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Does Iron Increase the Risk of Malaria in Pregnancy?

ABSTRACT: Background. ?Pregnancy-associated malaria (PAM) remains a significant health concern in sub-Saharan Africa. Cross-sectional studies report that iron might be associated with increased malaria morbidity, raising fears that current iron supplementation policies will cause harm in the present context of increasing resistance against intermittent preventive treatment in pregnancy (IPTp). Therefore, it is necessary to assess the relation of iron levels with malaria risk during the entire pregnancy. Methods. ?To investigate the association of maternal iron levels on malaria risk in the context of an IPTp clinical trial, 1005 human immunodeficiency virus-negative, pregnant Beninese women were monitored throughout their pregnancy between January 2010 and May 2011. Multilevel models with random intercept at the individual levels and random slope for gestational age were used to analyze the factors associated with increased risk of a positive blood smear and increased Plasmodium falciparum density. Results. ?During the follow-up, 29% of the women had at least 1 episode of malaria. On average, women had 0.52 positive smears (95% confidence interval [CI], 0.44-0.60). High iron levels (measured by the log10 of ferritin corrected on inflammation) were significantly associated with increased risk of a positive blood smear (adjusted odds ratio = 1.75; 95% CI, 1.46-2.11; P < .001) and high P falciparum density (beta estimate = 0.22; 95% CI, 0.18-0.27; P < .001) during the follow-up period adjusted on pregnancy parameters, comorbidities, environmental and socioeconomic indicators, and IPTp regime. Furthermore, iron-deficient women were significantly less likely to have a positive blood smear and high P falciparum density (P < .001 in both cases). Conclusions. ?Iron levels were positively associated with increased PAM during pregnancy in the context of IPTp. Supplementary interventional studies are needed to determine the benefits and risks of differently dosed iron and folate supplements in malaria-endemic regions.

SUBMITTER: Moya-Alvarez V

PROVIDER: S-EPMC4567087 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Does Iron Increase the Risk of Malaria in Pregnancy?

Moya-Alvarez Violeta V Cottrell Gilles G Ouédraogo Smaila S Accrombessi Manfred M Massougbodgi Achille A Cot Michel M

Open forum infectious diseases 20150320 2

Background. Pregnancy-associated malaria (PAM) remains a significant health concern in sub-Saharan Africa. Cross-sectional studies report that iron might be associated with increased malaria morbidity, raising fears that current iron supplementation policies will cause harm in the present context of increasing resistance against intermittent preventive treatment in pregnancy (IPTp). Therefore, it is necessary to assess the relation of iron levels with malaria risk during the entire pregnancy. M ...[more]

PMID: 26380338

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Project description:Background & aimsLow iron stores may protect from malaria infection, therefore improving iron stores in early pregnancy in line with current recommendations could increase malaria susceptibility. To test this hypothesis we compared iron biomarkers and red cell indices in nulliparae and primigravidae who participated in a randomized controlled trial of long-term weekly iron supplementation.MethodsCross-sectional and longitudinal data analysis from a randomized controlled trial of long-term weekly iron supplementation in rural Burkina Faso. Malaria parasitaemia was monitored and biomarkers and red cell indices measured at study end-points: plasma ferritin, transferrin receptor (sTfR), zinc protoporphyrin, hepcidin, sTfR/log10 ferritin ratio, body iron, haemoglobin, red cell distribution width; mean corpuscular haemoglobin concentration/volume, and C-reactive protein. Correlation coefficients between biomarkers and red cell indices were determined. A regression correction approach based on ferritin was used to estimate iron body stores, allowing for inflammation. Body iron differences were compared between nulliparae and primigravidae, and the association determined of iron biomarkers and body iron stores with malaria.ResultsIron and haematological indices of 972 nulliparae (mean age 16.5 years) and 314 primigravidae (median gestation 18 weeks) were available. Malaria prevalence was 54.0% in primigravidae and 41.8% in nulliparae (relative risk 1.28, 95% CI 1.13-1.45, P < 0.001), anaemia prevalence 69.7% and 43.4% (P < 0.001), and iron deficient erythropoiesis (low body iron) 8.0% and 11.7% (P = 0.088) respectively. Unlike other biomarkers the sTfR/log10 ferritin ratio showed no correlation with inflammation as measured by CRP. Most biomarkers indicated reduced iron deficiency in early pregnancy, with the exception of haemoglobin. Body iron increased by 0.6-1.2 mg/kg in early gestation, did not differ by malaria status in nulliparae, but was higher in primigravidae with malaria (6.5 mg/kg versus 5.0 mg/kg; relative risk 1.53, 95% CI 0.67-2.38, P < 0.001).ConclusionIn primigravidae, early pregnancy haemoglobin was not a good indicator of requirement for iron supplementation, which could be detrimental given the association of better iron status with increased malaria infection.Trial registrationclinicaltrials.gov:NCT01210040. Until placed in a public repository, data relating to the current study can be requested from the corresponding author and will be made available following an end user data agreement and sponsor approval.

Project description:BackgroundWHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode.ObjectivesWe aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk.MethodsWe conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo-5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n = 79) or severe malarial anemia (SMA; n = 77). Asymptomatic community children (CC; n = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg-1 · d-1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo.ResultsAll children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12).ConclusionsIn children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence.This trial was registered at clinicaltrials.gov as NCT01093989.

Project description:Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired since 2000 on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP) include low maternal age, low parity, and low gestational age. The main effects of MIP include maternal anaemia, low birth weight (LBW), preterm delivery and increased infant and maternal mortality.P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA), that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non-recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery), anaemia, and high cytokines levels have been implicated.Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections in African women, respectively. Compared to microscopy, RDTs have a lower sensitivity though when the quality of microscopy is low RDTs may be more reliable. Insecticide treated nets (ITN) and intermittent preventive treatment in pregnancy (IPTp) are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28-47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria during the first trimester, quinine plus clindamycin for 7 days is the first line treatment and artesunate plus clindamycin for 7 days is indicated if this treatment fails; in the 2(nd) and 3(rd) trimester first line treatment is an artemisinin-based combination therapy (ACT) known to be effective in the region or artesunate and clindamycin for 7 days or quinine and clindamycin. For severe malaria, in the second and third trimester parenteral artesunate is preferred over quinine. In the first trimester, both artesunate and quinine (parenteral) may be considered as options. Nevertheless, treatment should not be delayed and should be started immediately with the most readily available drug.

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Does Iron Increase the Risk of Malaria in Pregnancy?

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Does Iron Increase the Risk of Malaria in Pregnancy?

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