Blood Transfusion and Breast Milk Transmission of Cytomegalovirus in Very Low-Birth-Weight Infants : A Prospective Cohort Study | Breastfeeding | JAMA Pediatrics | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.204.186.91. Please contact the publisher to request reinstatement.
1.
Yeager  AS, Grumet  FC, Hafleigh  EB, Arvin  AM, Bradley  JS, Prober  CG.  Prevention of transfusion-acquired cytomegalovirus infections in newborn infants.  J Pediatr. 1981;98(2):281-287.PubMedGoogle ScholarCrossref
2.
Gilbert  GL, Hayes  K, Hudson  IL, James  J; Neonatal Cytomegalovirus Infection Study Group.  Prevention of transfusion-acquired cytomegalovirus infection in infants by blood filtration to remove leukocytes.  Lancet. 1989;1(8649):1228-1231.PubMedGoogle ScholarCrossref
3.
Eisenfeld  L, Silver  H, McLaughlin  J,  et al.  Prevention of transfusion-associated cytomegalovirus infection in neonatal patients by the removal of white cells from blood.  Transfusion. 1992;32(3):205-209.PubMedGoogle ScholarCrossref
4.
Roback  JD, Josephson  CD.  New insights for preventing transfusion-transmitted cytomegalovirus and other white blood cell–associated viral infections.  Transfusion. 2013;53(10):2112-2116.PubMedGoogle Scholar
5.
Lanzieri  TM, Dollard  SC, Josephson  CD, Schmid  S, Bialek  SR.  Breast milk–acquired cytomegalovirus infection and disease in VLBW and premature infants.  Pediatrics. 2013;131(6):e1937. doi:10.1542/peds.2013-0076. PubMedGoogle ScholarCrossref
6.
Reynolds  DW, Stagno  S, Hosty  TS, Tiller  M, Alford  CA  Jr.  Maternal cytomegalovirus excretion and perinatal infection.  N Engl J Med. 1973;289(1):1-5.PubMedGoogle ScholarCrossref
7.
Cunha  BA.  Cytomegalovirus pneumonia: community-acquired pneumonia in immunocompetent hosts.  Infect Dis Clin North Am. 2010;24(1):147-158.PubMedGoogle ScholarCrossref
8.
Colugnati  FA, Staras  SA, Dollard  SC, Cannon  MJ.  Incidence of cytomegalovirus infection among the general population and pregnant women in the United States.  BMC Infect Dis. 2007;7:71. doi:10.1186/1471-2334-7-71.PubMedGoogle ScholarCrossref
9.
Josephson  CD, Castillejo  MI, Caliendo  AM,  et al.  Prevention of transfusion-transmitted cytomegalovirus in low-birth weight infants (≤1500 g) using cytomegalovirus-seronegative and leukoreduced transfusions.  Transfus Med Rev. 2011;25(2):125-132.PubMedGoogle ScholarCrossref
10.
Abdul-Ali  D, Kraft  CS, Ingersoll  J, Frempong  M, Caliendo  AM.  Cytomegalovirus DNA stability in EDTA anti-coagulated whole blood and plasma samples.  J Clin Virol. 2011;52(3):222-224.PubMedGoogle ScholarCrossref
11.
Mannonen  L, Loginov  R, Helantera  I,  et al.  Comparison of two quantitative real-time CMV-PCR tests calibrated against the 1st WHO international standard for viral load.  J Med Virol. 2014;86(4):576-584. PubMedGoogle ScholarCrossref
12.
Olsen  IE, Groveman  SA, Lawson  ML, Clark  RH, Zemel  BS.  New intrauterine growth curves based on United States data.  Pediatrics. 2010;125(2):e214-e224.PubMedGoogle ScholarCrossref
13.
Lee  EW, Wei  LJ, Amato  DA. Cox-type regression analysis for large numbers of small groups of correlated failure time observations. In: Klein J, Goel P, eds.  Survival Analysis. Dordrecht, the Netherlands: Kluwer Academic; 1992:237-247.
14.
Drew  WL, Tegtmeier  G, Alter  HJ, Laycock  ME, Miner  RC, Busch  MP.  Frequency and duration of plasma CMV viremia in seroconverting blood donors and recipients.  Transfusion. 2003;43(3):309-313.PubMedGoogle ScholarCrossref
15.
Roback  JD.  CMV and blood transfusions.  Rev Med Virol. 2002;12(4):211-219.PubMedGoogle ScholarCrossref
16.
Bowden  RA, Slichter  SJ, Sayers  M,  et al.  A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant.  Blood. 1995;86(9):3598-3603.PubMedGoogle Scholar
17.
Laupacis  A, Brown  J, Costello  B,  et al.  Prevention of posttransfusion CMV in the era of universal WBC reduction: a consensus statement.  Transfusion. 2001;41(4):560-569.PubMedGoogle ScholarCrossref
18.
Dumont  LJ, Luka  J, VandenBroeke  T, Whitley  P, Ambruso  DR, Elfath  MD.  The effect of leukocyte-reduction method on the amount of human cytomegalovirus in blood products: a comparison of apheresis and filtration methods.  Blood. 2001;97(11):3640-3647.PubMedGoogle ScholarCrossref
19.
 Breastfeeding and the use of human milk.  Pediatrics. 2012;129(3):e827-e841.PubMedGoogle ScholarCrossref
20.
Walker  SP, Palma-Dias  R, Wood  EM, Shekleton  P, Giles  ML.  Cytomegalovirus in pregnancy: to screen or not to screen.  BMC Pregnancy Childbirth. 2013;13:96. doi:10.1186/1471-2393-13-96. PubMedGoogle ScholarCrossref
21.
Meier  J, Lienicke  U, Tschirch  E, Krüger  DH, Wauer  RR, Prösch  S.  Human cytomegalovirus reactivation during lactation and mother-to-child transmission in preterm infants.  J Clin Microbiol. 2005;43(3):1318-1324.PubMedGoogle ScholarCrossref
22.
Goelz  R, Hihn  E, Hamprecht  K,  et al.  Effects of different CMV-heat-inactivation-methods on growth factors in human breast milk.  Pediatr Res. 2009;65(4):458-461.PubMedGoogle ScholarCrossref
23.
Marshall  BC, Koch  WC.  Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events.  Paediatr Drugs. 2009;11(5):309-321.PubMedGoogle ScholarCrossref
24.
Bopegamage  S, Kacerovsky  M, Tambor  V,  et al.  Preterm prelabor rupture of membranes (PPROM) is not associated with presence of viral genomes in the amniotic fluid.  J Clin Virol. 2013;58(3):559-563.PubMedGoogle ScholarCrossref
25.
Naresh  A, Simhan  H.  Absence of viruses in amniotic fluid of women with PPROM: a case series.  J Reprod Immunol. 2012;96(1-2):79-83.PubMedGoogle ScholarCrossref
26.
Tengsupakul  S, Birge  ND, Bendel  CM,  et al.  Asymptomatic DNAemia heralds CMV-associated NEC: case report, review, and rationale for preemption.  Pediatrics. 2013;132(5):e1428-e1434. doi:10.1542/peds.2013-0087.PubMedGoogle ScholarCrossref
27.
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 Neonat Ed. 2013;98(5):F430-F433. PubMedGoogle ScholarCrossref
28.
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. doi:10.1111/j.1651-2227.2011.02538.x. PubMedGoogle ScholarCrossref
29.
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. doi:10.1542/peds.2013-2217. PubMedGoogle ScholarCrossref
Original Investigation
November 2014

Blood Transfusion and Breast Milk Transmission of Cytomegalovirus in Very Low-Birth-Weight Infants : A Prospective Cohort Study

Author Affiliations
  • 1Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, Georgia
  • 2Department of Pathology, Children’s Healthcare of Atlanta, Atlanta, Georgia
  • 3Aflac Cancer Center and Blood Disorders Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia
  • 4Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island
  • 5Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia
  • 6Neonatology Associates of Atlanta, Northside Hospital, Atlanta, Georgia
  • 7Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
  • 8Children's Healthcare of Atlanta, Atlanta, Georgia
  • 9New York Blood Center, New York, New York
JAMA Pediatr. 2014;168(11):1054-1062. doi:10.1001/jamapediatrics.2014.1360
Abstract

Importance  Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low-birth-weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, as well as the efficacy of approaches to prevent CMV transmission, are poorly characterized.

Objective  To estimate the risk of postnatal CMV transmission from 2 sources: (1) transfusion of CMV-seronegative and leukoreduced blood and (2) maternal breast milk.

Design, Setting, and Participants  A prospective, multicenter birth-cohort study was conducted from January 2010 to June 2013 at 3 neonatal intensive care units (2 academically affiliated and 1 private) in Atlanta, Georgia. Cytomegalovirus serologic testing of enrolled mothers was performed to determine their status. Cytomegalovirus nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. A total of 539 VLBW infants (birth weight, ≤1500 g) who had not received a blood transfusion were enrolled, with their mothers (n = 462), within 5 days of birth. The infants underwent serum and urine CMV NAT at birth to evaluate congenital infection and surveillance CMV NAT at 5 additional intervals between birth and 90 days, discharge, or death.

Exposures  Blood transfusion and breast milk feeding.

Main Outcomes and Measures  Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT.

Results  The seroprevalence of CMV among the 462 enrolled mothers was 76.2% (n = 352). Among the 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI, 4.2%-9.2%); 5 of 29 infants (17.2%) with postnatal CMV infection developed symptomatic disease or died. A total of 2061 transfusions were administered among 57.5% (n = 310) of the infants; none of the CMV infections was linked to transfusion, resulting in a CMV infection incidence of 0.0% (95% CI, 0.0%-0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence, 15.3%; 95% CI, 9.3%-20.2%).

Conclusions and Relevance  Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants whose care is managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection.

Trial Registration  clinicaltrials.gov Identifier: NCT00907686

×