Abstract
Objective:
Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD) but the true impact of PH in patients with BPD remains unclear. We sought to systematically review and meta-analyze incidence of PH in BPD and compare clinical outcomes of BPD patients with PH to those without PH in preterm infants.
Study Design:
Medline, Embase, PsychINFO and CINAHL were searched from January 2000 through December 2015. Cohort, case–control and randomized studies were included. Case-reports, case-series and letters to editors and studies with high risk of bias were excluded. Study design, inclusion/exclusion criteria, diagnostic criteria for BPD and PH and outcomes were extracted independently by two co-authors.
Results:
The pooled incidence of PH in patients with BPD (any severity) was 17% (95% confidence interval (CI) 12 to 21; 7 studies) and 24% (95% CI 17 to 30; 9 studies) in moderate-severe BPD. Patients with BPD have higher unadjusted odds of developing PH compared to those without BPD (odds ratio (OR) 3.00; 95% CI 1.18 to 7.66; 4 studies). Patients with BPD and PH were at higher odds of mortality (OR 5.29; 95% CI 2.07 to 13.56; 3 studies) compared with BPD without PH, but there was no significant difference in duration of initial hospitalization, duration of supplemental oxygen requirement or need for home oxygen. No studies included in this review reported on long-term pulmonary or neurodevelopmental outcomes.
Conclusions:
PH occurs in one out of 4 to 5 preterm neonates with BPD. Patients with BPD and PH may have higher odds of mortality; however, there is urgent need for high quality studies that control for confounders and provide data on long-term outcomes.
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References
Stenmark KR, Abman SH . Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol 2005; 67: 623–661.
Niedermaier S, Hilgendorff A . Bronchopulmonary dysplasia - an overview about pathophysiologic concepts. Mol Cell Pediatr 2015; 2 (1): 2.
De Paepe ME, Chu S, Hall SJ, McDonnell-Clark E, Heger NE, Schorl C et al. Intussusceptive-like angiogenesis in human fetal lung xenografts: Link with bronchopulmonary dysplasia-associated microvascular dysangiogenesis? Exp Lung Res 2015; 41 (9): 477–488.
Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA 2015; 314 (10): 1039–1051.
Shah PS, Sankaran K, Aziz K, Allen AC, Seshia M, Ohlsson A et al. Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern? J Perinatol 2012; 32 (2): 132–138.
Kim DH, Kim HS, Choi CW, Kim EK, Kim BI, Choi JH . Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology 2012; 101 (1): 40–46.
Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC et al. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 2007; 120 (6): 1260–1269 10p.
Slaughter JL, Pakrashi T, Jones DE, South AP, Shah TA . Echocardiographic detection of pulmonary hypertension in extremely low birth weight infants with bronchopulmonary dysplasia requiring prolonged positive pressure ventilation. J Perinatol 2011; 31 (10): 635–640.
Ambalavanan N, Mourani P . Pulmonary hypertension in bronchopulmonary dysplasia. Birth Defects Res 2014; 100 (3): 240–246.
An HS, Bae EJ, Kim GB, Kwon BS, Beak JS, Kim EK et al. Pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. Korean Circ J 2010; 40 (3): 131–136.
Kumar VH, Hutchison AA, Lakshminrusimha S, Morin FC 3rd, Wynn RJ, Ryan RM . Characteristics of pulmonary hypertension in preterm neonates. J Perinatol 2007; 27 (4): 214–219.
Gough A, Spence D, Linden M, Halliday HL, McGarvey LP . General and respiratory health outcomes in adult survivors of bronchopulmonary dysplasia: a systematic review. Chest 2012; 141 (6): 1554–1567.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283 (15): 2008–2012.
Jobe AH, Bancalari E . Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163 (7): 1723–1729.
Rossor T, Greenough A . Advances in paediatric pulmonary vascular disease associated with bronchopulmonary dysplasia. Expert Rev Respir Med 2015; 9 (1): 35–43.
Newcastle Ottawa Scale 2014 Available at www.ohri.ca/programs/clinical_epidemiology/nosgen.pdf. Accessed on 28 April 2016.
Higgins J, Green S 2011 Available at: http://www.cochrane-handbook.org. Accessed on 3 July 2016.
Hozo SP, Djulbegovic B, Hozo I . Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13.
Ali Z, Schmidt P, Dodd J, Jeppesen DL . Predictors of bronchopulmonary dysplasia and pulmonary hypertension in newborn children. Dan Med J 2013; 60 (8): A4688.
Aswani R, Hayman L, Nichols G, Luciano AA, Amankwah EK, Leshko JL et al. Oxygen requirement as a screening tool for the detection of late pulmonary hypertension in extremely low birth weight infants. Cardiol Young 2016; 26 (3): 521–527.
Bhat R, Salas AA, Foster C, Carlo WA, Ambalavanan N . Prospective analysis of pulmonary hypertension in extremely low birth weight infants. Pediatrics 2012; 129 (3): e682–e689.
Bruno CJ, Meerkov M, Capone C, Vega M, Sutton N, Kim M et al. CRIB scores as a tool for assessing risk for the development of pulmonary hypertension in extremely preterm infants with bronchopulmonary dysplasia. Am J Perinatol 2015; 32 (3): 1031–1037.
Check J, Gotteiner N, Liu X, Su E, Porta N, Steinhorn R et al. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia. J Perinatol 2013; 33 (7): 553–557.
Choi EK, Jung YH, Kim H-S, Shin SH, Choi CW, Kim E-K et al. The Impact of atrial left-to-right shunt on pulmonary hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Pediatr Neonatol 2015; 56 (5): 317–323.
Guaman MC, Gien J, Baker CD, Zhang H, Austin ED, Collaco JM . Point prevalence, clinical characteristics, and treatment variation for infants with severe bronchopulmonary dysplasia. Am J Perinatol 2015; 32 (10): 960–967.
Mestan KK, Check J, Minturn L, Yallapragada S, Farrow KN, Liu X et al. Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension. Placenta 2014; 35 (8): 570–574.
Mirza H, Ziegler J, Ford S, Padbury J, Tucker R, Laptook A . Pulmonary hypertension in preterm infants: prevalence and association with bronchopulmonary dysplasia. J Pediatr 2014; 165 (5): 909–14.e1.
Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD et al. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 2015; 191 (1): 87–95.
Trittmann JK, Nelin LD, Zmuda EJ, Gastier-Foster JM, Chen B, Backes CH et al. Arginase I gene single-nucleotide polymorphism is associated with decreased risk of pulmonary hypertension in bronchopulmonary dysplasia. Acta Paediatr 2014; 103 (10): e439–e443.
Trittmann JK, Peterson E, Rogers LK, Chen B, Backes CH, Klebanoff MA et al. Plasma asymmetric dimethylarginine levels are increased in neonates with bronchopulmonary dysplasia-associated pulmonary hypertension. J Pediatr 2015; 166 (2): 230–233.
Mourani PM, Abman SH . Pulmonary vascular disease in bronchopulmonary dysplasia: pulmonary hypertension and beyond. Curr Opin Pediatr 2013; 25 (3): 329–337.
Wilson JMG, Junger G . Principles and Practice of Screening for Disease 1968 World Health Organization. Public Health Papers, no. 34..
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Study registration and registration number: PROSPERO CRD42016042104.
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Data from this research were presented at Pediatric Academic Societies, San Diego 2016.
Supplementary Information accompanies the paper on the Journal of Perinatology website
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Al-Ghanem, G., Shah, P., Thomas, S. et al. Bronchopulmonary dysplasia and pulmonary hypertension: a meta-analysis. J Perinatol 37, 414–419 (2017). https://doi.org/10.1038/jp.2016.250
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DOI: https://doi.org/10.1038/jp.2016.250
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