In longitudinal studies, adolescents who had been iron-deficient anemic in infancy continued to score lower than their non-anemic peers in IQ, social problems, and inattention, even though they were given iron treatment as infants. Prenatal iron supplementation may prevent some of these deficits.
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However, among three randomized trials of maternal iron supplementation during pregnancy that measured subsequent cognitive development of the children, only one showed positive results. Provision of iron to infants in low- and middle-income countries, where rates of iron deficiency are usually high, has consistently led to improved outcomes at the end of the intervention period. These trials are different from treatment trials in that all children are included, even if they have not been diagnosed with IDA, and the dose of iron is lower.
However, two recent follow-up studies reported no effect of iron supplementation in infancy on motor and cognitive ability at age 3. Further long-term follow-up studies that examine cognitive, motor, and socioemotional skills are needed.
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Importantly, the provision of iron in malaria-endemic regions should be accompanied by adequate malaria surveillance and treatment. Taken as a whole, the evidence indicates that IDA during infancy is a strong risk factor for cognitive, motor, and socioemotional impairment in both the short and long term. Avoiding such consequences may require control of iron deficiency before it becomes severe or chronic, starting with adequate maternal iron intake before and during pregnancy and delayed cord clamping at birth.
Iodine is necessary for the synthesis of thyroid hormones, which are essential for central nervous system development, including neurogenesis, neuronal migration, axon and dendrite growth, synaptogenesis, and myelination Table 1. Pregnant women with severe iodine deficiency may underproduce thyroid hormones, leading to cretinism in the child.
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Cretinism is a disorder characterized by mental retardation, facial deformities, deaf-mutism, and severely stunted growth. Cretinism cannot be reversed after birth but can be prevented by the correction of iodine deficiency before conception. Even in the absence of overt cretinism, the evidence suggests that chronic iodine deficiency negatively affects intelligence. A meta-analysis showed a Although striking, these correlational studies may be confounded by uncontrolled factors, and randomized controlled trials of iodine supplementation in school-age children have yielded inconsistent results.
Pregnancy seems to be a sensitive period with regard to the effects of iodine deficiency on neurodevelopment, since cretinism develops during this period. In an iodine-deficient region in China, 4—7-year-old children whose mothers were given iodine during pregnancy performed better on a psychomotor test than those who were supplemented beginning at 2 years of age. Among over 1, 8-year-old children in the UK, those whose mothers had been iodine deficient in the first trimester of pregnancy were more likely to have scores in the lowest quartile for verbal IQ and reading comprehension.
The authors concluded that additional well-designed randomized controlled trials are needed to quantify more precisely the contribution of iodine deficiency to brain development in young children, including trials examining iodized salt. Though few well-designed controlled studies have been reported, adequate iodine intake is clearly necessary for normal brain development. Prevention of iodine deficiency, especially for pregnant mothers, is an important way to promote healthy brain development in children worldwide.
Zinc is the fourth most abundant ion in the brain, where it contributes to brain structure and function through its role in DNA and RNA synthesis and the metabolism of protein, carbohydrates, and fat. Randomized trials of zinc supplementation during pregnancy in the United States, Peru, Nepal, and Bangladesh have shown no effects , , or negative effects of zinc compared to placebo or other micronutrients on the motor and cognitive abilities of children between the ages of 13 months and 9 years.
Similarly, infant zinc supplementation has not been demonstrated to improve cognitive development. Four of these provided zinc with or without iron or other micronutrients , , — and one provided zinc with or without psychosocial stimulation. In these nine trials, positive effects on motor development were more commonly found.
The Interplay between Maternal Nutrition and Stress during Pregnancy: Issues and Considerations
Four of the trials showed that zinc supplementation improved motor development, 56 , , , though one of these found an effect on the motor quality rating of the Bayley Behavior Rating Scale rather than on the Bayley Motor score, and another showed an impact of zinc only when given in combination with iron. Two other trials in India and Guatemala indicated that zinc supplementation in children under 2 years of age increased activity levels. The available evidence suggests that zinc supplementation during pregnancy does not seem to improve childhood cognitive or motor development.
Zinc supplementation during infancy may positively affect motor development and activity levels, but it does not seem to affect early cognitive ability. A meta-analysis of randomized controlled trials of zinc supplementation in infants did not find any evidence of impact on BSID mental or motor scores; however, the authors concluded that the number of available studies is still relatively small, and the duration of supplementation in these studies may be too short to permit detection of such effects.
Like zinc, B-vitamins, including thiamine, are important for brain development and function through many mechanisms. They play a role in carbohydrate metabolism which helps to provide the brain's energy supply , membrane structure and function, and synapse formation and function. In high-income countries, thiamine deficiency in infants has become a rare condition since food has been enriched with thiamine. However, recent evidence suggests that the prevalence of thiamine deficiency may be relatively high in some low-income countries.
Of infants who were admitted to a hospital in Laos without clinical signs of thiamine deficiency, These children showed impaired language ability compared to control children at 5 years of age, even though they had not displayed any neurological symptoms during infancy. Other observational studies have demonstrated associations between infant development and maternal niacin and vitamin B 6 intake during pregnancy, maternal riboflavin, niacin, and vitamin B 6 intake during lactation, and infant cobalamin and folate status. Individuals who are deficient in one micronutrient are commonly at risk for deficiencies in others as well.
Supplementation with any single micronutrient may not affect cognitive and motor development in individuals who are also deficient in other micronutrients. In these groups, supplementation with multiple micronutrients may be more beneficial than supplementation with a single micronutrient. The conversion of EFAs to DHA also depends on certain micronutrients and, thus, micronutrient deficiency may influence development through fatty acid status.
Three randomized trials have reported positive effects of multiple micronutrient supplementation during pregnancy on child development between the ages of 6 and 18 months, including motor development in Bangladesh and Tanzania 70 , and cognitive development in China. As described above, children of mothers in this same study in Nepal who received iron, folic acid, and vitamin A scored higher than those whose mothers received vitamin A alone on five of six cognitive and motor tests.
Studies of multiple micronutrient supplementation during infancy have shown some benefits immediately after the supplementation period. Three randomized trials in Ghana, China, and South Africa demonstrated positive effects on motor development in children between the ages of 12 and 18 months , , and one trial also showed an effect on the overall developmental quotient. When a child is adequately nourished from conception through infancy, the essential energy, protein, fatty acids, and micronutrients necessary for brain development are available during this foundational period, establishing the basis for lifetime brain function.
The well-nourished child is also better able to interact with his or her caregivers and environment in a way that provides the experiences necessary for optimal brain development. Children who are not adequately nourished are at risk for failing to reach their developmental potential in cognitive, motor, and socioemotional abilities.
These abilities are strongly linked to academic achievement and economic productivity. Therefore, preventing or reversing developmental losses in early childhood is crucial for fostering economic development in low- and middle-income countries as well as reducing economic disparities in high-income countries. The evidence is clear that the following conditions are key risk factors for poor motor, cognitive, and socioemotional development: severe acute malnutrition very low weight for height , chronic undernutrition as evidenced by intrauterine growth retardation and linear growth retardation or stunting , IDA, and iodine deficiency.
Preventing these conditions should be a global health priority. The following interventions are examples of strategies that have been found to be effective in preventing or improving these conditions: salt iodization to prevent iodine deficiency, provision of iron via home fortification e. Strategies to promote exclusive breastfeeding during the first 6 months of life and continued breastfeeding thereafter, along with adequate complementary feeding, are also likely to improve cognitive development, though additional evidence for the effectiveness of these strategies is also needed.
However, additional robust research in low- and middle-income countries that evaluates the long-term effects of these interventions is needed. The design and interpretation of further research should take into account the factors discussed above: the timing of nutrient deficiency or supplementation, the degree of deficiency, the possibility of recovery, and the potential for additive, interacting, or mediating effects with regard to the children's experiential input from the environment.
Interventions to improve the home environment and the quality of caregiver-infant interaction are also recommended to complement and enhance the effect of improved nutrition.
These types of interventions are crucial to offset the negative effects of adverse environmental conditions for example, poverty and low maternal education that often coexist in populations in which undernutrition is common. Integrated strategies targeting multiple risk factors, including nutrition, are necessary to reduce inequality and promote cognitive, motor, and socioemotional development in disadvantaged children worldwide, ensuring that all children have the opportunity to fulfill their developmental potential. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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Factors Influencing the Impact of Undernutrition. Brief Review of Human Studies. Nutrition and brain development in early life Elizabeth L Prado. E-mail: elprado ucdavis. Oxford Academic.