Quality Improvement Interventions to Prevent Intraventricular Hemorrhage: A Systematic Review.

OBJECTIVES: Quality improvement may reduce the incidence and severity of intraventricular hemorrhage in preterm infants. We evaluated quality improvement interventions (QIIs) that sought to prevent or reduce the severity of intraventricular hemorrhage. METHODS: PubMed, CINAHL, Embase, and citations of selected articles were searched. QIIs that had reducing incidence or severity of intraventricular hemorrhage in preterm infants as the primary outcome. Paired reviewers independently extracted data from selected studies. RESULTS: Eighteen quality improvement interventions involving 5906 infants were included. Clinical interventions in antenatal care, the delivery room, and the NICU were used in the QIIs. Four of 10 QIIs reporting data on intraventricular hemorrhage (IVH) and 9 of 14 QIIs reporting data on severe IVH saw improvements. The median Quality Improvement Minimum Quality Criteria Set score was 11 of 16. Clinical intervention heterogeneity and incomplete information on quality improvement methods challenged the identification of the main reason for the observed changes. Publication bias may result in the inclusion of more favorable findings. CONCLUSIONS: QIIs demonstrated reductions in the incidence and severity of intraventricular hemorrhage in preterm infants in some but not all settings. Which specific interventions and quality improvement methods were responsible for those reductions and why they were successful in some settings but not others are not clear. This systematic review can assist teams in identifying potentially better practices for reducing IVH, but improvements in reporting and assessing QIIs are needed if systematic reviews are to realize their potential for guiding evidence-based practice.

Transcatheter and Surgical Ductus Arteriosus Closure in Very Low Birth Weight Infants: 2018-2022.

BACKGROUND AND OBJECTIVE: The optimal patent ductus arteriosus (PDA) closure method in very low birth weight (VLBW) infants is uncertain. In 2019, the first transcatheter occlusion device was approved in the United States for infants ≥700 g. We described survival and short-term outcomes among VLBW infants who underwent transcatheter or surgical PDA closure (2018-2022). METHODS: Vermont Oxford Network members submitted data on infants born from 401 to 1500 g or 22 to 29 weeks' gestational age. Adjusted risk ratios (aRR) for survival, length of stay (LOS), prematurity complications, and discharge support were used to compare transcatheter versus surgical closure. Subgroup analyses were conducted for infants with birth weight ≥700 g and born in 2020-2022. RESULTS: Overall, 6410 of 216 267 infants at 726 hospitals received invasive PDA treatment. Transcatheter closure increased from 29.8% in 2018 to 71.7% in 2022. VLBW infants undergoing transcatheter closure had higher survival (adjusted rate ratio [aRR] 1.03; 1.02-1.04) with similar LOS (aRR 1.00; 0.97-1.03), neonatal complications (aRR 1.00; 0.98-1.01), and receipt of discharge support (aRR 0.94; 0.89-1.01). In subgroup analyses, survival (aRR 1.02; 1.00-1.04) and discharge support (aRR 0.90; 0.81-1.01) were similar between groups, whereas selected neonatal complications (aRR 0.95; 0.93-0.98) and LOS (aRR 0.95; 0.90-0.99) were lower after transcatheter closure. CONCLUSIONS: Transcatheter PDA closure in VLBW infants was increasingly used after 2018. Selected short-term outcomes for infants receiving transcatheter closure may be more favorable, compared with surgical, and warrants further clinical investigation.

Association between type of feeding at hospital discharge and nutritional status of Brazilian very preterm infants: a multicenter study.

OBJECTIVES: To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer. METHODS: The authors studied 4062 surviving very preterm infants born < 32 weeks' gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed. Outcomes were weight and head circumference at hospital discharge and the change in each from birth to discharge. The authors used linear regression to estimate adjusted associations of diet type with infant size, overall, and stratified by fetal growth category (small vs. appropriate for gestational age). The authors also examined trends in diet and infant size at discharge over the years. RESULTS: Infants' mean gestational age at birth was 29.3 weeks, and the mean birth weight was 1136 g. Diet at discharge/transfer was exclusive human milk for 22 %, mixed for 62 %, and exclusive formula for 16 %. Infant size in weight and head circumference were substantially below the growth chart reference for all diets. Infants fed human milk and mixed diets were lighter and had smaller heads at discharge/transfer than infants fed formula only (weight z: -2.0, -1.8, and -1.5; head z: -1.3, -1.2 and -1.1 for exclusive human milk, mixed and exclusive formula respectively). CONCLUSION: Results suggest high human milk use but gaps in nutrient delivery among hospitalized Brazilian very preterm infants, with little evidence of improvement over time.

Caught in the Act: Incipient Speciation at the Southern limit of Viburnum in the Central Andes.

A fundamental objective of evolutionary biology is to understand the origin of independently evolving species. Phylogenetic studies of species radiations rarely are able to document ongoing speciation; instead, modes of speciation, entailing geographic separation and/or ecological differentiation, are posited retrospectively. The Oreinotinus clade of Viburnum has radiated recently from north to south through the cloud forests of Mexico and Central America to the Central Andes. Our analyses support a hypothesis of incipient speciation in Oreinotinus at the southern edge of its geographic range, from central Peru to northern Argentina. Although several species and infraspecific taxa of have been recognized in this area, multiple lines of evidence and analytical approaches (including analyses of phylogenetic relationships, genetic structure, leaf morphology, and climatic envelopes) favor the recognition of just a single species, V. seemenii. We show that what has previously been recognized as V. seemenii f. minor has recently occupied the drier Tucuman-Bolivian forest region from Samaipata in Bolivia to Salta in northern Argentina. Plants in these populations form a well-supported clade with a distinctive genetic signature and they have evolved smaller, narrower leaves. We interpret this as the beginning of a within-species divergence process that has elsewhere in the neotropics resulted repeatedly in Viburnum species with a particular set of leaf ecomorphs. Specifically, the southern populations are in the process of evolving the small, glabrous, and entire leaf ecomorph that has evolved in four other montane areas of endemism. As predicted based on our studies of leaf ecomorphs in Chiapas, Mexico, these southern populations experience generally drier conditions, with large diurnal temperature fluctuations. In a central portion of the range of V. seemenii, characterized by wetter climatic conditions, we also document what may be the initial differentiation of the leaf ecomorph with larger, pubescent, and toothy leaves. The emergence of these ecomorphs thus appears to be driven by adaptation to subtly different climatic conditions in separate geographic regions, as opposed to parapatric differentiation along elevational gradients as suggested by Viburnum species distributions in other parts of the neotropics.

University herbaria are uniquely important.

University herbaria play critical roles in biodiversity research and training and provide interdisciplinary academic environments that foster innovative uses of natural history collections. Universities have a responsibility to steward these important collections in perpetuity, in alignment with their academic missions and for the good of science and society.

Potentially Better Practices for Follow Through in Neonatal Intensive Care Units.

OBJECTIVE: To ascertain how NICU teams are undertaking action to follow through, involving teams, families, and communities as partners to address health-related social needs of infants and families. METHODS: Nineteen potentially better practices (PBPs) for follow through first published in 2020 were reported and analyzed as a sum, overall, and by safety-net hospital status, hospital ownership, and NICU type, among US NICUs that finalized Vermont Oxford Network data collection in 2023. RESULTS: One hundred percent of 758 eligible hospitals completed the annual membership survey, of which 57.5% reported screening for social risks. Almost all NICUs offered social work, lactation support, and translation services, but only 16% included a lawyer or paralegal on the team. Overall, 90.2% helped families offset financial costs while their infants were in the hospital, either with direct services or vouchers. At discharge, 94.0% of NICUs connected families with appropriate community organizations and services, 52.9% provided telemedicine after discharge, and 11.7% conducted home visits. The median number of PBPs at each hospital was 10 (25th percentile: 8, 75th percentile: 12). The number of PBPs reported differed by hospital control or ownership and level of NICU care. There were no differences by safety-net hospital status. CONCLUSIONS: Despite concerns about time and resources, a diverse set of US NICUs reported adopting potentially better practices for follow through. However, the marked variation among NICUs and the lower rates at for-profit and lower-level NICUs suggest there is substantial opportunity for improvement.

Comparing Healthcare Needs in Extremely Low Birth Weight Infants With NEC and Spontaneous Intestinal Perforation.

BACKGROUND: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) affect 6-8% of extremely low birth weight (ELBW) infants. SIP has lower mortality than NEC, but with similar short-term morbidity in length of stay, growth failure, and supplemental oxygen requirements. Comparative long-term neurodevelopmental outcomes have not been clarified. METHODS: Data were prospectively collected from 59 North American neonatal units, regarding ELBW infants (401-1000 g or 22-27 weeks gestational age) born between 2011 and 2018 and evaluated again at 16-26 months corrected age. Outcomes were collected from infants with laparotomy-confirmed NEC, laparotomy-confirmed SIP, and those without NEC or SIP. The primary outcome was severe neurodevelopmental disability. Secondary outcomes were weight <10th percentile, medical readmission, post-discharge surgery and medical support at home. Adjusted risk ratios (ARR) were calculated. RESULTS: Of 13,673 ELBW infants, 6391 (47%) were followed including 93 of 232 (40%) with NEC and 100 of 235 (42%) with SIP. There were no statistically significant differences in adjusted risk of any outcomes when directly comparing NEC to SIP (ARR 2.35; 95% CI 0.89, 6.26). However, infants with NEC had greater risk of severe neurodevelopmental disability (ARR 1.43; 1.09-1.86), rehospitalization (ARR 1.46; 1.17-1.82), and post-discharge surgery (ARR 1.82; 1.48-2.23) compared to infants without NEC or SIP. Infants with SIP only had greater risk of post-discharge surgery (ARR 1.64; 1.34-2.00) compared to infants without NEC or SIP. CONCLUSIONS: ELBW infants with NEC had significantly increased risk of severe neurodevelopmental disability and post-discharge healthcare needs, consistent with prior literature. We now know infants with SIP also have increased healthcare needs. LEVELS OF EVIDENCE: Level II.

Predictors of Mortality in Very Low Birth Weight Neonates With Congenital Diaphragmatic Hernia.

BACKGROUND: Limited data exists regarding the mortality of very low birth weight (VLBW) neonates with congenital diaphragmatic hernia (CDH). This study aims to quantify and determine predictors of mortality in VLBW neonates with CDH. METHODS: This analysis of 829 U.S. NICUs included VLBW [birth weight ≤1500g] neonates, born 2011-2021 with and without CDH. The primary outcome was in-hospital mortality. A generalized estimating equation regression model determined the adjusted risk ratio (ARR) of mortality. RESULTS: Of 426,140 VLBW neonates, 535 had CDH. In neonates with CDH, 48.4% had an additional congenital anomaly vs 5.5% without. In-hospital mortality for neonates with CDH was 70.4% vs 12.6% without. Of those with CDH, 73.3% died by day of life 3. Of VLBW neonates with CDH, 38% were repaired. A subgroup analysis was performed on 60% of VLBW neonates who underwent delivery room intubation or mechanical ventilation, as an indicator of active treatment. Mortality in this group was 62.7% for neonates with CDH vs 16.4% without. Higher Apgars at 1 min and repair of CDH were associated with lower mortality (ARR 0.91; 95%CI 0.87,0.96 and ARR 0.28; 0.21,0.39). The presence of additional congenital anomalies was associated with higher mortality (ARR 1.14; 1.01,1.30). CONCLUSION: These benchmark data reveal that VLBW neonates with CDH have an extremely high mortality. Almost half of the cohort have an additional congenital anomaly which significantly increases the risk of death. This study may be utilized by providers and families to better understand the guarded prognosis of VLBW neonates with CDH. TYPE OF STUDY: Level II. LEVEL OF EVIDENCE: Level II.

Quality improvement in maternal and reproductive health services.

As maternal mortality and morbidity rates stagnate or increase worldwide, there is an urgent need to address health system issues that impede access to high-quality care. Learning from efforts to address the value, safety, and effectiveness of reproductive and maternal health care is essential to advancing quality improvement efforts.

Predicting photosynthetic pathway from anatomy using machine learning.

Plants with Crassulacean acid metabolism (CAM) have long been associated with a specialized anatomy, including succulence and thick photosynthetic tissues. Firm, quantitative boundaries between non-CAM and CAM plants have yet to be established - if they indeed exist. Using novel computer vision software to measure anatomy, we combined new measurements with published data across flowering plants. We then used machine learning and phylogenetic comparative methods to investigate relationships between CAM and anatomy. We found significant differences in photosynthetic tissue anatomy between plants with differing CAM phenotypes. Machine learning-based classification was over 95% accurate in differentiating CAM from non-CAM anatomy, and had over 70% recall of distinct CAM phenotypes. Phylogenetic least squares regression and threshold analyses revealed that CAM evolution was significantly correlated with increased mesophyll cell size, thicker leaves, and decreased intercellular airspace. Our findings suggest that machine learning may be used to aid the discovery of new CAM species and that the evolutionary trajectory from non-CAM to strong, obligate CAM requires continual anatomical specialization.

Transfer Patterns Among Infants Born at 28 to 34 Weeks' Gestation.

BACKGROUND: Although postnatal transfer patterns among high-risk (eg, extremely preterm or surgical) infants have been described, transfer patterns among lower-risk populations are unknown. The objective was to examine transfer frequency, indication, timing, and trajectory among very and moderate preterm infants. METHODS: Observational study of the US Vermont Oxford Network all NICU admissions database from 2016 to 2021 of inborn infants 280/7 to 346/7 weeks. Infants' first transfer was assessed by gestational age, age at transfer, reason for transfer, and transfer trajectory. RESULTS: Across 467 hospitals, 294 229 infants were eligible, of whom 12 552 (4.3%) had an initial disposition of transfer. The proportion of infants transferred decreased with increasing gestational age (9.6% [n = 1415] at 28 weeks vs 2.4% [n = 2646] at 34 weeks) as did the median age at time of transfer (47 days [interquartile range 30-73] at 28 weeks vs 8 days [interquartile range 3-16] at 34 weeks). The median post menstrual age at transfer was 34 or 35 weeks across all gestational ages. The most common reason for transfer was growth or discharge planning (45.0%) followed by medical and diagnostic services (30.2%), though this varied by gestation. In this cohort, 42.7% of transfers were to a higher-level unit, 10.2% to a same-level unit, and 46.7% to a lower-level unit, with indication reflecting access to specific services. CONCLUSIONS: Over 4% of very and moderate preterm infants are transferred. In this population, the median age of transfer is later and does not reflect immediate care needs after birth, but rather the provision of risk-appropriate care.

Association between neurodevelopmental outcomes and concomitant presence of NEC and IVH in extremely low birth weight infants.

OBJECTIVE: To quantify the association between necrotizing enterocolitis (NEC) and neurodevelopmental disability (NDI) in extremely low birth weight (ELBW) infants with intraventricular hemorrhage (IVH). STUDY DESIGN: ELBW survivors born 2011-2017 and evaluated at 16-26 months corrected age in the Vermont Oxford Network (VON) ELBW Follow-Up Project were included. Logistic regression determined the adjusted relative risk (aRR) of severe NDI in medical or surgical NEC compared to no NEC, stratified by severity of IVH. RESULTS: Follow-up evaluation occurred in 5870 ELBW survivors. Compared to no NEC, medical NEC had no impact on NDI, regardless of IVH status. Surgical NEC increased risk of NDI in patients with no IVH (aRR 1.69; 95% CI 1.36-2.09), mild IVH (aRR 1.36;0.97-1.92), and severe IVH (aRR 1.35;1.13-1.60). CONCLUSIONS: ELBW infants with surgical NEC carry increased risk of neurodevelopmental disability within each IVH severity stratum. These data describe the additive insult of surgical NEC and IVH on neurodevelopment, informing prognostic discussions and highlighting the need for preventative interventions.

Does faster weight trajectory lead to improved neurodevelopmental outcomes in ELBW infants with bronchopulmonary dysplasia?

OBJECTIVE: Examine the relationship between weight trajectory and 2-year neurodevelopmental outcomes for extremely low birthweight (ELBW) infants with BPD. STUDY DESIGN: Secondary analysis of infants born from 2010 to 2019. The predictor was BPD severity and the outcome was neurodevelopmental impairment, defined as any Bayley Scales of Infant Development (BSID) III score <70 at 24 months' corrected age. Repeated measures logistic regression was performed. RESULTS: In total, 5042 infants were included. Faster weight trajectory was significantly associated with a decreased probability of having at least one BSID III score <70 for infants with grade 1-2 BPD (p < 0.0001) and an increased probability of at least one BSID III score <70 for infants with grade 3 BPD (p < 0.009). There was no significant association between weight trajectory and BSID III score <70 for infants with grade 0 BPD. CONCLUSION: The association between postnatal weight trajectory and neurodevelopmental outcome in this study differs by BPD severity.

Trends in Mortality and Morbidities for Infants Born 24 to 28 Weeks in the US: 1997-2021.

BACKGROUND: Mortality and morbidity for very preterm infants in the United States decreased for years. The current study describes recent changes to assess whether the pace of improvement has changed. METHODS: Vermont Oxford Network members contributed data on infants born at 24 to 28 weeks' gestation from 1997 to 2021. We modeled mortality, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, severe intraventricular hemorrhage, severe retinopathy of prematurity, and death or morbidity by year of birth using segmented relative risk regression, reporting risk-adjusted annual percentage changes with 95% confidence intervals overall and by gestational age week. RESULTS: Analyses of data for 447 396 infants at 888 hospitals identified 3 time point segments for mortality, late onset sepsis, chronic lung disease, severe intraventricular hemorrhage, severe retinopathy of prematurity, and death or morbidity, and 4 for necrotizing enterocolitis. Mortality decreased from 2005 to 2021, but more slowly since 2012. Late-onset sepsis decreased from 1997 to 2021, but more slowly since 2012. Severe retinopathy of prematurity decreased from 2002 to 2021, but more slowly since 2011. Necrotizing enterocolitis, severe intraventricular hemorrhage, and death or morbidity were stable since 2015. Chronic lung disease has increased since 2012. Trends by gestational age generally mirror those for the overall cohort. CONCLUSIONS: Improvements in mortality and morbidity have slowed, stalled, or reversed in recent years. We propose a 3-part strategy to regain the pace of improvement: research; quality improvement; and follow through, practicing social as well as technical medicine to improve the health and well-being of infants and families.

Impact of an Educational Clinical Video Combined with Standard Helping Babies Breathe Training on Acquisition and Retention of Knowledge and Skills among Ethiopian Midwives.

Helping Babies Breathe (HBB) is an evidence-based neonatal resuscitation program designed for implementation in low-resource settings. While HBB reduces rates of early neonatal mortality and stillbirth, maintenance of knowledge and skills remains a challenge. The extent to which the inclusion of educational clinical videos impacts learners' knowledge and skills acquisition, and retention is largely unknown. We conducted a cluster-randomized controlled trial at two public teaching hospitals in Addis Ababa, Ethiopia. We randomized small training group clusters of 84 midwives to standard HBB vs. standard HBB training supplemented with exposure to an educational clinical video on newborn resuscitation. Midwives were followed over a 7-month time period and assessed on their knowledge and skills using standard HBB tools. When comparing the intervention to the control group, there was no difference in outcomes across all assessments, indicating that the addition of the video did not influence skill retention. Pass rates for both the control and intervention group on bag and mask skills remained low at 7 months despite frequent assessments. There is more to learn about the use of educational videos along with low-dose, high-frequency training and how it relates to retention of knowledge and skills in learners.

High inter-rater reliability between physicians and nurses utilising modified Downes' scores in preterm respiratory distress.

AIM: To assess the inter-rater reliability of modified Downes' scores assigned by physicians and nurses in the Ethiopian Neonatal Network and to calculate the concordance of score-based treatment for preterm infants with respiratory distress. METHODS: We included preterm infants admitted from June 2020 to July 2021 to four tertiary neonatal intensive care units (NICUs) of the Ethiopian Neonatal Network that presented with respiratory distress. We calculated the kappa statistic to determine the nurse and physician correlation for each component of the modified Downes' score and total score on admission and evaluated the concordance of scores above and below the treatment threshold of 4. RESULTS: Of the 1151 eligible infants admitted, 817 infants (71%) had scores reported concurrently and independently by nurse and physician. The kappa statistic for modified Downes' score components ranged from 0.88 to 0.92 and was 0.89 for the total score. There was 98% concordance for score-based treatment. CONCLUSION: Incorporation of the modified Downes' score on admission for preterm infants with respiratory distress was feasible in tertiary NICUs in Ethiopia. The kappa statistics showed near-perfect agreement between nurse and physician assessments, translating to a very high degree of concordance in score-based treatment recommendations. These results highlight an opportunity for task-shifting assessments and empowering nurses.

Reconciling continuous and discrete models of C4 and CAM evolution.

BACKGROUND: A current argument in the CAM biology literature has focused on the nature of the CAM evolutionary trajectory: whether there is a smooth continuum of phenotypes between plants with C3 and CAM photosynthesis or whether there are discrete steps of phenotypic evolutionary change such as has been modelled for the evolution of C4 photosynthesis. A further implication is that a smooth continuum would increase the evolvability of CAM, whereas discrete changes would make the evolutionary transition from C3 to CAM more difficult. SCOPE: In this essay, I attempt to reconcile these two viewpoints, because I think in many ways this is a false dichotomy that is constraining progress in understanding how both CAM and C4 evolved. In reality, the phenotypic space connecting C3 species and strong CAM/C4 species is both a continuum of variably expressed quantitative traits and yet also contains certain combinations of traits that we are able to identify as discrete, recognizable phenotypes. In this sense, the evolutionary mechanics of CAM origination are no different from those of C4 photosynthesis, nor from the evolution of any other complex trait assemblage. CONCLUSIONS: To make progress, we must embrace the concept of discrete phenotypic phases of CAM evolution, because their delineation will force us to articulate what aspects of phenotypic variation we think are significant. There are some current phenotypic gaps that are limiting our ability to build a complete CAM evolutionary model: the first is how a rudimentary CAM biochemical cycle becomes established, and the second is how the 'accessory' CAM cycle in C3+CAM plants is recruited into a primary metabolism. The connections to the C3 phenotype we are looking for are potentially found in the behaviour of C3 plants when undergoing physiological stress - behaviour that, strangely enough, remains essentially unexplored in this context.