Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation

Alexandra J. Umbers, Philippe Boeuf, Caroline Clapham, Danielle I. Stanisic, Francesca Baiwog, Ivo Mueller, Peter Siba, Christopher L. King, James G. Beeson, Jocelyn Glazier, Stephen J. Rogerson

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background. The pathogenetic mechanisms of fetal growth restriction associated with placental malaria are largely unknown. We sought to determine whether placental malaria and related inflammation were associated with disturbances in the insulin-like growth factor (IGF) axis, a major regulator of fetal growth. Method. We measured IGF-1 and IGF-2 concentrations in plasma from 88 mother-neonate pairs at delivery and IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3, respectively) in cord plasma from a cohort of Papua New Guinean women with and without placental malaria. Messenger RNA levels of IGF-1, IGF-2, and the IGF receptors were measured in matched placental biopsy specimens. Results. Compared with those for uninfected pregnancies, IGF-1 levels were reduced by 28% in plasma samples from women with placental Plasmodium falciparum infection and associated inflammation (P = .007) and by 25% in their neonates (P = .002). Levels of fetal IGFBP-1 were elevated in placental malaria with and without inflammation (P = .08 and P = .006, respectively) compared with uninfected controls. IGF-2 and IGFBP-3 plasma concentrations and placental IGF ligand and receptor messenger RNA transcript levels were similar across groups. Conclusion. Placental malaria-associated inflammation disturbs maternal and fetal levels of IGFs, which regulate fetal growth. This may be one mechanism by which placental malaria leads to fetal growth restriction. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
    Original languageEnglish
    Pages (from-to)561-569
    Number of pages8
    JournalJournal of Infectious Diseases
    Volume203
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2011

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