful and under-resourced environments, such as Black youth living on the South Side of Chicago, for whom we observe racial disparities in health. Microbiome compositions/functions key to multiple neurodevelopmental facets have not been studied in Black children, a vulnerable population due to racial disparities in health; thus, a subsample of Black infants living in urban, low-income neighborhoods whose mothers participated in a prenatal nutrition study were recruited for testing associations between composition and function of the gut microbiome (16S rRNA gene sequencing, shotgun metagenomics, and targeted metabolomics of fecal samples) and neurodevelopment (developmental testing, maternal report of temperament, and observed stress regulation). Two microbiome community types, defined by high Lachnospiraceae or Enterobacteriaceae abundance, were discovered in this cohort from 16S rRNA gene sequencing analysis; the Enterobacteriaceae-dominant community type was significantly negatively associated with cognition and language scores, specifically in male children. Vitamin B12 biosynthesis emerged as a key microbiome function from shotgun metagenomics sequencing analysis, showing positive associations with all measured developmental skills (i.e., cognition, language, motor, surgency, effortful control, and observed stress regulation). Blautia spp. also were identified as substantial contributors of important microbiome functions, including vitamin B12 biosynthesis and related vitamin B12-dependent microbiome functions, anti-inflammatory microbial surface antigens, competitive mechanisms against pathobionts, and production of antioxidants. The results are promising with respect to the potential for exploring therapeutic candidates, such as vitamin B12 nutritional or Blautia spp. probiotic supplementation, to support the neurodevelopment of infants at risk for experiencing racial disparities in health.

The University of Chicago Clinical Excellence Scholars Track: Aligning Dynamic Students With Innovative Programming in Early Medical Education at the Undergraduate Level.

The Clinical Excellence Scholars Track was developed in 2012 as a shared initiative between the Bucksbaum Institute for Clinical Excellence, the University of Chicago (UChicago) Careers in Healthcare office, and the UChicago Medicine Office of Community and External Affairs. The goal of the Clinical Excellence Scholars Track is to foster an understanding of the physician career and the doctor-patient relationship for a select group of undergraduate students. The Clinical Excellence Scholars Track achieves this goal through carefully tailored curricular requirements and direct mentoring experiences between Bucksbaum Institute Faculty Scholars and the student scholars. After participating in the Clinical Excellence Scholars Track program, student scholars report that their career understanding and preparation have benefitted as a result and that they meet with success in the medical school application process as well.

Smartphone application links severity of retinopathy of prematurity to early motor behavior in a cohort of high-risk preterm infants.

PURPOSE: To evaluate the General Movement Assessment (GMA) with the Motor Optimality Score-Revised (MOS-R) as a neurodevelopmental marker in infants with retinopathy of prematurity (ROP). METHODS: Infants screened prospectively for ROP were evaluated at 3 months' post-term age using a smartphone application to complete the GMA and MOS-R. Results were analyzed by ROP severity. RESULTS: Of 105 enrolled infants, 83 completed the study. Of these, 54 (65%) had any ROP, 32 (39%) had severe ROP, and 13 (16%) had type 1 ROP. The proportion with aberrant GMA was significantly higher in infants with severe ROP (14/32 [44%]) compared with infants who had milder ROP (8/51 [16%]; P = 0.006). Of those with severe ROP, there was no significant difference comparing infants with type 1 ROP treated with bevacizumab (7/13 [54%]) to infants with type 2 ROP without treatment (7/19 [37%]; P = 0.47). Although the presence of any ROP, stage of ROP, and severe ROP each predicted lower MOS-R scores on univariate analyses, only severe bronchopulmonary dysplasia and markers of brain injury remained significant in the multivariate analysis. CONCLUSIONS: The GMA was a convenient, short-term method of data collection with low attrition. Although severe ROP initially appeared linked to poor early motor scores, this association is likely confounded by neurological and respiratory complications, which frequently accompany severe ROP.

Shifting Provider Attitudes and Institutional Resources Surrounding Resuscitation at the Limit of Gestational Viability.

OBJECTIVE: This study aimed to provide contemporary data regarding provider perceptions of appropriate care for resuscitation and stabilization of periviable infants and institutional resources available to providers. STUDY DESIGN: A Qualtrics survey was emailed to 672 practicing neonatologists in the United States by use of public databases. Participants were asked about appropriate delivery room care for infants born at 22 to 26 weeks gestational age, factors affecting decision-making, and resources utilized regarding resuscitation. Descriptive statistics were used to analyze the dataset. RESULTS: In total, 180 responses were received, and 173 responses analyzed. Regarding preferred course of care based on gestational age, the proportion of respondents endorsing full resuscitation decreased with decreasing gestational age (25 weeks = 99%, 24 = 64%, 23 = 16%, and 22 = 4%). Deference to parental wishes correspondingly increased with decreasing gestational age (25 weeks = 1%, 24 = 35%, 23 = 82%, and 22 = 46%). Provision of comfort care was only endorsed at 22 to 23 weeks (23 weeks = 2%, 22 = 50%). Factors most impacting decision-making at 22 weeks gestational age included: outcomes based on population data (79%), parental wishes (65%), and quality of life measures (63%). Intubation with a 2.5-mm endotracheal tube (84%), surfactant administration in the delivery room (77%), and vascular access (69%) were the most supported therapies for initial stabilization. Availability of institutional resources varied; the most limited were obstetric support for cesarean delivery at the limit of viability (37%), 2.0-mm endotracheal tube (45%), small baby protocols (46%), and a consulting palliative care teams (54%). CONCLUSION: There appears to be discordance in provider attitudes surrounding preferred actions at 23 and 22 weeks. Provider attitudes regarding decision-making at the limit of viability and identified resource limitations are nonuniform. Between-hospital variations in outcomes for periviable infants may be partly attributable to lack of provider consensus and nonuniform resource availability across institutions. KEY POINTS: · Within the past decade, there has been a shift in the gray zone from 23-24 to 22-23 weeks gestation.. · Attitudes around resuscitation of infants are nonuniform despite perceived standardized approaches.. · Institutional variability in resources may contribute to variation in outcomes of periviable infants..

Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment.

The early life microbiome plays critical roles in host development, shaping long-term outcomes including brain functioning. It is not known which initial infant colonizers elicit optimal neurodevelopment; thus, this study investigated the association between gut microbiome succession from the first week of life and head circumference growth (HCG), the earliest validated marker for neurodevelopment. Fecal samples were collected weekly from a preterm infant cohort during their neonatal intensive care unit stay and subjected to 16S rRNA gene sequencing for evaluating gut microbiome composition, in conjunction with clinical data and head circumference measurements. Preterm infants with suboptimal HCG trajectories had a depletion in the abundance/prevalence of Bacteroidota and Lachnospiraceae, independent of morbidity and caloric restriction. The severity of gut microbiome depletion matched the timing of significant HCG pattern separation between study groups at 30-week postmenstrual age demonstrating a potential mediating relationship resultant from clinical practices. Consideration of the clinical variables indicated that optimal infant microbiome succession is primarily driven by dispersal limitation (i.e., delivery mode) and secondarily by habitat filtering (i.e., antibiotics and enteral feeding). Bacteroidota and Lachnospiraceae are known core taxa of the adult microbiome, with roles in dietary glycan foraging, beneficial metabolite production and immunity, and our work provides evidence that their integration into the gut microbiome needs to occur early for optimal neurodevelopment.

Multicenter Validation of the Neonatal Sequential Organ Failure Assessment Score for Prognosis in the Neonatal Intensive Care Unit.

Infants in the neonatal intensive care unit are at risk of life-threatening organ dysfunction, but few objective tools with utility exist. In a multicenter cohort of 20 152 infants, we show the neonatal sequential organ failure assessment score had good-to-excellent discrimination of mortality across centers, birth weights, and time points after admission.

Changes in Neurodevelopmental Outcomes From Age 2 to 10 Years for Children Born Extremely Preterm.

OBJECTIVES: Evidence-based care of extremely preterm infants (<28 weeks' gestation) depends heavily on research in which a primary outcome is infant neurodevelopmental impairment (NDI), yet it is unclear how well NDI in infancy predicts long-term NDI. In this study, we aim to assess the relationship between 2- and 10-year neurodevelopment using a well-known 2-year definition and a 10-year definition developed by an expert panel. METHODS: Using data from the Extremely Low Gestational Age Newborn Study cohort, we classified 2-year NDI using definitions developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. We classified 10-year NDI using definitions developed by an expert panel, which added epilepsy and ASD at 10 years. RESULTS: Of 1506 infants, 80% survived. Data sufficient to classify severity of NDI at both 2 and 10 years were available for 67% of survivors (n = 802). Among children classified as having moderate to severe NDI at 2 years, 63% had none to mild NDI at 10 years; among children classified as having profound NDI at 2 years, 36% had none to mild NDI at 10 years. Cohen's κ statistic indicated minimal to fair agreement between NDI at 2 and 10 years (0.34, P < .001). CONCLUSIONS: NDI in infancy, as defined in this study, only weakly predicts NDI in middle childhood. For the parents at risk for delivery of an extremely preterm infant, a hopeful message can be taken from our findings that one-third of surviving children classified as having profound NDI and nearly two-thirds of those classified as having moderate to severe NDI at 2 years had none to mild NDI at 10 years.

Protocol for implementation of an evidence based parentally administered intervention for preterm infants.

BACKGROUND: Multi-sensory behavioral interventions for preterm infants have the potential to accelerate feeding, growth, and optimize developmental trajectories and increase parents' interactive engagement with their infants. However, few neonatal intensive care units (NICUs) provide evidence-based standardized early behavioral interventions as routine care. Lack of implementation is a major gap between research and clinical practice. H-HOPE, is a standardized behavioral intervention with an infant- directed component (Massage+) and a parent-directed component (four participatory guidance sessions that focus on preterm infants' behaviors and appropriate responses). H-HOPE has well documented efficacy. The purpose of this implementation study is to establish H-HOPE as the standard of care in 5 NICUs. METHODS: The study employs a Type 3 Hybrid design to simultaneously examine the implementation process and effectiveness in five NICUs. To stagger implementation across the clinical sites, we use an incomplete stepped wedge design. The five participating NICUs were purposively selected to represent different acuity levels, number of beds, locations and populations served. Our implementation strategy integrates our experience conducting H-HOPE and a well-established implementation model, the Consolidated Framework for Implementation Research (CFIR). The CFIR identifies influences (facilitators and barriers) that affect successful implementation within five domains: intervention characteristics, outer setting (the hospital and external events and stakeholders), inner setting (NICU), implementers' individual characteristics, and the implementation process. NICUs will use the CFIR process, which includes three phases: Planning and Engaging, Executing, and Reflecting and Evaluating. Because sustaining is a critical goal of implementation, we modify the CFIR implementation process by adding a final phase of Sustaining. DISCUSSION: This study builds on the CFIR, adding Sustaining H-HOPE to observe what happens when sites begin to maintain implementation without outside support, and extends its use to the NICU acute care setting. Our mixed methods analysis systematically identifies key facilitators and barriers of implementation success and effectiveness across the five domains of the CFIR. Long term benefits have not yet been studied but may include substantial health and developmental outcomes for infants, more optimal parent-child relationships, reduced stress and costs for families, and substantial indirect societal benefits including reduced health care and special education costs. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT04555590 , Registered on 8/19/2020.

Ethical Cultures in Perinatal Care: Do They Exist? Correlation of Provider Attitudes with Periviability Practices at Six Centers.

OBJECTIVE: This study aimed to compare attitudes of providers regarding perinatal management and outcomes for periviable newborns of caregivers at centers with higher resuscitation (HR) and lower resuscitation (LR) rates in the delivery room. STUDY DESIGN: All obstetric and neonatal clinical providers at six U.S. sites were invited to complete an anonymous online survey. Survey responses were compared with clinical data collected from a previous retrospective study comparing centers' rates of planned resuscitation. Responses were analyzed by multivariable logistic and linear regression to assess how HR versus LR center respondents differed in management preferences and outcome predictions. RESULTS: Paradoxically, HR versus LR respondents, when adjusting for other variables, were less likely to respond that interventions such as antenatal steroids (odds ratio: 0.61, 95% confidence interval [CI]: 0.42-0.88, p < 0.009) and resuscitation (OR: 0.59, 95% CI: 0.44-0.78, p < 0.001) should be given at 22 weeks. HR versus LR respondents also reported lower likelihood of survival and acceptable quality of life (OR: 0.7, 95% CI: 0.53-0.93, p = 0.012) at 23 weeks. CONCLUSION: Despite higher rates of planned resuscitation at 22 and 23 weeks, steroid usage and survival rates did not differ between HR and LR sites. In this subsequent survey, respondents from HR centers had a less favorable outlook on interventions for these newborns than those at LR centers, suggesting that instead of driving practices, attitudes may be more closely associated with experiences of clinical outcomes.

Intention to treat: obstetrical management at the threshold of viability.

BACKGROUND: Despite medical advances in the care of extremely preterm neonates and growing acceptance of resuscitation at 23 and even 22 weeks gestation, controversy remains concerning the use of antepartum obstetric intervention s that are intended to improve outcomes in the setting of anticipated extremely preterm birth. In the absence of demonstrated benefit at <23 weeks gestation and with uncertain benefit at 23 weeks gestation, previous obstetric committee opinions have advised against their use at these gestational ages. OBJECTIVE: The purpose of this study was to review the use of obstetric intervention s at the threshold of viability based on neonatal resuscitation plan and to review the odds of survival to neonatal intensive care unit discharge based on use of obstetric intervention s with adjustment for neonatal factors. STUDY DESIGN: This retrospective study of 6 study centers reviewed pregnant patients who were admitted between 22+0/7 and 24+6/7 weeks gestation facing delivery from 2011-2015. Patients with known anomalies or missing data were excluded. Records were reviewed for demographics, resuscitation plan, and obstetric intervention s. Mode of delivery, delivery room care, and final infant dispositions were recorded. Multiple gestations were included as 1 pregnancy in regard to the use of obstetric intervention s and were excluded from survival analysis. RESULTS: Four hundred seventy-eight mothers met the inclusion criteria. When resuscitation was planned, mothers were more likely to receive all conventional obstetric intervention s (antenatal steroids, magnesium sulfate for neuroprotection, tocolytics, and Group Beta Streptococcus prophylaxis), regardless of gestational age at admission, and were more likely to be delivered by cesarean section (P<.05). Analyzed as a group, when antenatal steroids, magnesium sulfate, tocolytics and Group Beta Streptococcus prophylaxis were administered, the odds of survival to neonatal intensive care unit discharge increased for newborn infants who were born at 22 (odds ratio, 11.33; 95% confidence interval, 1.405-91.4) and 23 weeks gestation (odds ratio, 15.5; 95% confidence interval, 3.747-64.11; P<.05). In singletons, the odds of survival to neonatal intensive care unit discharge was not improved by cesarean delivery vs vaginal delivery, even after adjustment for the use of additional interventions, weight, gender, and gestational age (odds ratio, 1.0; 95% confidence interval, 0.59-1.8; P=.912). CONCLUSION: In this study, when postnatal resuscitation was planned at 22 and 23 weeks gestation, women were more likely to receive antenatal steroids, magnesium sulfate, and antibiotics; provision of this bundle imparted survival benefit at 23 weeks gestation but could not be demonstrated at 22 weeks gestation because of the small sample size. These findings support of neonate-oriented obstetric interventions in the setting of delivery at 23 weeks gestation when resuscitation is planned and further exploration of optimal obstetric care when resuscitation of infants who were born at 22 weeks gestation is anticipated.

The early gut microbiome could protect against severe retinopathy of prematurity.

In this study, 6 infants with type 1 retinopathy of prematurity (ROP) were compared with 4 high-risk preterm neonates without any ROP but similar baseline neonatal comorbidities. The infants with type-1 ROP showed significant enrichment of Enterobacteriaceae at 28 weeks' postmenstrual age. Several metabolic pathways, including several amino acid metabolism pathways, were enriched in gut microbiota of infants without ROP. Based on these findings, we posit a possible association between early gut microbiome profile and ROP pathogenesis. Furthermore, it is possible that absence of Enterobacteriaceae overabundance, in addition to enrichment of amino acid biosynthesis pathways, may protect against severe ROP in high-risk preterm infants.

Antenatal Periviability Counseling and Decision Making: A Retrospective Examination by the Investigating Neonatal Decisions for Extremely Early Deliveries Study Group.

OBJECTIVE: To describe periviability counseling practices and decision making. STUDY DESIGN: This is a retrospective review of mothers and newborns delivering between 22 and 24 completed weeks from 2011 to 2015 at six U.S. centers. Maternal and fetal/neonatal clinical and maternal sociodemographic data from medical records and geocoded sociodemographic information were collected. Separate analyses examined characteristics surrounding receiving neonatology consultation; planning neonatal resuscitation; and centers' planned resuscitation rates. RESULTS: Neonatology consultations were documented for 40, 63, and 72% of 498 mothers delivering at 22, 23, and 24 weeks, respectively. Consult versus no-consult mothers had longer median admission-to-delivery intervals (58.7 vs. 8.7 h, p < 0.001). Consultations were seen more frequently when parental decision making was evident. In total, 76% of mothers had neonatal resuscitation planned. Resuscitation versus no-resuscitation newborns had higher mean gestational ages (24.0 vs. 22.9 weeks, p < 0.001) and birthweights (618 vs. 469 g, p < 0.001). Planned resuscitation rates differed at higher (HR) versus lower (LR) rate centers at 22 (43 vs. 7%, p < 0.001) and 23 (85 vs. 58%, p < 0.001) weeks. HR versus LR centers' populations had more socioeconomic hardship markers but fewer social work consultations (odds ratio: 0.31; confidence interval: 0.15-0.59, p < 0.001). CONCLUSION: Areas requiring improvement included delivery/content of neonatology consultations, social work support, consideration of centers' patient populations, and opportunities for shared decisions.

Neurodevelopmental Outcomes Comparing Bevacizumab to Laser for Type 1 ROP.

BACKGROUND AND OBJECTIVE: To evaluate neurodevelopmental outcomes among infants treated for retinopathy of prematurity (ROP) at the authors' institution. PATIENTS AND METHODS: Before-and-after retrospective chart reviews identified 40 infants treated with laser and 46 treated with primary intravitreal bevacizumab (IVB). Primary outcomes were death, hearing loss, bilateral visual impairment (BVI), and cerebral palsy (CP); odds ratios (ORs) were calculated to determine factors associated with CP. Secondary outcomes were mean Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores. RESULTS: Overall, there were no significant differences in primary outcome measures by treatment group. However, adjusted odds of BVI were significantly higher with laser compared to IVB (OR = 13.1; P = .038). Although IVB was not associated with CP, both hydrocephalus and BVI were strongly correlated with CP. Mean Bayley-III scores were similar when comparing nine laser-treated infants to 13 IVB-treated infants. CONCLUSIONS: Visual outcomes are an important aspect of neurodevelopment. IVB was not associated with severe developmental disabilities and may protect against vision loss in this analysis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:337-343.].