Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT01308112.
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands2School of Public Health and Community Development, Maseno University, Maseno, Kenya.
Martin N
MN
Mwangi
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands3KIT Biomedical Research, Royal Tropical Institute, Amsterdam, the Netherlands.
Johanna M
JM
Roth
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands.
Menno R
MR
Smit
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands.
Laura
L
Trijsburg
Applied Nutrition Programme, University of Nairobi, Nairobi, Kenya.
Alice M
AM
Mwangi
Laboratory for Clinical Chemistry, Meander Medical Centre, Amersfoort, the Netherlands.
Ayşe Y
AY
Demir
Laboratory for Clinical Chemistry, Meander Medical Centre, Amersfoort, the Netherlands.
Jos P M
JP
Wielders
KIT Biomedical Research, Royal Tropical Institute, Amsterdam, the Netherlands.
Petra F
PF
Mens
Laboratory for Medical Microbiology and Immunology, St Elisabeth Hospital, Tilburg, the Netherlands.
Jaco J
JJ
Verweij
MRC International Nutrition Programme, London School of Hygiene and Tropical Medicine, England8MRC International Nutrition Programme, Medical Research Council, Keneba, the Gambia.
Sharon E
SE
Cox
MRC International Nutrition Programme, London School of Hygiene and Tropical Medicine, England8MRC International Nutrition Programme, Medical Research Council, Keneba, the Gambia.
Andrew M
AM
Prentice
Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.
Inge D
ID
Brouwer
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands.
Huub F J
HF
Savelkoul
School of Public Health and Community Development, Maseno University, Maseno, Kenya.
Pauline E A
PE
Andang'o
Cell Biology and Immunology Group, Wageningen University, Wageningen, the Netherlands7MRC International Nutrition Programme, London School of Hygiene and Tropical Medicine, England8MRC International Nutrition Programme, Medical Research Council, Keneba, t.
Hans
H
Verhoef
D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D019587:Dietary Supplements / Q000009:adverse effects*; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage*; D005865:Gestational Age; D006441:Hemoglobin A / Q000032:analysis; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects*; D007630:Kenya; D016778:Malaria, Falciparum / Q000209:etiology* / Q000517:prevention & control; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000209:etiology* / Q000517:prevention & control; D011295:Prenatal Care; D012424:Rural Population
D005296:Ferrous Compounds; D006441:Hemoglobin A; D007501:Iron; C031621:ferrous fumarate