Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh

Abstract

BACKGROUNDUniversal provision of iron supplements (drops or syrup) or multiple micronutrient powders to young children in low-to-middle-income countries where anemia is prevalent is recommended by the World Health Organization and widely implemented. The functional benefits and safety of these interventions are unclear. METHODSWe conducted a three-group, double-blind, double-dummy, individually randomized, placebo-controlled trial to assess the immediate and medium-term benefits and risks of 3 months of daily supplementation with iron syrup or iron-containing multiple micronutrient powders, as compared with placebo, in 8-month-old children in rural Bangladesh. The primary outcome was cognitive development, as assessed by the cognitive composite score on the Bayley Scales of Infant and Toddler Development, third edition, immediately after completion of the assigned 3-month regimen; scores range from 55 to 145, with higher scores indicating better cognitive performance. Secondary outcomes included the cognitive composite score at 9 months after completion of the assigned regimen; behavioral, language, and motor development, as well as growth and hematologic markers, immediately after completion and at 9 months after completion; and safety. RESULTSWe randomly assigned 3300 infants to receive iron syrup (1101 infants), multiple micronutrient powders (1099), or placebo (1100) daily. After completion of the assigned 3-month regimen, no apparent effect on the cognitive composite score was observed with iron syrup as compared with placebo (mean between-group difference in change in score from baseline, −0.30 points; 95% confidence interval [CI], −1.08 to 0.48) or with multiple micronutrient powders as compared with placebo (mean between-group difference in change in score from baseline, 0.23 points; 95% CI, −0.55 to 1.00). No apparent effect on any other developmental or growth outcome was observed immediately after completion of the assigned regimen or at 9 months after completion. At 9 months after completion of the assigned regimen, the prevalences of anemia, iron deficiency, and iron deficiency anemia increased in all three trial groups but remained lower among the children who received iron syrup or multiple micronutrient powders than among those who received placebo. The risk of serious adverse events and incidence of symptoms of infection were similar in the three trial groups. CONCLUSIONSIn this trial involving infants in Bangladesh, 3 months of daily supplementation with iron syrup or multiple micronutrient powders did not appear to have an effect on child development or other functional outcomes as compared with placebo.

An implementation research programme to support an intravenous iron intervention for pregnant women with moderate and severe anaemia in Malawi: study protocol

“…Globally, antenatal anaemia continues to pose serious risks to both mother and child [ 1 – 3 ]. Iron supplementation to infants has limited benefit on functional outcomes [ 60 ], potentially raising the priority for anaemia control in pregnancy. Given that IV iron has been demonstrated to be an effective and safe treatment in HICs for pregnant women with moderate and severe anaemia [ 14 , 15 , 61 ], there is an opportunity to adopt this vital intervention to LMICs, such as Malawi, to ensure equitable access to health care [ 23 ].…”

Shooting shadows: India’s struggle to reduce the burden of anaemia

“…However, various research studies and reports indicate an over-reliance of government programmes on pharmacological intervention of prophylactic IFA supplementation to mitigate IDA, especially among women and children, which may not result in anaemia reduction (31) . A recent randomised placebo-controlled trial in Bangladesh (71) concluded that 3 months of daily supplementation with Fe syrup or multiple micronutrient powders had no effect on child development or other functional outcomes compared with infants who received a placebo. Weekly Iron and Folic Acid Supplementation programme currently focuses on adolescents aged 10-19 years guided by the National Iron Plus Initiative, which provides guidelines for the overall IFA intervention strategy.…”

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“…Recommendations are for daily doses of 10–12.5 mg elemental iron for 3 consecutive months per year for infants and children aged 6–23 months, which increases to 30 mg for preschool-aged children ( 29 ). However, a recent placebo-controlled study of iron supplementation for 12 weeks in ∼8 month old Bangladeshi infants concluded that although rates of anemia were reduced, there was no effect on developmental functional outcomes, including cognitive ability ( 30 ). An important caveat to iron supplementation recommendations is in areas with endemic malaria where iron supplementation is only recommended to those infants with access to malaria-prevention strategies ( 30 ).…”

“…However, a recent placebo-controlled study of iron supplementation for 12 weeks in ∼8 month old Bangladeshi infants concluded that although rates of anemia were reduced, there was no effect on developmental functional outcomes, including cognitive ability ( 30 ). An important caveat to iron supplementation recommendations is in areas with endemic malaria where iron supplementation is only recommended to those infants with access to malaria-prevention strategies ( 30 ). This follows comprehensive meta-analyses which concluded that there is a possible link between iron supplementation and increased risk of mortality or hospitalization from malaria ( 31 ).…”