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

• Type of Material: Article
• Authors: Jane E Brumbaugh, Mayo Clinic; Edward F Bell, University of Iowa; Barbara T Do, RTI International; Rachel G Greenberg, Duke University; Barbara Stoll, Emory University; Sara B DeMauro, University of Pennsylvania; Heidi M Harmon, University of Iowa; Susan R Hintz, Stanford University; Abhik Das, RTI International; Karen M Puopolo, University of Pennsylvania
• Language: English
• Date: 2022-12-21
• Publisher: AMER MEDICAL ASSOC
• Publication Version: Final Published Version
• Copyright Statement: 2022 Brumbaugh JE et al. JAMA Network Open.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1001/jamanetworkopen.2022.45826
• Title of Journal or Parent Work: JAMA NETWORK OPEN
• Volume: 5
• Issue: 12
• Start Page: E2245826
• End Page: E2245826
• Grant/Funding Information: The National Institutes of Health, the Eunice Kennedy Shriver NICHD, the National Center for Research Resources, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network’s Generic Database and Follow-up Studies through cooperative agreements.
• Keywords: BACTERIAL-MENINGITIS; Life Sciences & Biomedicine; LUMBAR PUNCTURE; SEPSIS; INFANTS; Medicine, General & Internal; General & Internal Medicine; NEONATAL MENINGITIS; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery

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 13372 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.