Abstract
BackgroundThe effects of iron interventions and host iron status on infection risk have been a recurrent clinical concern, although there has been little research on this interaction in pregnant women.MethodsCross-sectional and longitudinal analyses were undertaken to determine the association of whole blood zinc erythrocyte protoporphyrin (ZPP) with malaria parasitaemia in pregnant women attending antenatal and delivery care at Montfort and Chikwawa Hospitals, Shire Valley, Malawi. Prevalence of antenatal, delivery and placental malaria was assessed in relation to maternal ZPP levels. The main outcome measures were prevalence of peripheral and placental Plasmodium falciparum parasitaemia and odds ratios of malaria risk.ResultsA total of 4,103 women were evaluated at first antenatal visit, of whom at delivery 1327 were screened for peripheral and 1285 for placental parasitaemia. Risk of malaria at delivery (peripheral or placental) was higher in primigravidae (p < 0.001), and lower (peripheral) with use of intermittent preventive anti-malarials during pregnancy (p < 0.001). HIV infection was associated with increased malaria parasitaemia (p < 0.02, peripheral or placental). Parasitaemia prevalence was lower in women with normal ZPP levels compared to those with raised concentrations at both first antenatal visit (all gravidae, p = 0.048, and at delivery (all gravidae, p < 0.001; primigravidae, p = 0.056). Between first antenatal visit and delivery women who transitioned from raised (at first antenatal visit) to normal ZPP values (at delivery) had lower peripheral parasitaemia prevalence at delivery compared to those who maintained normal ZPP values at both these visits (all gravidae: 0.70, 95%CI 0.4-1.1; primigravidae: 0.3, 0.1-0.8). In regression analysis this difference was lost with inclusion of HIV infection in the model.ConclusionsRaised ZPP concentrations in pregnancy were positively associated with P. falciparum parasitaemia and were probably secondary to malaria inflammation, rather than indicating an increased malaria risk with iron deficiency. It was not possible from ZPP measurements alone to determine whether iron deficiency or repletion alters malaria susceptibility in pregnancy.
Highlights
The effects of iron interventions and host iron status on infection risk have been a recurrent clinical concern, there has been little research on this interaction in pregnant women
This study showed that anaemic children with iron deficiency who received iron and folic acid supplementation had lower malariarelated adverse events than children receiving placebo, the analysis did not control for malaria treatments given
Cross-sectional malaria prevalence was assessed at first antenatal visit, and in longitudinal zinc erythrocyte protoporphyrin (ZPP) categories for women seen at both first antenatal visit and at delivery, allowing a possible directional influence of gestational iron status to be assessed
Summary
The effects of iron interventions and host iron status on infection risk have been a recurrent clinical concern, there has been little research on this interaction in pregnant women. The effects of iron interventions and host iron status on infection risk have been a recurrent clinical concern [1] and this interaction has been examined in several metaanalyses [2,3,4] and a Cochrane Review [5]. Iron status was assessed using either the serum transferrin receptor: log ferritin ratio [7], or serum ferritin corrected for elevated C - reactive protein [8] These studies suggested that iron biomarkers may be useful predictors of malaria risk in pregnancy. Cross-sectional malaria prevalence was assessed at first antenatal visit, and in longitudinal ZPP categories for women seen at both first antenatal visit and at delivery, allowing a possible directional influence of gestational iron status to be assessed
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