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.
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.
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.
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.
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This work was supported by the National
Health and Medical Research Council of Australia
(project grant and training award to Freya J. I.
Fowkes; Infrastructure for Research Institutes
Support Scheme grant, Senior Research
Fellowship and Program Grant to JGB and IM,
NHMRC Independent Research Institutes
Infrastructure Support to the Burnet Institute and
WEHI), Australian Research Council (Future
Fellowship to Freya J. I. Fowkes), and Victorian
State Government Operational Infrastructure
Support grant to the Burnet Institute. Alistair R. D.
McLean is supported by an Australian
Postgraduate Award. Shoklo Malaria Research Unit
is part of the Mahidol Oxford University Tropical
Medicine Research Unit supported by the
Wellcome Trust of Great Britain. The Christophe
and Rodolphe Me´rieux Foundation supported the
study through a prize (2008) to Franc¸ois Nosten.