Pre-existing maternal IgG antibodies as a protective factor against congenital cytomegalovirus infection: A mother-child prospective cohort study

BACKGROUND: An understanding of the correlation between maternal immunity and congenital cytomegalovirus (CMV) infection is critical for informing the design and evaluation of an effective maternal vaccine. This study aimed to quantitatively measure the protective effect of pre-existing maternal immunity against congenital CMV (cCMV) infection. METHODS: A mother-child cohort study was conducted in three maternal and child health hospitals in China from 2015 to 2018. Pregnant women were consecutively enrolled, and anti-CMV pp150 IgG concentration at early, middle and late gestational ages were evaluated. Their newborns were screened for cCMV infection by CMV-DNA testing of saliva and urine. FINDINGS: In total, 6729 pregnant women were enrolled, and 6602 of them (98·11%) were positive for CMV IgG at their early gestational age visit (median time: 13 gestational weeks (GW); time range: 6–25 GW). In total, 6228 live newborns were born to seropositive mothers, and 48 (0·77%) of these infants were diagnosed with cCMV infection. The geometric mean concentration (GMC) of CMV IgG at an early gestational age in the women who delivered cCMV-positive newborns (i.e., the transmitters) was 8·54 IU/mL; this was significantly lower than the GMC in the non-transmitters (11·01 IU/mL; P=0·04). In early gestation, the risk of cCMV infection decreased as maternal IgG antibody levels increased (P=0·020); however, the same was not true in middle or late gestation (P>0·05). Using receiver operating characteristic analysis, a CMV IgG concentration of 12·83 IU/mL was established as the optimal diagnostic threshold. Compared to lower levels of CMV IgG (<12·83 IU/mL) in seropositive pregnant women, higher maternal CMV IgG levels (≥12·83 IU/mL) were associated with a 50% reduction in cCMV infection risk in infants (relative risk=0·50; 95% confidence interval: 0·27–0·93; P=0·028). INTERPRETATION: For seropositive women, a higher level of CMV IgG at an early gestational age is associated with a lower risk of cCMV infection in their newborns. FUNDING: National Natural Science Foundation of China; Science and Technology Key Project in Fujian Province; Merck Sharp & Dohme Corp., Kenilworth, NJ, USA; Fieldwork Funds for graduate students of Xiamen University.