Echocardiographic Assessment of Pulmonary Arterial Hypertension Following Inhaled Nitric Oxide in Infants with Severe Bronchopulmonary Dysplasia.

OBJECTIVES: Inhaled nitric oxide (iNO) is an effective pulmonary vasodilator. However, the efficacy of iNO in former premature infants with established bronchopulmonary dysplasia (BPD) has not been studied. This study aimed to determine the efficacy of iNO in reducing pulmonary artery pressure in infants with severe BPD as measured by echocardiography. STUDY DESIGN: Prospective, observational study enrolling infants born at less than 32 weeks gestation and in whom (1) iNO therapy was initiated after admission to our institution, or (2) at the outside institution less than 48 h before transfer and received an echocardiogram prior to iNO initiation, and (3) had severe BPD. Data were collected at three time-points: (1) before iNO; (2) 12-48 h after initiation of iNO; and (3) 48-168 h after initiation of iNO. The primary outcome was the effect of iNO on pulmonary artery pressure measured by echocardiography in patients with severe BPD between 48 and 168 h after initiating iNO therapy. RESULTS: Of 37 enrolled, 81% had echocardiographic evidence of pulmonary arterial hypertension (PAH) before iNO and 56% after 48 h of iNO (p = 0.04). FiO2 requirements were significantly different between time-points (1) and (3) (p = 0.05). There were no significant differences between Tricuspid Annular Plane Systolic Excursion (TAPSE) Z-Scores, time to peak velocity: right ventricular ejection time (TPV:RVET), and ventilator changes. CONCLUSIONS: Although we found a statistically significant reduction of PAH between time-point (1) and (3), future trials are needed to further guide clinical care.

The promise and pitfalls of precision medicine to resolve black-white racial disparities in preterm birth.

Differences in preterm birth rates between black and white women are the largest contributor to racial disparities in infant mortality. In today's age of precision medicine, analysis of the genome, epigenome, metabolome, and microbiome has generated interest in determining whether these biomarkers can help explain racial disparities. We propose that there are pitfalls as well as opportunities when using precision medicine analyses to interrogate disparities in health. To conclude that racial disparities in complex conditions are genetic in origin ignores robust evidence that social and environmental factors that track with race are major contributors to disparities. Biomarkers measured in omic assays that may be more environmentally responsive than genomics, such as the epigenome or metabolome, may be on the causal pathway of race and preterm birth, but omic observational studies suffer from the same limitations as traditional cohort studies. Confounding can lead to false conclusions about the causal relationship between omics and preterm birth. Methodological strategies (including stratification and causal mediation analyses) may help to ensure that associations between biomarkers and exposures, as well as between biomarkers and outcomes, are valid signals. These epidemiologic strategies present opportunities to assess whether precision medicine biomarkers can uncover biology underlying perinatal health disparities.

Factors influencing decision making in neonatology: inhaled nitric oxide in preterm infants.

OBJECTIVE: We studied decision making regarding inhaled nitric oxide (iNO) in preterm infants with Pulmonary Hypertension (PH). STUDY DESIGN: We asked members of the AAP-Society of Neonatal-Perinatal Medicine and Division-Chiefs to select from three management options- initiate iNO, engage parents in shared decision making or not consider iNO in an extremely preterm with PH followed by rating of factors influencing their decision. RESULTS: Three hundred and four respondents (9%) completed the survey; 36.5% chose to initiate iNO, 42% to engage parents, and 21.5% did not consider iNO. Provider's prior experience, safety, and patient-centered care were rated higher by those who initiated or offered iNO; lack of effectiveness and cost considerations by participants who did not chose iNO. CONCLUSIONS: Most neonatologists offer or initiate iNO therapy based on their individual experience. The minority who chose not to consider iNO placed higher value on lack of effectiveness and cost. These results demonstrate a tension between evidence and pathophysiology-based-therapy/personal experience.

Risk and benefits of Bubble Continuous Positive Airway Pressure for neonatal and childhood respiratory diseases in Low- and Middle-Income countries.

Over 80% of the global burden of childhood deaths occur in Low- and Middle-Income Countries (LMIC). Of the leading causes of death, respiratory failure is common to the top three. Bubble Continuous Positive Airway Pressure (bCPAP) is a standard therapy considered safe and cost effective in high resource settings. Although high-quality trials from LMIC are few, pooled available trial data considered alongside studies from high-income countries suggest that bCPAP: (i) reduces mortality; (ii) reduces the need for mechanical ventilation; and (iii) prevents extubation failure. Wider availability and optimal use at all levels of the health care system in LMIC are important steps to improve childhood survival. Studies aimed at effectively implementing, and sustaining safe use of bCPAP in the resource limited setting of LMIC are required.

Evidence, Quality, and Waste: Solving the Value Equation in Neonatology.

Rising health care costs challenge governments, payers, and providers in delivering health care services. Tremendous pressures result to deliver better quality care while simultaneously reducing costs. This has led to a wholesale re-examination of current practice methods, including explicit consideration of efficiency and waste. Traditionally, reductions in the costs of care have been considered as independent, and sometimes even antithetical, to the practice of high-quality, intensive medicine. However, it is evident that provision of evidence-based, locally relevant care can result in improved outcomes, lower resource utilization, and opportunities to reallocate resources. This is particularly relevant to the practice of neonatology. In the United States, 12% of the annual birth cohort is affected by preterm birth, and 3% is affected by congenital anomalies. Both of these conditions are associated with costly health care during, and often long after, the NICU admission. We will discuss how 3 drivers of clinical practice in neonatal care (evidence-based medicine, evidence-based economics, and quality improvement) can together optimize clinical and fiscal outcomes.

Accuracy of tidal volume, compliance, and resistance measurements on neonatal ventilator displays: an in vitro assessment.

OBJECTIVE: To determine the accuracy of measures of respiratory mechanics derived from neonatal ventilators using an in vitro passive physical lung model to simulate newborn pulmonary conditions. DESIGN: Test lung models. SETTING: Laboratory-based measurements. INTERVENTIONS: Three test lungs were constructed to simulate three severities of neonatal lung disease, with ranges of compliance from 0.5 to 2.0 mL/cm H2O and resistance from 25 to 150 cm H2O/(L/sec). Each ventilator was tested using 27 combinations of peak inspiratory pressure (15-25 cm H2O), positive end-expiratory pressure (5-7 cm H2O), and rate settings (20-60 B/min). Data were compared for five different ventilators across simulated lung severity as the ratio of ventilator readout to test lung reference value. A ratio of 1.0 indicated a completely unbiased result. MAIN RESULTS: Overall, four of the five ventilators under-read expired tidal volume by about 1%-12% across all lung conditions, whereas the VIP Bird readout ranged from -4% to +4% bias. Changes in ventilator settings had only a modest effect on mechanics readout. As peak inspiratory pressure progressed from 15 to 25 cm H2O, bias in tidal volume readout changed from +5.0% to -2.5% (p < .001) in the VIP Bird, and from -11% to -9% (p < .001) in the Draeger Babylog VN500. Between positive end-expiratory pressure levels of 5 and 7 cm H2O, tidal volume bias in the Babylog varied between -13% and -7% (p < .001). In progressing from simulated normal to severely ill lung condition, bias in compliance measurements by the Avea and SLE5000 increased from -18% to -40% whereas in the VIP Bird it remained between -17% to -13%, and in the Draeger Evita XL-neo it changed from +17% to -13% and from -8% to -16% in the Babylog. Ratio of ventilator resistance readout to reference value with progressing simulated lung condition changed from 2.0 to 1.0 for the Draeger Evita, 1.6 to 1.1 for the Babylog, 4.2 to 2.0 for the SLE, and from 11.7 to 5.6 for the VIP Bird. The Avea, by design, did not display resistances >100 cm H2O/(L/sec), but overestimated the simulated normal lung resistance of 25 cm H2O/(L/sec) by a factor of 2.5. CONCLUSIONS: Neonatal ventilator respiratory mechanics measurements and computation methods need further standardization to be useful in clinical settings.

Economic evaluation alongside the Premature Infants in Need of Transfusion randomised controlled trial.

BACKGROUND: The Premature Infants in Need of Transfusion (PINT) Outcome Study showed no significant difference in the primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants. However, a post-hoc analysis expanding the definition of NDI to include borderline intellectual functioning (Mental Development Index (MDI) <85) found an improvement in outcomes in the group maintained at higher haemoglobin levels. OBJECTIVE: To determine the cost effectiveness of more frequent red blood cell transfusions (high-Hb threshold) compared with less frequent transfusions (low-Hb threshold) in ELBW infants. DESIGN/METHODS: The authors performed an economic evaluation using patient-level data collected during the PINT randomised trial. The authors measured comprehensive costs from a third-party payer's perspective over a time horizon from birth through 18-21 months corrected age. RESULTS: The average total cost in the high-Hb threshold group was CAN$149 767 compared with CAN$150 227 in the low-Hb threshold group (difference of CAN$460, p=0.96). Cost-effectiveness analysis estimated savings of CAN$6879 for every additional infant surviving without severe NDI. There was a 48% chance that the high-Hb threshold reduced costs while improving outcome and a 90% chance that it would be cost effective at a willingness-to-pay threshold of CAN$250 000 per additional survivor without severe NDI. Post-hoc analysis defining cognitive delay as MDI score <85, instead of <70, revealed savings in the high-Hb threshold group of CAN$4457 per additional survivor without NDI. Results were robust to deterministic sensitivity analyses. CONCLUSION: A high-Hb threshold for transfusion, as measured in ELBW PINT study infants through 18 months corrected gestational age, may be an economically appealing intervention. The estimates were associated with moderate statistical uncertainty that should be targeted in larger, future studies.