Neonatal Antibody Titers Against Varicella-Zoster Virus in Relation to Gestational Age, Birth Weight, and Maternal Titer

Abstract

OBJECTIVE: Varicella-zoster virus (VZV) can cause severe disease in premature neonates. The fetus receives protective maternal VZV-immunoglobulin G (IgG) mainly in the third trimester of pregnancy. Therefore, premature neonates are considered at risk for VZV infection. Administration of varicella-zoster immunoglobulin (VZIG) within 96 hours after exposure effectively prevents severe illness in susceptible patients. The objectives of this study were to define the major determinants of the neonatal VZV-IgG titer and to determine the half-life of transplacentally acquired VZV-IgG. Guidelines provided by the Centers for Disease Control and Prevention for the use of VZIG in (premature) neonates were evaluated. METHODS: VZV-IgG titers were measured in sera of 221 neonates and 43 mothers using a quantitative enzyme-linked immunosorbent assay. In 27 neonates, VZV-IgG titers were followed for up to 14 weeks. RESULTS: In a linear regression model, the maternal antibody titer was the major determinant of the neonatal titer (beta = 0.89); gestational age was only of minor importance (beta = 0.18). The median half-life of VZV-IgG in neonates was 25.5 days (range: 14.6-76.0 days). In the first weeks of life, major fluctuations of the VZV-IgG titer occurred in >50% of the neonates. The predictive value of Centers for Disease Control and Prevention guidelines for identification of neonates who should receive VZIG in case of exposure to VZV was poor: positive and negative predictive values were 0.80 and 0.43, respectively. CONCLUSIONS: The neonatal VZV-IgG titer is predominantly predicted by the maternal VZV-IgG titer, whereas birth weight and gestational age are much less predictive than previously reported.