JAMA
September 8, 2015, Vol 314, No. 10
http://jama.jamanetwork.com/issue.aspx

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Editorial | September 8, 2015
Antenatal Iron Use in Malaria Endemic Settings: Evidence of Safety?
Parul Christian, DrPH, MSc1; Robert E. Black, MD, MPH2
Author Affiliations
JAMA. 2015;314(10):1003-1005. doi:10.1001/jama.2015.10032.
Extract
Anemia related to iron deficiency during pregnancy occurs in 19% of women worldwide and in 20% of women in sub-Saharan Africa.1 Findings from observational studies reveal a linear, inverse relationship between maternal anemia and risk of maternal mortality across the entire distribution of hemoglobin concentrations, although confounding may be an issue.2,3 Severe anemia in pregnancy may result in maternal death due to cardiac failure. The current World Health Organization (WHO) guideline is to provide 30 to 60 mg of elemental iron and 400 µg of folic acid daily throughout pregnancy. This recommendation is mainly based on the proven effects of supplementation in reducing maternal anemia, iron deficiency, and low birth weight.4 In addition, approximately 35 million pregnant women, nearly all of whom live in sub-Saharan Africa, are at risk of Plasmodium falciparum infection annually.5 Across Africa, the prevalence of infection among children aged 2 to 10 years has declined from 26% in 2000 to 14% in 2013.5 Still, in 2013, an estimated 437 000 malaria deaths occurred in children younger than 5 years, representing 83% of all deaths due to malaria in Africa.5

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Original Investigation | September 8, 2015
Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial
Martin N. Mwangi, PhD1,2; Johanna M. Roth, MSc1,3; Menno R. Smit, MD1; Laura Trijsburg, MSc1; Alice M. Mwangi, PhD4; Ayşe Y. Demir, MD, PhD5; Jos P. M. Wielders, PhD5; Petra F. Mens, PhD3; Jaco J. Verweij, PhD6; Sharon E. Cox, PhD7,8; Andrew M. Prentice, PhD, FMedSci7,8; Inge D. Brouwer, PhD9; Huub F. J. Savelkoul, PhD1; Pauline E. A. Andang’o, PhD2; Hans Verhoef, PhD1,7,8
Author Affiliations
JAMA. 2015;314(10):1009-1020. doi:10.1001/jama.2015.9496.
Abstract
Importance
Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden.
Objective
To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes.
Design, Setting, and Participants
Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given.
Interventions Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum.
Main Outcomes and Measures
Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth.
Results
Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, −1.2%, 95% CI, −11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, −0.11 to 0.52; P  = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 µg/L vs 14.4 µg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 µg/L vs 138.7 µg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use.
Conclusions and Relevance
Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight.
Trial Registration clinicaltrials.gov Identifier: NCT01308112