title: Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension.
abstract: BACKGROUND
  Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH.
  
  
  METHODS
  We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates.
  
  
  RESULTS
  Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P < 0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P < 0.001).
  
  
  CONCLUSIONS
  Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease.
  
  
  CONCLUSIONS
  Our findings have important implications for providing earlier and more effective therapies for BPD.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 East Chicago Avenue, Box #45, Chicago, IL, 60611, USA. Electronic address: k-mestan@northwestern.edu.
authors.forename: K K
authors.initials: KK
authors.lastname: Mestan
authors.affiliation: Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 East Chicago Avenue, Box #45, Chicago, IL, 60611, USA.
authors.forename: J
authors.initials: J
authors.lastname: Check
authors.affiliation: Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 East Chicago Avenue, Box #45, Chicago, IL, 60611, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: L
authors.initials: L
authors.lastname: Minturn
authors.affiliation: Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 East Chicago Avenue, Box #45, Chicago, IL, 60611, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yallapragada
authors.affiliation: Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 East Chicago Avenue, Box #45, Chicago, IL, 60611, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Farrow
authors.affiliation: Department of Pediatrics, Mary Ann and J. Milburn Smith Child Health Research Program, Ann & Robert H. Lurie Children's Hospital Research Center, Chicago, IL, 60611, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Divisions of Maternal Fetal Medicine & Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: E
authors.initials: E
authors.lastname: Su
authors.affiliation: Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, 225 East Chicago Avenue, Box #45, Chicago, IL, 60611, USA.
authors.forename: N
authors.initials: N
authors.lastname: Porta
authors.affiliation: Department of Pediatrics, Division of Cardiology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, 60611, USA.
authors.forename: N
authors.initials: N
authors.lastname: Gotteiner
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Ernst
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D010920:Placenta / Q000098:blood supply* / Q000473:pathology; D011247:Pregnancy; D012189:Retrospective Studies
keywords: Bronchopulmonary dysplasia; Fetal growth restriction; Placenta; Preeclampsia; Premature infant; Pulmonary hypertension