Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: A randomized controlled trial

The third trimester of pregnancy is a critical time for neurodevelopment, and babies born preterm or with a low birthweight are at an increased risk for lower cognitive scores or behavioral problems during childhood. Low-birthweight babies are also at an increased risk for iron deficiency. Given that iron plays a role in neurodevelopment, researchers have proposed that cognitive and behavioral problems in low birthweight babies may be mediated in part by low iron status. 

Researchers in Sweden published a randomized controlled trial in 2015, demonstrating that iron supplementation given from 6-weeks to 6-months of age in marginally low-birthweight infants decreased the risk of behavioral problems but had no effect on cognitive scores at age 3 and a half. Those same researchers conducted a subsequent study to evaluate whether early iron supplementation would improve cognitive and behavioral health at the age of 7 years. 

Methods

The double-blind, randomized, controlled trial included 285 infants who were born at a weight of 2000-2500 grams (4.4-5.5 lbs.). An additional 95 children were included as a reference group. Low-birthweight infants were randomized to receive 0 (placebo), 1, or 2mg/kg/day of ferrous succinate drops from 6-weeks to 6-months of age. Parents were advised to follow general Swedish infant dietary guidelines, which recommend breastfeeding or iron-fortified formula until 4-6 months. 

Low-birthweight babies are at an increased risk for iron deficiency.

Results

At 7 years of age, 205 of the low-birthweight children and 74 of the reference group were evaluated. No significant differences were found between the intervention groups or the reference group on the intelligence quotient (IQ) or the Five-To-Fifteen (FTF) behavioral scale. However, significant differences were observed on results of the Child Behavioral Checklist (CBCL). 

The proportion of children with an internalizing, externalizing, or total behavioral problem score above the cutoff for clinical problems was highest in the placebo group. When comparing placebo with the 2 intervention groups, the placebo group had significantly higher scores for externalizing behavior (p=.013). On the sub-scores of the CBCL, the placebo group had significantly higher scores for aggressive and rule-breaking behavior as well as thought problems. 

Conclusions

The results of this study suggest that early iron supplementation in low-birthweight infants does not influence IQ but does reduce the risk of behavioral problems in childhood. Whereas an earlier study showed this protective effect was apparent at the age of 3.5, the current study shows that the effect persists until at least the age of 7.

Berglund, S.K., Chmielewska, A., Starnberg, J., Westrup, B., Hägglöf, B., Norman, M., & Domellöf, M. (2018). Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: A randomized controlled trial. Pediatric Research, 83(1-1), 111-118.