The Association between Malaria and Iron Status or Supplementation in Pregnancy: A Systematic Review and Meta-Analysis

Abstract

IntroductionMalaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment.Methods and FindingsWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI) 0.66–1.20, I2 = 78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14–2.70 for 1–15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24–0.51, I2 = 59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection.ConclusionsIron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.

Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study

“…Clinicians monitored children's health statuses during sick visits and at routine visits occurring on a biweekly basis during the first 12 months of life and a monthly basis for any follow-up beyond the first year. Children's hemoglobin was measured at sick visits and during routine visits at approximately 3,6,12,18,24,30,36,42, and 48 months of age. Parasitemia by P. falciparum was determined after counting 200 leukocytes on Giemsa-stained thick blood smear of a sample collected by heel or finger prick during child visits.…”

“…12 In addition, recent experiments have also found that hepcidin-induced iron redistribution away from hepatocytes arrests the growth of intrahepatocytic parasites and thereby prevents the occurrence of malaria superinfections. 13 Epidemiological studies lend support to these findings: pregnant women and children who are iron deficient are observed to have lower risks of malarial disease, [14][15][16][17][18] and pediatric iron supplementation has been shown to heighten the risk of both clinical and severe malaria. 19,20 In addition to malaria, elevated iron has been associated with poor prognoses in cases of bacterial and viral infections 21 and may be associated with child mortality in communities with high burdens of communicable disease.…”

Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review

“…In a systematic review of 28 observational studies, iron deficiency (indicated by circulating ferritin concentration) was found to be associated with protection against Plasmodium infection in pregnancy (Sangaré et al , 2014). …”

“…In their systematic review Sangaré et al (2014) found one single study from Asia that assessed the association between iron supplementation and P. vivax infection. In this prospective cohort study, supplementation with iron and folic acid for less than 30 days was associated with an increased risk P. vixax parasitaemia.…”

“…Both were published before the publication of the CONSORT guidelines and were rated as low quality, mostly because allocation concealment was not described (Sangaré et al , 2014). No routine medical malaria prevention was used in these trials, and they were conducted before the wide‐scale introduction of insecticide‐treated nets.…”