Maternal iron status and total immunoglobulin-G influence transplacental antibody transfer across eight diverse geographical settings

Transfer of antibodies across the placenta provides critical early life protection for neonates against infection. Understanding factors influencing efficient transfer is vital for enhancing neonatal immunity and improving maternal vaccination strategies. Stored maternal and cord serum samples from studies in The Gambia, Guatemala, Mali, The Netherlands, Pakistan, Thailand, UK and Vietnam were processed for measles plaque reduction neutralisation titres (PRNT), and measles, mumps and rubella immunoglobulin G (IgG) (multiplex immunoassay) at a central laboratory (N = 557 pairs). Nutritional indicators (ferritin, soluble transferrin receptor, retinol binding protein) and total IgG, were measured in subsets of maternal serum. Transplacental transfer ratios (TPTRs) were calculated and factors associated with maternal IgG, cord IgG and TPTRs explored in multivariable regression. At delivery, most mothers (range 78 % Guatemala to 100 % Pakistan, Netherlands) and infants (range 86 % Guatemala to 100 % Netherlands, UK) had PRNT above the threshold of clinical protection (0.12 IU/mL). Maternal and cord antibody concentrations across diverse geographical settings were highly correlated. TPTRs were highest in high-income countries; geometric mean range 0.7 (Pakistan) to 2.2 (Netherlands), and were correlated across antigens. However, TPTRs varied widely within low/middle-income countries. In models adjusting for country, higher maternal total IgG was consistently associated with lower TPTR. In multivariable regression, lower iron status, indicated by increasing soluble transferrin receptor concentration, was significantly associated with lower TPTR for measles neutralising antibody. There is marked geographical variation in TPTRs, and following adjustment for this, measurable factors in maternal blood can inform estimates of transplacental transfer efficiency.