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Morbidity of Persistent Pulmonary Hypertension of the Newborn in the First Year of Life

Published:August 06, 2019DOI:https://doi.org/10.1016/j.jpeds.2019.06.053

      Objective

      To assess postdischarge mortality and morbidity in infants diagnosed with different etiologies and severities of persistent pulmonary hypertension of the newborn (PPHN), and to identify risk factors for these adverse clinical outcomes.

      Study design

      This was a population-based study using an administrative dataset linking birth and death certificates, hospital discharge and readmissions records from 2005 to 2012 in California. Cases were infants ≥34 weeks' gestational age with International Classification of Diseases, 9th edition, codes consistent with PPHN. The primary outcome was defined as postdischarge mortality or hospital readmission during the first year of life. Crude and adjusted risk ratio (aRR) with 95% CIs were calculated to quantify the risk for the primary outcome and to identify risk factors.

      Results

      Infants with PPHN (n = 7847) had an aRR of 3.5 (95% CI, 3.3-3.7) for the primary outcome compared with infants without PPHN (n = 3 974 536), and infants with only mild PPHN (n = 2477) had an aRR of 2.2 (95% CI, 2.0-2.5). Infants with congenital diaphragmatic hernia as etiology for PPHN had an aRR of 8.6 (95% CI, 7.0-10.6) and infants with meconium aspiration syndrome had an aRR of 4.0 (95% CI, 3.6-4.4) compared with infants without PPHN. Hispanic ethnicity, small for gestational age, severe PPHN, and etiology of PPHN were risk factors for the primary outcome.

      Conclusions

      The postdischarge morbidity burden of infants with PPHN is large. These findings extend to infants with mild PPHN and etiologies with pulmonary vascular changes that are thought to be short term and recoverable. These data could inform counseling of parents.

      Abbreviations:

      aRR (Adjusted risk ratio), CDH (Congenital diaphragmatic hernia), ED (Emergency department), ICD-9 (International Classification of Diseases, 9th Revision, Clinical Modification), MAS (Meconium aspiration syndrome), OSHPD (California Office of Statewide Health Planning and Development), PPHN (Persistent pulmonary hypertension of the newborn), RDS (Respiratory distress syndrome), RR (Risk ratio)
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      References

        • Steinhorn R.H.
        Neonatal pulmonary hypertension.
        Pediatr Crit Care Med. 2010; 11: S79-S84
        • Oishi P.E.
        • Keller R.L.
        When persistent pulmonary hypertension of the newborn persists*.
        Pediatr Crit Care Med. 2012; 13: 224-225
        • Walsh-Sukys M.C.
        • Tyson J.E.
        • Wright L.L.
        • Bauer C.R.
        • Korones S.B.
        • Stevenson D.K.
        • et al.
        Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes.
        Pediatrics. 2000; 105: 14-20
        • Clark R.H.
        • Kueser T.J.
        • Walker M.W.
        • Southgate W.M.
        • Huckaby J.L.
        • Perez J.A.
        • et al.
        Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group.
        N Engl J Med. 2000; 342: 469-474
        • Roberts J.D.
        • Fineman J.R.
        • Morin F.C.
        • Shaul P.W.
        • Rimar S.
        • Schreiber M.D.
        • et al.
        Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.
        N Engl J Med. 1997; 336: 605-610
        • Neonatal Inhaled Nitric Oxide Study Group
        Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure.
        N Engl J Med. 1997; 336: 597-604
        • Konduri G.G.
        • Vohr B.
        • Robertson C.
        • Sokol G.M.
        • Solimano A.
        • Singer J.
        • et al.
        Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: neurodevelopmental follow-up.
        J Pediatr. 2007; 150 (240.e1): 235-240
        • Clark R.H.
        • Huckaby J.L.
        • Kueser T.J.
        • Walker M.W.
        • Southgate W.M.
        • Perez J.A.
        • et al.
        Low-dose nitric oxide therapy for persistent pulmonary hypertension: 1-year follow-up.
        J Perinatol. 2003; 23: 300-303
        • Group TNINOS
        Inhaled nitric oxide in term and near-term infants: neurodevelopmental follow-up of the neonatal inhaled nitric oxide study group (NINOS).
        J Pediatr. 2000; 136: 611-617
        • Ellington M.
        • O'Reilly D.
        • Allred E.N.
        • McCormick M.C.
        • Wessel D.L.
        • Kourembanas S.
        Child health status, neurodevelopmental outcome, and parental satisfaction in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn.
        Pediatrics. 2001; 107: 1351-1356
        • Group UCE
        The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up to 1 year of age.
        Pediatrics. 1998; 101: E1
        • Baer R.J.
        • Chambers C.D.
        • Jones K.L.
        • Shew S.B.
        • MacKenzie T.C.
        • Shaw G.M.
        • et al.
        Maternal factors associated with the occurrence of gastroschisis.
        Am J Med Genet A. 2015; 167: 1534-1541
        • Baer R.J.
        • Lyell D.J.
        • Norton M.E.
        • Currier R.J.
        • Jelliffe-Pawlowski L.L.
        First trimester pregnancy-associated plasma protein-A and birth weight.
        Eur J Obstet Gynecol Reprod Biol. 2016; 198: 1-6
        • Jelliffe-Pawlowski L.L.
        • Norton M.E.
        • Baer R.J.
        • Santos N.
        • Rutherford G.W.
        Gestational dating by metabolic profile at birth: a California cohort study.
        Am J Obstet Gynecol. 2016; 214: 511.e1-511.e13
        • Stey A.
        • Barnert E.S.
        • Tseng C.H.
        • Keeler E.
        • Needleman J.
        • Leng M.
        • et al.
        Outcomes and costs of surgical treatments of necrotizing enterocolitis.
        Pediatrics. 2015; 135: e1190-e1197
        • Gage S.
        • Kan P.
        • Lee H.C.
        • Gould J.B.
        • Stevenson D.K.
        • Shaw G.M.
        • et al.
        Maternal asthma, preterm birth, and risk of bronchopulmonary dysplasia.
        J Pediatr. 2015; 167: 875-880.e1
        • Jelliffe-Pawlowski L.L.
        • Norton M.E.
        • Shaw G.M.
        • Baer R.J.
        • Flessel M.C.
        • Goldman S.
        • et al.
        Risk of critical congenital heart defects by nuchal translucency norms.
        Am J Obstet Gynecol. 2015; 212: 518.e1-518.e10
        • Crisham Janik M.D.
        • Newman T.B.
        • Cheng Y.W.
        • Xing G.
        • Gilbert W.M.
        • Wu Y.W.
        Maternal diagnosis of obesity and risk of cerebral palsy in the child.
        J Pediatr. 2013; 163: 1307-1312
        • Steurer M.A.
        • Jelliffe-Pawlowski L.L.
        • Baer R.J.
        • Partridge J.C.
        • Rogers E.E.
        • Keller R.L.
        Persistent pulmonary hypertension of the newborn in late preterm and term infants in California.
        Pediatrics. 2016; : 1-15
        • Stege G.
        • Fenton A.
        • Jaffray B.
        Nihilism in the 1990s: the true mortality of congenital diaphragmatic hernia.
        Pediatrics. 2003; 112: 532-535
        • Colvin J.
        • Bower C.
        • Dickinson J.E.
        • Sokol J.
        Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia.
        Pediatrics. 2005; 116: e356-e363
        • Burgos C.M.
        • Modée A.
        • Öst E.
        • Frenckner B.
        Addressing the causes of late mortality in infants with congenital diaphragmatic hernia.
        J Pediatr Surg. 2017; 52: 526-529
        • Wynn J.
        • Aspelund G.
        • Zygmunt A.
        • Stolar C.J.H.
        • Mychaliska G.
        • Butcher J.
        • et al.
        Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study.
        J Pediatr Surg. 2013; 48: 1995-2004
        • Rozance P.J.
        • Seedorf G.J.
        • Brown A.
        • Roe G.
        • O'Meara M.C.
        • Gien J.
        • et al.
        Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep.
        Am J Physiol Lung Cell Mol Physiol. 2011; 301: L860-L871
        • Huybrechts K.F.
        • Bateman B.T.
        • Palmsten K.
        • Desai R.J.
        • Patorno E.
        • Gopalakrishnan C.
        • et al.
        Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn.
        JAMA. 2015; 313: 2142-2151
        • Palmsten K.
        • Huybrechts K.F.
        • Kowal M.K.
        • Mogun H.
        • Hernández-Díaz S.
        Validity of maternal and infant outcomes within nationwide Medicaid data.
        Pharmacoepidem Drug Safe. 2014; 23: 646-655

      Linked Article

      • Corrigendum
        The Journal of PediatricsVol. 215
        • Preview
          In the article “Morbidity of Persistent Pulmonary Hypertension of the Newborn in the First Year of Life” by Steurer et al (J Pediatr 2019;213:58-65.e4), an error occurred in the second sentence of the Results section of the abstract. The correct sentence should read “Infants with congenital diaphragmatic hernia as the etiology for PPHN had an aRR of 8.2 (95% CI, 6.7-10.2) and infants with meconium aspiration syndrome had an aRR of 4.2 (95% CI, 3.7-4.6) compared with infants without PPHN.”
        • Full-Text
        • PDF
      • Defining severity of illness in persistent pulmonary hypertension of the newborn still not settled
        The Journal of PediatricsVol. 216
        • Preview
          Steurer et al addressed postdischarge mortality and morbidity in infants diagnosed with persistent pulmonary hypertension of the newborn (PPHN).1 Although the study reported that the mild PPHN group had significantly better results than the severe PPHN group, we believe the study reveals a problem with the definitions of “mild” and “severe” PPHN, which bring their results into question. In this report, requiring only noninvasive respiratory support was defined as mild PPHN, whereas requiring invasive positive pressure ventilation or continuous positive expiratory pressure during birth hospitalization was defined as severe PPHN.
        • Full-Text
        • PDF