Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting

Nelmary Hernandez-Alvarado; Ryan Shanley; Mark R. Schleiss; Jensina Ericksen; Jenna Wassenaar; Lulua Webo; Katherine Bodin; Katelyn Parsons; Erin A. Osterholm

doi:10.3390/v13101897

Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting

Nelmary Hernandez-Alvarado, Ryan Shanley, Mark R. Schleiss, Jensina Ericksen, Jenna Wassenaar, Lulua Webo, Katherine Bodin, Katelyn Parsons, Erin A. Osterholm

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Cytomegalovirus (CMV) infections acquired by very-low-birthweight (VLBW) infants are incompletely characterized. To examine CMV transmission in VLBW infants, we evaluated maternal DNAlactia, infant DNAemia, and presence of clinical disease in a blinded study in VLBW infants in our newborn intensive care unit (NICU). To examine these issues, 200 VLBW infants were en-rolled in a surveillance study, with weekly breast milk and infant whole blood samples collected, as available. Virologic (breast milk and infant whole blood real time PCR) and immunologic (IgG, IgM, and IgG avidity) correlates were evaluated. A chart review examined whether infants had symptoms compatible with CMV disease. DNAlactia was identified in 65/150 (43%) of lactating mothers. Nine CMV infections were identified in 9/75 CMV-exposed infants (12% of exposed in-fants). A higher median breast milk viral load (DNAlactia) correlated with an increased likelihood of DNAemia (p = 0.05). Despite potential symptoms compatible with CMV infection, clinicians had not considered the diagnosis of CMV in 6/9 cases (66%). All of these infants had chronic lung disease at discharge. There was no correlation between IgG antibody titer or IgG avidity index and the likelihood of transmission or CMV disease. In conclusion, in VLBW infants receiving milk from seroposi-tive mothers, CMV infections are commonly acquired, and are frequently unrecognized. Future studies are needed to determine whether routine surveillance for CMV of either breast milk or infant plasma is beneficial in preventing or recognizing infection.

Original language	English (US)
Article number	1897
Journal	Viruses
Volume	13
Issue number	10
DOIs	https://doi.org/10.3390/v13101897
State	Published - Oct 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the University of South Carolina’s Disability Research and Dissemination Center (DRDC) through its Cooperative Agreement (Number 6U19DD001218) with the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the DRDC or CDC. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The UL1TR002494 funding mechanism also included a CTSA-funded “Pathways to Research Scholar” Program (PReP) Award (LW). LW was also funded by a Department of Pediatrics “SUPER” Award. KP was funded by an Infectious Diseases Society of America IDSA “Grants for Emerging Researcher/Clinician Mentorship” (G.E.R.M.) program grant, and a University of Minnesota Foundation Medical Student Research Grant. The corresponding authors also acknowledge a UMN Department of Pediatrics “Cross-Divisional” award which helped support these studies.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Breast milk
CMV antivirals
Cytomegalovirus (CMV)
Post-natal CMV

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hernandez-Alvarado, N., Shanley, R., Schleiss, M. R., Ericksen, J., Wassenaar, J., Webo, L., Bodin, K., Parsons, K., & Osterholm, E. A. (2021). Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting. Viruses, 13(10), Article 1897. https://doi.org/10.3390/v13101897

Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting. / Hernandez-Alvarado, Nelmary ; Shanley, Ryan ; Schleiss, Mark R. et al.
In: Viruses, Vol. 13, No. 10, 1897, 10.2021.

Research output: Contribution to journal › Article › peer-review

Hernandez-Alvarado, N , Shanley, R , Schleiss, MR, Ericksen, J, Wassenaar, J, Webo, L, Bodin, K, Parsons, K & Osterholm, EA 2021, 'Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting', Viruses, vol. 13, no. 10, 1897. https://doi.org/10.3390/v13101897

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abstract = "Cytomegalovirus (CMV) infections acquired by very-low-birthweight (VLBW) infants are incompletely characterized. To examine CMV transmission in VLBW infants, we evaluated maternal DNAlactia, infant DNAemia, and presence of clinical disease in a blinded study in VLBW infants in our newborn intensive care unit (NICU). To examine these issues, 200 VLBW infants were en-rolled in a surveillance study, with weekly breast milk and infant whole blood samples collected, as available. Virologic (breast milk and infant whole blood real time PCR) and immunologic (IgG, IgM, and IgG avidity) correlates were evaluated. A chart review examined whether infants had symptoms compatible with CMV disease. DNAlactia was identified in 65/150 (43%) of lactating mothers. Nine CMV infections were identified in 9/75 CMV-exposed infants (12% of exposed in-fants). A higher median breast milk viral load (DNAlactia) correlated with an increased likelihood of DNAemia (p = 0.05). Despite potential symptoms compatible with CMV infection, clinicians had not considered the diagnosis of CMV in 6/9 cases (66%). All of these infants had chronic lung disease at discharge. There was no correlation between IgG antibody titer or IgG avidity index and the likelihood of transmission or CMV disease. In conclusion, in VLBW infants receiving milk from seroposi-tive mothers, CMV infections are commonly acquired, and are frequently unrecognized. Future studies are needed to determine whether routine surveillance for CMV of either breast milk or infant plasma is beneficial in preventing or recognizing infection.",

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note = "Funding Information: Funding: This research was funded by the University of South Carolina{\textquoteright}s Disability Research and Dissemination Center (DRDC) through its Cooperative Agreement (Number 6U19DD001218) with the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the DRDC or CDC. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The UL1TR002494 funding mechanism also included a CTSA-funded “Pathways to Research Scholar” Program (PReP) Award (LW). LW was also funded by a Department of Pediatrics “SUPER” Award. KP was funded by an Infectious Diseases Society of America IDSA “Grants for Emerging Researcher/Clinician Mentorship” (G.E.R.M.) program grant, and a University of Minnesota Foundation Medical Student Research Grant. The corresponding authors also acknowledge a UMN Department of Pediatrics “Cross-Divisional” award which helped support these studies. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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N1 - Funding Information: Funding: This research was funded by the University of South Carolina’s Disability Research and Dissemination Center (DRDC) through its Cooperative Agreement (Number 6U19DD001218) with the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the DRDC or CDC. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The UL1TR002494 funding mechanism also included a CTSA-funded “Pathways to Research Scholar” Program (PReP) Award (LW). LW was also funded by a Department of Pediatrics “SUPER” Award. KP was funded by an Infectious Diseases Society of America IDSA “Grants for Emerging Researcher/Clinician Mentorship” (G.E.R.M.) program grant, and a University of Minnesota Foundation Medical Student Research Grant. The corresponding authors also acknowledge a UMN Department of Pediatrics “Cross-Divisional” award which helped support these studies. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - Cytomegalovirus (CMV) infections acquired by very-low-birthweight (VLBW) infants are incompletely characterized. To examine CMV transmission in VLBW infants, we evaluated maternal DNAlactia, infant DNAemia, and presence of clinical disease in a blinded study in VLBW infants in our newborn intensive care unit (NICU). To examine these issues, 200 VLBW infants were en-rolled in a surveillance study, with weekly breast milk and infant whole blood samples collected, as available. Virologic (breast milk and infant whole blood real time PCR) and immunologic (IgG, IgM, and IgG avidity) correlates were evaluated. A chart review examined whether infants had symptoms compatible with CMV disease. DNAlactia was identified in 65/150 (43%) of lactating mothers. Nine CMV infections were identified in 9/75 CMV-exposed infants (12% of exposed in-fants). A higher median breast milk viral load (DNAlactia) correlated with an increased likelihood of DNAemia (p = 0.05). Despite potential symptoms compatible with CMV infection, clinicians had not considered the diagnosis of CMV in 6/9 cases (66%). All of these infants had chronic lung disease at discharge. There was no correlation between IgG antibody titer or IgG avidity index and the likelihood of transmission or CMV disease. In conclusion, in VLBW infants receiving milk from seroposi-tive mothers, CMV infections are commonly acquired, and are frequently unrecognized. Future studies are needed to determine whether routine surveillance for CMV of either breast milk or infant plasma is beneficial in preventing or recognizing infection.

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KW - CMV antivirals

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KW - Post-natal CMV

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Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting

Abstract

Bibliographical note

Keywords

UN SDGs

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