Early Bubble CPAP Protocol Implementation and Rates of Death or Severe BPD.

BACKGROUND: A multidisciplinary comprehensive protocol to use bubble continuous positive airway pressure (bCPAP) as the primary respiratory support in the delivery room (DR) and the NICU was introduced. With this study, we aimed to assess the association of this change with respiratory outcomes over time. METHODS: Infants with gestational age <32 weeks and birth weight <1250 g admitted between January 2012 and June 2020 were included and categorized into 4 periods, including pre-implementation (P0: 2012-2014), and post-implementation (P1: 2014-2016, P2: 2016-2018, P3: 2018-2020). The primary outcome was the rates of death and severe bronchopulmonary dysplasia (BPD), and the secondary outcomes included the rates of DR and NICU intubation ≤7 days of age, need of surfactant, and pneumothorax. Multivariate logistic regression models accounting for relevant risk factors were used to calculate adjusted odds ratios (ORs). RESULTS: The study included 440 infants (P0 = 90, P1 = 91, P2 = 128, P3 = 131). Over time, more infants were free of BPD (P < .001), and the rates of death and severe BPD decreased significantly: P1 = OR 1.21 (95% confidence interval [CI] 0.56-2.67), P2 = OR 0.45 (95% CI 0.20-0.99), and P3 = OR 0.37 (95% CI 0.15-0.84). DR intubation decreased from 66% (P0) to 24% (P3) in the entire cohort (P < .001) and from 96% (P0) to 40% (P3) in infants <26 weeks of age (P < .001). The need for NICU intubation was similar (P = .98), with a decreased need for surfactant (P = .001) occurring at higher FiO2 (P0 = 0.35 vs P3 = 0.55, P < .001). Pneumothorax rates were unchanged. CONCLUSIONS: In very preterm infants, the implementation of a comprehensive bCPAP protocol led to a significant and consistent improvement in respiratory practices and the rates of death and severe BPD.

Early cardiac function and death, severe bronchopulmonary dysplasia and pulmonary hypertension in extremely preterm infants.

BACKGROUND: Association between early cardiac function and neonatal outcomes are scarcely reported. The aim of the current study was to describe this association with death, severe bronchopulmonary dysplasia (BPD) and BPD-related pulmonary hypertension (PH). METHODS: Retrospective cohort study of infants <29 weeks born between 2015 and 2019. Infants with clinically acquired echocardiography at ≤21 days after birth were included and data were extracted by an expert masked to outcomes. RESULTS: A total of 176 infants were included. Echocardiogram was performed at a median of 9 days (IQR 5-13.5). Of these, 31 (18%) had death/severe BPD and 59 (33.5%) had death/BPD-related PH. Infants with death/severe BPD were of lower birth weight (745 [227] vs 852 [211] grams, p = 0.01) and more exposed to invasive ventilation, late-onset sepsis, inotropes and/or postnatal steroids. Early echocardiograms demonstrated decreased right ventricular [Tricuspid Annular Plane Systolic Excursion: 5.2 (1.4) vs 6.2 (1.5) cm, p = 0.03] and left ventricular function [Ejection fraction 53 (14) vs 58 (10) %, p = 0.03]. Infants with death/BPD-related PH had an increased Eccentricity index (1.35 [0.20] vs 1.26 [0.19], p = 0.02), and flat/bowing septum (19/54 [35%] vs 20/109 [18%], p = 0.021). CONCLUSIONS: In extremely premature infants, altered ventricular function and increased pulmonary pressure indices within the first 21 days after birth, were associated with the combined outcome of death/severe BPD and death/BPD-related PH. IMPACT: Decreased cardiac function on echocardiography performed during first three weeks of life is associated with severe bronchopulmonary dysplasia in extremely premature infants. In extreme preterm infants, echocardiographic signs of pulmonary hypertension in early life are associated with later BPD-related pulmonary hypertension close to 36 weeks post-menstrual age. Early cardiac markers should be further studied as potential intervention targets in this population. Our study is adding comprehensive analysis of echocardiographic data in infants born below 29 weeks gestational age.

Association of Gestational Age at Birth With Left Cardiac Dimensions at Near-Term Corrected Age Among Extremely Preterm Infants.

BACKGROUND: Remodeling and altered ventricular geometry have been described in adults born preterm. Although they seem to have an adverse cardiac phenotype, the impact of various degrees of prematurity on cardiac development has been scarcely reported. In this study, we evaluated the impact of gestational age (GA) at birth on cardiac dimensions and function at near-term age among extremely preterm infants. METHODS: This is a retrospective single-center cohort study of infants born at <29 weeks of GA between 2015 and 2019. Infants with available clinically acquired echocardiography between 34 and 43 weeks were included. Two groups were investigated: those born <26 weeks and those born ≥26 weeks. All measurements were done by an expert masked to clinical data using the raw images. The primary outcome was measurements of cardiac dimensions and function based on GA group. Secondary outcomes were the association between cardiac dimensions and postnatal steroid exposure and with increments of GA at birth. RESULTS: A total of 205 infants were included (<26 weeks, n = 102; ≥26 weeks, n = 103). At time of echocardiography, weight (2.4 ± 0.5 vs 2.5 ± 0.5 kg, P = .86) and age (37.2 ± 1.6 vs 37.1 ± 1.9 weeks, P = .74) were similar between groups. There was no difference in metrics of right-sided dimensions and function. However, left-sided dimensions were decreased in infants born <26 weeks, including systolic left ventricle (LV) diameter (1.06 ± 0.20 cm vs 1.12 ± 0.18 cm, P = .02), diastolic LV length (2.85 ± 0.37 vs 3.02 ± 0.57 cm, P = .02), and estimated LV end-diastolic volume (5.36 ± 1.69 vs 6.01 ± 1.79 mL, P = .02). CONCLUSIONS: In our cohort of very immature infants, birth at the extreme of prematurity was associated with smaller left cardiac dimensions around 36 weeks of corrected age. Future longitudinal prospective studies should evaluate further the impact of prematurity on LV development and performance and their long-term clinical impact.

The biventricular contribution to chronic pulmonary hypertension of the extremely premature infant.

OBJECTIVE: Evaluate factors associated with significant pulmonary hypertension [PH] (≥2/3 systemic) and its impact on ventricular function at 36 weeks postmenstrual age (PMA). STUDY DESIGN: Retrospective cohort of infants born at <29 weeks who survived to their echocardiography screening for PH at 36 weeks PMA. Masked experts extracted conventional and speckle-tracking echocardiography [STE] data. RESULTS: Of 387 infants, 222 were included and 24 (11%) categorized as significant PH. Significant PH was associated with a decrease in tricuspid annular plane systolic excursion (0.79 vs 0.87 cm, p = 0.03), right peak longitudinal strain [pLS] by STE (-19.6 vs -23.1%, p = 0.003) and left pLS (-25.0 vs -22.7%, p = 0.02). The association between biventricular altered function by STE and significant PH persisted after adjustment for potential confounders - LV-pLS (p = 0.007) and RV-pLS (p = 0.01). CONCLUSION: Our findings are suggestive that premature newborns with significant PH at 36 weeks PMA have a biventricular cardiac involvement to their pathophysiology.

Pulmonary lymphangiectasia in myotubular myopathy: a novel unrecognized association?

Chylothorax has been reported in rare cases of X-linked myotubular myopathy, but the pathophysiology of this association is not fully understood. We report a case of a neonate presenting prenatally with hydrops and chylothorax. The patient died at 17 days of life due to respiratory failure secondary to severe pulmonary hypertension. Comprehensive genetic testing identified a de novo hemizygous frameshift mutation in the MTM1 gene (c.142-143del, p.Glu48Serfs*12) with subsequent autopsy confirming the diagnosis of X-linked myotubular myopathy. Lung microscopy demonstrated primary pulmonary lymphangiectasia as the cause for the massive chylothorax. To the best of our knowledge, this is the first reported case of molecularly confirmed X-linked myotubular myopathy with pulmonary lymphangiectasia with prenatal findings of hydrops, chylothorax and postnatal severe pulmonary hypertension.

Natural evolution of the patent ductus arteriosus in the extremely premature newborn and respiratory outcomes.

OBJECTIVE: Evaluate spontaneous closure of the patent ductus arteriosus (PDA) in extremely preterm infants and their respiratory outcomes, especially at <26 weeks gestational age (GA). STUDY DESIGN: Retrospective study in <29 weeks, admitted within 24 h after birth (Feb 2015 and Dec 2019). Infants without any intervention to promote ductal closure, ≥1 echocardiography, and alive at discharge were included. RESULTS: Two hundred and fourteen infants (average GA 26.3 ± 1.5 weeks) were included; 84 (39%) <26 weeks. PDA closed spontaneously in 194 (91%); 76/84 (90%) for infants <26 weeks. PDA closure was ascertained on an echocardiography performed at a median age of 36.4 [34.4-40.1] weeks. Rate of moderate-to-severe bronchopulmonary dysplasia decreased throughout the study period (OR for year of birth: 0.70 [95% CI: 0.57-0.87], p = 0.001). CONCLUSION: Majority of extremely preterm infants, including <26 weeks, had spontaneous closure of the ductus before term corrected age. There was a concomitant improvement of respiratory outcomes.