Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation

The Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Journal of perinatology: official journal of the California Perinatal Association (Impact Factor: 2.07). 02/2011; 31(10):635-40. DOI: 10.1038/jp.2010.213
Source: PubMed


The goal of this study was to delineate the epidemiology of echocardiographically diagnosed pulmonary hypertension (PH) in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) requiring prolonged positive pressure ventilation (PPV), and to determine the independent relationship between PH and mortality in these patients.
Our retrospective cohort included ELBW infants, with BPD requiring prolonged PPV, hospitalized in Cincinnati, Ohio during 2003-2009, as recorded in the National Institute of Child Health and Human Development Neonatal Research Network Database. Following chart review, a logistic regression model was constructed to understand the contribution of PH to mortality in infants with BPD requiring prolonged PPV.
We identified 216 patients (19%) with BPD requiring prolonged PPV among 1156 ELBW infants. Of these patients, 41% received echocardiography after 4 weeks of life, with 37% showing evidence of PH. Logistic regression analysis demonstrated that infants with BPD requiring prolonged PPV, with PH detectable by echocardiogram, were four times more likely to die (adjusted odds ratio): 4.6, 95% confidence interval: 1.3-16.5) when compared with infants with BPD requiring prolonged PPV without echocardiographic evidence of PH.
Pulmonary hypertension appears to be an important, independent determinant of death in infants with BPD requiring prolonged PPV.

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    • "Sex-based differences have also been observed in diseases such as idiopathic pulmonary fibrosis and asthma [12]–[15]. In premature neonates, male sex is considered to be an independent risk factor for the development of BPD [12], [16]–[18]. The reasons behind these sex-biased differences in lung injury are not well elucidated yet. "
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    ABSTRACT: Exposure to high concentration of oxygen (hyperoxia) leads to lung injury in experimental animal models and plays a role in the pathogenesis of diseases such as Acute Respiratory Distress Syndrome (ARDS) and Bronchopulmonary dysplasia (BPD) in humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. The major goal of this study was to characterize the changes in the pulmonary transcriptome following hyperoxia exposure and further elucidate the sex-specific changes. Male and female (8-10 wk) wild type (WT) (C57BL/6J) mice were exposed to hyperoxia (FiO2>0.95) and gene expression in lung tissues was studied at 48 h. A combination of fold change ≥1.4 and false discovery rate (FDR)<5% was used to define differentially expressed genes (DEGs). Overrepresentation of gene ontology terms representing biological processes and signaling pathway impact analysis (SPIA) was performed. Comparison of DEG profiles identified 327 genes unique to females, 585 unique to males and 1882 common genes. The major new findings of this study are the identification of new candidate genes of interest and the sex-specific transcriptomic changes in hyperoxic lung injury. We also identified DEGs involved in signaling pathways like MAP kinase and NF-kappa B which may explain the differences in sex-specific susceptibility to hyperoxic lung injury. These findings highlight changes in the pulmonary transcriptome and sex-specific differences in hyperoxic lung injury, and suggest new pathways, whose components could serve as sex-specific biomarkers and possible therapeutic targets for acute lung injury (ALI)/acute respiratory distress (ARDS) in humans.
    PLoS ONE 07/2014; 9(7):e101581. DOI:10.1371/journal.pone.0101581 · 3.23 Impact Factor
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    • "Bronchopulmonary dysplasia (BPD), which is characterized pathologically by diffuse alveolar enlargement, thinning of the septae and narrowing of bronchiolar diameters, also known as chronic lung disease of prematurity is the most common morbidity affecting premature babies with an incidence as high as 52% in extremely low birth weight (birth weights < 1000 g) neonates (Natarajan et al., 2012). It also has long-term consequences such as chronic pulmonary morbidity, increased re-hospitalization rates, development of pulmonary hypertension and delayed neurodevelopment (Ambalavanan et al., 2011; Natarajan et al., 2012; Slaughter et al., 2011). Oxygen toxicity is thought to play a role in both acute lung injury and BPD. "
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    ABSTRACT: Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25mg/Kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore,these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon.
    Toxicology Letters 03/2014; 230(2). DOI:10.1016/j.toxlet.2014.03.006 · 3.26 Impact Factor
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    • "Pulmonary hypertension (PH) is increasingly recognized as an important complication of prematurity and bronchopulmonary dysplasia (BPD) [1,2]. Retrospective studies have estimated that 25 to 37% of infants with BPD develop PH [3,4], and a recent prospective study showed that 1 out of 6 extremely low birth weight (ELBW) infants develop PH [5]. This is concerning as PH in the BPD population is associated with worse outcomes, with mortality rates ranging between 14% and 38% in retrospective studies [3,4,6-8] and 12% in one prospective study [5]. "
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    ABSTRACT: B-type natriuretic peptide (BNP) is a strong predictor of mortality in adult patients with various forms of pulmonary hypertension (PH) and may be a strong prognostic marker in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) associated PH as well. We sought to assess the relationship between BNP levels and all-cause mortality in a cohort of ELBW infants with BPD and PH. We retrospectively identified ELBW infants with BPD and PH who had serum BNP levels measured as part of routine clinical care in the neonatal intensive care unit. Peak serum BNP levels were correlated with survival to discharge or death. Thirty-six ELBW infants (mean gestational age 26.0 +/- 1.9 weeks and mean birth weight 740 +/- 290 grams) with BPD and PH had available survival data and had serum BNP levels measured. Peak BNP level was significantly lower among infants who survived than among those who died (128 pg/ml, [IQR 23 to 463] vs. 997 pg/ml, [IQR 278 to 1770], P < 0.004). On multivariate Cox proportional hazard analysis, BNP predicted survival independent of age, gender, and BPD severity. Area under receiver operator characteristic analysis identified a BNP value of 220 pg/ml to have 90% sensitivity and 65% specificity in predicting mortality. BNP estimation may be useful as a prognostic marker of all-cause mortality in ELBW infants with BPD associated PH.
    BMC Pediatrics 03/2014; 14(1):68. DOI:10.1186/1471-2431-14-68 · 1.93 Impact Factor
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