Iron supplements do not improve infant development

Low-dose iron supplementation given to infants did not improve early development or iron status in a randomized controlled trial.

Among 221 infants 4 to 9 months of age, randomization to iron supplementation versus placebo did not improve Bayley III motor scores for infants and toddlers (adjusted mean difference [aMD] −1.07 points, 95% CI −4.69 to 2.55), cognitive scores (aMD −1.14, 95% CI −4.26 to 1.99), or language scores (aMD 0.75, 95% CI −2.31 to 3.82) at 12 months of age, reported Anna Chmielewska, MD, PhD, of Umeå University in Sweden, and colleagues.

There was also no benefit at 12 months in reducing the risk of iron deficiency (RR 0.46, 95% CI 0.16-1.30) or iron deficiency anemia (RR 0.78, 95% CI 0.05- 12.46), the group noted in JAMA Pediatrics.

At 24 and 36 months, developmental scores were also similar between groups.

“Exclusive breastfeeding is recommended for approximately 6 months after birth,” write Chmielewska and colleagues. "However, because the iron content of breast milk is low and iron intake from complementary foods is often insufficient, prolonged breastfeeding is known to be associated with iron deficiency."

“The association between iron deficiency anemia and impairments in cognitive function, motor function and behavior is well established, and the negative effects may be irreversible,” they added.

However, high-quality evidence that iron supplementation actually makes a difference is lacking, leading to mixed recommendations for supplementation for infants after 4 months. The American Academy of Pediatrics recommends 1 mg/kg/day of iron for all infants who are predominantly or exclusively breastfed starting at 4 months until their diet will be able to provide sufficient iron. European guidelines do not recommend routine iron supplementation for exclusively breastfed, healthy infants of normal birth weight.

"For general practitioners and pediatricians," Chmielewska told MedPage Today, this study provides "more confidence in avoiding iron supplementation for healthy infants."

As for why the supplement didn't even affect iron levels, she added: "In this low-risk population, infants were likely adjusting their iron intake between the end of the intervention (9 months) and the time of blood draw (12 months), so that there was no difference at this point in time."

The study included healthy identical infants born at term, for whom breastfeeding constituted more than 50% of daily nutrition and who were not anemic at 4 months of age.

The trial randomized 220 infants 1:1 to receive iron (1 mg/kg micronized microencapsulated ferrous pyrophosphate mixed with water or breast milk) or placebo (maltodextrin) once daily from 4 to 9 months of age.

The study was conducted from December 2015 to May 2020 with follow-up until May 2023 in outpatient settings in Poland and Sweden. A total of 64.7% of infants completed all three Bayley assessments.

Limitations of the study include that of eligible families, only 15% agreed to participate, “which may raise concerns about the generalizability of the results,” Chmielewska and colleagues noted. They also acknowledged that the development assessment was conducted using two different versions of the Bayley assessments in two countries (Poland and Sweden).