Malaria early in the first pregnancy: Potential impact of iron status.

BACKGROUND & AIMS: Low 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.

METHODS

Cross-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/log 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.

RESULTS

Iron 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/log 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).

CONCLUSION

In 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 REGISTRATION

clinicaltrials.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.