Fetal Responses during Placental Malaria Modify the Risk of Low Birth Weight

ABSTRACT Inflammation during placental malaria (PM) is associated with low birth weight (LBW), especially during the first pregnancy, but the relative contribution of maternal or fetal factors that mediate this effect remains unclear and the role of gamma interferon (IFN-γ) has been controversial. We examined the relationship of maternal and cord plasma levels of IFN-γ, tumor necrosis factor alpha, interleukin-10, ferritin, and leptin to birth weight for Tanzanian women delivering in an area where there is a high rate of malaria transmission. The placental levels of inflammatory cytokines, including IFN-γ, increased significantly during PM in primigravid and multigravid women but not in secundigravid women. PM also increased maternal peripheral levels of all inflammatory markers except IFN-γ but had strikingly little effect on cord levels of these proteins. In a multivariate analysis, placental IFN-γ was negatively associated (P = 0.01) and cord ferritin was positively associated (P < 0.0001) with birth weight in infected (PM-positive [PM+]) first-time mothers. This relationship was not observed in other mothers, consistent with the epidemiology of PM and disease. Cord leptin had a strong positive relationship with birth weight in offspring of PM-negative women (P = 0.02 to P < 0.0001) but not in offspring of PM+ women (all differences were not significant) in the three gravidity groups. The results confirmed that placental IFN-γ is related to LBW due to PM during first pregnancies and suggest that fetal ferritin plays a protective role. Because fetal cells are a source of placental IFN-γ and cord ferritin, the fetal response to PM may modify the risk of LBW.

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CXC Ligand 9 Response to Malaria during Pregnancy Is Associated with Low-Birth-Weight Deliveries

Infection and Immunity ◽

10.1128/iai.00220-12 ◽

2012 ◽

Vol 80 (9) ◽

pp. 3034-3038 ◽

Cited By ~ 17

Author(s):

Shu Dong ◽

Jonathan D. Kurtis ◽

Sunthorn Pond-Tor ◽

Edward Kabyemela ◽

Patrick E. Duffy ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Strong Association ◽

Placental Malaria ◽

Necrosis Factor Alpha ◽

Content Type ◽

Tnf Α ◽

Malaria During Pregnancy ◽

Placental Blood ◽

Ifn Γ

ABSTRACTPlacental infection withPlasmodium falciparumis associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area ofP. falciparumholoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.

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Placental Cytokine and Chemokine Profiles Reflect Pregnancy Outcomes in Women Exposed to Plasmodium falciparum Infection

Infection and Immunity ◽

10.1128/iai.01922-14 ◽

2014 ◽

Vol 82 (9) ◽

pp. 3783-3789 ◽

Cited By ~ 18

Author(s):

Arnaud Chêne ◽

Valérie Briand ◽

Samad Ibitokou ◽

Sébastien Dechavanne ◽

Achille Massougbodji ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Birth Weight ◽

Low Birth Weight ◽

Gestational Age ◽

Pregnancy Outcomes ◽

Preterm Births ◽

Interleukin 10 ◽

Maternal Anemia ◽

Content Type ◽

Ifn Γ

ABSTRACTPregnancy-associated malaria (PAM) can lead to severe complications for both mother and baby. Certain placental cytokine/chemokine profiles have been shown to reflect poor pregnancy outcomes, including maternal anemia and low birth weight. In intervillous plasma samples from 400 Beninese women living in an area wherePlasmodium falciparumis endemic, we quantified 16 cytokines/chemokines. We assessed their profiles in groups with PAM, with maternal anemia, with preterm births, or with a low birth weight for gestational age. Repeated ultrasound measurements ensured that prematurity and low birth weight were highly accurate. Preliminary analyses revealed trends for lower cytokine/chemokine concentrations in placental plasma associated both with babies with low birth weight for gestational age and withP. falciparuminfection during pregnancy, while, as a function of the latter, the concentration of gamma interferon (IFN-γ)-inducible protein 10 (IP-10) was higher. Multivariate analyses showed that (i) higher placental plasma interleukin-10 (IL-10) levels were associated withP. falciparuminfections and (ii) independently ofP. falciparuminfections, lower concentrations of both IFN-γ and IL-5 were associated with low birth weight for gestational age. Our data further strengthen the idea that IL-10 and IP-10 could be useful diagnostic markers ofP. falciparuminfection during pregnancy. The concentrations of cytokines/chemokines in placental plasma may represent previously unrecognized markers of poor fetal growth.

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The relative contribution of prematurity and fetal growth retardation to low birth weight in developing and developed societies

American Journal of Obstetrics and Gynecology ◽

10.1016/0002-9378(82)90012-6 ◽

1982 ◽

Vol 143 (7) ◽

pp. 793-798 ◽

Cited By ~ 191

Author(s):

José Villar ◽

JoséM. Belizán

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Fetal Growth ◽

Growth Retardation ◽

Fetal Growth Retardation ◽

Relative Contribution

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A Defect in Interleukin-10 Leads to Enhanced Malarial Disease in Plasmodium chabaudi chabaudi Infection in Mice

Infection and Immunity ◽

10.1128/iai.67.9.4435-4442.1999 ◽

1999 ◽

Vol 67 (9) ◽

pp. 4435-4442 ◽

Cited By ~ 166

Author(s):

Ching Li ◽

Inés Corraliza ◽

Jean Langhorne

Keyword(s):

Body Weight ◽

Knockout Mice ◽

Interleukin 10 ◽

Plasmodium Chabaudi ◽

Double Knockout ◽

Direct Stimulation ◽

Necrosis Factor Alpha ◽

Glucose Levels ◽

Tnf Α ◽

Ifn Γ

ABSTRACT Infection of interleukin-10 (IL-10)-nonexpressing (IL-10−/−) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10−/−mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10−/− mice produced more gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-γ in IL-10−/− mice by the injection of anti-IFN-γ antibodies or by the generation of IL-10−/− IFN-γ receptor−/− double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-γ-independent pathways may be responsible for these pathological features of P. chabaudimalaria and may be due to direct stimulation of TNF-α by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-γ or TNF-α produced.

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Differential Activation of Fetal Hofbauer Cells in Primigravidas Is Associated with Decreased Birth Weight in Symptomatic Placental Malaria

Malaria Research and Treatment ◽

10.1155/2019/1378174 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Stephanie L. Gaw ◽

Bethann S. Hromatka ◽

Sadiki Ngeleza ◽

Sirirak Buarpung ◽

Nida Ozarslan ◽

...

Keyword(s):

Birth Weight ◽

Placental Malaria ◽

Perinatal Outcomes ◽

Protective Role ◽

Cross Sectional ◽

Macrophage Response ◽

Hofbauer Cells ◽

Infant Birth ◽

First Time

Background. Placental malaria is a leading global cause of low birth weight neonates, especially in first-time mothers. To better understand the role of innate immunity in placental malaria, we investigated the relationships between histopathological markers of placental malaria, fetal and maternal macrophage responses, and perinatal outcomes in a cross-sectional case control study of pregnant women presenting with symptomatic malaria at the time of delivery. Results. Primigravidas showed increased hemozoin deposition in placental villi (p=0.02), syncytiotrophoblasts (p=0.01), and fetal Hofbauer cells (p=0.01). The percentage of hemozoin-positive villi negatively correlated with infant birth weight (regression coefficient [b] = -0.03 kg decrease in birth weight per % increase in hemozoin-positive villi, p=0.035). Malaria-infected placentas showed a twofold increase in Hofbauer cells (p<0.001) and maternal macrophages (p<0.001). Placental malaria was associated with a threefold increase in the percentage of M2 maternal macrophages (19.2% vs 6.4%, p=0.01). Primigravidas showed a significant decrease in the Hofbauer cell M2-percentage in placental malaria (92.7% vs. 97.0%, p=0.04), which was predictive of infant birth weight (b=0.08 kg increase in birth weight per % increase in M2 Hofbauer cells, p=0.001). There was no association between maternal macrophage response and infant birth weights. Conclusions. Placentas with malarial infection had increased numbers of fetal Hofbauer cells in the villous stroma and maternal macrophages in the intervillous space. In primigravidas, decreased anti-inflammatory M2-type Hofbauer cells were predictive of lower birth weight. M2-type maternal macrophages were increased in placental malaria, but there was no association with gravidity or birth weight. These results suggested a protective role of M2 Hofbauer cells in fetal growth restriction.

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Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight

Scientific Reports ◽

10.1038/srep24508 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 6

Author(s):

Jared Lybbert ◽

Justin Gullingsrud ◽

Olga Chesnokov ◽

Eleanor Turyakira ◽

Mehul Dhorda ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Placental Malaria

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Associated Factors to Immunization Timeliness and Completion in Preterm and Low Birth Weight Infants at Essos Hospital Center Yaounde

10.21203/rs.3.rs-110589/v1 ◽

2020 ◽

Author(s):

Marie Kouya ◽

Annie Carole Nga Motaze ◽

Jeannette Epee Ngoué ◽

Arsene Brunelle Sandie ◽

Paul Olivier Koki Ndombo ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight ◽

High Rate ◽

Routine Immunization ◽

Low Birth Weight Infants ◽

Cross Sectional ◽

Immunization Practice ◽

The Mean ◽

Hospital Center

Abstract Introduction. Vaccination is very often delayed in premature and low birth weight infants. However, timely vaccination is even more important in the latter because of their increased susceptibility to infection.Objective. To assess immunization practice and factors associated with vaccine promptness and completeness in former preterm and low-birth-weight infants.Methods. We conducted a retrospective analytical cross-sectional study (January 2017 to February 2019). Main measurement : Promptness and completeness at each contact, Statistical analysis was performed using R software version 3.6.2, logistic regression was used to estimate the Odds Ratio (OR) and their 95% Confidence Interval (CI).Results. We recruited 310 children aged 12 to 36 months born before 37 weeks with low birth weight, 163 (52.6%) of whom were female. Two hundred and fifty-three had received the vaccines at the indicated age, with promptness rate of 81.6%, and 97.7% had completed routine immunization at 9 months. The mean age at vaccination initiation was 6 days ±11 and the mean weight at vaccination initiation was 2233g ±494. High prematurity and very low birth weight were associated with a high rate of vaccine delay: 61.5% [OR: 15.56; (CI: 3.22-118.52; p=0.002)] and 66.7% [OR: 19.19; (CI: 4.67-92.52; p<0.001)] respectively. Distance > 5 km with HEC [OR: 3.48; (CI: 1.68-7.47; p=0.001)] was associated with poor vaccination. Women in common-law unions had the lowest vaccine readiness rate (60.6%), (OR: 3.36; CI: 1.006-10.70; p=0.038). The frequency of occurrence of post immunization adverse events was 24.5%, with fever type in 94.7%.Conclusion. Nearly all premature and/or low-birth-weight children hospitalized at Essos Hospital Center had completed routine immunization at 9 months, and the majority had received the vaccines in a timely manner. Similar study is needed in rural area.

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Association between Parasite Density and Cytokines in Malaria Infected Human Placentas

Annals of Medical Laboratory Science ◽

10.51374/annalsmls.2021.1.2.0040 ◽

2021 ◽

Vol 1 (2) ◽

pp. 30-38

Author(s):

Okezie C. Okamgba

Keyword(s):

Parasite Density ◽

Human Placenta ◽

Malaria Parasite ◽

Post Partum ◽

Placental Malaria ◽

Interleukin 10 ◽

Interleukin 4 ◽

Enzyme Linked Immunosorbent Assay ◽

Necrosis Factor Alpha ◽

Immune Balance

Background: Placental malaria is a major cause of infection induced adverse conditions in pregnancy and is attributed to the sequestration of malaria parasite in the intervillous space. We investigated if any relationship exists between the parasite density and cytokines in malaria parasite infected human placentas. Methods: Sixty (60) malaria parasite infected placentas from apparently healthy immediate post-partum women and 40 malaria parasite uninfected placentas which served as control were studied. Blood from the human placenta was aseptically collected and tested for HIV and malaria parasite using standard methods. Interferon-Gamma (IFNγ), Tumor Necrosis Factor alpha (TNFα), Interleukin-4 (IL-4), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) were measured by Enzyme-Linked Immunosorbent Assay (ELISA) technique. Data were analysed using appropriate statistical tools. Results: The result revealed P. falciparum with a mean parasite density of 762.47±459.62 parasite/μl of blood. The mean±SD (11.71±6.55pg/ml) and 55.57±43.13pg/ml for IFNγ and IL-10 respectively for infected placenta was statistically higher on comparison with 5.58±2.86pg/ml and 16.60±4.88pg/ml for IFNγ and IL10 respectively for uninfected human placenta (P<0.05). Positive correlation existed between parasite density and IL-6 (r = 0.59, p = 0.001) and between parasite density and IL-10 (r =0.41, p=0.024). Conclusion: The study showed upregulated levels of IL-6 and IL-10 which indicates disruption of normal immune balance in the parasite infected placenta and the amount of IL-6 and IL-10 secreted could reflect the level of parasitaemia and could serve for diagnostic assessment of placental malaria.

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