Viral pathogens such as cytomegalovirus (CMV) and varicella-zoster virus (VZV), pose severe threats to neonates, in particular to preterm infants. CMV is the leading cause of congenital viral infection and can result in long-term neurodevelopmental sequelae, while VZV infection in neonates can lead to disseminated disease with high mortality rates. The transplacental transfer of maternal antibodies to the foetus is a crucial mechanism that provides passive immunity to newborns against these deleterious viral infections during their first months of life [1].
However, the efficiency of this antibody transfer is not uniform and can be influenced by various factors, including, but not limited to, maternal antibody concentrations, maternal age, health conditions, placental function, and, most notably, gestational age [2], [3].
Maternal IgG antibodies are actively transported across the placenta as early as the first trimester [4]. This process is mediated by the neonatal Fc receptor (FcRn) expressed on syncytiotrophoblasts, which facilitates the specific transcytosis of IgG from the maternal to the foetal circulation [5].
While the transfer of anti-CMV and anti-VZV IgG has been studied in term and near term infants, there is a notable lack of comprehensive data across a wide spectrum of gestational ages, particularly in extremely preterm infants born before 28 weeks of gestation [6], [7]. This gap is clinically most relevant, as these infants are especially vulnerable to severe congenital as well as peri- and postnatal infections due to their immature immune systems and potentially lower levels of received maternal antibodies. For extreme low birth weight infants (ELBWI) born to CMV-seropositive mothers, it is recommended, for example, to pasteurise the mother’s milk [8], [9], as postnatal CMV infections can result in severe diseases like bronchopulmonary dysplasia [10], Colitis [11] and, in rare cases, even death [10], [12]. From 28 weeks of gestation onwards, postnatal CMV infections are described to be less severe [13], as these infants have a better immunocompetence on the basis of, among others, higher antibody levels and elevated neutralisation capacity due to increased transplacental transfer of competent maternal antibodies during the later stages of pregnancy. Although previous studies [7] have shown that both quantitative and qualitative IgG transfer increases with gestational age, a detailed week-by-week analysis of both CMV and VZV antibodies, spanning from the edge of viability to term, remains elusive.
This study aims to address the current knowledge gap by investigating the correlation between gestational age and the efficiency of materno-foetal transplacental transfer of CMV- and VZV-specific IgG, with a particular focus on extremely preterm infants born before 28 weeks of gestation. Our analysis includes the largest known cohort in this field to date, comprising a mean of 21 CMV-seropositive and 30 VZV-seropositive mother–child pairs per gestational week. In addition, we have assessed the quality of the transferred IgG in terms of their neutralisation competence against CMV in order to get a better understanding of the pathophysiology and prevention of breast milk-mediated postnatal CMV infections in ELBWI. Furthermore, the potential influence of gender and multiple pregnancies on transplacental antibody transfer was investigated. By elucidating these relationships, we provide valuable insights helping to develop clinical management strategies for preterm infants at risk of congenital as well as postnatal CMV- and VZV infections.
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