Association between Use of Prophylactic Indomethacin and the Risk for Bronchopulmonary Dysplasia in Extremely Preterm Infants

Erik A Jensen, Kevin C Dysart, Marie G Gantz, Benjamin Carper, Rosemary D Higgins, Martin Keszler, Matthew M Laughon, Brenda B Poindexter, Barbara J Stoll, Michele C Walsh, Barbara Schmidt, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Michael S Caplan, Richard A Polin, Abbot R Laptook, Martin Keszler, Angelita M Hensman, Kristin M Basso, Elisa Vieira, Emily Little, Avroy A Fanaroff, Anna Marie Hibbs, Nancy S Newman, William E Truog, Howard W Kilbride, Eugenia K Pallotto, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Knutson, Kurt Schibler, Edward F Donovan, Barbara Alexander, Cathy Grisby, Jody Hessling, Estelle E Fischer, Lenora D Jackson, Kristin Kirker, Greg Muthig, Ronald N Goldberg, C Michael Cotten, Kimberley A Fisher, Kathy J Auten, Katherine A Foy, Sandra Grimes, Joanne Finkle, Matthew M Laughon, Carl L Bose, Janice Bernhardt, Gennie Bose, David P Carlton, Ellen C Hale, Stephanie Wilson Archer, Brenda B Poindexter, Gregory M Sokol, Leslie Dawn Wilson, Dianne E Herron, Pablo J Sánchez, Leif D Nelin, Sudarshan R Jadcherla, Patricia Luzader, Christine A Fortney, Gail E Besner, Nehal A Parikh, Abhik Das, Dennis Wallace, Jeanette O'Donnell Auman, Margaret M Crawford, Carolyn M Petrie Huitema, Kristin M Zaterka-Baxter, Krisa P Van Meurs, Marian M Adams, David K Stevenson, M Bethany Ball, Andrew W Palmquist, Melinda S Proud, Ivan D Frantz 3rd, John M Fiascone, Brenda L MacKinnon, Ellen Nylen, Waldemar A Carlo, Namasivayam Ambalavanan, Monica V Collins, Shirley S Cosby, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Edward F Bell, Dan L Ellsbury, John A Widness, Karen J Johnson, Donia B Campbell, Kristi L Watterberg, Robin K Ohls, Conra Backstrom Lacy, Rebecca A Montman, Sandra Brown, Theresa Wussow, Carol Hartenberger, Barbara Schmidt, Haresh Kirpalani, Sara B DeMauro, Aasma S Chaudhary, Soraya Abbasi, Toni Mancini, Dara M Cucinotta, Carl T D'Angio, Ronnie Guillet, Satyan Lakshminrusimha, Ann Marie Reynolds, Linda J Reubens, Rosemary Jensen, Deana Maffett, Holly I M Wadkins, Michael G Sacilowski, Ashley Williams, Stephanie Guilford, Cassandra A Horihan, Kathleen A Kennedy, Jon E Tyson, Katrina Burson, Beverly Foley Harris, Georgia E McDavid, Patti L Pierce Tate, Sharon L Wright, Pablo J Sánchez, Luc P Brion, Lijun Chen, Alicia Guzman, Melissa H Leps, Nancy A Miller, Janet S Morgan, Diana M Vasil, Lizette E Torres, Roger G Faix, Bradley A Yoder, Karen A Osborne, Karie Bird, Jill Burnett, Jennifer J Jensen, Cynthia Spencer, Kimberlee Weaver-Lewis, Karen Zanetti, Seetha Shankaran, John Barks, Rebecca Bara, Mary Johnson, Mary Christensen, Stephanie Wiggins, Richard A Ehrenkranz, Harris Jacobs, Patricia Cervone, Monica Konstantino, JoAnn Poulsen, Janet Taft, Erik A Jensen, Kevin C Dysart, Marie G Gantz, Benjamin Carper, Rosemary D Higgins, Martin Keszler, Matthew M Laughon, Brenda B Poindexter, Barbara J Stoll, Michele C Walsh, Barbara Schmidt, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Michael S Caplan, Richard A Polin, Abbot R Laptook, Martin Keszler, Angelita M Hensman, Kristin M Basso, Elisa Vieira, Emily Little, Avroy A Fanaroff, Anna Marie Hibbs, Nancy S Newman, William E Truog, Howard W Kilbride, Eugenia K Pallotto, Cheri Gauldin, Anne Holmes, Kathy Johnson, Allison Knutson, Kurt Schibler, Edward F Donovan, Barbara Alexander, Cathy Grisby, Jody Hessling, Estelle E Fischer, Lenora D Jackson, Kristin Kirker, Greg Muthig, Ronald N Goldberg, C Michael Cotten, Kimberley A Fisher, Kathy J Auten, Katherine A Foy, Sandra Grimes, Joanne Finkle, Matthew M Laughon, Carl L Bose, Janice Bernhardt, Gennie Bose, David P Carlton, Ellen C Hale, Stephanie Wilson Archer, Brenda B Poindexter, Gregory M Sokol, Leslie Dawn Wilson, Dianne E Herron, Pablo J Sánchez, Leif D Nelin, Sudarshan R Jadcherla, Patricia Luzader, Christine A Fortney, Gail E Besner, Nehal A Parikh, Abhik Das, Dennis Wallace, Jeanette O'Donnell Auman, Margaret M Crawford, Carolyn M Petrie Huitema, Kristin M Zaterka-Baxter, Krisa P Van Meurs, Marian M Adams, David K Stevenson, M Bethany Ball, Andrew W Palmquist, Melinda S Proud, Ivan D Frantz 3rd, John M Fiascone, Brenda L MacKinnon, Ellen Nylen, Waldemar A Carlo, Namasivayam Ambalavanan, Monica V Collins, Shirley S Cosby, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Edward F Bell, Dan L Ellsbury, John A Widness, Karen J Johnson, Donia B Campbell, Kristi L Watterberg, Robin K Ohls, Conra Backstrom Lacy, Rebecca A Montman, Sandra Brown, Theresa Wussow, Carol Hartenberger, Barbara Schmidt, Haresh Kirpalani, Sara B DeMauro, Aasma S Chaudhary, Soraya Abbasi, Toni Mancini, Dara M Cucinotta, Carl T D'Angio, Ronnie Guillet, Satyan Lakshminrusimha, Ann Marie Reynolds, Linda J Reubens, Rosemary Jensen, Deana Maffett, Holly I M Wadkins, Michael G Sacilowski, Ashley Williams, Stephanie Guilford, Cassandra A Horihan, Kathleen A Kennedy, Jon E Tyson, Katrina Burson, Beverly Foley Harris, Georgia E McDavid, Patti L Pierce Tate, Sharon L Wright, Pablo J Sánchez, Luc P Brion, Lijun Chen, Alicia Guzman, Melissa H Leps, Nancy A Miller, Janet S Morgan, Diana M Vasil, Lizette E Torres, Roger G Faix, Bradley A Yoder, Karen A Osborne, Karie Bird, Jill Burnett, Jennifer J Jensen, Cynthia Spencer, Kimberlee Weaver-Lewis, Karen Zanetti, Seetha Shankaran, John Barks, Rebecca Bara, Mary Johnson, Mary Christensen, Stephanie Wiggins, Richard A Ehrenkranz, Harris Jacobs, Patricia Cervone, Monica Konstantino, JoAnn Poulsen, Janet Taft

Abstract

Objective: To assess the association between prophylactic indomethacin and bronchopulmonary dysplasia (BPD) in a recent, large cohort of extremely preterm infants.

Study design: Retrospective cohort study using prospectively collected data for infants with gestational ages < 29 weeks or birth weights of 401-1000 g born between 2008 and 2012 at participating hospitals of the National Institute of Child Health and Human Development Neonatal Research Network. Infants treated with indomethacin in the first 24 hours of life were compared with those who were not. Study outcomes were BPD, defined as use of supplemental oxygen at 36 weeks postmenstrual age among survivors to that time point, death, and the composite of death or BPD. Prespecified subgroup analyses were performed.

Results: Prophylactic indomethacin use varied by hospital. Treatment of a patent ductus arteriosus after the first day of life was less common among 2587 infants who received prophylactic indomethacin compared with 5244 who did not (21.0% vs 36.1%, P < .001). After adjustment for potential confounders, use of prophylactic indomethacin was not associated with higher or lower odds of BPD (OR 0.89, 95% CI 0.72-1.10), death (OR 0.80, 95% CI 0.64-1.01), or death or BPD (OR 0.87, 95% CI 0.71-1.05). The only evidence of subgroup effects associated with prophylactic indomethacin were lower odds of death among infants with birth weights above the 10th percentile and those who were not treated for a patent ductus arteriosus after the first day of life.

Conclusions: Prophylactic indomethacin was not associated with either reduced or increased risk for BPD or death.

Trial registration: ClinicalTrials.gov: NCT00063063.

Keywords: bronchopulmonary dysplasia; extreme prematurity; indomethacin; prophylaxis.

Conflict of interest statement

The authors declare no conflicts of interest.

Copyright © 2017 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Flow diagram of the infants included in the analysis and those alive at 36 weeks postmenstrual age (PMA) and assessed for the primary study outcome.
Figure 2
Figure 2
Proportion of infants treated with prophylactic indomethacin at each of the 35 study hospitals.
Figure 3. BPD among survivors to 36…
Figure 3. BPD among survivors to 36 weeks postmenstrual age
Unadjusted rates and risk-adjusted odds ratios for the full cohort and 5 infant subgroups are shown. n indicates the number of infants with the outcome and N indicates the total number of infants in each group. OR indicates odds ratio. CI indicates confidence interval. Odds ratios were determined with adjustment for hospital as a random affect and birth weight, gestational age, sex, birth weight th percentile for sex and gestational age, maternal gestational hypertension, antenatal antibiotic exposure, antenatal corticosteroid exposure, rupture of amniotic membranes for greater than 18 hr, cesarean delivery, intubation or cardiopulmonary resuscitation in the delivery room, and invasive mechanical ventilation at 24hr of life as fixed effects.

Source: PubMed

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