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Late-onset Sepsis in Extremely Premature Infants: 2000–2011

Greenberg, Rachel G. MD, MHS*†; Kandefer, Sarah BS; Do, Barbara T. MSPH; Smith, P. Brian MD, MPH, MHS*†; Stoll, Barbara J. MD§; Bell, Edward F. MD; Carlo, Waldemar A. MD; Laptook, Abbot R. MD**; Sánchez, Pablo J. MD††; Shankaran, Seetha MD‡‡; Van Meurs, Krisa P. MD§§; Ball, M. Bethany BS§§; Hale, Ellen C. RN, BS§; Newman, Nancy S. RN¶¶; Das, Abhik PhD‖‖; Higgins, Rosemary D. MD***; Cotten, C. Michael MD, MHS*; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

Pediatric Infectious Disease Journal: August 2017 - Volume 36 - Issue 8 - p 774–779
doi: 10.1097/INF.0000000000001570
Maternal-Neonatal Reports

Background: Late-onset sepsis (LOS) is an important cause of death and neurodevelopmental impairment in premature infants. The purpose of this study was to assess overall incidence of LOS, distribution of LOS-causative organisms and center variation in incidence of LOS for extremely premature infants over time.

Methods: In a retrospective analysis of infants 401–1000 g birth weight and 22–28 6/7 weeks of gestational age born at 12 National Institute of Child Health and Human Development Neonatal Research Network centers in the years 2000–2005 (era 1) or 2006–2011 (era 2) who survived >72 hours, we compared the incidence of LOS and pathogen distribution in the 2 eras using the χ2 test. We also examined the effect of birth year on the incidence of LOS using multivariable regression to adjust for nonmodifiable risk factors and for center. To assess whether the incidence of LOS was different among centers in era 2, we used a multivariable regression model to adjust for nonmodifiable risk factors.

Results: Ten-thousand one-hundred thirty-one infants were studied. LOS occurred in 2083 of 5031 (41%) infants in era 1 and 1728 of 5100 (34%) infants in era 2 (P < 0.001). Birth year was a significant predictor of LOS on adjusted analysis, with birth years 2000–2009 having a significantly higher odds of LOS than the reference year 2011. Pathogens did not differ, with the exception of decreased fungal infection (P < 0.001). In era 2, 9 centers had significantly higher odds of LOS compared with the center with the lowest incidence.

Conclusions: The incidence of LOS decreased over time. Further investigation is warranted to determine which interventions have the greatest impact on infection rates.

From the *Department of Pediatrics, Duke University School of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, and Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, Durham, North Carolina; §Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; Department of Pediatrics, University of Iowa, Iowa City, Iowa; Division of Neonatology, University of Alabama at Birmingham, Birmingham, Alabama; **Department of Pediatrics, Women & Infants Hospital, Brown University, Providence, Rhode Island; ††Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas; ‡‡Department of Pediatrics, Wayne State University, Detroit, Michigan; §§Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Lucile Packard Children’s Hospital, Palo Alto, California; ¶¶Department of Pediatrics, Rainbow Babies & Children’s Hospital, Case Western Reserve University, Cleveland, Ohio; ‖‖Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland; and ***Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Accepted for publication January 17, 2017.

R.G.G. wrote the first draft of the article (no honorarium/grant/specific payment received).

Research reported in this publication was supported by grant from the National Institutes of Health (NIH) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for the Neonatal Research Network’s Generic Database Study. The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the article; and decision to submit the article for publication.

R.G.G. received funding from an NIH training grant (5T32HD043728-10). P.B.S. receives salary support for research from the NIH, the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the NICHD (HHSN275201000003I and 1R01-HD081044-01) and the Food and Drug Administration (1R18-FD005292-01). He receives research support from Cempra Pharmaceuticals (subaward to HHS0100201300009C) and industry for neonatal and pediatric drug development ( C.M.C. receives salary support from the US Department of Health and Human Services (DHHS-1R18AE000028-01). The other authors have no conflicts of interest to disclose.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Address for correspondence: C. Michael Cotten, MD, MHS, Department of Pediatrics, Duke University Medical Center, Box 2739, Durham, NC 27710. E-mail:

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