Iron Intervention No Boon for Baby’s Cognitive Development

Iron supplements did not improve cognitive development in infants, according to a randomized trial conducted in rural Bangladesh.

Cognitive development was no different among 3,300 infants randomized to iron syrup, multiple micronutrient powders, or placebo daily over 3 months, reported Sant-Rayn Pasricha, PhD, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

The supplements also failed to improve other developmental and growth outcomes, though daily iron syrup reduced findings of anemia at 3 months (prevalence ratio [PR] 0.48, 95% CI 0.41-0.56), as did the iron-containing micronutrient powder (PR 0.52, 95% CI 0.45-0.60), Pasricha’s group wrote in the New England Journal of Medicine.

And prevalence of anemia was lower at 9 months among children randomized to iron supplements compared to placebo at 9 months, they added.

Anemia affects over 40% of all children under age 5 globally with the burden highest in Southeast Asia and Africa, according to the WHO. Some have argued that the WHO’s recommended thresholds of anemia in adults and children are outdated, however.

The authors added that the WHO recommends that children ages 6 months to 23 months who live in areas with prevalent anemia receive either micronutrient powders containing iron or iron drops or syrup. Iron supplements are a public health strategy for children around the world, reaching more than 18 million individuals across 61 countries in 2018, they noted. In the U.S., many commercial baby formulas are fortified with iron.

“Given that iron interventions produced sustained improvements in the hemoglobin level and iron stores but did not improve developmental, behavioral, or growth outcomes in the immediate or medium term, our results address this knowledge gap,” Pasricha and colleagues said.

This double-blind, placebo-controlled trial is unique in a field where there have been few high-quality studies on the impact of iron interventions on child development, they said.

The Benefits and Risks of Iron Interventions in Children (BRISC) study was conducted in the rural, low-income region of Rupganj Upazila, Bangladesh from July 6, 2017 to February 20, 2019. Eligible infants were 8 months old. Exclusion criteria included “marked anemia” (hemoglobin level of less than 8.0 g per deciliter), fever, severe acute malnutrition, a known inherited red-cell disorder or previous transfusion or known developmental delay. Children were also excluded if the iron levels in their local drinking water exceeded 1 mg per liter.

Double-dummy randomization placed participants into one of three groups:

• Iron syrup plus placebo powder (n=1,101)
• Micronutrient powders (containing iron, vitamin A, vitamin C, folic acid, zinc, and maltodextrin) to be mixed with food plus placebo syrup (n=1,099)
• Placebo syrup plus placebo powder (n=1,100)

Investigators conducted home visits after completion of the assigned 3-month treatment and again after 9 months. During these visits, cognitive development was assessed using the Bayley Scales of Infant and Toddler Development, third edition. Blood hemoglobin and ferritin levels were also measured.

“Although a longer duration of supplementation may have further increased iron stores, it is uncertain whether this would have had an effect on functional outcomes, because iron deficiency anemia was virtually eliminated after 3 months,” Pasricha’s team wrote.

Baseline characteristics were similar between groups, with almost an even split of boys and girls. At baseline, 45% of participants had anemia, 28% had iron deficiency and 19% had iron deficiency anemia.

Secondary outcomes, such as child behavior and temperament, height, and weight, did not differ significantly between study arms.

There were two deaths, one in the micronutrient powder group and one in the placebo group. About 2% of patients experienced at least one serious adverse event, and about 2% were hospitalized. The most common specific reason for an unscheduled clinic visit was fever (12%-13%), followed by cough or difficulty breathing (11%).

The authors cautioned that approximately 36% of infants did not have their venous hemoglobin concentrations measured at their 3- and 9-month visits since their parents did not consent. However, no meaningful differences were found in the baseline characteristics between infants for whom consent was given and for whom consent was not given.