Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Dec 1;5(12):e2245826.
doi: 10.1001/jamanetworkopen.2022.45826.

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

Jane E Brumbaugh  1 , Edward F Bell  2 , Barbara T Do  3 , Rachel G Greenberg  4 , Barbara J Stoll  5   6 , Sara B DeMauro  7 , Heidi M Harmon  2 , Susan R Hintz  8 , Abhik Das  9 , Karen M Puopolo  7 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations
Multicenter Study

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

Jane E Brumbaugh et al. JAMA Netw Open. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bell reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Do reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Greenberg reported consulting for Provepharm and Tellus Therapeutics outside the submitted work. Dr DeMauro reported receiving grants from the National Institutes of Health during the conduct of the study and receiving grants from the National Institutes of Health, Agency for Healthcare Research and Quality, and the Thrasher Research Fund outside the submitted work. Dr Hintz reported receiving grants from the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) Neonatal Research Network during the conduct of the study. Dr Das reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Puopolo reported receiving grants from the National Institutes of Health and the US Centers for Disease Control and Prevention outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
The cohort was broken into 3 groups, those affected by late-onset meningitis (LOM), those affected by late-onset sepsis (LOS) without LOM, and those affected by neither LOS nor LOM. NICHD indicates National Institute of Child Health and Human Development.
Figure 2.
Figure 2.. Incidence of Late-Onset Meningitis by Birth Year
The incidence of late-onset meningitis decreased across the study period, 2003 to 2017.
Figure 3.
Figure 3.. Incidence of Late-Onset Sepsis From 2003 to 2017 and Lumbar Puncture (LP) Among Those With Late-Onset Sepsis From 2011 to 2017
While the incidence of late-onset sepsis decreased from 2003 to 2017, it was relatively stable from 2011 to 2017. However, performance of LP among infants affected by late-onset sepsis decreased from 2011 to 2017.
See this image and copyright information in PMC

References

    1. Schlech WF III, Ward JI, Band JD, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States, 1978 through 1981: the National Bacterial Meningitis Surveillance Study. JAMA. 1985;253(12):1749-1754. doi:10.1001/jama.1985.03350360075022 - DOI - PubMed
    1. Feigin RD, McCracken GH Jr, Klein JO. Diagnosis and management of meningitis. Pediatr Infect Dis J. 1992;11(9):785-814. doi:10.1097/00006454-199209000-00039 - DOI - PubMed
    1. Furyk JS, Swann O, Molyneux E. Systematic review: neonatal meningitis in the developing world. Trop Med Int Health. 2011;16(6):672-679. doi:10.1111/j.1365-3156.2011.02750.x - DOI - PubMed
    1. Huang SH, Stins MF, Kim KS. Bacterial penetration across the blood-brain barrier during the development of neonatal meningitis. Microbes Infect. 2000;2(10):1237-1244. doi:10.1016/S1286-4579(00)01277-6 - DOI - PubMed
    1. Aleem S, Greenberg RG. When to include a lumbar puncture in the evaluation for neonatal sepsis. Neoreviews. 2019;20(3):e124-e134. doi:10.1542/neo.20-3-e124 - DOI - PubMed

Publication types