Describe inpatient pulmonary hypertension (PH) treatment and factors associated with therapy at discharge in a multicenter cohort of infants with CDH.
Six years linked records from Children’s Hospitals Neonatal Database and Pediatric Health Information System were used to describe associations between prenatal/perinatal factors, clinical outcomes, echocardiographic findings and PH medications (PHM), during hospitalization and at discharge.
Of 1106 CDH infants from 23 centers, 62.8% of infants received PHM, and 11.6% of survivors were discharged on PHM. Survivors discharged on PHM more frequently had intrathoracic liver, small for gestational age, and low 5 min APGARs compared with those discharged without PHM (p < 0.0001). Nearly one-third of infants discharged without PHM had PH on last inpatient echo.
PH medication use is common in CDH. Identification of infants at risk for persistent PH may impact ongoing management. Post-discharge follow-up of all CDH infants with echocardiographic evidence of PH is warranted.
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
The data set used for this study is derived from the Children’s Hospital Neonatal Database (CHND), and is not publicly available due to data use agreement restrictions from the member institutions. Data are however available from the authors upon reasonable request and with permission of the CHND.
Badillo A, Gingalewski C. Congenital diaphragmatic hernia: treatment and outcomes. Semin Perinatol. 2014;38:92–96.
Lally KP. Congenital diaphragmatic hernia - the past 25 (or so) years. J Pediatr Surg. 2016;51:695–8.
Wynn J, Krishnan U, Aspelund G, Zhang Y, Duong J, Stolar CJH, et al. Outcomes of congenital diaphragmatic hernia in the modern era of management. J Pediatr. 2013;163:114–119.e111.
Petroze RT, Caminsky NG, Trebichavsky J, Bouchard S, Le-Nguyen A, Laberge JM, et al. Prenatal prediction of survival in congenital diaphragmatic hernia: an audit of postnatal outcomes. J Pediatr Surg. 2019;54:925–31.
Dillon PW, Cilley RE, Mauger D, Zachary C, Meier A, Altman RP, et al. The relationship of pulmonary artery pressure and survival in congenital diaphragmatic hernia. J Pediatr Surg. 2004;39:307–12.
Lusk LA, Wai KC, Moon-Grady AJ, Steurer MA, Keller RL. Persistence of pulmonary hypertension by echocardiography predicts short-term outcomes in congenital diaphragmatic hernia. J Pediatr. 2015;166:251–256.e251.
Brindle ME, Cook EF, Tibboel D, Lally PA, Lally KP. A clinical prediction rule for the severity of congenital diaphragmatic hernias in newborns. Pediatrics. 2014;134:e413–e419.
Ameis D, Khoshgoo N, Keijzer R. Abnormal lung development in congenital diaphragmatic hernia. Semin Pediatr Surg. 2017;26:123–8.
Mous DS, Kool HM, Wijnen R, Tibboel D, Rottier RJ. Pulmonary vascular development in congenital diaphragmatic hernia. Eur Respir Rev. 2018;27:170104.
Finer NM. Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics. 1997;99:838–5.
Lan NSH, Massam BD, Kulkarni SS, Lang CC. Pulmonary arterial hypertension: pathophysiology and treatment. Diseases. 2018;6:38.
Kelly LE, Ohlsson A, Shah PS. Sildenafil for pulmonary hypertension in neonates. Cochrane Database Systematic Rev. 2017;2017:CD005494.
Gao XF, Zhang JJ, Jiang XM, Ge Z, Wang ZM, Li B, et al. Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials. Patient Preference Adherence. 2017;11:871–85.
Rosenzweig EB, Abman SH, Adatia I, Beghetti M, Bonnet D, Haworth S, et al. Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management. Eur Respir. J. 2019;53:1801916.
Gien J, Kinsella JP. Management of pulmonary hypertension in infants with congenital diaphragmatic hernia. J Perinatol. 2016;36:S28–S31.
Pierro M, Thébaud B. Understanding and treating pulmonary hypertension in congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2014;19:357–63.
Murthy K, Dykes FD, Padula MA, Pallotto EK, Reber KM, Durand DJ, et al. The children’s hospitals neonatal database: an overview of patient complexity, outcomes and variation in care. J Perinatol. 2014;34:582–6.
Lakshminrusimha S, Keszler M, Kirpalani H, Van Meurs K, Chess P, Ambalavanan N, et al. Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study protocol, review of literature and survey of current practices. Matern Health Neonatol Perinatol. 2017;3:27.
Kumar VHS, Dadiz R, Koumoundouros J, Guilford S, Lakshminrusimha S. Response to pulmonary vasodilators in infants with congenital diaphragmatic hernia. Pediatr Surg Int. 2018;34:735–42.
Fisher MR, Forfia PR, Chamera E, Housten-Harris T, Champion HC, Girgis RE, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med. 2009;179:615–21.
Malowitz JR, Hornik CP, Laughon MM, Testoni D, Cotten CM, Clark RH, et al. Management practice and mortality for infants with congenital diaphragmatic hernia. Am J Perinatol. 2015;32:887–94.
Putnam LR, Tsao K, Morini F, Lally PA, Miller CC, Lally KP, et al. Evaluation of variability in inhaled nitric oxide use and pulmonary hypertension in patients with congenital diaphragmatic hernia. JAMA Pediatrics. 2016;170:1188–94.
Campbell BT, Herbst KW, Briden KE, Neff S, Ruscher KA, Hagadorn JI. Inhaled nitric oxide use in neonates with congenital diaphragmatic hernia. Pediatrics. 2014;134:e420–e426.
Murthy K, Pallotto EK, Gien J, Brozanski BS, Porta NFM, Zaniletti I, et al. Predicting death or extended length of stay in infants with congenital diaphragmatic hernia. J Perinatol. 2016;36:654–9.
Cauley RP, Potanos K, Fullington N, Bairdain S, Sheils CA, Finkelstein JA, et al. Pulmonary support on day of life 30 is a strong predictor of increased 1 and 5-year morbidity in survivors of congenital diaphragmatic hernia. J Pediatr Surg. 2015;50:849–55.
Carpentier E, Mur S, Aubry E, Pognon L, Rakza T, Flamein F, et al. Safety and tolerability of subcutaneous treprostinil in newborns with congenital diaphragmatic hernia and life-threatening pulmonary hypertension. J Pediatr Surg. 2017;52:1480–3.
Lawrence KM, Hedrick HL, Monk HM, Herkert L, Waqar LN, Hanna BD, et al. Treprostinil improves persistent pulmonary hypertension associated with congenital diaphragmatic hernia. J Pediatrics. 2018;200:44–49.
Olson E, Lusk LA, Fineman JR, Robertson L, Keller RL. Short-term treprostinil use in infants with congenital diaphragmatic hernia following repair. J Pediatrics. 2015;167:762–4.
Lawrence KM, Berger K, Herkert L, Franciscovich C, O’Dea CLH, Waqar LN, et al. Use of prostaglandin E1 to treat pulmonary hypertension in congenital diaphragmatic hernia. J Pediatr Surg. 2019;54:55–59.
Bialkowski A, Moenkemeyer F, Patel N. Intravenous sildenafil in the management of pulmonary hypertension associated with congenital diaphragmatic hernia. Eur J Pediatric Surg. 2013;25:171–6.
Kipfmueller F, Schroeder L, Berg C, Heindel K, Bartmann P, Mueller A. Continuous intravenous sildenafil as an early treatment in neonates with congenital diaphragmatic hernia. Pediatr Pulmonol. 2018;53:452–60.
Lawrence KM, Monos S, Adams S, Herkert L, Peranteau WH, Munson DA, et al. Inhaled nitric oxide is associated with improved oxygenation in a subpopulation of infants with congenital diaphragmatic hernia and pulmonary hypertension. J Pediatr. 2020;219:167–72.
Fliman PJ, deRegnier RA, Kinsella JP, Reynolds M, Rankin LL, Steinhorn RH. Neonatal extracorporeal life support: impact of new therapies on survival. J Pediatr. 2006;148:595–9.
Harting MT, Lally KP. The congenital diaphragmatic hernia study group registry update. Semin Fetal Neonatal Med. 2014;19:370–5.
Kinsella JP, Ivy DD, Abman SH. Pulmonary vasodilator therapy in congenital diaphragmatic hernia: acute, late, and chronic pulmonary hypertension. Semin Perinatol. 2005;29:123–8.
Mous DS, Buscop-van Kempen MJ, Wijnen RMH, Tibboel D, Rottier RJ. Changes in vasoactive pathways in congenital diaphragmatic hernia associated pulmonary hypertension explain unresponsiveness to pharmacotherapy. Respir Res. 2017;18:187.
Kinsella JP, Steinhorn RH, Mullen MP, Hopper RK, Keller RL, Ivy DD, et al. The left ventricle in congenital diaphragmatic hernia: implications for the management of pulmonary hypertension. J Pediatr. 2018;197:17–22.
Patel N, Lally PA, Kipfmueller F, Massolo AC, Luco M, Van Meurs KP, et al. Ventricular dysfunction is a critical determinant of mortality in congenital diaphragmatic hernia. Am J Respir Crit Care Med. 2019;220:1522–30.
Patel N, Massolo AC, Paria A, Stenhouse EJ, Hunter L, Finlay E, et al. Early postnatal ventricular dysfunction is associated with disease severity in patients with congenital diaphragmatic hernia. J Pediatr. 2018;203:400–407.e401.
Keller RL, Tacy TA, Hendricks-Munoz K, Xu J, Moon-Grady AJ, Neuhaus J, et al. Congenital diaphragmatic hernia: endothelin-1, pulmonary hypertension, and disease severity. Am J Respir Crit Care Med. 2010;182:555–61.
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.
American Academy of Pediatrics Section on Surgery. American Academy of Pediatrics Committee on Fetus and Newborn Lally KP, Engle W. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics. 2008;121:627–32.
Hollinger LE, Harting MT, Lally KP. Long-term follow-up of congenital diaphragmatic hernia. Semin Pediatr Surg. 2017;26:178–84.
Jeanette Asselin, Beverly Brozanski, David Durand (ex officio), Francine Dykes (ex officio), Jacquelyn Evans (Executive Director), Theresa Grover, Karna Murthy (Chair), Michael Padula, Eugenia Pallotto, Anthony Piazza, Kristina Reber and Billie Short are members of the Children’s Hospitals Neonatal Consortium, Inc. For more information, please contact: email@example.com.
We are indebted to the following institutions that serve the infants and their families, and these institutions also have invested in and continue to participate in the Children’s Hospital’s Neonatal Database (CHND). The site sponsors/contributors for the CHND are also included: Anthony Piazza, Children’s Healthcare of Atlanta, Atlanta, GA; Gregory Sysyn, Children’s Healthcare of Atlanta at Scottish Rite; Carl Coghill, Children’s Hospital of Alabama, Birmingham, AL; Ajay Talati, Le Bonheur Children’s Hospital, Memphis, TN; Anne Hansen, Tanzeema Houssain, Children’s Hospital Boston, Boston, MA; Karna Murthy, Gustave Falciglia, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL; Beth Haberman, Cincinnati Children’s Hospital, Cincinnati, OH; Kristina Reber, Nationwide Children’s Hospital, Columbus, OH; Rashmin Savani, Children’s Medical Center, Dallas, TX; Theresa Grover, Children’s Hospital Colorado, Aurora, CO; Girija Natarajan, Children’s Hospital of Michigan, Detroit, MI; Annie Chi, Yvette Johnson, Cook Children’s Health Care System, Fort Worth, TX; Gautham Suresh, Texas Children’s Hospital, Houston, TX; William Engle, Riley Children’s Hospital, Indianapolis, IN; Eugenia Pallotto, Children’s Mercy Hospitals & Clinics, Kansas City, MO; Robert Lyle, Becky Rogers, Arkansas Children’s Hospital, Little Rock, AR; Rachel Chapman, Children’s Hospital Los Angeles, Los Angeles, CA; Jamie Limjoco, American Family Children’s Hospital, Madison, WI; Priscilla Joe, Children’s Hospital & Research Center Oakland, Oakland, CA; Jacquelyn Evans, Michael Padula, David Munson, The Children’s Hospital of Philadelphia, Philadelphia, PA; Suzanne Touch, St. Christopher’s Hospital for Children, Philadelphia, PA; Beverly Brozanski, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA; Rakesh Rao, Amit Mathur, St. Louis Children’s Hospital, St Louis, MO; Victor McKay, All Children’s Hospital, St. Petersburg, FL; Mark Speziale, Laurel Moyer, Rady Children’s Hospital, San Diego, CA; Billie Short, Children’s National Medical Center, Washington, DC; Kevin Sullivan, AI DuPont Hospital for Children, Wilmington, DE; Con Yee Ling, Primary Children’s Medical Center, Salt Lake City, UT; Michael Uhing, Ankur Datta, Children’s Hospital of Wisconsin, Milwaukee, WI; Lynne Willett, Nicole Birge, Children’s Hospital of Omaha; Rajan Wadhawan, Florida Hospital for Children; Elizabeth Jacobsen-Misbe, Robert DiGeronimo, Seattle Children’s Hospital, Seattle, WA; Kyong-Soon Lee, Hospital for Sick Children, Toronto, ON; Michel Mikhael, Children’s Hospital Orange County, Los Angeles, CA.
Conflict of interest
BB, TG, and KM are board members of the Children’s Hospitals Neonatal Consortium, 501(c)(3) non-profit organization that manages and owns the Children’s Hospitals Neonatal Database, a data source used in this study. None of the remaining authors have any financial or other conflicts of interest as described in the author instructions.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Members of the Children’s Hospitals Neonatal Consortium Congenital Diaphragmatic Hernia Focus Group are listed below acknowledgements.
About this article
Cite this article
Seabrook, R.B., Grover, T.R., Rintoul, N. et al. Treatment of pulmonary hypertension during initial hospitalization in a multicenter cohort of infants with congenital diaphragmatic hernia (CDH). J Perinatol 41, 803–813 (2021). https://doi.org/10.1038/s41372-021-00923-z