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

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 &amp;lt; .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P &amp;lt; .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 &amp;lt; .001) and among those with culture-confirmed LOS (23%-79%, P &amp;lt; .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.