Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial

Gies, Sabine; Diallo, Seydou; Roberts, Stephen A; Powney, Matthew; Brabin, Loretta; Ouédraogo, Sayouba; Swinkels, Dorine W.; Geurts-Moespot, Anneke; Claeys, Yves; D’Alessandro, Umberto; Tinto, Halidou; Faragher, Brian; Brabin, Bernard J.

doi:10.1093/infdis/jiy257

Cited by 20 publications

(64 citation statements)

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“…The trial protocol and amendments were approved by ethical review boards and regulatory authorities at each collaborating centre. This birth outcome analysis was conducted within a randomized trial of the safety of weekly iron and folic acid supplementation in young women exposed to malaria [8, 9]. Specified birth outcomes were: gestational age, preterm birth (PTB), small for gestational age and low birthweight.…”

Section: Methodsmentioning

confidence: 99%

“…The regimen followed World Health Organization (WHO) guidelines, updated in 2016 [1, 2]. The primary outcome result of Plasmodium falciparum parasitaemia prevalence at ANC1, and secondary outcome results on lower genital infections have been reported [8, 9]. Weekly iron supplementation did not increase malaria risk at the first antenatal visit [8].…”

Section: Methodsmentioning

confidence: 99%

“…Gestational age was estimated by crown rump length in the first trimester and by biparietal diameter, femur length and abdominal circumference afterward. A blood sample was obtained for measurement of haemoglobin, iron biomarkers, and malaria screening as malaria end-points were the primary outcome measure for the trial [8]. A syphilis test was done (RPR VDRL Carbon, ELITechGroup).…”

Section: Methodsmentioning

confidence: 99%

“…A single measure of blood pressure was taken at ANC1 and ANC2 with explanation to the mother who rested 5 min before use of the sphygmomanometer (Riester). Weekly follow-up continued till delivery, and adherence was recorded [8]. All women received a first dose of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) at ANC1 if gestational age was > 13 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Existing systematic reviews on iron supplementation in pregnancy include few studies from malaria endemic areas, and those cited are from locations with no, or very little malaria [7]. A safety trial was conducted in young women in Burkina Faso in an area of high malaria endemicity to investigate the effects of periconceptional iron supplementation on malaria and genital tract infection risk in non-pregnant and pregnant women [8, 9]. This safety trial measured malaria prevalence at first antenatal visit (ANC1) as the primary (non-inferiority) outcome, and reported that weekly supplementation did not increase malaria risk (risk ratio 1.00, 95% CI 0.97–1.03), or improve iron status (iron deficiency risk ratio 0.84 (0.46–1.54), or reduce anaemia (risk ratio 0.96, 0.83–1.10) in these young, mostly adolescent menstruating women [8].…”

Section: Introductionmentioning

confidence: 99%

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Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso

Brabin

Gies

Roberts

et al. 2019

Malar J

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Background Iron supplementation before a first pregnancy may improve the future health of mother and baby by reducing maternal anaemia. Iron supplementation could, however, increase malaria infections, notably in primigravidae who are most susceptible. The pathogenicity of other iron-utilizing pathogens could also increase, causing inflammation leading to increased risk of adverse birth outcomes. This paper reports pre-specified secondary birth outcomes from a safety trial in Burkina Faso in an area of high malaria endemicity. Primary outcomes from that trial had investigated effects of long-term weekly iron supplementation on malaria and genital tract infections in non-pregnant and pregnant women. Methods A double-blind, randomized controlled trial. Nulliparous, mainly adolescent women, were individually randomized periconceptionally to receive weekly either 60 mg elemental iron and 2.8 mg folic acid, or 2.8 mg folic acid alone, continuing up to the first antenatal visit for those becoming pregnant. Secondary outcomes were ultrasound-dated gestational age, fetal growth, placental malaria, chorioamnionitis and iron biomarkers. Seasonal effects were assessed. Analysis was by intention to treat. Results 478 pregnancies occurred to 1959 women: 258/980 women assigned iron and folic acid and 220/979 women assigned folic acid alone. Malaria prevalence at the first antenatal visit was 53% (iron) and 55% (controls). Mean birthweight was 111 g lower in the iron group (95% CI 9:213 g, P = 0.033). Mean gestational ages were 264 days (iron) and 269 days (controls) (P = 0.012), with 27.5% under 37 weeks compared to 13.9% in controls (adjRR = 2.22; 95% CI 1.39–3.61) P < 0.001). One-third of babies were growth restricted, but incidence did not differ by trial arm. Half of placentae had evidence of past malaria infection. C–reactive protein > 5 mg/l was more common prior to births < 37 weeks (adjRR = 2.06, 95% CI 1.04–4.10, P = 0.034). Preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001). Chorioamnionitis prevalence peaked in the dry season (P = 0.046), with no difference by trial arm (P = 0.14). Conclusion Long-term weekly iron supplementation given to nulliparous women in a malaria endemic area was associated with higher risk of preterm birth in their first pregnancy. Trial Registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010 Electronic supplementary material The online version of this article (10.1186/s12936-019-2797-8) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso

Brabin

Gies

Roberts

et al. 2019

Malar J

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

et al. 2020

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Summary Background and 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/log10 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/log10 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 to 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.

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Approaches to Address the Anemia Challenge

Loechl,

Datta-Mitra,

Fenlason

et al. 2023

The Journal of Nutrition

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Effects of Weekly Iron and Folic Acid Supplements on Malaria Risk in Nulliparous Women in Burkina Faso: A Periconceptional, Double-Blind, Randomized Controlled Noninferiority Trial

Abstract: Weekly iron supplementation, given to young nulliparous women living in a malaria-endemic area, neither improved iron status nor increased malaria risk, suggesting that current iron recommendations may need revisiting for these women.

Cited by 20 publications

References 18 publications

Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso

Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso

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

Approaches to Address the Anemia Challenge

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