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Am J Perinatol 2016; 33(09): 894-902
DOI: 10.1055/s-0036-1581080
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Symptomatic Postnatal Cytomegalovirus Testing among Very Low-Birth-Weight Infants: Indications and Outcomes

Sagori Mukhopadhyay
1   Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
2   Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
,
Sarah A. Meyer
3   Department of Pediatric Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
,
Sallie R. Permar
4   Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
5   Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina
,
Karen M. Puopolo
1   Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
2   Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
› Author Affiliations
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Publication History

24 October 2015

12 February 2016

Publication Date:
08 April 2016 (online)

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Abstract

Objective The objective of this study was to describe the indications for postnatal cytomegalovirus (CMV) testing among very low-birth-weight (VLBW, birth weight [BW] < 1,500 g) infants, clinical characteristics of infected infants, and adverse outcomes associated with CMV infection.

Study Design This is a single-center, retrospective study of 2,132 VLBW infants from 1999 to 2013.

Results In this study, 145 (6.8%) infants out of 2,132 were evaluated for postnatal CMV infection and 27 (18.6%) infants out of 145 were infected. CMV-tested infants were of significantly lower gestational age and BW compared with untested VLBW infants (p < 0.001). Respiratory decompensation and thrombocytopenia were the findings most commonly associated with infection. CMV-infected infants had significantly more exposure to mechanical ventilation and longer duration of hospitalization. Adjusting for multiple predictors of respiratory morbidity, the incidence of bronchopulmonary dysplasia (BPD) was significantly elevated among infants diagnosed with postnatal CMV infection (odds ratio, 4.0 [95% confidence interval, 1.3–12.4); p, 0.02.)

Conclusion Symptomatic postnatal CMV infection was diagnosed in 1.3% of VLBW infants, most commonly among infants with BW < 1,000 g with respiratory instability and thrombocytopenia. Similar to late-onset bacterial infection, symptomatic postnatal CMV infection may be an independent contributor to the development of BPD. This possibility should be addressed in a prospective study of extremely low BW infants.

Keywords

cytomegalovirus - breast milk - postnatal transmission - premature - bronchopulmonary dysplasia
 

  • References

  • 1 Hamprecht K, Maschmann J, Vochem M, Dietz K, Speer CP, Jahn G. Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Lancet 2001; 357 (9255) 513-518
    CrossrefPubMedGoogle Scholar
  • 2 Josephson CD, Caliendo AM, Easley KA , et al. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr 2014; 168 (11) 1054-1062
    CrossrefPubMedGoogle Scholar
  • 3 Miron D, Brosilow S, Felszer K , et al. Incidence and clinical manifestations of breast milk-acquired Cytomegalovirus infection in low birth weight infants. J Perinatol 2005; 25 (5) 299-303
    CrossrefPubMedGoogle Scholar
  • 4 Hamprecht K, Maschmann J, Jahn G, Poets CF, Goelz R. Cytomegalovirus transmission to preterm infants during lactation. J Clin Virol 2008; 41 (3) 198-205
    CrossrefPubMedGoogle Scholar
  • 5 Jim WT, Shu CH, Chiu NC , et al. High cytomegalovirus load and prolonged virus excretion in breast milk increase risk for viral acquisition by very low birth weight infants. Pediatr Infect Dis J 2009; 28 (10) 891-894
    CrossrefPubMedGoogle Scholar
  • 6 Vollmer B, Seibold-Weiger K, Schmitz-Salue C , et al. Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants. Pediatr Infect Dis J 2004; 23 (4) 322-327
    CrossrefPubMedGoogle Scholar
  • 7 Neuberger P, Hamprecht K, Vochem M , et al. Case-control study of symptoms and neonatal outcome of human milk-transmitted cytomegalovirus infection in premature infants. J Pediatr 2006; 148 (3) 326-331
    CrossrefPubMedGoogle Scholar
  • 8 Hayashi S, Kimura H, Oshiro M , et al. Transmission of cytomegalovirus via breast milk in extremely premature infants. J Perinatol 2011; 31 (6) 440-445
    CrossrefPubMedGoogle Scholar
  • 9 Capretti MG, Lanari M, Lazzarotto T , et al. Very low birth weight infants born to cytomegalovirus-seropositive mothers fed with their mother's milk: a prospective study. J Pediatr 2009; 154 (6) 842-848
    CrossrefPubMedGoogle Scholar
  • 10 Goelz R, Meisner C, Bevot A, Hamprecht K, Kraegeloh-Mann I, Poets CF. Long-term cognitive and neurological outcome of preterm infants with postnatally acquired CMV infection through breast milk. Arch Dis Child Fetal Neonatal Ed 2013; 98 (5) F430-F433
    CrossrefPubMedGoogle Scholar
  • 11 Dorn M, Lidzba K, Bevot A, Goelz R, Hauser TK, Wilke M. Long-term neurobiological consequences of early postnatal hCMV-infection in former preterms: a functional MRI study. Hum Brain Mapp 2014; 35 (6) 2594-2606
    CrossrefPubMedGoogle Scholar
  • 12 Bevot A, Hamprecht K, Krägeloh-Mann I, Brosch S, Goelz R, Vollmer B. Long-term outcome in preterm children with human cytomegalovirus infection transmitted via breast milk. Acta Paediatr 2012; 101 (4) e167-e172
    CrossrefPubMedGoogle Scholar
  • 13 Nijman J, van Zanten BG, de Waard AK, Koopman-Esseboom C, de Vries LS, Verboon-Maciolek MA. Hearing in preterm infants with postnatally acquired cytomegalovirus infection. Pediatr Infect Dis J 2012; 31 (10) 1082-1084
    PubMedGoogle Scholar
  • 14 Lanzieri TM, Dollard SC, Josephson CD, Schmid DS, Bialek SR. Breast milk-acquired cytomegalovirus infection and disease in VLBW and premature infants. Pediatrics 2013; 131 (6) e1937-e1945
    CrossrefPubMedGoogle Scholar
  • 15 Luck S, Sharland M. Postnatal cytomegalovirus: innocent bystander or hidden problem?. Arch Dis Child Fetal Neonatal Ed 2009; 94 (1) F58-F64
    PubMedGoogle Scholar
  • 16 Buxmann H, Falk M, Goelz R, Hamprecht K, Poets CF, Schloesser RL. Feeding of very low birth weight infants born to HCMV-seropositive mothers in Germany, Austria and Switzerland. Acta Paediatr 2010; 99 (12) 1819-1823
    CrossrefPubMedGoogle Scholar
  • 17 Gunkel J, Wolfs TF, de Vries LS, Nijman J. Predictors of severity for postnatal cytomegalovirus infection in preterm infants and implications for treatment. Expert Rev Anti Infect Ther 2014; 12 (11) 1345-1355
    CrossrefPubMedGoogle Scholar
  • 18 Mehler K, Oberthuer A, Lang-Roth R, Kribs A. High rate of symptomatic cytomegalovirus infection in extremely low gestational age preterm infants of 22–24 weeks' gestation after transmission via breast milk. Neonatology 2014; 105 (1) 27-32
    CrossrefPubMedGoogle Scholar
  • 19 Sawyer MH, Edwards DK, Spector SA. Cytomegalovirus infection and bronchopulmonary dysplasia in premature infants. Am J Dis Child 1987; 141 (3) 303-305
    PubMedGoogle Scholar
  • 20 Okulu E, Akin IM, Atasay B, Ciftçi E, Arsan S, Türmen T. Severe postnatal cytomegalovirus infection with multisystem involvement in an extremely low birth weight infant. J Perinatol 2012; 32 (1) 72-74
    CrossrefPubMedGoogle Scholar
  • 21 Papazian L, Fraisse A, Garbe L , et al. Cytomegalovirus. An unexpected cause of ventilator-associated pneumonia. Anesthesiology 1996; 84 (2) 280-287
    CrossrefPubMedGoogle Scholar
  • 22 Yeager AS, Palumbo PE, Malachowski N, Ariagno RL, Stevenson DK. Sequelae of maternally derived cytomegalovirus infections in premature infants. J Pediatr 1983; 102 (6) 918-922
    CrossrefPubMedGoogle Scholar
  • 23 Prösch S, Lienicke U, Priemer C , et al. Human adenovirus and human cytomegalovirus infections in preterm newborns: no association with bronchopulmonary dysplasia. Pediatr Res 2002; 52 (2) 219-224
    CrossrefPubMedGoogle Scholar
  • 24 Pinninti SG, Ross SA, Shimamura M , et al; National Institute on Deafness and Other Communication Disorders CMV and Hearing Multicenter Screening (CHIMES) Study. Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection. Pediatr Infect Dis J 2015; 34 (5) 536-537
    CrossrefPubMedGoogle Scholar
  • 25 Turner KM, Lee HC, Boppana SB, Carlo WA, Randolph DA. Incidence and impact of CMV infection in very low birth weight infants. Pediatrics 2014; 133 (3) e609-e615
    CrossrefPubMedGoogle Scholar
  • 26 Vohr BR, Poindexter BB, Dusick AM , et al; NICHD Neonatal Research Network. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics 2006; 118 (1) e115-e123
    Google Scholar
  • 27 Sisk PM, Lovelady CA, Dillard RG, Gruber KJ, O'Shea TM. Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants. J Perinatol 2007; 27 (7) 428-433
    CrossrefPubMedGoogle Scholar
  • 28 Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 2012; 129 (3) e827-e841
    CrossrefPubMedGoogle Scholar
  • 29 Maschmann J, Hamprecht K, Weissbrich B, Dietz K, Jahn G, Speer CP. Freeze-thawing of breast milk does not prevent cytomegalovirus transmission to a preterm infant. Arch Dis Child Fetal Neonatal Ed 2006; 91 (4) F288-F290
    CrossrefPubMedGoogle Scholar
  • 30 Oliver SE, Cloud GA, Sánchez PJ , et al; National Institute of Allergy, Infectious Diseases Collaborative Antiviral Study Group. Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system. J Clin Virol 2009; 46 (Suppl. 04) S22-S26
    PubMedGoogle Scholar
  • 31 Kimberlin DW, Lin CY, Sánchez PJ , et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 2003; 143 (1) 16-25
    CrossrefPubMedGoogle Scholar
  • 32 Kimberlin DW, Jester PM, Sánchez PJ , et al; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 2015; 372 (10) 933-943
    CrossrefPubMedGoogle Scholar