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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 log 2  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 log 2  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.

P. falciparum infection and maternofetal antibody transfer in malaria-endemic settings of varying transmission