K K Mestan1, J Check2, L Minturn3, S Yallapragada2, K N Farrow2, X Liu4, E Su5, N Porta2, N Gotteiner6, L M Ernst7. 1. 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. 2. 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. 3. 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. 4. 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. 5. Department of Obstetrics and Gynecology, Divisions of Maternal Fetal Medicine & Reproductive Biology Research, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. 6. Department of Pediatrics, Division of Cardiology, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital, Chicago, IL, 60611, USA. 7. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Abstract
INTRODUCTION: 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). DISCUSSION: 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.
INTRODUCTION: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). DISCUSSION: 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.
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