Association of Patent Ductus Arteriosus Ligation With Death or Neurodevelopmental Impairment Among Extremely Preterm Infants

Dany E Weisz; Lucia Mirea; Erin Rosenberg; Maximus Jang; Linh Ly; Paige T Church; Edmond Kelly; S Joseph Kim; Amish Jain; Patrick J McNamara; Prakesh S Shah

doi:10.1001/jamapediatrics.2016.5143

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Association of Patent Ductus Arteriosus Ligation With Death or Neurodevelopmental Impairment Among Extremely Preterm Infants

Journal article

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Peer reviewed

Association of Patent Ductus Arteriosus Ligation With Death or Neurodevelopmental Impairment Among Extremely Preterm Infants

Dany E Weisz, Lucia Mirea, Erin Rosenberg, Maximus Jang, Linh Ly, Paige T Church, Edmond Kelly, S Joseph Kim, Amish Jain, Patrick J McNamara, …

JAMA pediatrics, Vol.171(5), pp.443-449

05/01/2017

DOI: 10.1001/jamapediatrics.2016.5143

PMCID: PMC5470355

PMID: 28264088

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Abstract

Observational studies have associated patent ductus arteriosus (PDA) ligation among preterm infants with adverse neonatal outcomes and neurodevelopmental impairment in early childhood, with a resultant secular trend away from surgical treatment. However, to our knowledge, studies have inadequately addressed sources of residual bias, including survival bias and major neonatal morbidities arising before exposure to ligation. Evaluate the association between PDA ligation vs medical management and neonatal and neurodevelopmental outcomes. This retrospective cohort study of preterm infants younger than 28 weeks gestational age born between January 1, 2006, and December 31, 2012, with clinical and echocardiography diagnoses of hemodynamically significant PDA was conducted at 3 tertiary neonatal intensive care units and affiliated follow-up programs. Surgical ligation vs medical management. The primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18 to 24 months corrected age. Secondary outcomes included death before discharge, NDI, moderate-severe chronic lung disease, and severe retinopathy of prematurity. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. Of 754 infants with hemodynamically significant PDA (mean [standard deviation] gestational age 25.7 [1.2] weeks and birth weight 813 [183] grams), 184 (24%) underwent ligation. Infants who underwent ligation had a higher frequency of morbidities before PDA closure, including sepsis, necrotizing enterocolitis, and a dependence on mechanical ventilation. After adjusting for perinatal characteristics and preligation morbidities, there was no difference in the odds of death or NDI (adjusted odds ratio (aOR), 0.83; 95% CI, 0.52-1.32), NDI (aOR, 1.27; 95% CI, 0.78-2.06), chronic lung disease (aOR, 1.36; 95% CI, 0.78-2.39) or severe retinopathy of prematurity (aOR, 1.61; 95% CI, 0.85-3.06). Ligation was associated with lower odds of mortality (aOR, 0.09; 95% CI, 0.04-0.21). Patent ductus arteriosus ligation among preterm neonates younger than 28 weeks gestational age was not associated with the composite outcome of death or NDI, and there were no differences in chronic lung disease, retinopathy of prematurity, or NDI among survivors. Mortality was lower among infants who underwent ligation, though residual survival bias could not be excluded. Previously reported associations of ligation with increased morbidity may be because of bias from confounding by indication.

Neurodevelopmental Disorders - epidemiology

Ductus Arteriosus, Patent - surgery

Infant Mortality

Ductus Arteriosus, Patent - drug therapy

Humans

Child, Preschool

Infant

Logistic Models

Male

Treatment Outcome

Ligation - methods

Ductus Arteriosus, Patent - mortality

Intensive Care Units, Neonatal

Female

Infant, Extremely Premature

Retrospective Studies

Ligation - adverse effects

Infant, Newborn

Ligation - mortality

Neurodevelopmental Disorders - etiology

Cohort Studies

Details

Title: Subtitle: Association of Patent Ductus Arteriosus Ligation With Death or Neurodevelopmental Impairment Among Extremely Preterm Infants
Creators: Dany E Weisz - Department of Newborn and Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Canada2Department of Pediatrics, University of Toronto, Toronto, Canada
Lucia Mirea - Phoenix Children's Hospital, Phoenix, Arizona
Erin Rosenberg - Department of Pediatrics, Hospital for Sick Children, Toronto, Canada
Maximus Jang - Department of Pediatrics, Mt. Sinai Hospital, Toronto, Canada
Linh Ly - Department of Pediatrics, University of Toronto, Toronto, Canada4Department of Pediatrics, Hospital for Sick Children, Toronto, Canada
Paige T Church - Department of Newborn and Developmental Pediatrics, Sunnybrook Health Sciences Centre, Toronto, Canada2Department of Pediatrics, University of Toronto, Toronto, Canada
Edmond Kelly - Department of Pediatrics, University of Toronto, Toronto, Canada5Department of Pediatrics, Mt. Sinai Hospital, Toronto, Canada
S Joseph Kim - Department of Medicine, University of Toronto, Toronto, Canada
Amish Jain - Department of Pediatrics, University of Toronto, Toronto, Canada5Department of Pediatrics, Mt. Sinai Hospital, Toronto, Canada
Patrick J McNamara - Department of Pediatrics, University of Toronto, Toronto, Canada4Department of Pediatrics, Hospital for Sick Children, Toronto, Canada7Department of Physiology, University of Toronto and Physiology and Experimental Medicine, SickKids Research Institute, Toronto, Canada
Prakesh S Shah - Department of Pediatrics, University of Toronto, Toronto, Canada5Department of Pediatrics, Mt. Sinai Hospital, Toronto, Canada8Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
Resource Type: Journal article
Publication Details: JAMA pediatrics, Vol.171(5), pp.443-449
DOI: 10.1001/jamapediatrics.2016.5143
PMID: 28264088
PMCID: PMC5470355
NLM abbreviation: JAMA Pediatr
ISSN: 2168-6203
eISSN: 2168-6211
Language: English
Date published: 05/01/2017
Academic Unit: Stead Family Department of Pediatrics; Neonatology; Internal Medicine
Record Identifier: 9984093460802771

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