Cited by 90Pregnancy and preeclampsia studiesMalaria Research and ControlGrowth Hormone and Insulin-like Growth Factors

Placental Malaria-Associated Inflammation Disturbs the Insulin-like Growth Factor Axis of Fetal Growth Regulation

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Umbers, Alexandra J., Boeuf, Philippe, Clapham, Caroline, Stanisic, Danielle I., Baiwog, Francesca, Mueller, Ivo, Siba, Peter, King, Christopher L. +3 more·2011·The Journal of Infectious Diseases

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.

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  • Placental endocrine changes related to falciparum infection have been suggested as another possible mechanism leading to IUGR.

    “Placental endocrine changes related to falciparum infection have been suggested as another possible mechanism leading to IUGR.87”

    From Malaria in pregnancy. (2013) · cites this paper as [87]

  • In P. falciparum, adherence of infected erythrocytes to chondroitin sulfate A (CSA) on the trophoblast surface is crucial in the pathophysiology of the disease, since parasite sequestration results in inflammatory responses that can be harmful to both the mother and the foetus.

    “In the case of P. falciparum, adherence of infected erythrocytes to chondroitin sulfate A (CSA), present on the trophoblast surface, is crucial in the pathophysiology of the disease [4], since parasite sequestration results in inflammatory responses that can be harmful to both the mother and the foetus [5].”

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  1. Murphy VE. The effect of maternal asthma during pregnancy on pla- cental function and fetal development [doctoral thesis]. Newcastle, New South Wales, Australia: School of Medical Practice and Pop- ulation Health, University of Newcastle, 2004.

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Authors
Umbers, A. J., Boeuf, P., Clapham, C., Stanisic, D. I., Baiwog, F., Mueller, I., Siba, P., King, C. L., Beeson, J. G., Glazier, J., & Rogerson, S. J.
Affiliations
  • The Royal Melbourne Hospital (AU)
  • The University of Melbourne (AU)
  • The Alfred Hospital (AU)
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • Papua New Guinea Institute of Medical Research (PG)
  • Case Western Reserve University (US)
  • University of Manchester (GB)
Corresponding author
Umbers, Alexandra J.
Venue
The Journal of Infectious Diseases
Published
2011-01-07
Volume
203
Issue
4
Pages
561-569
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
OpenAlex
W2125071456
Cited by
90
References
53
Citations by year
2026: 3 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 4 · 2015: 13 · 2014: 4 · 2013: 13 · 2012: 8
FWCI
11.53
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • Griffith Research Online (submittedVersion)
Funders
  • Medical Research Council
  • Australian Research Council
  • National Health and Medical Research Council (575534)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
placental malaria, Plasmodium falciparum, fetal growth restriction, insulin-like growth factor axis, insulin-like growth factor I, insulin-like growth factor II, IGF binding proteins, placental inflammation, IGF receptors, umbilical cord blood, maternal-fetal infection
MeSH terms
Adult, Female, Fetal Growth Retardation, Humans, Inflammation, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Papua New Guinea, Placenta, Plasma, Plasmodium falciparum, Pregnancy, Pregnancy Complications, Infectious, RNA, Messenger, Malaria, Falciparum, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Gene Expression Profiling

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