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Original research
Observational study of cytomegalovirus from breast milk and necrotising enterocolitis
  1. Ravi Mangal Patel1,2,
  2. Neeta Shenvi3,
  3. Andrea Knezevic3,4,
  4. Michael Hinkes5,
  5. George W Bugg1,2,
  6. Sean R Stowell6,
  7. John D Roback6,
  8. Kirk A Easley3,
  9. Cassandra Josephson1,2,6
    1. 1 Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
    2. 2 Pediatrics, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA
    3. 3 Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, Georgia, USA
    4. 4 Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    5. 5 Neonatology, Northside Hospital, Atlanta, Georgia, USA
    6. 6 Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
    1. Correspondence to Dr Ravi Mangal Patel; rmpatel{at}emory.edu, ravipatelmd{at}gmail.com

    Abstract

    Objective To evaluate the relationship between cytomegalovirus (CMV) exposure from breast milk and risk of necrotising enterocolitis (NEC).

    Design Secondary analysis of a multicentre, observational cohort study. Maternal breast milk and infant serum or urine were serially evaluated by nucleic acid testing at scheduled intervals for CMV. Infants with evidence of congenital infection were excluded. Competing-risks Cox models, with adjustment for confounders, were used to evaluate the relationship between breast milk CMV exposure or postnatal CMV infection and NEC.

    Setting Three neonatal intensive care units in Atlanta, Georgia.

    Patients Infants with a birth weight≤1500 grams.

    Exposures Maximal CMV viral load in breast milk in the first 14 days after birth or postnatal CMV infection. Two different approaches were used to assess the timing of onset of CMV infection (midpoint or early).

    Main outcome measures NEC, defined as Bell stage II or greater.

    Results Among 596 enrolled infants, 457 (77%) were born to CMV seropositive mothers and 33 developed postnatal CMV infection (cumulative incidence 7.3%, 95% CI 5.0% to 10.1%). The incidence of NEC was 18% (6/33) among infants with CMV infection, compared with 7% (37/563) among infants without infection (adjusted cause-specific HR (CSHR): 2.81; 95% CI 0.73 to 10.9 (midpoint); 6.02; 95% CI 1.28 to 28.4 (early)). Exposure to higher breast milk CMV viral load was associated with a higher risk of NEC (adjusted CSHR per twofold increase 1.28; 95% CI 1.06 to 1.54).

    Conclusions CMV exposure from breast milk may be associated with the development of NEC in very low birth weight infants.

    • neonatology
    • infant feeding
    https://creativecommons.org/licenses/by-nc/4.0/

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

    https://doi.org/10.1136/archdischild-2018-316613

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      Footnotes

      • Contributors All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The following are the specific contributions of each study author: RMP designed the study, analysed and interpreted the data, drafted the initial version of the manuscript and approved the final manuscript as submitted. NS performed statistical analysis, interpreted the data, critically revised the manuscript and approved the final manuscript as submitted. AK performed statistical analysis, interpreted the data, critically revised the manuscript and approved the final manuscript as submitted. MH acquired study data, critically revised the manuscript and approved the final manuscript as submitted. GWB helped acquire study data, provided study supervision, critically revised the manuscript and approved the final manuscript as submitted. SRS helped interpret the data, revised the manuscript and approved the final manuscript as submitted. JDR designed the study, interpreted the data, provided study supervision, revised the manuscript and approved the final manuscript as submitted. KAE assisted in conceptualising and designing the study, supervised statistical analysis and helped interpret the data, critically revised the manuscript and approved the final manuscript as submitted. CJ obtained funding, designed the study, helped acquire data, analysed and interpreted the data, revised the manuscript and approved the final manuscript as submitted.

      • Funding This study was supported by the National Institutes of Health (NIH). RMP received salary support from the NIH National Center for Advancing Translational Sciences (NCATS) under awards UL1 TR000454 and KL2 TR000455 and from the National Heart Lung Blood Institute (NHLBI) under award K23 HL128942. The parent study was funded by the NHLBI under award P01 HL086773 (JDR and CJ).

      • Competing interests Dr. Patel received travel support from Danone Nutricia to attend the SIGNEC UK meeting.

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

      • Data sharing statement Data requestors should contact the corresponding author to request the relevant data and provide a protocol or outline for the proposed study that will use the data. After a data use agreement has been executed, the study data coordinating center will generate the requested data files, in a de-identified format, and provide appropriate accompanying documentation.

      • Patient consent for publication Not required.

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