Maternal cytomegalovirus-specific immune responses and symptomatic postnatal cytomegalovirus transmission in very low-birth-weight preterm infants

Abstract

Introduction: Transmission of cytomegalovirus (CMV) via breast milk can lead to severe acute illness in very low-birth-weight (VLBW) preterm infants. Although the majority of CMV-seropositive women shed CMV in milk, symptomatic postnatal infection of VLBW infants occurs infrequently, suggesting that virologic or immunologic factors in milk may be associated with the risk and severity of postnatal CMV infection.

Methods: We investigated the magnitude of CMV-specific cellular and humoral immune responses in milk of 30 seropositive mothers of VLWB preterm infants and assessed their relationship to milk CMV load and symptomatic CMV transmission.

Results: Milk immunoglobulin G (IgG) avidity was inversely correlated to milk CMV load (r = -0.47; P = .009). However, milk CMV load and CMV-specific cellular and humoral immune responses were similar in mothers of VLBW infants with and those without symptomatic postnatal CMV infection.

Conclusions: Similar immunologic parameters in milk of CMV-seropositive mothers of VLBW infants with and without symptomatic postnatal CMV infection indicate that screening milk by these parameters may not predict disease risk. However, the inverse correlation between milk CMV IgG avidity and CMV load may suggest that enhancement of maternal CMV-specific IgG responses could aid in reduction of CMV shedding into breast milk.

Figure 1.

Low-magnitude cytomegalovirus (CMV)–specific cellular and humoral immune responses in milk compared with that in blood of CMV-seropositive mothers of very low-birth-weight (VLBW) infants including CMV-specific cellular responses (A), CMV-binding immunoglobulin (Ig) G and IgA titers (B), normalized CMV-binding IgG and IgA titers (C), CMV IgG and IgA avidity (D), CMV-neutralizing titers (E), and normalized CMV-neutralizing titers (F) in milk (open symbols) and blood (filled symbols) of CMV-seropositive mothers of VLBW preterm infants. Lines indicate median value; *P < .05. Abbreviation: ND, not detectable.

Figure 2.

Direct correlation of cytomegalovirus (CMV)–neutralizing and CMV-binding immunoglobulin (Ig) G responses in milk and plasma of CMV-seropositive mothers of very low–birth-weight (VLBW) infants, including CMV-specific cellular responses (A), neutralizing antibody responses (B), normalized CMV-binding IgG (C) and IgA (D) titers, and CMV-binding IgG (E) and IgA (F) avidity. Antibody titers were normalized by total IgG or IgA content in milk or plasma. *P < .05. Abbreviation: ND, not detectable.

Figure 3.

Cytomegalovirus (CMV)–specific cellular and humoral immune responses are similar in milk of seropositive mothers of preterm and full-term infants. Superantigen (staphylococcal enterotoxin B) (A) and CMV-specific cellular responses (B) in milk are shown for mothers of preterm (circles) and full-term (triangles), along with total immunoglobulin (Ig) G (C) and IgA (D) concentrations and CMV-binding IgG (E) and IgA (F) titers normalized for total IgG (G) or IgA (H) content in milk. Lines indicate median values. Abbreviation: ND, not detectable.

Figure 4.

Milk cytomegalovirus (CMV) load and CMV-specific cellular and humoral immune responses are similar in seropositive mothers of very low-birth-weight (VLBW) infants diagnosed with symptomatic postnatal CMV and mothers of control VLBW infants. CMV-specific cellular responses (A), CMV-binding immunoglobulin (Ig) G titers (B), CMV-binding IgA titers (C), normalized CMV-binding IgG titers (D), normalized CMV-binding IgA titers (E), CMV-binding IgG avidity (F), CMV-binding IgA avidity (G), CMV-neutralizing antibody 50% inhibitory dose (ID₅₀) titers (H), and normalized CMV-neutralizing antibody ID₅₀ titers (I) in milk and plasma are shown for mothers of CMV-symptomatic (triangles) and asymptomatic (circles) VLBW infants. Lines indicate median values. Abbreviation: ND, not detectable.