Angulo-Barroso RM, Li M, Santos DC, et al. Iron supplementation in pregnancy or infancy and motor development: a randomized controlled trial. Pediatrics. 2016;137(4).
To assess the effects of iron supplementation in pregnancy and/or infancy on motor development at 9 months
The study was a randomized controlled trial (RCT) of iron supplementation in early infancy; the results were linked to an RCT of prenatal iron supplementation (conducted in Hebei, China) to compare effects of prenatal vs postnatal supplementation.
The studies included a total of 2,371 women with single uncomplicated pregnancies and 1,482 infants. Infants were randomly assigned to receive either supplemental iron (n=752) or placebo (n=730) from 6 weeks to 9 months. Maternal and infant iron status and infant growth outcomes were considered in the criteria. The infants with cord ferritin levels suggesting brain iron deficiency (<35 ug/L) were excluded from the study. Developmental testing for the infants at 9 months occurred at the Peking University Maternity and Child Health Care Center.
Investigators used the Peabody Developmental Motor Scale to assess gross motor development (primary outcome) and neurologic integrity and motor quality (secondary outcomes).
The authors compared the effects of iron/folate supplementation for prenatal patients and iron supplementation for infants from ages 6 weeks to 9 months. Iron supplementation in infancy, with or without iron supplementation in pregnancy, improved gross motor test scores at 9 months. There was improvement in gross motor scores: overall, P<0.001; reflexes, P=0.03; stationary, P<0.001; and locomotion, P<0.001. Iron supplementation in infancy improved motor scores by 0.3 SD compared with no supplementation or supplementation during pregnancy alone.
This study is one of many to show how the benefits of iron supplementation during early infancy can affect the developmental outcomes of growing infants. Overall, there was a positive effect on gross motor and neurological development for the infants supplemented with iron from early infancy as well as infants whose mothers received supplementation during pregnancy. Thus, this study confirms the importance of supporting potential nutritional deficiencies in early infancy—the period of most rapid growth and changes in motor development.1
Insufficient iron levels for optimal fetal and infant development are a concern during pregnancy and infancy with lasting effects into childhood.
The study supports the assertion that iron supplementation during infancy significantly improves gross motor skills during a child’s first year of life. The infants receiving iron supplementation during this rapid period of growth performed better on developmental milestones such as sitting upright, crawling, standing with lateral progression, and transitions from sitting to standing than the group who received no supplementation. Existing research shows a strong connection between iron deficiency and a child’s cognitive, social-emotional, and gross and fine motor development.2 In these studies, iron-deficient infants exhibited slower progression, delayed milestones, withdrawal, and lower spontaneous activity. Because areas of the brain mature at different times, it is critical to initiate iron supplementation during the earliest developmental periods and consider prenatal support as well.3
Iron deficiency is the most prevalent nutritional deficiency in the late infancy/toddler period.4 Notably, the study period focused on the specific ages (between 6 weeks and 9 months) when an infant’s brain matures most rapidly and iron is needed most in the formation of the brain’s neural network. The significant growth of the complex brain areas within the first year of life relies on iron and is most vulnerable to iron deficiencies or insufficiencies through the breast milk, diet, or during growth and development in the perinatal period.5 Periods of peak development and metabolic activity in the brain are sensitive to substrates that support metabolism, such as iron and thyroid hormone. This time period is characterized by peak hippocampal and cortical regional development, as well as proper myelin and synapse formation and oligodendrocyte function in the brain.
Recent studies have shown a relationship between perinatal iron deficiency and negative effects on the developing hippocampus in infants as young as 2 months. Infants who showed consistent and sufficient iron levels had greater auditory recognition memory when compared to infants who had fetal-neonatal iron deficiency.6 Results from a 2016 study of iron deficiency and its effects on thyroid development and function in neonates (Hu et al) support the strong relationship between maternal iron levels and thyroid peroxidase synthesis, which is key to neonatal neurodevelopment because it depends so heavily on healthy perinatal iron levels and optimal thyroid function.7 Iron deficiency has a direct effect on sensory input which, combined with cognitive, motor, and affective changes, may adversely affect the infant’s interactions with the physical and social environment. Treating and resolving iron deficiencies in early infancy and childhood has been shown to decrease the likelihood of long-lasting neural and behavioral effects.8
Insufficient iron levels for optimal fetal and infant development are a concern during pregnancy and infancy, with lasting effects into childhood.9 Despite the results of this study on iron supplementation in the prenatal period and its effect on motor development in infancy, other research shows a solid connection between the mother’s dietary and nutritional status during fetal development and the child’s overall growth and development. Although this current study of pregnant women in China did not show greater benefits in the child’s motor development with the addition of iron and folate supplementation, it is still important to support the critical nutritional needs for both mother and child.10
Previous trials in China exploring prenatal iron supplementation and its effects on both mother and child found that supplementation had a positive response in reducing anemia overall, but iron deficiency still exists in more than 45% of children and about 70% of mothers, despite supplementation.11 In contrast, a study of prenatal iron supplementation in pregnant women in the United States revealed that only about 18% of women who did not receive supplementation experienced iron deficiency.12,13 Therefore, we should consider other factors that may account for the results of studies from rural China, such as whether or not poor nutrition or environmental toxicities can affect the study participants in the long term. For example, deficiencies of essential nutrients, such as iron, calcium, and zinc, may increase the absorption of lead. These nutritional deficiencies are likely to be more prevalent in vulnerable groups such as low-income or minority populations.14 According to the study by Jain et al on lead intoxication, there is considerable research regarding the effects of lead toxicity on iron absorption and iron-deficiency anemia.15 Thus, the research supports the importance of supplementing iron for women in China during the prenatal period and preventing the deficiencies in early infancy and childhood.
Overall, the results of this study from Angulo-Barroso et al confirm the developmental benefits of iron supplementation early in infancy and indicate that supplementation should be an important part of routine care for all infants and mothers, especially those with demonstrated iron deficiency, as well as populations at risk for malnutrition and nutritional deficiencies.16
- Georgieff M. The role of iron in neurodevelopment: fetal iron deficiency and the developing hippocampus. Biochem Soc Trans. 2008; 36 (6):1267-1271.
- Grantham-McGregor S, Baker-Henningham H. Iron deficiency in childhood: causes and consequences for childhood development. Annales Nestle. 2010;68(3):105-119.
- Lozoff B. Iron deficiency and child development. Food Nutr Bull. 2007;28(4 Suppl):S560-571.
- Wang M. Iron deficiency and other types of anemia in infants and children. Am Fam Physician. 2016;93(4):270-278.
- Lozoff B, Georgieff MK. Iron deficiency and brain development. Semin Pediatr Neurol. 2006;13(3):158-165.
- Geng F, Mai X, Zhan J, et al. Impact of fetal-neonatal iron deficiency on recognition memory at 2 months of age. J Pediatr. 2015;167(6):1226-1232.
- Hu X, Wang R, Shan Z, et al. Perinatal iron deficiency-induced hypothyroxinemia impairs early brain development regardless of normal iron levels in the neonatal brain. Thyroid. [published on line ahead of print May 27, 2016].
- Lozoff B, Beard J, Connor J, Felt B, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006;64(5 Pt2):S34–S43.
- Szajewska H, Ruszczynski M, Chmielewska A. Effects of iron supplementation in nonanemic pregnant women, infants, and young children on the mental performance and psychomotor development of children: a systematic review of randomized controlled trials. Am J Clin Nutr. 2010;9(6)1684-1690.
- Saintand SE, Frick JE. Prenatal supplementation and its effects on early childhood cognitive outcome. In: Wallace TC, ed. Dietary Supplements in Health Promotion. Boca Raton, FL: Taylor and Francis Group; 2015:75-104.
- Zhao G, Xu G, Zhou M, et al. Prenatal iron supplementation reduces maternal anemia, iron deficiency, and iron deficiency anemia in a randomized clinical trial in rural China, but iron deficiency remains widespread in mothers and neonates. J Nutr. 2015;145(8):1916-1923.
- Mei Z, Cogswell ME, Looker AC, et al. Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Am J Clin Nutr. 2011;93(6):1312-1320.
- McDonagh M, Cantor A, Bougatsos C, Dana T, Blazina I. Routine Iron Supplementation and Screening for Iron Deficiency Anemia in Pregnant Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Rockville, MD: Agency for Healthcare Research and Quality (US); 2015.
- Qiu J, Wang K, Wu X, et al. Blood lead levels in children aged 0–6 years old in Hunan Province, China from 2009-2013. PLoS One. 10(4):e0122710.
- Jain A, Wolfe LC, Jain G. Impact of lead intoxication in children with iron deficiency anemia in low- and middle-income countries. Blood. 2013;122(13):2288-2289.
- Janus J, Moerschel SK. Evaluation of anemia in children. Am Fam Physician. 2010;81(12):1462-1471.