Deaths in a Modern Cohort of Extremely Preterm Infants From the Preterm Erythropoietin Neuroprotection Trial
Authors: Sandra E. Juul, Thomas R. Wood, Bryan A. Comstock, Krystle Perez, Semsa Gogcu, Mihai Puia-Dumitrescu, Sara Berkelhamer, Patrick J. Heagerty, Kaashif A. Ahmad, Mariana Baserga, Ellen Bendel-Stenzel, Sherry E. Courtney, L. Corbin Downey, Nancy Fahim, Ivan D. Frantz, Maureen M. Gilmore, Janine Khan, Edmund F. LaGamma, Andrea Lampland, Jean Lowe, Dennis E. Mayock, Victor McKay, Robin K. Ohls, Jorge E. Perez, Raghavendra Rao, Tonya Robinson, Nishant Srinivasan, Rajan Wadhawan, Michael Weiss, Billy Thomas, Nahed Elhassan, Sarah Mulkey, Vivek K. Vijayamadhavan, Neil Mulrooney, Bradley Yoder, Jordan S. Kase, Jennifer Check, Erin Osterholm, Thomas George, Michael Georgieff, Camilia R. Martin, Deirdre O’Reilly, Raye-Ann deRegnier, Nicolas Porta, Catalina Bazacliu, Frances Northington, Raul Chavez Valdez, Patel Saurabhkumar, Magaly Diaz-Barbosa, Arturo E. Serize, Jorge Jordan, John Widness, Adam Hartman, Roberta  Ballard, Michael O’Shea , Christopher Nefcy, Mark A. Konodi, Phuong T. Vu, John B. Feltner, Isabella Esposito, Stephanie Hauge, Samantha Nikirk, Amy Silvia, Bailey Clopp, Debbie Ott, Ariana Franco Mora, Pamela Hedrick, Vicki Flynn, Andrea Wyatt, Emilie Loy, Natalie Sikes, Melanie Mason, Jana McConnell, Tiffany Brown, Henry Harrison, Denise Pearson, Tammy Drake, Jocelyn Wright, Debra Walden, Annette Guy, Jennifer Nason, Morgan Talbot, Kristen Lee, Sarah Penny, Terri Boles, Melanie Drummond, Katy Kohlleppel, Charmaine Kathen, Brian Kaletka, Shania Gonzales, Cathy Worwa, Molly Fisher, Tyler Richter, Alexander Ginder, Brixen Reich, Carrie Rau, Manndi Loertscher, Laura Cole, Kandace McGrath, Kimberlee Weaver Lewis, Jill Burnett, Susan Schaefer, Karie Bird, Clare Giblin, Rita Daly, Kristi Lanier, Kelly Warden, Jenna Wassenaar, Jensina Ericksen, Bridget Davern, Brittany Gregorich, Mary Pat Osborne, Neha Talele, Evelyn Obregon, Tiglath Ziyeh, Molly Clarke, Rachel E Wegner, Palak Patel, Molly Schau, Annamarie Russow, Kelly Curry, Lisa Barnhart, Charlamaine Parkinson, Sandra Beauman, Mary Hanson, Elizabeth Kuan, Conra Backstrom Lacy, Edshelee M. Galvis, Susana Bombino, Denise Martinez, Suzi Bell, Corrie Long
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Understanding why and how extremely preterm infants die is important for practitioners caring for these infants. <h3>Objective</h3> To examine risk factors, causes, timing, and circumstances of death in a modern cohort of extremely preterm infants. <h3>Design, Setting, and Participants</h3> A retrospective cohort review of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial between December 13, 2013, and September 26, 2016, was conducted. A total of 941 infants born between 24 0/7 and 27 6/7 weeks of gestation enrolled at 19 US sites comprising 30 neonatal intensive care units were included. Data analysis was performed from October 16, 2020, to December 1, 2021. <h3>Main Outcomes and Measures</h3> Risk factors, proximal causes, timing, and circumstances of in-hospital death. <h3>Results</h3> Of the 941 enrolled infants, 108 died (11%) before hospital discharge: 38% (n = 41) at 24 weeks' gestation, 30% (n = 32) at 25 weeks' gestation, 19% (n = 20) at 26 weeks' gestation, and 14% (n = 15) at 27 weeks' gestation. An additional 9 infants (1%) died following hospital discharge. In descending order, the primary causes of death included respiratory distress or failure, pulmonary hemorrhage, necrotizing enterocolitis, catastrophic intracranial hemorrhage, sepsis, and sudden unexplained death. Fifty percent of deaths occurred within the first 10 days after birth. The risk of death decreased with day of life and postmenstrual age such that an infant born at 24 weeks' gestation who survived 14 days had the same risk of death as an infant born at 27 weeks' gestation: conditional proportional risk of death, 0.08 (95% CI, 0.03-0.13) vs 0.06 (95% CI, 0.01-0.11). Preterm labor was associated with a decreased hazard of death (hazard ratio [HR], 0.45; 95% CI, 0.31-0.66). Infant clinical factors associated with death included birth weight below the tenth percentile for gestational age (HR, 2.11; 95% CI, 1.38-3.22), Apgar score less than 5 at 5 minutes (HR, 2.19; 95% CI, 1.48-3.24), sick appearance at birth (HR, 2.49; 95% CI, 1.69-3.67), grade 2b-3 necrotizing enterocolitis (HR, 7.41; 95% CI, 5.14-10.7), pulmonary hemorrhage (HR, 10.0; 95% CI, 6.76-18.8), severe intracranial hemorrhage (HR, 4.60; 95% CI, 3.24-5.63), and severe sepsis (HR, 4.93; 95% CI, 3.67-7.21). Fifty-one percent of the infants received comfort care before death. <h3>Conclusions and Relevance</h3> In this cohort study, an association between mortality and gestational age at birth was noted; however, for each week that an infant survived, their risk of subsequent death approximated the risk observed in infants born 1 to 2 weeks later, suggesting the importance of an infant's postmenstrual age. This information may be useful to include in counseling of families regarding prognosis of survival.