Placental Malaria-Associated Inflammation Disturbs the Insulin-like Growth Factor Axis of Fetal Growth Regulation
Open accessAbstract
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 claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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].”
From Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia (2014) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., & Speleman, F. (2002) · Genome Biology · doi:10.1186/gb-2002-3-7-research0034 · Cited by 20,038 · see citing works
Epidemiology and burden of malaria in pregnancy
Desai, M., ter Kuile, F. O., Nosten, F., McGready, R., Asamoa, K., Brabin, B., & Newman, R. D. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70021-x · Cited by 1,432 · see citing works
Impact of malaria during pregnancy on low birth weight in sub-Saharan Africa
Guyatt, H. L., & Snow, R. W. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.4.760-769.2004 · Cited by 458 · see citing works
LASSARRE, C., Hardouin, S., Daffos, F., Forestier, F., Frankenne, F., & Binoux, M. (1991) · Pediatric Research · doi:10.1203/00006450-199103000-00001 · Cited by 409 · see citing works
Efstratiadis, A. (1998) · The International Journal of Developmental Biology · doi:10.1387/ijdb.9853827 · Cited by 349 · see citing works
Fried, M., Muga, R., Misore, A. O., & Duffy, P. E. (1998) · PubMed · Cited by 321 · see citing works
ROGERSON, S. J., POLLINA, E., GETACHEW, A., TADESSE, E., LEMA, V. M., & MOLYNEUX, M. E. (2003) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2003.68.1.0680115 · Cited by 275 · see citing works
Self-citationMassive chronic intervillositis of the placenta associated with malaria infection
Ordi, J., Ismail, M. R., Ventura, P. J., Kahigwa, E., Hirt, R., Cardesa, A., Alonso, P. L., & Menendez, C. (1998) · The American Journal of Surgical Pathology · doi:10.1097/00000478-199808000-00011 · Cited by 265 · see citing works
Fried, M., Muga, R. O., Misore, A. O., & Duffy, P. E. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.5.2523 · Cited by 262 · see citing works
The role of the insulin-like growth factor system in prenatal growth
Randhawa, R. S., & Cohen, P. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2005.07.028 · Cited by 229 · see citing works
Ong, K. K., Kratzsch, J., Kieß, W., Costello, M., Scott, C. D., & Dunger, D. B. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6998 · Cited by 228 · see citing works
Forbes, K. A., Westwood, M., Baker, P. N., & Aplin, J. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00035.2008 · Cited by 187 · see citing works
Han, V. K. M., & Carter, A. M. (2000) · Placenta · doi:10.1053/plac.1999.0498 · Cited by 176 · see citing works
McIntyre, D. H., Serek, R., Crane, D. I., Veveris-Lowe, T. L., Parry, A., Johnson, S. L., Leung, K. C., Ho, K. K. Y., Bougoussa, M., Hennen, G. P., et al. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.3.6480 · Cited by 175 · see citing works
The IGF Axis and Placental Function
Forbes, K. A., & Westwood, M. (2008) · Hormone Research in Paediatrics · doi:10.1159/000112585 · Cited by 164 · see citing works
Rogerson, S. J., Brown, H. C., Pollina, E., Abrams, E. T., Tadesse, E., Lema, V. M., & Molyneux, M. E. (2003) · Infection and Immunity · doi:10.1128/iai.71.1.267-270.2003 · Cited by 163 · see citing works
Self-citationDa, K., Pj, S., Pd, Z., Mb, L., & Sg, G. (1994) · PubMed · Cited by 160 · see citing works
Sexual Dimorphism in the Growth Hormone and Insulin-Like Growth Factor Axis at Birth
Geary, M. P., Pringle, P. J., Rodeck, C. H., Kingdom, J. C., & Hindmarsh, P. C. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-022006 · Cited by 130 · see citing works
Brameld, J. M., Mostyn, A., Dandrea, J., Stephenson, T. J., Dawson, J. M., BUTTERY, P. J., & Symonds, M. E. (2000) · Journal of Endocrinology · doi:10.1677/joe.0.1670429 · Cited by 121 · see citing works
Street, M. E., Seghini, P., Fieni, S., Ziveri, M. A., Volta, C., Martorana, D., Viani, I., Gramellini, D., & Bernasconi, S. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02251 · Cited by 115 · see citing works
MIELL, J. P., Taylor, A. M., Jones, J. L., et al. (1993) · Journal of Endocrinology · doi:10.1677/joe.0.1360525 · Cited by 106 · see citing works
Fiévet, N., Moussa, M., Tami, G., Maubert, B., Cot, M., Deloron, P., & Chaouat, G. (2001) · The Journal of Infectious Diseases · doi:10.1086/320201 · Cited by 102 · see citing works
Holmes, R. P., Montemagno, R., Jones, J. L., Preece, M. A., Rodeck, C. H., & SOOTHILL, P. W. (1997) · Early Human Development · doi:10.1016/s0378-3782(97)01867-7 · Cited by 98 · see citing works
Lo, H., Tsao, L., Hsu, W., Chen, H.-N., Yu, W.-K., & Chi, C. (2002) · Nutrition · doi:10.1016/s0899-9007(01)00811-5 · Cited by 87 · see citing works
McLellan, K. C., Hooper, S. B., Bocking, A. D., et al. (1992) · Endocrinology · doi:10.1210/endo.131.4.1382958 · Cited by 83 · see citing works
Klauwer, D., Blum, W., Hanitsch, S., Rascher, W., Lee, P., & Kiess, W. (1997) · Acta Paediatrica · doi:10.1111/j.1651-2227.1997.tb08605.x · Cited by 82 · see citing works
Insulin-like growth factor binding proteins as glucoregulators
Baxter, R. C. (1995) · Metabolism · doi:10.1016/0026-0495(95)90215-5 · Cited by 79 · see citing works
Arkins, S., Rebeiz, N., Brunke-Reese, D., Biragyn, A., & Kelley, K. W. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.3.7776981 · Cited by 77 · see citing works
Osorio, M., Torres, J., Moya, F. R., Pezzullo, J. C., Salafia, C. M., Baxter, R. C., Schwander, J., & Fant, M. E. (1996) · Early Human Development · doi:10.1016/0378-3782(96)01737-9 · Cited by 75 · see citing works
Eremia, S. C., de Boo, H. A., Bloomfield, F. H., Oliver, M. H., & Harding, J. E. (2007) · Endocrinology · doi:10.1210/en.2006-1701 · Cited by 66 · see citing works
Sheikh, S. (2001) · Molecular Human Reproduction · doi:10.1093/molehr/7.3.287 · Cited by 63 · see citing works
Li, C., Schlabritz‐Loutsevitch, N., Hubbard, G. B., et al. (2009) · Endocrinology · doi:10.1210/en.2008-1648 · Cited by 58 · see citing works
Spatial Polarization of Insulin-Like Growth Factor Receptors on the Human Syncytiotrophoblast
Fang, J., Furesz, T. C., Laurent, R. S., Smith, C. H., & Fant, M. E. (1997) · Pediatric Research · doi:10.1203/00006450-199702000-00017 · Cited by 55 · see citing works
Gratton, R. J., Asano, H., & Han, V. K. M. (2002) · Placenta · doi:10.1053/plac.2001.0780 · Cited by 54 · see citing works
Lee, M. H., Jeon, Y. J., Lee, S. M., et al. (2010) · Early Human Development · doi:10.1016/j.earlhumdev.2010.01.001 · Cited by 54 · see citing works
Kajantie, E., Hytinantti, T. K., Koistinen, R. A., Risteli, J., Rutanen, E., Seppälä, M. T., & Andersson, S. (2001) · Pediatric Research · doi:10.1203/00006450-200104000-00008 · Cited by 53 · see citing works
Gallaher, B. W., Breier, B. H., Oliver, M. H., et al. (1992) · European Journal of Endocrinology · doi:10.1530/acta.0.1260049 · Cited by 51 · see citing works
Cortisol and loss of malaria immunity in human pregnancy
VLEUGELS, M. P. H., Eling, W. M. C., Rolland, R., & de Graaf, R. (1987) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1987.tb03722.x · Cited by 50 · see citing works
Placental Hypoxia during Placental Malaria
Boeuf, P., Tan, A., Romagosa, C., Radford, J., Mwapasa, V., Molyneux, M. E., Meshnick, S. R., Hunt, N. H., & Rogerson, S. J. (2008) · The Journal of Infectious Diseases · doi:10.1086/526521 · Cited by 50 · see citing works
Self-citationStreet, M. E., Grossi, E., Volta, C., Faleschini, E., & Bernasconi, S. (2008) · BMC Pediatrics · doi:10.1186/1471-2431-8-24 · Cited by 49 · see citing works
Clifton, V. L., Hodyl, N. A., Murphy, V. E., Giles, W. B., Baxter, R. C., & Smith, R. (2009) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2009.07.004 · Cited by 49 · see citing works
Diouf, I., Fiévet, N., Doucouré, S., Ngom, M., Andrieu, M., Mathieu, J.-F., Gaye, A., Thiaw, O. T., & Deloron, P. (2006) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2006.10.001 · Cited by 49 · see citing works
Cortisol and Plasmodium falciparum infection in pregnant women in Kenya
VLEUGELS, M. P. H., Brabin, B. J., Eling, W. M. C., & de Graaf, R. (1989) · Transactions of the Royal Society of Tropical Medicine and Hygiene · doi:10.1016/0035-9203(89)90632-9 · Cited by 47 · see citing works
Holmes, R. P., Porter, H. J., Newcomb, P. V., et al. (1999) · Placenta · doi:10.1053/plac.1998.0387 · Cited by 42 · see citing works
Hu, Y., Tan, R., MacCalman, C. D., et al. (2008) · Molecular Human Reproduction · doi:10.1093/molehr/gan018 · Cited by 33 · see citing works
Fang, J., Mao, D., Smith, C. H., & Fant, M. E. (2006) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2006.08.002 · Cited by 28 · see citing works
Bayoumi, N. K., Elhassan, E. M., Elbashir, M. I., & Adam, I. (2009) · Annals of Tropical Medicine and Parasitology · doi:10.1179/136485909x385045 · Cited by 28 · see citing works
Price, W. A., Moats‐Staats, B. M., & Stiles, A. D. (2002) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.26.3.4601 · Cited by 28 · see citing works
Hashimoto, R., Sakai, K., Matsumoto, H., & Iwashita, M. (2010) · Endocrine Journal · doi:10.1507/endocrj.k09e-189 · Cited by 26 · see citing works
Kajantie, E. (2003) · Hormone Research in Paediatrics · doi:10.1159/000074513 · Cited by 26 · see citing works
Harris, T. G., Strickler, H. D., Yu, H., et al. (2006) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2006.01.002 · Cited by 24 · see citing works
The Role of IGF-1 and Ghrelin in the Compensation of Intrauterine Growth Restriction
Kyriakakou, M., Malamitsi‐Puchner, A., Mastorakos, G. P., Boutsikou, Τ., Hassiakos, D., Papassotiriou, I., & Kanaka‐Gantenbein, C. (2009) · Reproductive Sciences · doi:10.1177/1933719109344629 · Cited by 22 · see citing works
Bennet, L., Oliver, M. H., Gunn, A. J., et al. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0835h.x · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 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.
Cited by
Sorted by citations
Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem
Rogerson, S. J., Desai, M., Mayor, A., Sicuri, E., Taylor, S. M., & van Eijk, A. M. (2018) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(18)30066-5 · Cited by 306 · see citing works
Self-citationPlacental Responses to Changes in the Maternal Environment Determine Fetal Growth
Dimasuay, K. G., Boeuf, P., Powell, T. L., & Jansson, T. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00012 · Cited by 258 · see citing works
Self-citationMalaria in pregnancy: small babies, big problem
Umbers, A. J., Aitken, E. H., & Rogerson, S. J. (2011) · Trends in Parasitology · doi:10.1016/j.pt.2011.01.007 · Cited by 200 · see citing works
Self-citationTakem, E. N., & D'Alessandro, U. (2013) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2013.010 · Cited by 185 · see citing works
An overview of malaria in pregnancy
Bauserman, M., Conroy, A. L., North, K., Patterson, J., Bose, C., & Meshnick, S. (2019) · Seminars in Perinatology · doi:10.1053/j.semperi.2019.03.018 · Cited by 167 · see citing works
Effects of maternal obstructive sleep apnoea on fetal growth: a prospective cohort study
Fung, A. M., Wilson, D. L., Lappas, M., Howard, M., Barnes, M., O'Donoghue, F., Tong, S., Esdale, H., Fleming, G., & Walker, S. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068057 · Cited by 119 · see citing works
Moore, K. A., Simpson, J. A., Wiladphaingern, J., Min, A. M., Pimanpanarak, M., Paw, M. K., Raksuansak, J., Pukrittayakamee, S., Fowkes, F. J. I., White, N. J., et al. (2017) · BMC Medicine · doi:10.1186/s12916-017-0877-6 · Cited by 111 · see citing works
Atwell, J. E., Thumar, B., Robinson, L. J., Tobby, R., Yambo, P., Ome-Kaius, M., Siba, P. M., Unger, H. W., Rogerson, S. J., King, C. L., et al. (2016) · Journal of Infectious Diseases · doi:10.1093/infdis/jiv401 · Cited by 48 · see citing works
Self-citationDoes Malaria Affect Placental Development? Evidence from In Vitro Models
Umbers, A. J., Stanisic, D. I., Ome, M., Wangnapi, R., Hanieh, S., Unger, H. W., Robinson, L. J., Lufele, E., Baiwog, F., Siba, P. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055269 · Cited by 43 · see citing works
Self-citationUmbers, A. J., Unger, H. W., Rosanas-Urgell, A., Wangnapi, R. A., Kattenberg, J. H., Jally, S., Silim, S., Lufele, E., Karl, S., Ome-Kaius, M., et al. (2015) · Malaria Journal · doi:10.1186/s12936-015-0927-5 · Cited by 37 · see citing works
Self-citationAgudelo, O. M., Aristizabal, B. H., Yanow, S. K., Arango, E., Carmona-Fonseca, J., & Maestre, A. (2014) · Malaria Journal · doi:10.1186/1475-2875-13-122 · Cited by 37 · see citing works
Minja, D. T., Schmiegelow, C., Oesterholt, M., Magistrado, P. A., Boström, S., John, D., Pehrson, C., Andersen, D., Deloron, P., Salanti, A., et al. (2012) · Malaria Journal · doi:10.1186/1475-2875-11-211 · Cited by 37 · see citing works
Ayoola, O. O., Whatmore, A., Balogun, W. O., Jarrett, O. O., Cruickshank, J. K., & Clayton, P. E. (2012) · Malaria Journal · doi:10.1186/1475-2875-11-75 · Cited by 37 · see citing works
Effects of Vivax Malaria Acquired Before 20 Weeks of Pregnancy on Subsequent Changes in Fetal Growth
Machado Filho, A. C., da Costa, E. P., da Costa, E. P., Reis, I. S., Fernandes, E. A. C., Paim, B. V., & Martinez-Espinosa, F. E. (2014) · The American Society of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.13-0285 · Cited by 26 · see citing works
Submicroscopic placental infection by non-falciparum Plasmodium spp.
Doritchamou, J. Y. A., Akuffo, R. A., Moussiliou, A., Luty, A. J. F., Massougbodji, A., Deloron, P., & Tuikue Ndam, N. G. (2018) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0006279 · Cited by 25 · see citing works
Doritchamou, J., Sabbagh, A., Jespersen, J. S., Renard, E., Salanti, A., Nielsen, M. A., Deloron, P., & Tuikue Ndam, N. (2015) · PLOS ONE · doi:10.1371/journal.pone.0137695 · Cited by 22 · see citing works
Singh, K. P., Shakeel, S., Naskar, N., Bharti, A., Kaul, A., Anwar, S., Kumari, S., Kumar, A., Singh, J. K., Kumari, N., et al. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.03.019 · Cited by 19 · see citing works
- 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
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-01-07
- Volume
- 203
- Issue
- 4
- Pages
- 561-569
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC3071224
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review