Skip to main content
Top
Published in: BMC Pediatrics 1/2017

Open Access 01-12-2017 | Research article

Early characteristics of infants with pulmonary hypertension in a referral neonatal intensive care unit

Authors: Shilpa Vyas-Read, Usama Kanaan, Prabhu Shankar, Jane Stremming, Curtis Travers, David P. Carlton, Anne Fitzpatrick

Published in: BMC Pediatrics | Issue 1/2017

Login to get access

Abstract

Background

Approximately 8–23% of premature infants develop pulmonary hypertension (PH), and this diagnosis confers a higher possibility of mortality. As a result, professional societies recommend PH screening in premature infants. However, the risk factors for and the outcomes of PH may differ depending on the timing of its diagnosis, and little evidence is available to determine at-risk infants in the referral neonatal population. The objective of this study was to define clinical and echocardiographic characteristics of infants with pulmonary hypertension during the neonatal hospital course and at or near-term.

Methods

Infants who had the following billing codes: < 32 weeks, birth weight < 1500 g, neonatal unit, and echocardiograph had records abstracted from a data warehouse at Children’s Healthcare of Atlanta. The outcome was defined as late PH on the final echocardiogram for all patients, and, separately, for patients with multiple studies. Descriptive statistics, univariable, and multivariable models were evaluated, and odds ratios and 95% confidence intervals are expressed below as (OR, CI).

Results

556 infants were included in the overall study, 59 had PH on their final echocardiogram (11%). In multivariable analyses, atrial septal defect (2.9, 1.4–6.1), and intrauterine growth restriction (2.7, 1.2–6.3) increased the odds of late PH, whereas caffeine therapy decreased PH (0.4, 0.2–0.8). When the analyses were restricted to 32 infants who had multiple echocardiograms during their hospitalization, the association between atrial septal defect (5.9, 2.0–16.5) and growth restriction (3.7, 1.3–10.7) and late PH was strengthened, but the effect of caffeine therapy was no longer significant. In this smaller subgroup, infants with late PH had their final echocardiogram at a median of 116 days of life, and 42–74% of them had right ventricular pathology.

Conclusions

Early clinical variables are associated with PH persistence in a referral neonatal population. Identification of early clinical factors may help guide the ascertainment of infant risk for late PH, and may aid in targeting sub-groups that are most likely to benefit from PH screening.
Literature
1.
go back to reference Mourani PM, Abman SH. Pulmonary hypertension and vascular abnormalities in bronchopulmonary dysplasia. Clin Perinatol. 2015;42:839–55.CrossRefPubMed Mourani PM, Abman SH. Pulmonary hypertension and vascular abnormalities in bronchopulmonary dysplasia. Clin Perinatol. 2015;42:839–55.CrossRefPubMed
4.
go back to reference Abman SH. Bronchopulmonary dysplasia: "a vascular hypothesis". Am J Respir Crit Care Med. 2001;164:1755–6.CrossRefPubMed Abman SH. Bronchopulmonary dysplasia: "a vascular hypothesis". Am J Respir Crit Care Med. 2001;164:1755–6.CrossRefPubMed
5.
go back to reference 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;40:131–6.CrossRefPubMedPubMedCentral 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;40:131–6.CrossRefPubMedPubMedCentral
6.
go back to reference 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 American Academy of Pediatrics. 2007;120:1260–9. 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 American Academy of Pediatrics. 2007;120:1260–9.
7.
go back to reference 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;31:635–40.CrossRefPubMed 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;31:635–40.CrossRefPubMed
8.
go back to reference Bhat R, Salas AA, Foster C, Carlo WA, Ambalavanan N. Prospective analysis of pulmonary hypertension in extremely low birth weight infants. Pediatrics. 2012;129:e682–9.CrossRefPubMedPubMedCentral Bhat R, Salas AA, Foster C, Carlo WA, Ambalavanan N. Prospective analysis of pulmonary hypertension in extremely low birth weight infants. Pediatrics. 2012;129:e682–9.CrossRefPubMedPubMedCentral
9.
go back to reference Murthy K, Savani RC, Lagatta JM, Zaniletti I, Wadhawan R, Truog W, et al. Predicting death or tracheostomy placement in infants with severe bronchopulmonary dysplasia. J Perinatol. 2014;34:543–8.CrossRefPubMed Murthy K, Savani RC, Lagatta JM, Zaniletti I, Wadhawan R, Truog W, et al. Predicting death or tracheostomy placement in infants with severe bronchopulmonary dysplasia. J Perinatol. 2014;34:543–8.CrossRefPubMed
10.
go back to reference Naumburg E, Soderstrom L, Huber D, Axelsson I. Risk factors for pulmonary arterial hypertension in children and young adults. Pediatr Pulmonol. 2017;52:636–41.CrossRefPubMed Naumburg E, Soderstrom L, Huber D, Axelsson I. Risk factors for pulmonary arterial hypertension in children and young adults. Pediatr Pulmonol. 2017;52:636–41.CrossRefPubMed
11.
go back to reference Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037–99.CrossRefPubMed Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037–99.CrossRefPubMed
12.
go back to reference Kim D-H, Kim HS, Choi CW, Kim EK, Kim BI, Choi J-H. Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology. 2012;101:40–6.CrossRefPubMed Kim D-H, Kim HS, Choi CW, Kim EK, Kim BI, Choi J-H. Risk factors for pulmonary artery hypertension in preterm infants with moderate or severe bronchopulmonary dysplasia. Neonatology. 2012;101:40–6.CrossRefPubMed
13.
go back to reference 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;165:909–14.e1. 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;165:909–14.e1.
14.
go back to reference Ali Z, Schmidt P, Dodd J, Jeppesen DL. Predictors of bronchopulmonary dysplasia and pulmonary hypertension in newborn children. Dan Med J. 2013;60:A4688.PubMed Ali Z, Schmidt P, Dodd J, Jeppesen DL. Predictors of bronchopulmonary dysplasia and pulmonary hypertension in newborn children. Dan Med J. 2013;60:A4688.PubMed
15.
go back to reference Al-Ghanem G, Shah P, Thomas S, Banfield L, Helou El S, Fusch C, et al. Bronchopulmonary dysplasia and pulmonary hypertension: a meta-analysis. J Perinatol. 2017;37:414–9.CrossRefPubMed Al-Ghanem G, Shah P, Thomas S, Banfield L, Helou El S, Fusch C, et al. Bronchopulmonary dysplasia and pulmonary hypertension: a meta-analysis. J Perinatol. 2017;37:414–9.CrossRefPubMed
16.
go back to reference 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;33:553–7.CrossRefPubMedPubMedCentral 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;33:553–7.CrossRefPubMedPubMedCentral
17.
go back to reference 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;35:570–4.CrossRefPubMedPubMedCentral 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;35:570–4.CrossRefPubMedPubMedCentral
18.
19.
go back to reference Waruingi W, Mhanna MJ. Pulmonary hypertension in extremely low birth weight infants: characteristics and outcomes. World J Pediatr. 2014;10:46–52.CrossRefPubMed Waruingi W, Mhanna MJ. Pulmonary hypertension in extremely low birth weight infants: characteristics and outcomes. World J Pediatr. 2014;10:46–52.CrossRefPubMed
20.
go back to reference Nagiub M, Kanaan U, Simon D, Guglani L. Risk factors for development of pulmonary hypertension in infants with bronchopulmonary dysplasia: systematic review and meta-analysis. Paediatr Respir Rev. 2017;23:27–32. Nagiub M, Kanaan U, Simon D, Guglani L. Risk factors for development of pulmonary hypertension in infants with bronchopulmonary dysplasia: systematic review and meta-analysis. Paediatr Respir Rev. 2017;23:27–32.
21.
go back to reference 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;191:87–95.CrossRefPubMedPubMedCentral 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;191:87–95.CrossRefPubMedPubMedCentral
22.
go back to reference Choi EK, Jung YH, Kim HS, Shin SH, Choi CW, Kim EK, 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;56:317–23.CrossRefPubMed Choi EK, Jung YH, Kim HS, Shin SH, Choi CW, Kim EK, 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;56:317–23.CrossRefPubMed
23.
go back to reference Weismann CG, Asnes JD, Bazzy-Asaad A, Tolomeo C, Ehrenkranz RA, Bizzarro MJ. Pulmonary hypertension in preterm infants: results of a prospective screening program. J Perinatol. 2017;37:572–7.CrossRefPubMed Weismann CG, Asnes JD, Bazzy-Asaad A, Tolomeo C, Ehrenkranz RA, Bizzarro MJ. Pulmonary hypertension in preterm infants: results of a prospective screening program. J Perinatol. 2017;37:572–7.CrossRefPubMed
24.
go back to reference Rondelet B, Kerbaul F, Van Beneden R, Hubloue I, Huez S, Fesler P, et al. Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2005;289:H2319–24.CrossRefPubMed Rondelet B, Kerbaul F, Van Beneden R, Hubloue I, Huez S, Fesler P, et al. Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2005;289:H2319–24.CrossRefPubMed
25.
go back to reference Lam C-F, Peterson TE, Croatt AJ, Nath KA, Katusic ZS. Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2005;289:H2334–41.CrossRefPubMed Lam C-F, Peterson TE, Croatt AJ, Nath KA, Katusic ZS. Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2005;289:H2334–41.CrossRefPubMed
26.
go back to reference Schwerzmann M, Pfammatter J-P. Approaching atrial septal defects in pulmonary hypertension. Expert Rev Cardiovasc Ther. 2015;13:693–701.CrossRefPubMed Schwerzmann M, Pfammatter J-P. Approaching atrial septal defects in pulmonary hypertension. Expert Rev Cardiovasc Ther. 2015;13:693–701.CrossRefPubMed
27.
go back to reference Wood AM, Holzer RJ, Texter KM, Hill SL, Gest AL, Welty SE, et al. Transcatheter elimination of left-to-right shunts in infants with bronchopulmonary dysplasia is feasible and safe. Congenit Heart Dis. 2011;6:330–7.CrossRefPubMed Wood AM, Holzer RJ, Texter KM, Hill SL, Gest AL, Welty SE, et al. Transcatheter elimination of left-to-right shunts in infants with bronchopulmonary dysplasia is feasible and safe. Congenit Heart Dis. 2011;6:330–7.CrossRefPubMed
28.
go back to reference Thomas VC, Vincent R, Raviele A, Diehl H, Qian H, Kim D. Transcatheter closure of secundum atrial septal defect in infants less than 12 months of age improves symptoms of chronic lung disease. Congenit Heart Dis. 2012;7:204–11.CrossRefPubMed Thomas VC, Vincent R, Raviele A, Diehl H, Qian H, Kim D. Transcatheter closure of secundum atrial septal defect in infants less than 12 months of age improves symptoms of chronic lung disease. Congenit Heart Dis. 2012;7:204–11.CrossRefPubMed
29.
go back to reference Bassareo PP, Marras AR, Cugusi L, Zedda AM, Mercuro G. The reasons why cardiologists should consider prematurity at birth and intrauterine growth retardation among risk factors. J Cardiovasc Med (Hagerstown). 2016;17(5):323–9. Bassareo PP, Marras AR, Cugusi L, Zedda AM, Mercuro G. The reasons why cardiologists should consider prematurity at birth and intrauterine growth retardation among risk factors. J Cardiovasc Med (Hagerstown). 2016;17(5):323–9.
30.
go back to reference Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, Figueras F, Sitges M, Bijnens B, et al. Fetal cardiovascular remodelling persists at 6 months of life in infants with intrauterine growth restriction. Ultrasound Obstet Gynecol. 2016;48(3):349–56. Cruz-Lemini M, Crispi F, Valenzuela-Alcaraz B, Figueras F, Sitges M, Bijnens B, et al. Fetal cardiovascular remodelling persists at 6 months of life in infants with intrauterine growth restriction. Ultrasound Obstet Gynecol. 2016;48(3):349–56.
31.
go back to reference Jayet P-Y, Rimoldi SF, Stuber T, Salmon CS, Hutter D, Rexhaj E, et al. Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia. Circulation. 2010;122:488–94.CrossRefPubMed Jayet P-Y, Rimoldi SF, Stuber T, Salmon CS, Hutter D, Rexhaj E, et al. Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia. Circulation. 2010;122:488–94.CrossRefPubMed
32.
go back to reference Taha D, Kirkby S, Nawab U, Dysart KC, Genen L, Greenspan JS, et al. Early caffeine therapy for prevention of bronchopulmonary dysplasia in preterm infants. J Matern Fetal Neonatal Med. 2014;27:1698–702.CrossRefPubMed Taha D, Kirkby S, Nawab U, Dysart KC, Genen L, Greenspan JS, et al. Early caffeine therapy for prevention of bronchopulmonary dysplasia in preterm infants. J Matern Fetal Neonatal Med. 2014;27:1698–702.CrossRefPubMed
33.
go back to reference Dobson NR, Patel RM, Smith PB, Kuehn DR, Clark J, Vyas-Read S, et al. Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants. J Pediatr. 2014;164:992–3.CrossRefPubMedPubMedCentral Dobson NR, Patel RM, Smith PB, Kuehn DR, Clark J, Vyas-Read S, et al. Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants. J Pediatr. 2014;164:992–3.CrossRefPubMedPubMedCentral
34.
go back to reference Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, et al. Caffeine for apnea of prematurity trial: benefits may vary in subgroups. J Pediatr. 2010;156:382–7.CrossRefPubMed Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, et al. Caffeine for apnea of prematurity trial: benefits may vary in subgroups. J Pediatr. 2010;156:382–7.CrossRefPubMed
35.
go back to reference Mourani PM, Sontag MK, Younoszai A, Ivy DD, Abman SH. Clinical utility of echocardiography for the diagnosis and management of pulmonary vascular disease in young children with chronic lung disease. Pediatrics. 2008;121:317–25.CrossRefPubMedPubMedCentral Mourani PM, Sontag MK, Younoszai A, Ivy DD, Abman SH. Clinical utility of echocardiography for the diagnosis and management of pulmonary vascular disease in young children with chronic lung disease. Pediatrics. 2008;121:317–25.CrossRefPubMedPubMedCentral
36.
go back to reference Nagiub M, Lee S, Guglani L. Echocardiographic assessment of pulmonary hypertension in infants with bronchopulmonary dysplasia: systematic review of literature and a proposed algorithm for assessment. Echocardiography. 2015;32:819–33.CrossRefPubMed Nagiub M, Lee S, Guglani L. Echocardiographic assessment of pulmonary hypertension in infants with bronchopulmonary dysplasia: systematic review of literature and a proposed algorithm for assessment. Echocardiography. 2015;32:819–33.CrossRefPubMed
37.
go back to reference Carlton EF, Sontag MK, Younoszai A, DiMaria MV, Miller JI, Poindexter BB, et al. Reliability of Echocardiographic Indicators of Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia. J Pediatr. 2017;186:29–33. Carlton EF, Sontag MK, Younoszai A, DiMaria MV, Miller JI, Poindexter BB, et al. Reliability of Echocardiographic Indicators of Pulmonary Vascular Disease in Preterm Infants at Risk for Bronchopulmonary Dysplasia. J Pediatr. 2017;186:29–33.
Metadata
Title
Early characteristics of infants with pulmonary hypertension in a referral neonatal intensive care unit
Authors
Shilpa Vyas-Read
Usama Kanaan
Prabhu Shankar
Jane Stremming
Curtis Travers
David P. Carlton
Anne Fitzpatrick
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2017
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-017-0910-0

Other articles of this Issue 1/2017

BMC Pediatrics 1/2017 Go to the issue