Analee J Etheredge1, Zul Premji2, Nilupa S Gunaratna3, Ajibola Ibraheem Abioye3, Said Aboud4, Christopher Duggan5, Robert Mongi2, Laura Meloney3, Donna Spiegelman6, Drucilla Roberts7, Davidson H Hamer8, Wafaie W Fawzi9. 1. Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts2Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Department of Parasitology/Medical Entomology, School of Public Health and Social Sciences, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 3. Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 4. Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 5. Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts2Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts5Department of. 6. Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts6Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts7Department of Biostatistics, Harvard T. H. Chan School of Public Healt. 7. Department of Pathology, Massachusetts General Hospital, Boston. 8. Department of Global Health, Boston University School of Public Health, Boston, Massachusetts10Center for Global Health and Development, Boston University, Boston, Massachusetts11Section of Infectious Diseases, Department of Medicine, Boston Medical Cente. 9. Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts5Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts6Department of Epidemiology, Harvard T. H. Chan School.
Abstract
IMPORTANCE: Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. OBJECTIVE: To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21,316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. INTERVENTIONS: Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. MAIN OUTCOMES AND MEASURES: The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. RESULTS: Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 µg/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41-1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). CONCLUSIONS AND RELEVANCE: Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01119612.
RCT Entities:
IMPORTANCE: Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. OBJECTIVE: To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21,316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. INTERVENTIONS:Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. MAIN OUTCOMES AND MEASURES: The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. RESULTS: Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 µg/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41-1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). CONCLUSIONS AND RELEVANCE: Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01119612.
Authors: Maria Makrides; Caroline A Crowther; Robert A Gibson; Rosalind S Gibson; C Murray Skeaff Journal: Am J Clin Nutr Date: 2003-07 Impact factor: 7.045
Authors: D P Barton; M T Joy; T R Lappin; M Afrasiabi; J G Morel; J O'Riordan; J F Murphy; C O'Herlihy Journal: Am J Obstet Gynecol Date: 1994-03 Impact factor: 8.661
Authors: Ramadhani A Noor; Ajibola I Abioye; Anne Marie Darling; Ellen Hertzmark; Said Aboud; Zulfiqarali Premji; Ferdinand M Mugusi; Christopher Duggan; Christopher R Sudfeld; Donna Spiegelman; Wafaie Fawzi Journal: J Nutr Date: 2020-02-01 Impact factor: 4.798
Authors: Ajibola I Abioye; Said Aboud; Zulfiqar Premji; Analee J Etheredge; Nilupa S Gunaratna; Christopher R Sudfeld; Robert Mongi; Laura Meloney; Anne Marie Darling; Ramadhani A Noor; Donna Spiegelman; Christopher Duggan; Wafaie Fawzi Journal: J Nutr Date: 2016-04-27 Impact factor: 4.798
Authors: Freya J I Fowkes; Kerryn A Moore; D Herbert Opi; Julie A Simpson; Freya Langham; Danielle I Stanisic; Alice Ura; Christopher L King; Peter M Siba; Ivo Mueller; Stephen J Rogerson; James G Beeson Journal: BMC Med Date: 2018-09-20 Impact factor: 8.775