Human cytomegalovirus reactivation during lactation and mother-to-child transmission in preterm infants

Abstract

In a clinical trial, the incidence of cytomegalovirus reactivation in breastfeeding mothers and transmission to their preterm infants were studied. Breast milk from 73 mothers as well as urine and tracheal and pharyngeal aspirates from their 89 infants were screened weekly for human cytomegalovirus (HCMV) DNA during the first 2 months after delivery. Of the 73 mothers, 48 (66%) were positive for HCMV DNA in the lactating breast. HCMV reactivation could be confirmed for 19 of 20 (95%) immunoglobulin G-positive mothers. Of the eight immunoglobulin G-negative mothers one was positive for HCMV DNA in breast milk. In only 2 out of 13 seropositive mothers with HCMV DNA in breast milk could viral DNA be detected in the peripheral blood. HCMV mother-to-child transmission was concluded for 20 of the 48 (42%) mothers positive for DNA or 7 of 19 (37%) seropositive for HCMV and positive for HCMV DNA in breast milk and one of one mother seronegative for HCMV but positive for HCMV DNA in breast milk. One mother transmitted the virus to her twins. In addition, one infant acquired postnatal HCMV infection despite the mother's being negative for HCMV DNA in breast milk; altogether, we found 22 infants with HCMV infection. In 13 of these 22 infants, virus infection occurred definitively postnatally; two of them developed severe symptomatic HCMV infection. HCMV-infected infants demonstrated higher incidences of amniotic infection, respiratory distress syndrome, bronchopulmonary dysplasia, and retinopathia praenatalis than noninfected infants, however, the differences were not statistically significant. In summary, our study confirmed a very high incidence of HCMV reactivation in mothers during lactation and a significant risk of transmission to preterm infants with the possibility of severe disease in these babies.

FIG. 1.

Incidence of HCMV reactivation and HCMV DNA in breast milk in breastfeeding mothers and the risk of HCMV transmission to their preterm infants. *, One mother transmitted the virus to both twins, resulting in eight HCMV-infected infants. The mode of infection for individual infants remains speculative, only for five of them was postnatal infection confirmed, supporting the hypothesis that HCMV-containing breast milk was the source of infection.

FIG. 2.

Autoradiogram of Southern blot analysis of HCMV PCR products. PCR products were separated on a 3% agarose gel, transferred to a nylon membrane, and hybridized with internal oligonucleotide P2 (21) end labeled by T4 polynucleotide kinase and [γ-³²P]ATP. Hybridization was carried out for 18 h at 52°C in 5× SSC-5× Denhardt's solution-0.1% sodium dodecyl sulfate. After washing, the filters were exposed to a phosphoscreen. Hybridization signals were visualized by phosphoimaging (PhosphorImager, type SI). P, positive control (0.1 pg of AD169 DNA); N, negative (buffer) control; M, breast milk; TA, tracheal aspirate; U, urine. The PCR products from one mother-child pair are underlined.