Alistair R.D. McLeanDanielle StanisicRose McGreadyKesinee ChotivanichCaroline ClaphamFrancesca BaiwogMupawjay PimanpanarakPeter SibaIvo MuellerChristopher L. KingFrançois NostenJames G. BeesonStephen RogersonJulie A. SimpsonFreya J.I. FowkesBurnet InstituteUniversity of MelbourneMyanmar Oxford Clinical Research UnitGriffith UniversityMahidol UniversityNuffield Department of Clinical MedicinePapua New Guinea Institute of Medical ResearchWalter and Eliza Hall Institute of Medical ResearchInstitut Pasteur, ParisCase Western Reserve UniversityMonash University2018-12-212019-03-142018-12-212019-03-142017-10-01PLoS ONE. Vol.12, No.10 (2017)193262032-s2.0-85031302857https://repository.li.mahidol.ac.th/handle/20.500.14594/41351© 2017 McLean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: During pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but mechanisms remain unclear. Methods: Mother-cord paired serum samples collected at delivery from Papua New Guinea (PNG) and the Thailand-Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum antigens and measles antigen, as well as total serum IgG. Multivariable linear regression was conducted to assess the association of peripheral P. falciparum infection during pregnancy or placental P. falciparum infection assessed at delivery with maternofetal antibody transfer efficiency. Path analysis assessed the extent to which associations between P. falciparum infection and antibody transfer were mediated by gestational age at delivery or levels of maternal total serum IgG. Results: Maternofetal antibody transfer efficiency of IgG1 and IgG3 was lower in PNG compared to TMBA (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.88 to 0.09, median of -0.20 log2 units). Placental P. falciparum infections were associated with substantially lower maternofetal antibody transfer efficiency in PNG primigravid women (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.62 to -0.10, median of -0.36 log2 units), but not multigravid women. The lower antibody transfer efficiency amongst primigravid women with placental infection was only partially mediated by gestational age at delivery (proportion indirect effect ranged from 0% to 18%), whereas no mediation effects of maternal total serum IgG were observed. Discussion: Primigravid women may be at risk of impaired maternofetal antibody transport with placental P. falciparum infection. Direct effects of P. falciparum on the placenta, rather than earlier gestational age and elevated serum IgG, are likely responsible for the majority of the reduction in maternofetal antibody transfer efficiency with placental infection.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1371/journal.pone.0186577