Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm

Authors: Jane E. Brumbaugh, Edward F. Bell, T. Barbara, Rachel G. Greenberg, Barbara J. Stoll, Sara B. DeMauro, Heidi M. Harmon, Susan R. Hintz, Abhik Das, Karen M. Puopolo, Namasivayam Ambalavanan, Kirstin J. Bailey, Fred J. Biasini, Waldemar A. Carlo, Stephanie A. Chopko, Monica V. Collins, Shirley S. Cosby, Kristen C. Johnston, Mary Beth Moses, Kathleen G. Nelson, Cryshelle S. Patterson, Myriam Peralta-Carcelén, Vivien A. Phillips, Julie Preskitt, Richard V. Rector, Sally Whitley, Barbara Alksninis, Carmena Bishop, Robert T. Burke, Melinda Caskey, Angelita M. Hensman, Laurie Hoffman, Katharine Johnson, Martin Keszler, Mary Lenore Keszler, Andrea M. Knoll, Vita Lamberson, Abbot R. Laptook, Theresa M. Leach, Emilee Little, Elizabeth C. McGowan, William Oh, Lucille St. Pierre, Bonnie E. Stephens, Suzy Ventura, Elisa Vieira, Betty R. Vohr, Victoria E. Watson, Kelly R. Coleman, Stephanie Guilford, Michelle Hartley-McAndrew, Satyan Lakshminrusimha, Emily Li, Anne Marie Reynolds, Michael G. Sacilowski, Ashley Williams, William Zorn, Monika Bhola, Avroy A. Fanaroff, Harriet Friedman, Anna Maria Hibbs, Nancy S. Newman, Allison H. Payne, Bonnie S. Siner, Michele C. Walsh, Deanne E. Wilson-Costello, Gulgun Yalcinkaya, Michael S. Caplan, Barbara D. Alexander, Traci Beiersdorfer, Kate Bridges, Tanya E. Cahill, Edward F. Donovan, Juanita Dudley, Estelle E. Fischer, Teresa L. Gratton, Cathy Grisby, Devan Hayes, Jody Hessling, Lenora Jackson, Alan H. Jobe, Suhas G. Kallapur, Kristin Kirker, Stephanie L. Merhar, Holly L. Mincey, Greg Muthig, Brenda B. Poindexter, Kurt Schibler, Sara Stacey, Jean J. Steichen, Stacey Tepe, Julia Thompson, Marcia Worley Mersmann, Sandra Wuertz, Kimberly Yolton, Richard A. Polin, Sally S. Adams, Luc P. Brion, Lijun Chen, Maria Magdalena Leon, Frances Eubanks, Alicia Guzman, Gaynelle Hensley, Elizabeth T. Heyne, Roy J. Heyne, Jackie F. Hickman, Lizette E. Lee, Melissa H. Leps, Linda A. Madden, E. Rebecca McDougald, Nancy A. Miller, Janet S. Morgan, Lara Pavageau, Charles R. Rosenfeld, Walid A. Salhab, Pablo J. Sánchez, Pollieanna Sepulveda, Catherine Twell Boatman, Diana M. Vasil, Jillian Waterbury, Myra H. Wyckoff, Patricia L. Ashley, Kathy J. Auten, C. Michael Cotten, Joanne Finkle, Kimberley A. Fisher, Ronald N. Goldberg, Ricki F. Goldstein, Sandra Grimes, Kathryn E. Gustafson, Melody B. Lohmeyer, William Malcolm, Ira Adams‐Chapman, Ann M. Blackwelder, Diane I. Bottcher, David P. Carlton, Sheena L. Carter, Ellen C. Hale, Salathiel Kendrick-Allwood, Judith Laursen, Yvonne Loggins, Colleen Mackie, Maureen Mulligan LaRossa, Ravi M. Patel, Amy Sanders, Irma Seabrook, Gloria V. Smikle, Lynn Wineski, Esther Akpa, Nora I. Alaniz, Elizabeth Allain, Julie Arldt-McAlister, Pamela J. Bradt, Katrina Burson, Allison G. Dempsey, Susan Dieterich, Andrea F. Duncan, Elizabeth Eason, Patricia W. Evans, Beverly Foley Harris, Claudia I. Franco, Carmen Garcia, Charles E. Green, Donna J. Hall, Margarita Jiménez, Janice John, Patrick M. Jones, Kathleen A. Kennedy, Amir Khan, Saba Khan Siddiki, Layne M. Lillie, Anna Lis, Terri L. Major-Kincade, Karen Martin, Sara C. Martin, Georgia E. McDavid, Shannon L. McKee, Brenda H. Morris, Patricia Ann Orekoya, Claudia Pedrozza, Carrie M. Perez, Patti L. Pierce Tate, Stacey Reddoch, Shawna Rodgers, Maegan C. Simmons, Daniel K. Sperry, Emily K. Stephens, Jon E. Tyson, Laura L. Whitely, Sharon L. Wright, Anna M. Dusick, Susan Gunn, Faithe Hamer, Dianne E. Herron, Abbey C. Hines, Jeffery Joyce, James A. Lemons, Carolyn Lytle, Lucy Miller, Heike M. Minnich, L.A. Papile, Leslie Richard, Lucy Smiley, Gregory M. Sokol, Leslie Dawn Wilson, Michael J. Acarregui, Tarah T. Colaizy, John M. Dagle, Diane L. Eastman, Claire A. Goeke, Karen Johnson, Jonathan M. Klein, Nancy J. Krutzfield, Mendi L. Schmelzel, Jacky R. Walker, John A. Widness, Donia B. Bass, Dan L. Ellsbury, Tracy L. Tud, Charles R. Bauer, Margarida Calejo, Shahnaz Duara, Ruth Everett‐Thomas, Sylvia Fajardo-Hiriart, Silvia M. Frade Eguaras, Andrea Garcia, Michelle Harwood Berkovits, Helina Pierre, Arielle Riguard, Alexandra Stoerger, Lisa Gaetano, Cheri Gauldin, Anne Holmes, Kathy Johnson, Howard W. Kilbride, Eugenia K. Pallotto, Prabhu S. Parimi, Allison Scott, William E. Truog, Gail E. Besner, Erna Clark, Christine A. Fortney, Julie Gutentag, Sudarshan R. Jadcherla, Patricia Luzader, Nathalie L. Maitre, Leif D. Nelin, Nehal A. Parikh, Courtney Park, Julie C. Shadd, Melanie Stein, Margaret Sullivan, Andrew A. Bremer, Rosemary D. Higgins, Stephanie Wilson Archer, Soraya Abbasi, Judy Bernbaum, Christine Catts, Aasma S. Chaudhary, Noah Cook, Dara M. Cucinotta, Eric C. Eichenwald, Marsha Gerdes, Sarvin Ghavam, Hallam Hurt, Haresh Kirpalani, Toni Mancini, Barbara Schmidt, Jonathan Snyder, Sarith Vangala, Kristina Ziolkowski, Julie Babish Johnson, Kyle Binion, Melissa Bowman, Erica Burnell, Carl T. D’Angio, Caitlin Fallone, Osman Farooq, Ronnie Guillet, Cassandra A. Horihan, Julianne Hunn, Diane Hust, Rosemary L. Jensen, Rachel Jones, Jennifer Kachelmeyer, Alison Kent, Emily Kushner, Deanna Maffett, Kimberly G. McKee, Joan Merzbach, Gary J. Myers, Constance Orme, Dale L. Phelps, Diane M. Prinzing, Linda J. Reubens, Daisy Rochez, Mary Rowan, Premini Sabaratnam, Ann Marie Scorsone, Holly I.M. Wadkins, Kelley Yost, Lauren Zwetsch, Carla Bann, Margaret M. Crawford, Jenna Gabrio, Marie G. Gantz, Betty K. Hastings, David LeBlond, Jamie E. Newman, Jeanette O’Donnell Auman, Carolyn M. Petrie Huitema, W. Kenneth Poole, Dennis Wallace, Kristin M. Zaterka-Baxter, Michelle Baack, Megan Broadbent, Chelsey Elenkiwich, Megan M. Henning, Laurie A. Hogden, Marian M. Adams, Dona Bahmani, M. Bethany Ball, Barbara Bentley, Elizabeth F. Bruno, Valerie Y. Chock, Alexis S. Davis, Maria Elena DeAnda, Anne M. DeBattista, Beth Earhart, Lynne C. Huffman, Magdy Ismael, Jean G. Kohn, Casey E. Krueger, Julie C. Lee-Ancajas, Janice Lowe, Ryan E. Lucash, Andrew W. Palmquist, Jessica Patel, Melinda S. Proud, Elizabeth N. Reichert, Dharshi Sivakumar, Nicholas H. St. John, David K. Stevenson, Heather Taylor, Krisa P. Van Meurs, Natalie Wager, R. Jordan Williams, Hali E. Weiss, Ana K. Brussa, Paige Church, John M. Fiascone, Ivan D. Frantz, Anne Furey, Anne Kurfiss, Brenda L. MacKinnon, Elisabeth C. McGowan, Ellen Nylen, Cecelia Sibley, Teresa Chanlaw, Uday Devaskar, Meena Garg, Rachel Geller, Isabell B. Purdy, Kathy Arnell, Clarence Demetrio, Neil N. Finer, Martha G. Fuller, Christopher Henderson, David Kaegi, Maynard R. Rasmussen, Wade Rich, Yvonne E. Vaucher, Paul R. Wozniak, Janice Bernhardt, Carl Bose, Gennie Bose, Cynthia L. Clark, Matthew M. Laughon, Diane Warner, Janice Wereszczak, Conra Backstrom Lacy, Tara L. DuPont, Janell Fuller, Mary Hanson, Carol H. Hartenberger, Elizabeth Kuan, Jean Lowe, Robin K. Ohls, Sandra Sundquist Beauman, Rebecca A. Thomson, Kristi L. Watterberg, John Barks, Martha Carlson, Mary Christensen, Stephanie A. Wiggins, Subrata Sarkar, Shawna Baker, Mariana Baserga, Karie Bird, Jill Burnett, Susan Christensen, Laura Cole Bledsoe, Sean D. Cunningham, Brandy Davis, Jennifer O. Elmont, Roger G. Faix, Becky Hall, Erika R. Jensen, Jennifer J. Jensen, Jamie Jordan, Manndi C. Loertscher, Trisha Marchant, Earl Maxson, Kandace M. McGrath, Stephen D. Minton, Galina Morshedzadeh, Karen A. Osborne, Dilys M. Parry, Carrie A. Rau, Brixen A. Reich, Susan T. Schaefer, Mark J. Sheffield, Cynthia Spencer, Michael Steffen, Kelly Stout, Ashley L. Stuart, Katherine Tice, Kimberlee Weaver-Lewis, Sarah Winter, Kathryn D. Woodbury, Bradley A. Yoder, Karen Zanetti, Korinne Chiu, Robert G. Dillard, Deborah Evans Allred, Donald J. Goldstein, Raquel Halfond, Barbara G. Jackson, T. Michael O’Shea, Nancy Peters, Carroll Peterson, Ellen Waldrep, Lisa K. Washburn, Cherrie D. Welch, Melissa Whalen Morris, Gail Hounshell, Stephen D. Kicklighter, Ginger Rhodes-Ryan, Donna L. White, Katherine Abramczyk, Prashant Agarwal, Monika Bajaj, Rebecca Bara, Elizabeth Billian, Sanjay Chawla, Kirsten Childs, Lilia C. De Jesus, D. Driscoll, Melissa February, Laura A. Goldston, Mary E. Johnson, Geraldine Muran, Girija Natarajan, Bogdan Panaitescu, Athina Pappas, Jeannette E. Prentice, Seetha Shankaran, Beena G. Sood, Diane F. White, Eunice Woldt, Christine G. Butler, Patricia Cervone, Richard A. Ehrenkranz, Patricia Gettner, Sheila Greisman, Harris C. Jacobs, Monica Konstantino, JoAnn Poulsen, Elaine Romano, Janet Taft, Joanne Williams - JAMA Network Open 2022 cited by 22

Importance: Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. Objective: To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months' corrected age. Design, Setting, and Participants: This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks' gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Exposures: Culture-confirmed LOM. Main Outcomes and Measures: Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Results: Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. Conclusions and Relevance: In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.