Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study

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.

Figure 1

Study flow diagram and laboratory testing schematic. *Weight inclusion criterion changed in November 2010 to increase recruitment.

Figure 2

In Panels A and B, the cumulative incidnce of CMV infection and mortality are given over the study period, including 95% confidence intervals at weeks 4, 8, and 12 (vertical bars). In Panel C, Log ₁₀ CMV viral load values were analyzed with a repeated measures model; mean estimates and their 95% confidence intervals were back transformed to the original scale and are reported as the geometric mean with 95% confidence intervals.