County-level Structural Vulnerabilities in Maternal Health and Geographic Variation in Infant Mortality.

OBJECTIVE: To evaluate whether community factors that differentially affect the health of pregnant people contribute to geographic differences in infant mortality across the United States. STUDY DESIGN: This retrospective cohort study sought to characterize the association of a novel composite measure of county-level maternal structural vulnerabilities, the Maternal Vulnerability Index (MVI), with risk of infant death. We evaluated 11,456,232 singleton infants born at 22 0/7 through 44 6/7 weeks' gestation from 2012 to 2014. Using county-level MVI, which ranges from 0-100, multivariable mixed effects logistic regression models quantified associations per 20-point increment in MVI, with odds of death clustered at the county level and adjusted for state, maternal, and infant covariates. Secondary analyses stratified by the social, physical, and health exposures that comprise the overall MVI score. Outcome was also stratified by cause of death. RESULTS: Odds of death were higher among infants from counties with the greatest maternal vulnerability (0.62% in highest quintile vs 0.32% in lowest quintile, [p<0.001]). Odds of death increased 6% per 20-point increment in MVI (aOR: 1.06, 95% CI 1.04, 1.07). The effect estimate was highest with theme of mental health and substance use (aOR 1.08; 95% CI 1.06, 1.09). Increasing vulnerability was associated with six of seven causes of death. CONCLUSIONS: Community-level social, physical, and healthcare determinants indicative of maternal vulnerability may explain some of the geographic variation in infant death, regardless of cause of death. Interventions targeted to county-specific maternal vulnerabilities may reduce infant mortality.

Associations of PM2.5 exposure with emergency department visits and readmissions among preterm infants with bronchopulmonary dysplasia.

OBJECTIVES: To quantify the association of ambient air pollution (particulate matter, PM2.5) exposure with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Single center, retrospective cohort study of preterm infants with BPD in Metropolitan Philadelphia. Multivariable logistic regression quantified associations of annual mean PM2.5 exposure (per µg/m3) at the census block group level with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge adjusting for age at neonatal intensive care unit (NICU) discharge, year, sex, race, insurance, BPD severity, and census tract deprivation. As a secondary analysis, we examined whether BPD severity modified the associations. RESULTS: Of the 378 infants included in the analysis, 189 were non-Hispanic Black and 235 were publicly insured. Census block PM2.5 level was not significantly associated with medically attended acute respiratory illnesses, ED visits, or hospital readmissions in the full study cohort. We observed significant effect modification by BPD grade; each 1 µg/m3 higher annual PM2.5 exposure was medically attended acute respiratory illness (adjusted odds ratio [aOR] 1.65, 95% CI: 1.06-2.63) among infants with Grade 1 BPD but not among infants with grade 3 BPD (aOR 0.83, 95% CI: 0.47-1.48) (interaction p = .024). CONCLUSIONS: Cumulative PM2.5 exposure in the year after NICU discharge was not significantly associated with medically attended acute respiratory illness among infants with BPD. However, infants with Grade 1 BPD had significantly higher odds with higher exposures. If replicated, these findings could inform anticipatory guidance for families of these infants to avoid outdoor activities during high pollution days after NICU discharge.

Association between video laryngoscopy characteristics and successful neonatal tracheal intubation: a prospective study.

OBJECTIVE: To identify associations between procedural characteristics and success of neonatal tracheal intubation (NTI) using video laryngoscopy (VL). DESIGN: Prospective single-centre observational study. SETTING: Quaternary neonatal intensive care unit. PATIENTS: Infants requiring NTI at the Children's Hospital of Philadelphia. INTERVENTIONS: VL NTI recordings were evaluated to assess 11 observable procedural characteristics hypothesised to be associated with VL NTI success. These characteristics included measures of procedural time and performance, glottic exposure and position, and laryngoscope blade tip location. MAIN OUTCOME MEASURE: VL NTI attempt success. RESULTS: A total of 109 patients underwent 109 intubation encounters with 164 intubation attempts. The first attempt success rate was 65%, and the overall encounter success rate was 100%. Successful VL NTI attempts were associated with shorter procedural duration (36 s vs 60 s, p<0.001) and improved Cormack-Lehane grade (63% grade I vs 49% grade II, p<0.001) compared with unsuccessful NTIs. Other factors more common in successful NTI attempts than unsuccessful attempts were laryngoscope blade placement to lift the epiglottis (45% vs 29%, p=0.002), fewer tracheal tube manoeuvres (3 vs 8, p<0.001) and a left-sided or non-visualised tongue location (76% vs 56%, p=0.009). CONCLUSION: We identified procedural characteristics visible on the VL screen that are associated with NTI procedural success. Study results may improve how VL is used to teach and perform neonatal intubation.

Association between video laryngoscopy characteristics and successful neonatal tracheal intubation: a prospective study.

OBJECTIVE: To identify associations between procedural characteristics and success of neonatal tracheal intubation (NTI) using video laryngoscopy (VL). DESIGN: Prospective single-centre observational study. SETTING: Quaternary neonatal intensive care unit. PATIENTS: Infants requiring NTI at the Children's Hospital of Philadelphia. INTERVENTIONS: VL NTI recordings were evaluated to assess 11 observable procedural characteristics hypothesised to be associated with VL NTI success. These characteristics included measures of procedural time and performance, glottic exposure and position, and laryngoscope blade tip location. MAIN OUTCOME MEASURE: VL NTI attempt success. RESULTS: A total of 109 patients underwent 109 intubation encounters with 164 intubation attempts. The first attempt success rate was 65%, and the overall encounter success rate was 100%. Successful VL NTI attempts were associated with shorter procedural duration (36 s vs 60 s, p<0.001) and improved Cormack-Lehane grade (63% grade I vs 49% grade II, p<0.001) compared with unsuccessful NTIs. Other factors more common in successful NTI attempts than unsuccessful attempts were laryngoscope blade placement to lift the epiglottis (45% vs 29%, p=0.002), fewer tracheal tube manoeuvres (3 vs 8, p<0.001) and a left-sided or non-visualised tongue location (76% vs 56%, p=0.009). CONCLUSION: We identified procedural characteristics visible on the VL screen that are associated with NTI procedural success. Study results may improve how VL is used to teach and perform neonatal intubation.

Environmental Determinants of Post-Discharge Acute Respiratory Illness among Preterm Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: To analyze the association of components of the Centers for Disease Control and Prevention (CDC) Environmental Justice Index (EJI) with respiratory health outcomes among infants with bronchopulmonary dysplasia (BPD) within one year after discharge from the neonatal intensive care unit. METHODS: This was a retrospective cohort study of a cohort of preterm infants with BPD. Multivariable logistic regression models estimated associations of EJI and its components with medically attended acute respiratory illness, defined as an ED visit or inpatient readmission, within one year of discharge from the neonatal intensive care unit. A mediation analysis was conducted to evaluate how environmental injustice may contribute to racial disparities in acute respiratory illness. RESULTS: Greater EJI was associated with an increased risk of medically attended respiratory illness (per EJI standard deviation increment, aOR 1.38, 95% CI: 1.12-1.69). Of the index's components, the Environmental Burden Module's Air pollution domain had the greatest association (aOR 1.44, 95% CI: 1.44-2.61). With respect to individual indicators within the EJI, Diesel Particulate Matter (DSLPM) and Air Toxic Cancer Risk (ATCR) demonstrated the strongest relationship (aOR 2.06, 95% CI: 1.57-2.71 and aOR 2.10, 95% CI: 1.59-2.78, respectively). Among non-Hispanic Black infants, 63% experienced a medically attended acute respiratory illness as compared to 18% of non-Hispanic White infants. DSLPM mediated 39% of the Black-White disparity in medically attended acute respiratory illness (p = 0.004). CONCLUSIONS: Environmental exposures, particularly air pollution, are associated with post-discharge respiratory health outcomes among preterm infants with BPD after adjusting for clinical, demographic, and social vulnerability risk factors. Certain types of air pollutants, namely, DSLPM, are more greatly associated with acute respiratory illness. Environmental exposures may contribute to racial disparities in medically attended acute respiratory illness among infants with BPD.

Unconditional cash transfers for preterm neonates: evidence, policy implications, and next steps for research.

To address socioeconomic disparities in the health outcomes of preterm infants, we must move beyond describing these disparities and focus on the development and implementation of interventions that disrupt the factors contributing to them. Unconditional cash transfers (UCTs), which provide unrestricted payments to individuals or households, can help mitigate income disparities and improve health outcomes. While UCTs have been utilized for other vulnerable populations, their full potential has yet to be realized for low-income families with preterm infants, who face significant financial strain. In this perspective, we review evidence supporting UCTs as an intervention for children in the U.S. (including those born term and preterm), discuss the potential benefits of recurring UCTs to low-income families of preterm infants, and propose a conceptual model through which UCTs may improve outcomes for preterm infants. We conclude with potential policy levers for implementing UCTs and key unanswered questions for researchers.

Place-Based Strategies Addressing Neighborhood Environments to Improve Perinatal and Preterm Infant Outcomes.

Preterm birth (defined as birth <37 weeks of gestation) is a significant health concern globally, with lasting implications for individuals, families, and society. In the United States, high preterm birth rates among Black and low-income populations likely result from differences in environmental exposures. Structural racism and economic disadvantage have led to unequal distribution of polluting industrial sites and roadways across society as well as differential access to health-promoting resources which contribute to preterm birth risk. Once born, preterm infants remain at risk for numerous environmentally responsive adverse health outcomes that affect growth and development throughout childhood and adulthood. In this commentary, we describe associations of neighborhood environments with pregnancy and preterm infant health outcomes and propose strategies to address harmful exposures that affect families across the lifespan.

Associations of neighborhood social vulnerability with emergency department visits and readmissions among infants with bronchopulmonary dysplasia.

OBJECTIVES: To characterize associations of the CDC Social Vulnerability Index (SVI) with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Retrospective cohort of 378 preterm infants with BPD from a single center. Multivariable logistic regression quantified associations of SVI with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge. Mediation analysis quantified the extent to which differences in SVI may explain known Black-White disparities in medically attended acute respiratory illness. RESULTS: SVI was associated with medically attended respiratory illness (per SVI standard deviation increment, aOR 1.44, 95% CI: 1.17-1.78). Adjustment for race and ethnicity attenuated the association (aOR 1.27, 95% CI: 0.97-1.64). SVI significantly mediated 31% of the Black-White disparity in ED visits (p = 0.04). CONCLUSIONS: SVI was associated with, and may partially explain racial disparities in, medically attended acute respiratory illness among infants with BPD.

Primary Palliative Care for Pediatric Residents: A Curricular Framework and Pilot.

PROBLEM: Palliative care (PC) is high-value, holistic care for a child and their family across the entire arc of an illness. All physicians should be competent in symptom management and providing goal-concordant care that acknowledges the quality of life; however, there is insufficient education in pediatric residency to develop competence in basic or ..úPrimary..Ñ PC. APPROACH: We completed a needs assessment and developed a longitudinal, comprehensive, and integrated primary PC curriculum for pediatric residents with the goal of developing foundational primary PC skills regardless of eventual career trajectory. After 1 year of implementation, we assessed resident comfort with primary PC skills via a retrospective pre-post survey. OUTCOMES: We found a statistically significant (P.ß<.ß.05) increase in residents... comfort with pain management, delivering serious news, and discussing goals of care. An increase in comfort with the management of other symptoms was not statistically significant. NEXT STEPS: After 1 year of implementation, residents describe an increase in comfort with primary PC skills. The next steps include more rigorous evaluation and expansion to include more education in medical ethics. While the educational need is universal, resident needs are constantly evolving and each institution should tailor this curriculum to fit their specific trainee needs and institutional expertise.

The association between diuretic class exposures and enteral electrolyte use in infants developing grade 2 or 3 bronchopulmonary dysplasia in United States children's hospitals.

OBJECTIVE: To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: Retrospective longitudinal cohort study in infants admitted to United States children's hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use. RESULTS: We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy. CONCLUSIONS: Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.

Loop Diuretics in Severe Bronchopulmonary Dysplasia: Cumulative Use and Associations with Mortality and Age at Discharge.

OBJECTIVES: To measure between-center variation in loop diuretic use in infants developing severe bronchopulmonary dysplasia (BPD) in US children's hospitals, and to compare mortality and age at discharge between infants from low-use centers and infants from high-use centers. STUDY DESIGN: We performed a retrospective cohort study of preterm infants at <32 weeks of gestational age with severe BPD. The primary outcome was cumulative loop diuretic use, defined as the proportion of days with exposure between admission and discharge. Infant characteristics associated with loop diuretic use at P < .10 were included in multivariable models to adjust for center differences in case mix. Hospitals were ranked from lowest to highest in adjusted use and dichotomized into low-use centers and high-use centers. We then compared mortality and postmenstrual age at discharge between the groups through multivariable analyses. RESULTS: We identified 3252 subjects from 43 centers. Significant variation between centers remained despite adjustment for infant characteristics, with use present in an adjusted mean range of 7.3% to 49.4% of days (P < .0001). Mortality did not differ significantly between the 2 groups (aOR, 0.98; 95% CI, 0.62-1.53; P = .92), nor did postmenstrual age at discharge (marginal mean, 47.3 weeks [95% CI, 46.8-47.9 weeks] in the low-use group vs 47.4 weeks [95% CI, 46.9-47.9 weeks] in the high-use group; P = .96). CONCLUSIONS: A marked variation in loop diuretic use for infants developing severe BPD exists among US children's hospitals, without an observed difference in mortality or age at discharge. More research is needed to provide evidence-based guidance for this common exposure.

A lung for all: Novel mechanical ventilator for emergency and low-resource settings.

AIMS: To create a low-cost ventilator that could be constructed with readily-available hospital equipment for use in emergency or low-resource settings. MAIN METHODS: The novel ventilator consists of an inspiratory limb composed of an elastic flow-inflating bag encased within a non-compliant outer sheath and an expiratory limb composed of a series of two, one-way bidirectional splitter valves derived from a self-inflating bag system. An Arduino Uno microcontroller controls a solenoid valve that can be programmed to open and close to produce a set respiratory rate and inspiratory time. Using an ASL 5000 Lung Simulator, we obtained flow, pressure, and volume waveforms at different lung compliances. KEY FINDINGS: At a static lung compliance of 50 mL/cm H2O and an airway resistance of 6 cm H2O/L/s, ventilated at a PIP and PEEP of 16 and 5 cm H2O, respectively, tidal volumes of approximately 540 mL were achieved. At a static lung compliance of 20 mL/cm H2O and an airway resistance of 6 cm H2O/L/s, ventilated at a PIP and PEEP of 38 and 15 cm H2O, respectively, tidal volumes of approximately 495 mL were achieved. SIGNIFICANCE: This novel ventilator is able to safely and reliably ventilate patients with a range of pulmonary disease in a simulated setting. Opportunities exist to utilize our ventilator in emergency situations and low-resource settings.

In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function.

Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure.

In vitro effects of exercise on the heart.

Pathologic and physiologic factors acting on the heart can produce consistent pressure changes, volume overload, or increased cardiac output. These changes may then lead to cardiac remodeling, ultimately resulting in cardiac hypertrophy. Exercise can also induce hypertrophy, primarily physiologic in nature. To determine the mechanisms responsible for each type of remodeling, it is important to examine the heart at the functional unit, the cardiomyocyte. Tests of individual cardiomyocyte function in vitro provide a deeper understanding of the changes occurring within the heart during hypertrophy. Examination of cardiomyocyte function during exercise primarily follows one of two pathways: the addition of hypertrophic inducing agents in vitro to normal cardiomyocytes, or the use of trained animal models and isolating cells following the development of hypertrophy in vivo. Due to the short lifespan of adult cardiomyocytes, a proportionately scant amount of research exists involving the direct stimulation of cells in vitro to induce hypertrophy. These attempts provide the only current evidence, as it is difficult to gather extensive data demonstrating cell growth as a result of in vitro physical stimulation. Researchers have created ways to combine skeletal myocytes with cardiomyocytes to produce functional muscle cells used to repair pathologic heart tissue, but continue to struggle with the short lifespan of these cells. While there have been promising findings regarding the mechanisms that surround cardiac hypertrophy in vitro, the translation of in vitro findings to in vivo function is not consistent. Therefore, the focus of this review is to highlight recent studies that have investigated the effect of exercise on the heart, both in vitro and in vivo.