title: Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Royal Parade, Parkville Victoria 3050, Australia. a.umbers2@pgrad.unimelb.edu.au
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Umbers
authors.forename: Philippe
authors.initials: P
authors.lastname: Boeuf
authors.forename: Caroline
authors.initials: C
authors.lastname: Clapham
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Stanisic
authors.forename: Francesca
authors.initials: F
authors.lastname: Baiwog
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Glazier
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
mesh_terms: D000328:Adult; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D016778:Malaria, Falciparum / Q000473:pathology; D010219:Papua New Guinea; D010920:Placenta / Q000473:pathology*; D010949:Plasma / Q000737:chemistry; D010963:Plasmodium falciparum / Q000472:pathogenicity; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification
chemical_list: C035170:IGF2 protein, human; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II