Association between Term Equivalent Brain Magnetic Resonance Imaging and 2-Year Outcomes in Extremely Preterm Infants: A Report from the Preterm Erythropoietin Neuroprotection Trial Cohort - 15/11/21

Doi : 10.1016/j.jpeds.2021.08.040

Dennis E. Mayock, MD ^1,^⁎ , Semsa Gogcu, MD, MPH ², Mihai Puia-Dumitrescu, MD, MPH ¹, Dennis W.W. Shaw, MD ³, Jason N. Wright, MD ³, Bryan A. Comstock, MS ⁴, Patrick J. Heagerty, PhD ⁴, Sandra E. Juul, MD, PhD ¹
for the
Preterm Erythropoietin Neuroprotection (PENUT) Trial Consortium^∗
List of additional members of the PENUT Trial Consortium is available at www.jpeds.com (Appendix).
Rajan Wadhawan, MD, Sherry E. Courtney, MD, Tonya Robinson, MD, Kaashif A. Ahmad, MBBS, MSc, Ellen Bendel-Stenzel, MD, Mariana Baserga, MD, Edmund F. LaGamma, MD, L. Corbin Downey, MD, Raghavendra Rao, MD, Nancy Fahim, MD, Andrea Lampland, MD, Ivan D. Frantz, MD, Janine Khan, MD, Michael Weiss, MD, Maureen M. Gilmore, MD, Robin K. Ohls, MD, Jean Lowe, PhD, Nishant Srinivasan, MD, Jorge E. Perez, MD, Victor McKay, MD, Billy Thomas, MS, MPH, Nahed Elhassan, MD, MPH, Sarah Mulkey, MD, PhD, Vivek K. Vijayamadhavan, MD, Neil Mulrooney, MD, Bradley Yoder, MD, Jordan S. Kase, MD, Jennifer Check, MD, MS, Erin Osterholm, MD, Thomas George, MD, Michael Georgieff, MD, Camilia R. Martin, MS, Deirdre O'Reilly, MD, MPH, Raye-Ann deRegnier, MD, Nicolas Porta, MD, Catalina Bazacliu, MD, Frances Northington, MD, Raul Chavez Valdez, MD, Patel Saurabhkumar, MD, MPH, Magaly Diaz-Barbosa, MD, Todd Richards, PhD, 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, 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, Christopher Nefcy, Mark A. Konodi, MS, Phuong T. Vu, PhD, Adam Hartman, MD, T. Michael O'Shea, MD, Roberta Ballard, MD, Mike O'Shea, MD, Karl Kuban, MD, Jean Lowe, PhD, John Widness, MD

¹ Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, WA
² Division of Neonatology, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC
³ Department of Radiology, University of Washington, Seattle, WA
⁴ Department of Biostatistics, University of Washington, Seattle, WA

^∗Reprint requests: Dennis E. Mayock, MD, Division of Neonatology, Department of Pediatrics, University of Washington Medical Center, Box 356320, Seattle, WA 98195-6320Division of NeonatologyDepartment of PediatricsUniversity of Washington Medical CenterBox 356320SeattleWA98195-6320

Abstract

Objectives

To compare the term equivalent brain magnetic resonance imaging (MRI) findings between erythropoietin (Epo) treated and placebo control groups in infants 24^0/7-27^6/7 weeks of gestational age and to assess the associations between MRI findings and neurodevelopmental outcomes at 2 years corrected age.

Study design

The association between brain abnormality scores and Bayley Scales of Infant Development, Third Edition at 2 years corrected age was explored in a subset of infants enrolled in the Preterm Erythropoietin Neuroprotection Trial. Potential risk factors for neurodevelopmental outcomes such as treatment assignment, recruitment site, gestational age, inpatient complications, and treatments were examined using generalized estimating equation models.

Results

One hundred ten infants were assigned to Epo and 110 to placebo groups. 27% of MRI scans were rated as normal, and 60%, 10%, and 2% were rated as having mild, moderate, or severe abnormality. Brain abnormality scores did not significantly differ between the treatment groups. Factors that increased the risk of higher brain injury scores included intubation; bronchopulmonary dysplasia; retinopathy of prematurity; opioid, benzodiazepine, or antibiotic treatment >7 days; and periventricular leukomalacia or severe intraventricular hemorrhage diagnosed on cranial ultrasound. Increased global brain abnormality and white matter injury scores at term equivalent were associated with reductions in cognitive, motor, and language abilities at 2 years of corrected age.

Conclusions

Evidence of brain injury on brain MRIs obtained at term equivalent correlated with adverse neurodevelopmental outcomes as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition at 2 years corrected age. Early Epo treatment had no effect on the MRI brain injury scores compared with the placebo group.

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Keywords : preterm, MRI, neurodevelopmental outcomes

Abbreviations : BPD, BSID-III, ELBW, Epo, GEE, IVH, MRI, NEURO, PENUT, PMA, PVL, ROP, WMA

Plan

	The PENUT Trial was funded by the National Institute of Neurological Disorders and Stroke (U01NS077955 and U01NS077953). The sponsors had no involvement in the study design, sample collection, analysis, interpretation of data, writing of the report or the decision to submit the manuscript for publication. The authors declare no conflicts of interest.
	Portions of this study were presented at the virtual Pediatric Academic Societies annual meeting, April 30, 2020, Philadelphia.

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Vol 239

P. 117 - décembre 2021 Retour au numéro

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Association between Term Equivalent Brain Magnetic Resonance Imaging and 2-Year Outcomes in Extremely Preterm Infants: A Report from the Preterm Erythropoietin Neuroprotection Trial Cohort - 15/11/21

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