SAN DIEGO – Iron supplementation, especially in pregnancy, improved toddler communication and social behaviors at 18 months in a large Chinese study.
“Iron deficiency in infancy is associated with altered social and emotional development,” Ming Li, Ph.D., said at the annual meeting of the Pediatric Academic Societies. “Some randomized, controlled trials of iron supplementation in infancy show social and emotional benefits.”
Dr. Ming Li
In an effort to assess the effects of iron supplementation and maternal iron status on infant communication and social interaction, Dr. Li of Peking University First Hospital in Beijing, China, in collaboration with Dr. Betsy Lozoff and her associates at the University of Michigan, Ann Arbor, used the 23-item Modified Checklist for Autism in Toddlers (M-CHAT) in 993 children in rural China who were part of two linked randomized, controlled trials. Their mothers had been randomized 1:1 to iron (300 mg ferrous sulfate) plus folate (400 micrograms) or placebo plus folate in pregnancy. As infants, they were randomized 1:1 to iron (liquid iron protein succinylate, about 1 mg Fe/kg per day) or placebo from 6 weeks to 9 months. In all, the two trials yielded four groups of prenatal or postnatal iron: placebo/placebo, placebo/iron, iron/placebo, and iron/iron.
The researchers administered the M-CHAT at 18 months to assess behaviors related to communication and social-emotional functioning, including imitation, joint attention, pretend play, and social referencing. The major outcome was the number of M-CHAT items failed. The threshold was two or more failed of the tool’s six most discriminating items or three or more failed of all 23 M-CHAT items. Bivariate correlation was used to consider the relation with maternal iron status.
The mean age of mothers was 25 years, and 78% were primiparous. More than 98% of the infants were born at term; mean birth weight was 3.36 kg. Their weight-for-age Z score was .90 at 9 months, and .53 at 18 months. Anemia, iron deficiency, and iron deficiency anemia declined with prenatal supplementation, but the majority of mothers were still iron deficient at term.
Dr. Li reported that the number of failed M-CHAT items varied depending on iron supplementation group, and was highest for the placebo/placebo group (3.1) and lowest for the iron/iron group (2.8) (P = 0.04 for linear trend). Mother’s iron status at enrollment was not associated with number of failed M-CHAT items, but late pregnancy iron status was. Lower maternal hemoglobin and higher soluble transferrin receptor predicted a higher number of failed M-CHAT items (P= .01 and P= .02, respectively).
Dr. Li emphasized that the study’s randomized, controlled design supports causal inferences. “These are best considered as behaviors [that are impacted], rather than autistic spectrum disorders,” he said. “The results suggest that iron supplementation in pregnancy has more effect than in infancy, but the infancy dose was low (1 mg/kg per day) and the impact on iron status at 9 months was minimal. Still, the combination of iron supplementation in pregnancy and infancy provided the greatest benefit.”
The pregnancy randomized, controlled trial was funded by Vifor Pharma, Ltd. The infancy randomized controlled trial and all iron measures were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with the Office of Dietary Supplements. Dr. Li reported having no relevant financial conflicts.
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