Study Questions Developmental Benefits of Widespread Early Iron Therapy

By Gene Emery

September 09, 2021

NEW YORK (Reuters Health) - Three months of iron supplementation in a large group of rural Bangladeshi children corrected their anemia but failed to produce any improvement in child development or other functional outcomes, according to new research.

The findings from the BRISC study, published in the New England Journal of Medicine, call into question the recommendation of the World Health Organization that calls for iron supplementation for all children age 6 to 23 months in areas where anemia is prevalent. WHO has been recommending supplementation for about two decades.

Whether the organization should continue to endorse iron treatment to cure anemia without expecting cognitive improvement "is a discussion our study will launch over the next few months and years," chief author Dr. Sant-Rayn Pasricha of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia, told Reuters Health by phone.

After three months of supplementation, the 1,101 eight-month-old children who were randomly assigned to receive iron syrup daily did not have a higher score on a 145-point cognitive development test than the 1,100 infants who received placebo.

The researchers also treated 1,099 infants with micronutrient powders that contained iron, vitamin A, vitamin C, folic acid and zinc. They found no significant improvement in developmental scores in that group either.

The children were followed for nine months. Adjustment for adherence, missing data, or baseline anemia did not affect the outcome.

There was a suggestion in the data, however, that giving iron to children who don't need it might increase their risk of infection and diarrhea.

Anemia affects 49% of children under age 5 in Southeast Asia and 60% in Africa. Faith in the value of supplementation is so widespread that more than 18 million children in 61 countries receive extra iron.

Animal studies have shown that iron deficiency impairs brain development and "there are countless observational studies - but no interventional studies - that link anemia to impaired functional outcomes in young kids," said Dr. Pasricha, head of the division of population health and immunity at WEHI. "The assumption was that if you reversed anemia you would improve child development. But the pivotal trial had not been done, and that's what we aimed to do with this study."

At the start of the test, 45% of the children had anemia, 28% had iron deficiency and 19% had iron-deficiency anemia.

Infants were excluded if they lived in an area where the groundwater had high iron levels, had a hemoglobin level above 8 g/dL, had a known developmental delay, suffered from severe acute malnutrition or had other problems.

At that nine-month mark, children who received some degree of iron supplementation were less likely to have anemia, iron deficiency or iron-deficiency anemia, but the rates of all three conditions increased after supplementation stopped.

The micronutrient powder and the iron syrup seemed equally effective in reducing the prevalence of anemia.

The researchers did not give the supplements for more than three months out of fear that they might increase the risk of diarrhea.

"Parental reports of symptoms of infection (diarrhea, fever, or respiratory symptoms) were similar in the three trial groups, both during the intervention period and during the follow-up period," the researchers write.

Because of the new findings, the emphasis of the research may shift to making sure pregnant women are properly fortified with iron in an attempt to improve developmental outcomes in their babies, said Dr. Pasricha. "We probably need more than a simple supplement to achieve the key functional outcomes we want to achieve for our children around the world."

SOURCE: The New England Journal of Medicine, online September 8, 2021