Bronchopulmonary dysplasia (BPD) is the most common serious morbidity of preterm birth. Short-term respiratory outcomes for infants with the most severe forms of BPD are highly variable. The ...mechanisms that explain this variability remain unknown and may be mediated by racial disparities.
To determine the association of maternal race with death and length of hospital stay in a multicenter cohort of infants with severe BPD.
This multicenter cohort study included preterm infants enrolled in the BPD Collaborative registry from January 1, 2015, to July 19, 2021, involving 8 BPD Collaborative centers located in the US. Included patients were born at less than 32 weeks' gestation, had a diagnosis of severe BPD as defined by the 2001 National Institutes of Health Consensus Criteria, and were born to Black or White mothers.
Maternal race: Black vs White.
Death and length of hospital stay.
Among 834 registry infants (median IQR gestational age, 25 24-27 weeks; 492 male infants 59%) meeting inclusion criteria, the majority were born to White mothers (558 67%). Death was observed infrequently in the study cohort (32 4%), but Black maternal race was associated with an increased odds of death (adjusted odds ratio, 2.1; 95% CI, 1.2-3.5) after adjusting for center. Black maternal race was also significantly associated with length of hospital stay (adjusted between-group difference, 10 days; 95% CI, 3-17 days).
In a multicenter severe BPD cohort, study results suggest that infants born to Black mothers had increased likelihood of death and increased length of hospital stay compared with infants born to White mothers. Prospective studies are needed to define the sociodemographic mechanisms underlying disparate health outcomes for Black infants with severe BPD.
Objective To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, ...safely improves survival without bronchopulmonary dysplasia (BPD). Study design Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. Results A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. Conclusion Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. Trial registration ClinicalTrials.gov : NCT01022580.
Background Nasal intermittent positive pressure ventilation (NIPPV) is a widely used mode of support in neonates, during which ventilator inflations may or may not coincide with spontaneous ...breathing. Objective We tested the hypothesis that inflations delivered with NIPPV via RAM.sup.® cannula and not accompanied by patient effort produce minimal tidal volume as measured by respiratory inductance plethysmography. Design/Methods Fourteen subjects were monitored while receiving NIPPV. We compared tidal volumes during ventilator-supported breaths, unsupported breaths, and ventilator inflations not accompanied by patient effort (defined using electrical activity of the diaphragm). Results Mean tidal volumes in arbitrary units were 0.30 plus or minus 0.22 in NIPPV inflations associated with patient effort and 0.27 plus or minus 0.15 in spontaneous breaths without ventilator assistance (p = 0.82). Tidal volumes during ventilator-only inflations were 0.06 plus or minus 0.04 (p < 0.005 vs. both ventilator-assisted and unassisted efforts). Conclusions NIPPV via RAM cannula produces minimal, clinically insignificant tidal volumes during non-spontaneous inflations.
To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 240/7-276/7 weeks of gestational age and to ...assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age.
The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models.
One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age.
Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.
Bronchopulmonary dysplasia in premature infants is a common and often severe lung disease with long-term sequelae. A genetic component is suspected but not fully defined. We performed an ancestry and ...genome-wide association study to identify variants, genes, and pathways associated with survival without bronchopulmonary dysplasia in 387 high-risk infants treated with inhaled nitric oxide in the Trial of Late Surfactant study. Global African genetic ancestry was associated with increased survival without bronchopulmonary dysplasia among infants of maternal self-reported Hispanic white race/ethnicity odds ratio (OR) = 4.5, P = 0.01. Admixture mapping found suggestive outcome associations with local African ancestry at chromosome bands 18q21 and 10q22 among infants of maternal self-reported African-American race/ethnicity. For all infants, the top individual variant identified was within the intron of NBL1, which is expressed in midtrimester lung and is an antagonist of bone morphogenetic proteins ( rs372271081 , OR = 0.17, P = 7.4 × 10
). The protective allele of this variant was significantly associated with lower nitric oxide metabolites in the urine of non-Hispanic white infants ( P = 0.006), supporting a role in the racial differential response to nitric oxide. Interrogating genes upregulated in bronchopulmonary dysplasia lungs indicated association with variants in CCL18, a cytokine associated with fibrosis and interstitial lung disease, and pathway analyses implicated variation in genes involved in immune/inflammatory processes in response to infection and mechanical ventilation. Our results suggest that genetic variation related to lung development, drug metabolism, and immune response contribute to individual and racial/ethnic differences in respiratory outcomes following inhaled nitric oxide treatment of high-risk premature infants.
Use of nontidal high-frequency oscillatory ventilation (HFOV) while the lungs are expanded by an imposed airway pressure (P(aw)) in neonates is increasingly based on evidence of decreased risk of ...lung injury. However, an objective method to optimize P(aw) is lacking. We measured lung volume changes (deltaV(L)t) via respiratory inductance plethysmography over a range of P(aw) settings in five piglets before and after lung lavage. These multiple deltaV(L)(t) were then simultaneously fit by an exponential rise to maximum model, deltaV(L)(t, P(aw)) = deltaV(L,max). (1 - e(-(t/tau))), where deltaV(L,max) was a sigmoidal function of P(aw) and tau varied with lung volume. Postlavage, the effective compliance (C(EFF) = deltaV(L,max)/P(aw)) was generally decreased, whereas tau increased, indicating a slower paced volume recruitment. Model-derived C(EFF)-deltaV(L,max) relationships were altered substantially after lavage and were sigmoidal with a bell-shaped derivative function. The maximum of its derivative corresponded to a favorable (or optimal) deltaV(L)/P(aw) where the maximal increase in compliance is achieved. In conclusion, C(EFF)-deltaV(L,max) data available from respiratory inductance plethysmography provided important insight to changes in lung mechanics. These also provided a basis of an objective method (1) to optimize P(aw) during HFOV and (2) to assess the efficacy of treatments and progression/regression of underlying disease in neonates managed with HFOV.
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