Tetsuya Isayama1, Satoshi Kusuda2, Brian Reichman3, Shoo K Lee4, Liisa Lehtonen5, Mikael Norman6, Mark Adams7, Dirk Bassler7, Kjell Helenius5, Stellan Hakansson8, Junmin Yang9, Amish Jain10, Prakesh S Shah11. 1. Division of Neonatology, Center for Maternal-Fetal Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan. 2. Neonatal Research Network Japan, Maternal and Perinatal Center, Tokyo Women's Medical University, Tokyo, Japan. 3. Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Centre, Tel Hashomer, Israel. 4. Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Maternal-infant Care Research Centre, Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada. 5. Department of Pediatrics and Adolescent Medicine, Turku University Hospita, Turku, Finland; Department of Clinical Medicine, University of Turku, Turku, Finland. 6. Department of Neonatal Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. 7. Swiss Neonatal Network, Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. 8. Department of Clinical Science/Pediatrics, Umeå University, Umeå, Sweden. 9. Maternal-infant Care Research Centre, Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada. 10. Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. 11. Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Maternal-infant Care Research Centre, Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address: Prakeshkumar.Shah@sinaihealthsystem.ca.
Abstract
OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.
OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.