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Poor postnatal weight growth is a late finding after sepsis in very preterm infants
  1. Dustin D Flannery1,2,3,
  2. Erik A Jensen1,2,3,
  3. Lauren A Tomlinson4,
  4. Yinxi Yu5,
  5. Gui-Shuang Ying5,6,
  6. Gil Binenbaum4
  7. The Postnatal Growth and ROP (G-ROP) Study Group
    1. 1 Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    2. 2 Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
    3. 3 Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    4. 4 Division of Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    5. 5 Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
    6. 6 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
    1. Correspondence to Dr Dustin D Flannery, Neonatology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; flanneryd{at}email.chop.edu

    Abstract

    Objective To characterise the association between sepsis and postnatal weight growth when accounting for the degree of growth restriction present at birth.

    Design Retrospective matched cohort study using data from the Postnatal Growth and Retinopathy of Prematurity study. Participants were born with birth weights of <1500 g or gestational ages of <32 weeks between 2006 and 2011 at 29 neonatal centres in the USA and Canada. Sepsis was defined as a culture-confirmed bacterial or fungal infection of the blood or cerebrospinal fluid before 36 weeks’ postmenstrual age (PMA). Growth was assessed as the change in weight z-score between birth and 36 weeks’ PMA.

    Results Of 4785 eligible infants, 813 (17%) developed sepsis and 693 (85%) were matched 1:1 to controls. Sepsis was associated with a greater decline in weight z-score (mean difference −0.09, 95% CI −0.14 to −0.03). Postnatal weight growth failure (decline in weight z- score>1) was present in 237 (34%) infants with sepsis and 179 (26%) controls (adjusted OR 1.49, 95% CI 1.12 to 1.97). Longitudinal growth trajectories showed similar initial changes in weight z-scores between infants with and without sepsis. By 3 weeks after sepsis onset, there was a greater decline in weight z-scores relative to birth values in those with sepsis than without sepsis (delta z-score −0.89 vs −0.77; mean difference −0.12, 95% CI −0.18 to −0.05). This significant difference persisted until 36 weeks or discharge.

    Conclusion Infants with sepsis had similar early weight growth trajectories as infants without sepsis but developed significant deficits in weight that were not apparent until several weeks after the onset of sepsis.

    • neonatology
    • growth
    • microbiology
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    Footnotes

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    • Collaborators The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study Group. The G-ROP Study Group investigators include the following: Office of Study Chair: The Children’s Hospital of Philadelphia: Gil Binenbaum, MD, MSCE (Principal Investigator [PI]), Lauren A. Tomlinson, BS (Project Manager), Trang B. Duros, Anh Nguyen. Data Coordinating Center - University of Pennsylvania Perelman School of Medicine: Gui-shuang Ying, PhD (PI), Maureen G. Maguire, PhD, Mary Brightwell-Arnold, BA, SCP, James Shaffer, MS, Yinxi Yu, MS, Maria Blanco BS, Trina Brown BS, Christopher P. Helker, MSPH. Clinical Centers: Emory University School of Medicine (Children’s Healthcare of Atlanta): Amy Hutchinson, MD (PI), Carrie Young, RN. University of Colorado Denver (University of Colorado Hospital, Children’s Hospital Colorado): Emily McCourt, MD (PI), Anne Lynch, MD (Co-I), Jennifer Cathcart, MPH, Ashlee Cerda, MPH, Levi Bonnell, MPH, Tamara Thevarajah, MS. Albany Medical College: Gerard P. Barry, MD (PI), Marilyn Fisher, MD, MS (Co-I), Maria V. Battaglia, BS, MS, Alex M. Drach. BA, Kevin Hughes, BA. Lehigh Valley Hospital: Nachammai Chinnakaruppan, MD (PI), Andrew Meyer, MD (PI), Christina Gogal, BS, CCRC, Cynthia Beitler, BS, MT,BB (ASCP), CCRC, Lauri Centolanza, BS, MT (ASCP), Keith T. Moyer, MS, Mary Sobotor CLA-ASCP, CCRC. Johns Hopkins University (Johns Hopkins Hospital): Pamela Donohue, ScD (PI), Michael X. Repka, MD (Co-I), Jennifer A. Shepard, CRNP, Megan Doherty, NNP. University at Buffalo (Women & Children's Hospital of Buffalo): James D. Reynolds, MD (PI), Erin Connelly. Medical University of South Carolina: Edward Cheeseman, MD, MBA (PI), Kinsey Shirer, RN, Carol Bradham, COA, CCRC, Allison McAlpine, Sudeep Sunthankar. University of Illinois at Chicago: Javaneh Abbasian, MD (PI), Janet Lim, MD. Cincinnati Children’s Hospital Medical Center (Cincinnati Children’s Hospital Medical Center, Good Samaritan Hospital, and University of Cincinnati Medical Center): Michael Yang, MD (PI), Patricia Cobb, MS, Elizabeth L. Alfano. Nationwide Children’s Hospital (Nationwide Children’s Hospital, Riverside Methodist Hospital, Grant Medical Center, Doctors Hospital): David Rogers, MD (PI), Rachel E. Reem, MD, Amanda Schreckengost, MA, Rae R. Fellows, M.Ed., CCRC, Kaitlyn Loh, Madeline A. McGregor, Thabit Mustafa, Ivy Dean, Rachel Miller, Tess Russell, Rebecca Stattler, Sara Maletic, Theran Jake Selph. Kapi’olani Medical Center for Women and Children: David Young, MD (PI), Andrea Siu, MPH, RAC, Michele Kanemori, George Kingston. University of Texas at Houston (Children’s Memorial Hermann Hospital): Megan Geloneck, MD (PI), Robert Feldman (PI), Ted Baker, Laura Baker, Ephrem Melese, MD. Indiana University (Riley Hospital for Children at Indiana University Health): Kathryn Haider, MD (PI), Jingyun Wang, PhD (PI), Elizabeth Hynes, RNC- NIC, CLC. University of Iowa (University of Iowa Stead Family Children’s Hospital): Edward F. Bell, MD (PI), Alina V. Dumitrescu, MD (Co-I), Jonathan M. Klein, MD (Co-I), Gretchen A. Cress, RN, MPH, Avanthi S. Ajjarapu, Kristine Berge, MSN, Eric Boeshart, Morgan Dorsey, Bethany M. Funk, Grace Hach, Claire L. Johnson, Kevin Kurian, Emily Miller, Angela C. Platt. Queen’s University (Kingston Health Sciences Center): Christine Law, MD (PI), Andrew Gissing. Loma Linda University (Loma Linda University Children’s Hospital): Leila Khazaeni, MD (PI), Jennifer Dunbar, MD (CoI), Kelley Hawkins, Sharon Lee, RN, Lily Sung, Carly Leggitt. University of Louisville (Norton Children’s Hospital): Aparna Ramasubramanian, MD (PI), Rahul Bhola, MD (PI), Michelle Bottorff, COA, CCRC, Neviana Dimova, MD, MS, Rachel Keith, PhD, MSN, NP-C, Laura Thomas RN, BSN, CCRN. University of Minnesota (Masonic Children’s Hospital, formerly University of Minnesota - Amplatz Children’s Hospital): Jill Anderson, MD (PI), Raymond G. Areaux, Jr., MD (Co-I), Ann Marie Holleschau, BA, CCRP, Jordan Gross, Andrea Kramer.Vanderbilt Eye Institute and Vanderbilt University Medical Center: (Monroe Carell Jr. Children's Hospital at Vanderbilt): David Morrison, MD (PI), Sean Donahue, MD, PhD (Co-I), Carsyn Saige Wilkins, Neva Fukuda, CO, Sandy Owings, COA, CCRP, Scott Ruark. University of Oklahoma (The Children’s Hospital at OU Medical Center / The University of Oklahoma Health Sciences Center): R. Michael Siatkowski, MD (PI), Faizah Bhatti, MD (Co-I), Vanessa Bergman, COT, CCRC, Karen Corff, APRN, NNP, Kari Harkey, RNC-NIC, Amy Manfredo, APRN-CNP, Ashley Helmbrecht, DNP, APRN-CNP, Shrenik Talsania, MBBS, MPH, CPH, Terri Whisenhunt, MS, RN. University of Nebraska (Nebraska Medicine): Donny Suh, MD, FAAP (PI), Ann Anderson Berry, MD, PhD (Co-I), Denise Lynes APRN-CNS, MSN, Kelly C. Erikson, MPH. The Children’s Hospital of Philadelphia (The Children’s Hospital of Philadelphia, Hospital of the University of Pennsylvania, Pennsylvania Hospital): Gil Binenbaum, MD, MSCE (PI), Soraya Abbasi, MD (PI), Haresh Kirpalani, MD, MSc, Graham E. Quinn MD, MSCE, Lindsay Dawson, MD, LaurenA. Tomlinson, BS. University of Pittsburgh (Children’s Hospital of Pittsburgh, Magee Women Hospital of UPMC): Christin Sylvester, MD (PI), Kanwal Nischal, MD (PI), Lauren Runkel, MA. Rhode Island Hospital (Women and Infants Hospital of Rhode Island): Wendy S. Chen, MD, PhD (PI), Deidrya Jackson. Saint Louis University (Cardinal Glennon Children’s Hospital): Bradley Davitt, MD (PI), Dawn Govreau, COT, Linda Breuer, LPN, September Noonan, RN. University of Utah (Primary Children’s Hospital and University of Utah Hospital): Robert Hoffman, MD (PI), Joanna Beachy, MD, PhD, Kelliann Farnsworth, COT, Katie Jo Farnsworth, CRC, Deborah Harrison, MS, Ashlie Bernhisel, Bonnie Carlstrom. University of California San Francisco (UCSF Benioff Children’s Hospital and Zuckerberg San Francisco General Hospital, formerly San Francisco General Hospital): Alejandra G. de Alba Campomanes, MD, MPH (PI), Yizhuo Bastea-Forte, Lucia Rivera Sanchez, Jacquelyn Kemmer, Alexandra Neiman, Sarah Sitati-Ng’Anda MD. Seattle Children’s Hospital (Seattle Children’s Hospital, University of Washington Medical Center): Kristina Tarczy-Hornoch, MD, D.Phil, (PI), Francine Baran, MD (PI), Lauren Eaton. The Hospital for Sick Children (Sick Kids), Toronto: Nasrin Najm-Tehrani, MB BCh, MSc, FRCS Ed (Ophth), FRCSC (PI), Tanya Grossi, Maram Isaac, Robin Knighton. Los Angeles Biomedical Research Institute (Harbor-UCLA Medical Center): Monica Ralli Khitri, MD (PI), Madeline Del Signore, RN. Crozer-Chester Medical Center (Crozer Chester Medical Center, Delaware County Memorial Hospital): Cynthia Dembofsky, MD (PI), Andrew Meyer, MD (PI), Karen Flaherty, Tracey Harris, Jamie Heeneke. Nemours/Alfred I. duPont Hospital for Children: Dorothy Hendricks, MD (PI), Christopher M. Fecarotta, MD (PI), Alicia Olivant Fisher, MS, Mark Paullin, MS. Cost- Effectiveness Component: Beth Israel Deaconess Medical Center: John Zupancic, MD, MS, ScD (PI). Executive Committee: Alejandra de Alba Campomanes, MD MPH, Edward F. Bell, MD, Gil Binenbaum, MD, MSCE, Pamela Donohue, ScD, Maureen Maguire, PhD, David Morrison, MD, Graham E. Quinn, MD, MSCE, Michael X. Repka, MD, David L. Rogers, MD, Lauren A. Tomlinson BS, Michael Yang, MD, Gui-shuang Ying, PhD.

    • Contributors DDF conceptualised and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. EAJ, GB and LAT conceptualised and designed the study and reviewed and revised the manuscript. G-SY and YY carried out the initial analyses and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

    • Funding DDF was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (grant T32HD060550), Agency for Healthcare Research and Quality (grant K08HS027468) and by a pilot grant from the Children’s Hospital of Philadelphia Office of Faculty Development. EAJ was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (grant K23HL136843). LAT, YY, G-SY and GB were supported by the National Eye Institute of the National Institutes of Health (grants R01EY021137-01A1 and R21EY029776-01). The funding organisations had no role in the design or conduct of the study; collection, management, analysis or interpretation of the data; preparation, review or approval of the manuscripts; or decision to submit the manuscript for publication.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The original study was approved by the institutional review board at the Children’s Hospital of Philadelphia (12–009727).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement The data are maintained by the Postnatal Growth and Retinopathy of Prematurity study investigators. Deidentified data are available upon reasonable request. The G-ROP study primary investigator (GB) can be contacted at binenbaum@email.chop.edu.

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