Iron and folic acid supplementation -- given prenatally during a time of critical neurologic development -- can improve children's later intellectual functioning, a randomized trial conducted in Nepal found.
On the Universal Nonverbal Intelligence Test, children whose mothers had received the iron and folic acid supplements had a mean score of 51.7, while those in a control group scored 48.2, which gave an adjusted mean difference of 2.38 points (95% CI 0.06 to 4.70, P=0.04), according to Parul Christian, DrPH, of Johns Hopkins in Baltimore, and colleagues.
Differences compared with controls were not seen, however, among children whose mothers had received additional supplements such as zinc and other vitamins, the researchers reported in the Dec. 22/29 Journal of the American Medical Association.
"Micronutrient inadequacy is a critical concern among pregnant women and young children throughout the world," Christian and colleagues wrote.
Iron in particular is crucial to many aspects of neurodevelopment, including myelin production, monoamine transmission, and synaptogenesis, they explained.
Previous studies of prenatal dietary supplementation have been inconclusive, so these researchers have followed a cohort of 676 children born in 2000 and 2001, assessing various aspects of their intellectual, motor, and executive functioning.
The researchers had previously observed that iron deficiency and anemia are common in rural Nepal.
At the time of the current assessment, children's mean age was 8.4 years, and 80% had begun attending school.
On the Stroop test, which measures inhibitory control, the adjusted mean difference in proportion of children who failed was −0.14 (95% CI −0.23 to −0.04, P=0.005) in the iron/folic acid group compared with controls, the researchers found.
The iron/folic acid group also performed better on other adjusted measures compared with controls:
- Backward digit span test, 0.36 (95% CI 0.01 to 0.71, P=0.02)
- Movement assessment battery for children (in which a lower score is a better score), −1.47 (95% CI −3.06 to 0.12, P=0.07)
- Finger-tapping test, 2.05 (95% CI 0.87 to 3.24, P=0.001)
These improvements were "attenuated or absent" among children who received zinc or multiple other micronutrients, the researchers observed.
For instance, the difference compared with controls on the universal nonverbal intelligence test among children who also received zinc was 0.73 (95% CI −0.95 to 2.42, P=0.39).
And the difference among those who received multiple micronutrients including vitamins D, B, K, niacin, and magnesium, was 1 (95% CI −0.55 to 2.56, P=0.20).
Furthermore, on the backward digit span test the differences were 0.04 (95% CI −0.17 to 0.26, P=0.70) and 0.07 (95% CI −0.11 to 0.25, P=0.44), respectively, in the two groups who had extra supplementation beyond iron and folic acid.
The lack of benefit seen with the addition of zinc, according to the researchers, may be a result of this compound's interference with iron absorption.
The researchers pointed out that the 2.4-point difference in the universal nonverbal intelligence test seen between the iron/folic acid group and controls "although of low clinical significance at the individual level, may be a meaningful difference at the population level."
Strengths of the study include its randomized design and its use of tests that are widely accepted and standardized for use across cultures.
A limitation may be possible sex differences in achievement relating to school attendance, with girls being more focused on household chores and care of younger siblings.
The researchers concluded that antenatal iron and folic acid supplementation should be encouraged internationally in low- and middle-income settings.
"The differences in intellectual and executive function tasks suggest that iron/folic acid, when provided during critical periods of development, may make an important difference in children's ability to learn tasks that are related to their academic achievement," Christian and colleagues wrote.