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