Iron Supplementation of Healthy, Term Infants: Is It Necessary?
Year: 2024
Type: article
Abstract: Source: Svensson L, Chmielewski G, Czyzewska E, et al. Effect of low-dose iron supplementation on early development in breastfed infants: a randomized clinical trial. JAMA Pediatr. 2024;178(7):649-656; doi: 10.1001/jamapediatrics.2024.1095.Investigators from Umea University, Umea, Sweden, and the Medical University of Warsaw, Warsaw, Poland, conducted a randomized controlled trial to assess the effect of low-dose iron supplementation on early development in breastfed infants. Study participants were healthy infants who were predominantly or exclusively breastfed (defined as >50% of daily feeds) and had been born at term and with birth weights >2,500g. Study infants were enrolled at a site in Sweden and a site in Poland. At 4 months of age, participants were randomized to receive 1 mg/kg/day of iron (micronized microencapsulated ferric pyrophosphate) or placebo until they were 9 months old. At approximately 12 months of age, development was assessed in participants with the Bayley Scales of Infant and Toddler Development (Bayley-III). Children were re-evaluated with the Bayley-III at 24 and 36 months of age. The primary study outcome was psychomotor development as measured with the Bayley-III at 12 months. Secondary outcomes included motor scores at 24 and 36 months, and cognitive and language scores at 12, 24, and 36 months of age. Study participants also were evaluated for iron deficiency, defined as serum ferritin <12 ng/mL) and iron deficiency anemia (hemoglobin <10.5 g/dL) when they were 12 months old. Differences in outcomes between infants in the iron supplementation group and those randomized to placebo were assessed with 1-way covariance using a general linear model after adjusting for gestational age, maternal education, and sex.A total of 221 infants were enrolled in the study, with 111 randomized to iron supplementation and 110 to placebo. Of these, 200 (90%) completed the Bayley-III at a mean age of 12.4 ±0.8 months, and 178 (80.5%) and 157 (71%) completed the Bayley-III at 24 and 36 months, respectively. At 12 months, mean Bayley-III motor scores were 100.7 ±13.2 for infants randomized to iron and 102 ±12 for placebo recipients (adjusted mean difference, -1.07; 95% confidence interval [CI], -4.69, 2.55). There also were no significant differences between treatment groups at 12 months for scores on the cognitive component of the Bayley-III (adjusted mean difference, -1.14; 95% CI, -4.26, 1.99) or language scores (adjusted mean difference, 0.75; 95% CI, -2.31, 3.82). Similarly, no significant differences in motor, cognitive, or language development scores between groups were found at 24 or 36 months of age. Rates of iron deficiency at 12 months of age were 6% and 13%, respectively, for children randomized to iron or placebo (relative risk, 0.46; 95% CI, 0.16, 1.30); 1 participant in each treatment group had iron deficiency anemia.The authors conclude that iron supplementation for healthy, breastfed infants was not associated with improved psychomotor, cognitive, or language development in early childhood.Dr Goyal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Globally, iron deficiency anemia is estimated to affect up to 20% of pregnant women and almost one-quarter of children.1 Numerous maternal conditions can impact infant iron deficiency, including maternal anemia and preterm delivery, as initial infant iron stores mostly accumulate during the third trimester of pregnancy.2 After 6 months of age, dietary iron is the infant’s primary source, and breastfeeding is associated with increased risk of iron deficiency. (See AAP Grand Rounds. 2021;45[3]:27.)3Multiple studies have demonstrated a clear association between iron deficiency and child development. (See AAP Grand Rounds. 2023;49[3]:31.)4 However, in high-income countries where iron deficiency is relatively uncommon, guidelines for routine iron supplementation vary. Currently, the AAP recommends supplemental iron for full-term breastfed infants starting at age 4 months until dietary iron intake is sufficient.2In the current study, breastfed infants were randomized to receive either daily iron or placebo from 4 to 9 months of age. The investigators observed no differences in developmental outcomes at 12, 24, or 36 months. They also observed no differences in iron deficiency anemia, which was diagnosed in a total of 2 infants. This was a rigorously designed study with close follow-up, well-matched comparison groups, and appropriate selection of outcomes. However, study participants had high levels of income and education, calling into question whether factors such as prenatal care and nutrition for this European sample are generalizable. Overall, findings suggest that routine iron supplementation for healthy, breastfed infants in high-income countries may not be necessary. However, questions remain regarding how best to identify iron deficiency in this population, as the current screening standard, hemoglobin at 12 months of age, has limited sensitivity and specificity.5In high-income countries where iron deficiency is relatively uncommon, iron supplementation for most healthy, breastfed infants born at term with normal birth weight may not be necessary.
Source: AAP Grand Rounds
DOI: 10.1542/gr.52-4-39
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4403005921