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

Media type: E-Article
Title: Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm
Contributor: 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.; 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; [...]
Published: American Medical Association (AMA), 2022
Published in: JAMA Network Open
Extent: e2245826
Language: English
DOI: 10.1001/jamanetworkopen.2022.45826
ISSN: 2574-3805
Keywords: General Medicine
Abstract: <jats:sec id="ab-zoi221294-4"><jats:title>Importance</jats:title><jats:p>Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.</jats:p></jats:sec><jats:sec id="ab-zoi221294-5"><jats:title>Objective</jats:title><jats:p>To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.</jats:p></jats:sec><jats:sec id="ab-zoi221294-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-zoi221294-7"><jats:title>Exposures</jats:title><jats:p>Culture-confirmed LOM.</jats:p></jats:sec><jats:sec id="ab-zoi221294-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec id="ab-zoi221294-9"><jats:title>Results</jats:title><jats:p>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 (<jats:italic>P</jats:italic> &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 (<jats:italic>P</jats:italic> &amp;lt; .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; <jats:italic>P</jats:italic> = .008). LP performance varied by center among all LOS evaluations (10%-59%, <jats:italic>P</jats:italic> &amp;lt; .001) and among those with culture-confirmed LOS (23%-79%, <jats:italic>P</jats:italic> &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 <jats:italic>Staphylococcus</jats:italic> (98 [59%]), <jats:italic>Candida albicans</jats:italic> (38 [23%]), and <jats:italic>Escherichia coli</jats:italic> (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative <jats:italic>Staphylococcus</jats:italic>, 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.</jats:p></jats:sec><jats:sec id="ab-zoi221294-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>
Description: <jats:sec id="ab-zoi221294-4"><jats:title>Importance</jats:title><jats:p>Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.</jats:p></jats:sec><jats:sec id="ab-zoi221294-5"><jats:title>Objective</jats:title><jats:p>To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.</jats:p></jats:sec><jats:sec id="ab-zoi221294-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-zoi221294-7"><jats:title>Exposures</jats:title><jats:p>Culture-confirmed LOM.</jats:p></jats:sec><jats:sec id="ab-zoi221294-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>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).</jats:p></jats:sec><jats:sec id="ab-zoi221294-9"><jats:title>Results</jats:title><jats:p>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 (<jats:italic>P</jats:italic> &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 (<jats:italic>P</jats:italic> &amp;lt; .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; <jats:italic>P</jats:italic> = .008). LP performance varied by center among all LOS evaluations (10%-59%, <jats:italic>P</jats:italic> &amp;lt; .001) and among those with culture-confirmed LOS (23%-79%, <jats:italic>P</jats:italic> &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 <jats:italic>Staphylococcus</jats:italic> (98 [59%]), <jats:italic>Candida albicans</jats:italic> (38 [23%]), and <jats:italic>Escherichia coli</jats:italic> (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative <jats:italic>Staphylococcus</jats:italic>, 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.</jats:p></jats:sec><jats:sec id="ab-zoi221294-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>
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