Bronchopulmonary Dysplasia-associated Pulmonary Hypertension Research Articles

A comprehensive study on machine learning models combining with oversampling for bronchopulmonary dysplasia-associated pulmonary hypertension in very preterm infants

BackgroundBronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) remains a devastating clinical complication seriously affecting the therapeutic outcome of preterm infants. Hence, early prevention and timely diagnosis prior to pathological change is the key to reducing morbidity and improving prognosis. Our primary objective is to utilize machine learning techniques to build predictive models that could accurately identify BPD infants at risk of developing PH.MethodsThe data utilized in this study were collected from neonatology departments of four tertiary-level hospitals in China. To address the issue of imbalanced data, oversampling algorithms synthetic minority over-sampling technique (SMOTE) was applied to improve the model.ResultsSeven hundred sixty one clinical records were collected in our study. Following data pre-processing and feature selection, 5 of the 46 features were used to build models, including duration of invasive respiratory support (day), the severity of BPD, ventilator-associated pneumonia, pulmonary hemorrhage, and early-onset PH. Four machine learning models were applied to predictive learning, and after comprehensive selection a model was ultimately selected. The model achieved 93.8% sensitivity, 85.0% accuracy, and 0.933 AUC. A score of the logistic regression formula greater than 0 was identified as a warning sign of BPD-PH.ConclusionsWe comprehensively compared different machine learning models and ultimately obtained a good prognosis model which was sufficient to support pediatric clinicians to make early diagnosis and formulate a better treatment plan for pediatric patients with BPD-PH.

Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Prospective observational study. Single-center, tertiary-level neonatal intensive care unit. Infant born <28 weeks gestation. Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

Association of the respiratory severity score with bronchopulmonary dysplasia-associated pulmonary hypertension in infants born extremely preterm.

To test the hypothesis that elevations in the respiratory severity score (RSS) are associated with increased probability of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH). Retrospective cohort study of infants born extremely preterm admitted to a BPD center between 2010 and 2018. Echocardiograms obtained ≥ 36 weeks' post-menstrual age (PMA) were independently adjudicated by two blinded cardiologists to determine the presence/absence of BPD-PH. Multivariable logistic regression estimated the association between RSS and BPD-PH. BPD-PH was observed in 68/223 (36%) of subjects. The median RSS at time of echocardiography was 3.04 (Range 0-18.3). A one-point increase in the RSS was associated with BPD-PH, aOR 1.3 (95% CI 1.2-1.4), after adjustment for gestational age and PMA at time of echocardiography. Elevations in the RSS were associated with a greater probability of BPD-PH. Prospective studies are needed to determine the validity and performance of RSS as a clinical susceptibility/risk biomarker for BPD-PH.

COVID-19 vaccination for children with pulmonary hypertension: efficacy, safety and reasons for opting against vaccination.

To determine the reasons why pulmonary hypertension (PH) children refused vaccination against COVID-19, evaluate the safety and efficacy of COVID-19 vaccine in PH children. This retrospective cohort study included congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) and bronchopulmonary dysplasia associated PH (BPD-PH) children who were divided into vaccinated group and non-vaccinated group. Univariate logistic regression analysis and multivariate logistic regression analysis were conducted to explore the reasons why PH children refused COVID-19 vaccine. Then, the prevalence, the number of symptoms, and the severity of COVID-19 disease were compared between the vaccinated and unvaccinated groups. We included 73 children and 61 children (83.6%) were unvaccinated. The main reasons for not being vaccinated were fear of worsening of existing diseases (31%). Age < 36 months (RR: 0.012; P < 0.001) and the presence of comorbidities (RR = 0.06; P = 0.023) were risk factors influencing willingness to vaccinate. The most common adverse events (AEs) were injection site pain (29.6%). COVID-19 vaccines are safe for PH children. The prevalence of COVID-19 disease decreased in PH children after vaccination (RR = 0.51; P = 0.009). 1 month after negative nucleic acid test or negative antigen test, PH children in the vaccinated group had fewer symptoms (P = 0.049). The vaccination rate of COVID-19 vaccine is low in CHD-PAH and BPD-PH children while COVID-19 vaccines are safe. Vaccination can reduce the prevalence of COVID-19 disease and the number of symptoms 1 month after negative nucleic acid or antigen tests.

Efficacy of Sildenafil in Infants with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a common comorbidity in infants with bronchopulmonary dysplasia (BPD). Sildenafil is a widely recognized therapy for PH, but its efficacy in infants with BPD is questionable. We propose to assess the efficacy of sildenafil in BPD-associated PH as evaluated based on transthoracic echocardiography (TTE) changes and clinical measures. Methods: Data were retrospectively and prospectively collected. Inclusion criteria were gestational age (GA) < 32 weeks, birth weight (BW) < 1500 g with severe BPD, diagnosis of PH via TTE on sildenafil treatment. PH was evaluated via TTE, which was performed monthly after 36 weeks post-menstrual age (PMA) as a standard of care, and re-reviewed by a single pediatric cardiologist, who was blind to the initial reading. Results: In total, 19 patients were enrolled in the study, having a median GA of 24 3/7 weeks (IQR 23 5/7-25 5/7) and a median BW of 598 g (IQR 572-735). Sildenafil treatment was started at a median PMA of 40.4 weeks. The median respiratory severity score (RSS) at 28 d was 6.5, RSS and FiO2 showed improvement about 12 weeks after starting sildenafil treatment. Conclusions: Improvement in PH was noted via TTE, and patients had improvement in their RSS and FiO2 after prolonged therapy. However, TTE improvements did not correlate with clinical improvements.

Neurodevelopmental Outcomes of Preterm Infants Born

This study aimed to determine neurodevelopmental outcomes of preterm infants born at <29 weeks' gestational age (GA) with bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) at 18 to 24 months' corrected age (CA). In this retrospective cohort study, preterm infants born at <29 weeks' GA between January 2016 and December 2019, admitted to level 3 neonatal intensive care units, who developed BPD and were evaluated at 18 to 24 months' CA in the neonatal follow-up clinics were included. We compared demographic characteristics and neurodevelopmental outcomes between the two groups: Group I: BPD with PH and Group II: BPD with no PH, using univariate and multivariate regression models. The primary outcome was a composite of death or neurodevelopmental impairment (NDI). NDI was defined as any Bayley-III score < 85 on one or more of the cognitive, motor, or language composite scores. Of 366 eligible infants, 116 (Group I [BPD-PH] =7, Group II [BPD with no PH] = 109) were lost to follow-up. Of the remaining 250 infants, 51 in Group I and 199 in Group II were followed at 18 to 24 months' CA. Group I and Group II had median (interquartile range [IQR]) birthweights of 705 (325) and 815 g (317; p = 0.003) and median GAs (IQR) were 25 (2) and 26 weeks (2; p = 0.015) respectively. Infants in the BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted odds ratio: 3.82; bootstrap 95% confidence interval; 1.44-40.87). BPD-PH in infants born at <29 weeks' GA is associated with increased odds of the composite outcome of death or NDI at 18 to 24 months' CA. · Long-term neurodevelopmental follow-up of preterm infants born <29 weeks' GA.. · Association of neurodevelopmental outcomes with BPD-associated PH.. · Need for longitudinal follow-up of children with BPD-associated PH..

Inhaled nitric oxide use in newborns.

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, is used as a therapeutic modality in infants with hypoxemic respiratory failure (HRF) associated with persistent pulmonary hypertension of the newborn (PPHN). iNO should ideally be initiated following echocardiographic confirmation of PPHN. Use of iNO is recommended in late preterm and term infants who develop HRF despite optimal oxygenation and ventilation strategies. However, routine iNO use in preterm infants on respiratory support is not recommended. iNO may be considered as a rescue modality in preterm infants with early-onset HRF when associated with prolonged rupture of membranes or oligohydramnios, or late-onset HRF in the context of bronchopulmonary dysplasia-associated pulmonary hypertension (PH) with severe right ventricular failure. A trial of iNO may also be considered for infants with congenital diaphragmatic hernia with persistent HRF despite optimal lung recruitment, and with echocardiographic evidence of supra-systemic PH and adequate left ventricular function.

A multidisciplinary approach to severe bronchopulmonary dysplasia is associated with resolution of pulmonary hypertension.

To describe our multidisciplinary bronchopulmonary dysplasia (BPD) consult team's systematic approach to BPD associated pulmonary hypertension (PH), to report our center outcomes, and to evaluate clinical associations with outcomes. Retrospective cohort of 60 patients with BPD-PH who were referred to the Seattle Children's Hospital BPD team from 2018 to 2020. Patients with critical congenital heart disease were excluded. Demographics, comorbidities, treatments, closure of hemodynamically relevant intracardiac shunts, and clinical outcomes including time to BPD-PH resolution were reviewed. Median gestational age of the 60 patients was 25 weeks (IQR: 24-26). 20% were small for gestational age (SGA), 65% were male, and 25% received a tracheostomy. With aggressive cardiopulmonary management including respiratory support optimization, patent ductus arteriosus (PDA) and atrial septal defect (ASD) closure (40% PDA, 5% ASD, 3% both), and limited use of pulmonary vasodilators (8%), all infants demonstrated resolution of PH during the follow-up period, including three (5%) who later died from non-BPD-PH morbidities. Neither SGA status nor the timing of PH diagnosis (<36 vs. ≥36 weeks PMA) impacted the time to BPD-PH resolution in our cohort [median 72 days (IQR 30.5-166.5)]. Our multidisciplinary, systematic approach to BPD-PH management was associated with complete resolution of PH with lower mortality despite less sildenafil use than reported in comparable cohorts. Unique features of our approach included aggressive PDA and ASD device closure and rare initiation of sildenafil only after lack of BPD-PH improvement with respiratory support optimization and diagnostic confirmation by cardiac catheterization.

Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension.

The aim of the study was to determine whether prolonged exposure to a moderate/large patent ductus arteriosus left-to-right shunt (PDA) increases the risk of late (beyond 36 weeks) pulmonary hypertension (BPD-PH) and pulmonary vascular disease (BPD-PVD) during the neonatal hospitalization in preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD). All infants requiring respiratory support ≥36 weeks had systematic echocardiographic evaluations for BPD-PH at planned intervals. Infants were classified as having either flow-associated BPD-PH (BPD-flow-PH) or BPD-PVD. 256 infants survived ≥36 weeks: 105 had NO BPD (were off respiratory support by 36 weeks); 151 had BPD. 22/151 had BPD-PH (12/22 had BPD-flow-PH from a PDA that persisted beyond 36 weeks; 10/22 had BPD-PVD). Moderate/large PDA shunts that persisted beyond 36 weeks were significantly associated with an increased incidence of BPD-PH due to BPD-flow-PH. We found no association between the duration of PDA exposure and the incidence of BPD-PVD. Moderate/large PDA shunts increase the risk of flow-associated BPD-PH when present beyond 36 weeks. Although term infants with PDA-congenital heart disease can develop pulmonary vascular remodeling and PVD after months of PDA exposure, we found no echocardiographic evidence in preterm infants that prolonged PDA exposure increases the incidence of BPD-PVD during the neonatal hospitalization. In our study, preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD) had a 15% incidence of pulmonary hypertension (PH) beyond 36 weeks' postmenstrual age as a comorbidity. Moderate/large patent ductus arteriosus (PDA) shunts increased the risk of flow-associated PH when present beyond 36 weeks. Although months of prolonged PDA exposure can cause pulmonary vascular remodeling and pulmonary vascular disease (PVD) in term infants with PDA-congenital heart disease, we found no echocardiographic evidence for an association between the duration of PDA exposure and the incidence of late PVD during the neonatal hospitalization in preterm infants with BPD.

433 - Achieved oxygen saturations and risk for bronchopulmonary dysplasia-associated pulmonary hypertension in preterm infants

433 - Achieved oxygen saturations and risk for bronchopulmonary dysplasia-associated pulmonary hypertension in preterm infants

Intermittent Hypoxemia and Bronchopulmonary Dysplasia with Pulmonary Hypertension in Preterm Infants.

Rationale: Bedside biomarkers that allow early identification of infants with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) are critically important, given the higher risk of death in these infants. Objectives: We hypothesized that infants with BPD-PH have patterns of intermittent hypoxemia (IH) that differ from infants with BPD without PH. Methods: We conducted a matched case-control study of extremely preterm infants from 22 weeks 0 days to 28 weeks 6 days born between 2018 and 2020 at the University of Alabama at Birmingham. BPD-PH status was determined using echocardiographic data performed after postnatal Day 28. Physiologic data were compared between infants with BPD-PH (cases) and BPD alone (control subjects). Receiver operating characteristic (ROC) analysis estimated the predictive ability of cumulative hypoxemia, desaturation frequency, and duration of intermittent hypoxemic events in the week preceding echocardiography to discriminate between cases and control subjects. Measurements and Main Results: Forty infants with BPD-PH were compared with 40 infants with BPD alone. Infants with and without PH had a similar frequency of IH events, but infants with PH had more prolonged hypoxemic events for desaturations below 80% (7 s vs. 6 s; P = 0.03) and 70% (105 s vs. 58 s; P = 0.008). Among infants with BPD-PH, infants who died had longer hypoxemic events below 70% (145 s vs. 72 s; P = 0.01). Using the duration of hypoxemic events below 70%, the areas under the ROC curves for diagnosis of BPD-PH and death in BPD-PH infants were 0.71 and 0.77, respectively. Conclusions: Longer duration of intermittent hypoxemic events was associated both with a diagnosis of BPD-PH and with death among infants with BPD-PH.

Patent Ductus Arteriosus and Development of Bronchopulmonary Dysplasia-associated Pulmonary Hypertension.

Rationale: Extremely preterm infants with evolving bronchopulmonary dysplasia (BPD) are at risk for development of BPD-associated pulmonary hypertension (BPD-PH). A patent ductus arteriosus (PDA) shunt may be a modifiable risk factor for BPD-PH development. Objective: To determine whether the presence and duration of ductus arteriosus patency differs between extremely preterm infants with and without BPD-PH. Methods: We conducted a retrospective case-control study among preterm infants of gestational age 22 weeks, 0 days, to 28 weeks, 6 days, who remained on respiratory support on postnatal day 28 at the University of Alabama at Birmingham from 2017 to 2020. Infants who were diagnosed with PH (cases) by echocardiography were compared with infants without PH (control subjects). Data from echocardiograms performed during the hospitalization after postnatal day 28 were included. Logistic regression adjusted for covariates that differed significantly between groups. A probit analysis related the duration of ductal patency to the development of BPD-PH. Measurements and Main Results: A total of 138 infants developed BPD alone, and 82 infants developed BPD-PH. After adjustment for differing covariates between groups, both PDA (adjusted odds ratio, 4.29; 95% confidence interval, 1.89-9.77) and moderate to large PDA (adjusted odds ratio, 4.15; 95% confidence interval, 1.78-9.64) remained significantly related to BPD-PH at discharge. By probit analysis, each additional month of PDA and hemodynamically significant PDA exposure was associated with an increased probability for the composite outcome of BPD-PH at discharge or death with coefficients of 0.40 (P < 0.001) and 0.45 (P < 0.001), respectively. Conclusions: In extremely preterm infants on respiratory support on postnatal day 28, both the presence of and a longer duration of ductus arteriosus patency were associated with the development of BPD-PH.

Pharmacokinetics of L-Citrulline in Neonates at Risk of Developing Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

Options to treat pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD) are few and largely ineffective. Improving the bioavailability of nitric oxide (NO) might be an efficacious treatment for BPD-PH. When administered orally, the NO-L-arginine precursor, L-citrulline, increases NO production in children and adults, however, pharmacokinetic (PK) studies of oral L-citrulline have not been performed in infants and children. This study characterized the PK of enterally administered L-citrulline in neonates at risk of developing BPD-PH to devise a model-informed dosing strategy. Ten premature neonates (≤28 weeks gestation) were administered a single dose of 150 mg/kg (powder form solubilized in sterile water) oral L-citrulline at 32 ± 1 weeks postmenstrual age. Due to the need to limit blood draws, time windows were used to maximize the sampling over the dosing interval by assigning neonates to one of two groups (ii) samples collected pre-dose and at 1- and 2.5-h post-dose, and (ii) pre-dose and 0.25- and 3-h post-dose. The L-arginine concentrations (µmol/L) and the L-citrulline (µmol/L) plasma concentration-time data were evaluated using non-compartmental analysis (Phoenix WinNonlin version 8.1). Optimal dosage strategies were derived using a simulation-based methodology. Simulated doses of 51.5 mg or 37.5 mg/kg given four times a day produced steady-state concentrations close to a target of 50 µmol/L. The volume of distribution (V/F) and clearance (CL/F) were 302.89ml and 774.96ml/h, respectively, with the drug exhibiting a half-life of 16 minutes. The AUC from the time of dosing to the time of last concentration was 1473.3h*μmol/L, with Cmax and Tmax of 799μmol/L and 1.55h, respectively. This is the first PK study in neonates presenting data that can be used to inform dosing strategies in future randomized controlled trials evaluating enteral L-citrulline as a potential treatment to reduce PH associated with BPD in premature neonates. Clinical trials.gov Identifier: NCT03542812.

27 Neurodevelopmental Outcomes of Preterm Infants Born &amp;lt;29 weeks with Bronchopulmonary Dysplasia Associated Pulmonary Hypertension: A Multicenter Study

Abstract Background More than 1 in 4 preterm infants with bronchopulmonary dysplasia (BPD) develop BPD-associated pulmonary hypertension (BPD-PH) that is associated with significant morbidity. Data regarding neurodevelopmental outcomes with BPD-PH in preterm infants are lacking. Objectives To determine neurodevelopmental outcomes of preterm infants born &amp;lt; 29 weeks gestational age (GA) with BPD associated pulmonary hypertension at 18 to 24 months corrected gestational age (CGA). Design/Methods In this retrospective cohort study, preterm infants born &amp;lt; 29 weeks GA between January 2016 and December 2019 at level 3 Neonatal Intensive Care Units at Foothills Hospital in Calgary and the University of Texas Medical Branch (UTMB) in Galveston, who were evaluated at 18-24 months CGA in the neonatal follow-up clinics were included. We compared demographic factors, neurodevelopmental status including Bayley-III scores and sensory impairments between the two groups based on the presence of PH at 36 weeks CGA: Group I: BPD with PH and Group II: BPD without PH, using univariate and multivariable regression models. The primary outcome was a composite of death or neurodevelopmental impairments (NDI). NDI was defined as any cerebral palsy (GMFCS≥1), Bayley-III score &amp;lt; 85 on one or more of the cognitive, motor, or language composite scores, sensorineural or mixed hearing impairment or unilateral or bilateral visual impairment. Results Of 372 eligible infants, 118 (Group I [BPD-PH] =7, Group II [BPD with no PH] =111) were lost to follow up. Of the remaining 254 infants, 52 in Group I and 202 in Group II were followed at 18-24 months CGA. Group I and Group II had median (IQR) birth weight of 710g (323) and 815g (314) [p=0.004] and median gestational ages (IQR) were 25 weeks (2) and 26 weeks (2) [p=0.020], respectively . Rates of associated impairments are shown in Figure 1. Infants in BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted Odds Ratio [aOR] 3.82; 95% CI: 1.17-12.41) (Table 1). Conclusion BPD-PH in preterm infants born &amp;lt; 29 weeks GA is associated with increased odds of the composite outcome of death or neurodevelopmental impairment and language delay at 18-24 months CGA.

Episodes of apnea and periodic breathing in premature infants with BPD-associated pulmonary hypertension

Premature infants with bronchopulmonary dysplasia-associated pulmonary hypertension have a longer persistence of apnea of prematurity and periodic breathing. We hypothesized that apnea of prematurity and periodic breathing may be associated with the persistence of pulmonary hypertension in infants with bronchopulmonary dysplasia.The aim of the study was to determine the characteristics of apnea episodes and periodic breathing in premature infants with bronchopulmonary dysplasia-associated pulmonary hypertension.Characteristics of children and research methods. Cardiorespiratory monitoring was conducted on 27 premature infants born at 22 0/7 — 29 0/7 weeks of gestation with a body weight of &lt;1000 grams. All infants had bronchopulmonary dysplasia, and 14 infants with severe bronchopulmonary dysplasia were diagnosed pulmonary hypertension (main cohort).Results. The group of infants with bronchopulmonary dysplasia + pulmonary hypertension had lower average SpO2, higher desaturation index and apnea/hypopnea index as compared to infants without pulmonary hypertension. Four infants from the main cohort had obstructive apnea index of ˃1 events/hour and had high values of 1,1; 2,5; 5,8, and 8,6/hour. In the comparison group, only one infant had a high obstructive apnea index (1,1/hour). Eleven infants(78%) with pulmonary hypertension had episodes of periodic breathing, at the same time only six infants (46%) in the group without pulmonary hypertension had such episodes. Periodic breathing episodes with a drop of SpO2 &lt;90% were registered in 82% of cases in the main cohort and in 67% of cases in infants of the comparison group.Conclusion. Premature infants with bronchopulmonary dysplasia and pulmonary hypertension had more significant decrease in mean SpO2, increased desaturation index and apnea/hypopnea index and tend to have obstructive apnea index &gt;1/hour and longer periodic breathing than infants without pulmonary hypertension.

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH). Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood. After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001]. In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity.

Use of Inhaled Nitric Oxide in Preterm Infants: Is There Sufficient Evidence?

Nitric oxide (NO) is a potent vasodilator. The inhaled form (iNO) improves outcomes in term infants with persistent pulmonary hypertension of the newborn (PPHN) or bronchopulmonary dysplasia-associated pulmonary hypertension in preterm infants. However, in preterm infants, the risks and benefits of iNO use are controversial. Substantial evidence reveals no significant impact on survival or other morbidities in preterm infants with iNO treatment, independent of indication, timing, or duration of use. Many scientific organizations do not recommend the use of iNO in preterm infants, except in unique clinical circumstances with echocardiographic findings of PPHN in the setting of presumed pulmonary hypoplasia.

Children with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension Treated with Pulmonary Vasodilators-The Pediatric Cardiologist Point of View.

Pulmonary hypertension in children with bronchopulmonary dysplasia (BPD-PH) significantly worsens the prognosis. Pulmonary vasodilators are often used in BPD-PH but the short-term outcome of treatment is not well described. The aim of this study was to evaluate BPD-PH children diagnosed beyond 36 weeks postmenstrual age treated with pulmonary vasodilators (sildenafil, bosentan, or both) and to assess the short and long-term effect of oral pulmonary vasodilators treatment. Twenty patients were included in the study. Cardiology evaluation (WHO-FC, NTproBNP, oxygen saturation, pulmonary to systemic pressure ratio PAP/SAP) was performed at diagnosis and after treatment initiation. In the majority of patients improvement in all evaluated factors was observed. No side effects of vasodilators were observed. PH resolved in 10 patients after a mean of 21.4 months of treatment. Six patients died. The number of poor prognostic factors commonly used to assess patients with pulmonary arterial hypertension (PAH) decreased significantly during BPD-PH treatment. The influence of BPD-PH perinatal risk factors on prognosis was considered but was not confirmed. In conclusion, the treatment of BPD-PH with pulmonary vasodilators was well tolerated and led to a clinical improvement with the possibility of discontinuation without recurrence of PH. Prognostic factors used in pediatric PAH risk stratification also seem to be useful in assessing treatment efficacy and prognosis in patients with BPD-PH.

Role of functional echocardiographic parameters in the diagnosis of bronchopulmonary dysplasia-associated pulmonary hypertension.

Echocardiogram (echo) is a commonly used noninvasive modality for the diagnosis of bronchopulmonary dysplasia associated pulmonary hypertension (BPD-PH). Though not considered the gold standard for the diagnosis of BPD-PH, it is an extremely valuable tool in the neonatal and pediatric population, especially when cardiac catheterization is not feasible. In addition to the traditional echo parameters that are used to assess the presence of BPD-PH, much attention has been recently placed on newer bedside echo measures, the so-called functional echo parameters, to aid and assist in the diagnosis. This review article provides a brief introduction to BPD-PH, describes the pitfalls of traditional echo parameters and details the newer echo modalities currently available for the diagnosis of neonatal PH.

Echocardiography evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension: a retrospective observational cohort study

BackgroundEchocardiography has poor accuracy in grading the severity of pulmonary hypertension (PH) compared to cardiac catheterization. However, the relationship between degree of PH and prognostic outcomes remains uncertain. Our primary objective was to determine whether echocardiogram-assessed PH severity is associated with mortality and hospital readmission in the first year of life.MethodsA retrospective cohort study of infants born less than 32 weeks of gestational age with bronchopulmonary dysplasia (BPD) underwent echocardiography was performed. Echocardiograms were performed at 36–38 weeks postmenstrual age. Data during hospitalization and post-discharge collected at 1-year age were analyzed with cox regression models and logistic regression models to identify the association of PH severity with mortality and readmission. Area under curve (AUC) was calculated to examine the accuracy of these models to reflect the likelihood of outcomes.ResultsFifty-six of 237 (23.6%) infants were diagnosed as PH. Moderate and severe PH was significantly associated with mortality during the first one year of life (moderate PH vs. none HR =26.58, 95% CI: 4.40–160.78, P<0.001; severe PH vs. none HR =36.49, 95% CI: 5.65–235.84, P<0.001). Male, preeclampsia and inhaled nitric oxide were also associated with mortality. Mild PH was significantly associated with readmission (OR =2.42, 95% CI: 1.12–5.26, P=0.025), but not associated with mortality (HR =2.09, 95% CI: 0.43–10.18, P=0.36). The PH severity model based on echocardiography accurately informed mortality (AUC 0.79).ConclusionsEchocardiogram-assessed PH severity is associated with prognostic outcomes, including mortality and readmission in very preterm infants with BPD. The severity of PH based on echocardiography is a potential predictor of mortality in the first year of life.