Cognition

Introduction

It is widely documented that neurodevelopment is influenced by genetic and environmental factors. Environmental factors, mainly represented by lifestyle, are modifiable contributors to neurodevelopment. Modifiable factors include dietary patterns, whole foods (e.g.,human milk), and intakes of specific nutrients from infancy to childhood. Accordingly, even the preconceptional period and pregnancy represent sensitive phases that should be monitored to optimize offspring’s brain growth and cognitive functions. This chapter includes a selection of studies performed in the area of nutrition and cognition, published between July 1, 2021 and June 30, 2022. Original articles comprising randomized controlled trials (RCTs), observational studies, and reviews have been selected and grouped into 4 categories, respectively:

1. Dietary patterns
2. Micronutrients
3. LC-PUFA (long-chain polyunsaturated fatty acid)
4. Toxicity

Dietary Patterns

Association of maternal dietary patterns during gestation and offspring neurodevelopment

Comments: The present prospective Jiangsu Birth Cohort (JBC) study investigated the role of maternal diet at different gestational weeks on neurodevelopment in children at 1 year of age. The authors included a total of 1,178 mother-infant pairs and have reported that a higher adherence score of “aquatic products, fresh vegetables, and homemade” food consumption in the second and third trimester was significantly associated with a decreased risk of nonoptimal cognitive development of infants.

Association between dietary patterns and cognitive ability in Chinese children aged 10–15 years: evidence from the 2010 China family panel studies

Comments: This cross-sectional study investigated the association between 3 dietary patterns (“high protein,” “high fat,” and “high salt-oil”) and cognitive ability in 2,029 Chinese children aged 10–15 years from the China Family Panel Studies. The results showed a positive relationship between “high protein” dietary patterns and mathematics and vocabulary test scores. In contrast, children with higher scores of “high fat” dietary patterns were associated with poorer cognitive ability.

Maternal diet quality during pregnancy and child cognition and behavior in a US cohort

Comments: The authors selected 1,580 mother-child pairs from an ongoing prospective pre birth cohort study (Project Viva). Children completed ≥1 cognitive/behavioral assessment at infancy, early childhood, or mid childhood, and mothers completed the early- and/or mid pregnancy study visits. Results showed that higher maternal MDS-P, a version of the Mediterranean diet score (MDS) modified for pregnancy, scores during pregnancy were associated with better verbal and nonverbal intelligence quotient scores and fewer metacognition problems in mid childhood. Higher maternal Alternate Healthy Eating Index scores, modified in occasion of pregnancy, were associated with better visual spatial skills in early childhood and with better verbal intelligence and executive function in mid childhood.

General comments: Given the recognized influence of nutrition on cognitive and behavioral development in early life, the association between maternal food habits and child cognition deserves further investigation to optimize, not only single nutrient intakes, but the entire maternal dietary patterns during gestation. An extension of these studies back to the preconceptional period warrants further investigations, to disentangle a possible role also on the rate of fertility, to ameliorate the outcome of this more frequent year-by-year practice.

Micronutrients

Benefits and risks of iron interventions in infants in rural Bangladesh

Comments: This double-blind, randomized, placebo-controlled trial aimed to assess the immediate and medium-term benefits and risks of daily supplementation in 8-month-old rural Bangladesh children. The authors included 3,300 infants, randomly assigned to receive iron syrup (first arm), iron-containing multiple micronutrient powders (second arm), or placebo, every day for 3 months. The sample size has been calculated to reach 80% power. The authors found no apparent effect of supplementations on child cognitive composite scores as compared to placebo. Neither iron syrup nor multiple micronutrient powders improved motor or language development, child behavior, temperament, either immediately after completion of the assigned regimen or at 9 months after completion.

Effects of iron intake on neurobehavioral outcomes in African children: a systematic review and meta-analysis of randomized controlled trials

Comments: The investigators performed a systematic review and meta-analysis including 35 RCT of which only 5 studies regarding 258 African children, whose range of age was 18 months up to 14 years. The authors found poor and heterogeneous evidence for the effects of iron supplementation or fortification on neurobehavioural outcomes. Once More, further well-designed studies should be performed on the developmental effects of nutritional interventions in African populations, with translational value as an approach to most developing and/or transition countries. A possible reason for discrepancies in results from narrative and/or systematic reviews may mainly depend on differences at baseline conditions among populations and groups that have been investigated as well as differences in study designs and nutritional interventions.

Pre-conceptional maternal vitamin B12 supplementation improves offspring neurodevelopment at 2 years of age: PRIYA trial

Comments: Within the Pune Rural Intervention in Young Adolescents (PRIYA) trial, this study aimed to evaluate the role of maternal preconceptional B12 and micronutrient supplementation (starting at 17 years) on offspring neurodevelopmental performance at 24–42 months of age, in India. The enrolment included 266 adolescent females, randomized to receive either a placebo (first arm), B12 plus multiple micronutrients (second arm), or B12 alone (third arm), from preconception stage until delivery. Intervention groups were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients. Among enrolled women, 149 delivered a live baby. After 2 years the parents of 85 children have been approached for the cognitive assessment, that has been stopped in February 2020, due to the COVID-19 pandemic, and the final analysis was based on 74 children. The supplementation of adolescents with 2 μg/day ofB12 significantly improved their own B12 status (total B12 and holo-transcobalamin,TC) and offspring cord blood holo-TC, with a positive impact on the cognitive development of their children at 2 years of age.

Maternal iodine intake and neurodevelopment of offspring: the Japan environment and children’s study

Comments: This study was based on the Japan Environment and Children’s Study (JECS), a prospective birth cohort, and investigated maternal iodine intake during gestation on neurodevelopmental delay in their children. In total, 75,249 and 66,604 mother-child pairs with children aged 1 and 3 years, respectively, were enrolled for analysis. The authors found out that low iodine intake levels in pregnancy increased the risk of delay in child neurodevelopment at 1 and 3 years of age, and the number of pregnant women with poor iodine status was almost widespread.

Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms

Comments: The authors used samples from their previous RCT of folic acid (FA) supplementation in either the second and third trimester, where significant improvements of cognition have been demonstrated in children from mothers supplemented with FA during pregnancy. Genes showing significant differences were identified using pyrosequencing and mechanistic approaches. Continued FA supplementation of pregnant mothers in the second and third trimester of pregnancy led to genome-wide hypomethylation in the cord blood of their offspring. Tissue-specific gene ontology analysis and analysis of top-ranking regions highlighted a strong association with neurodevelopmental steps. The results further support evidence for a continued supplementation FA throughout later gestation, even beyond the time limit suggested for the prevention of neural tube defects.

General Comments: We have presented a selection of studies on micronutrient intakes during preconception, pregnancy, and first phases of life in developing and developed countries, and their associations with neural performances. It is widely agreed that ensuring adequate maternal micronutrient intake, in particular, iron, vitamin B12, iodine, and folic, is mandatory to optimize early-life neurodevelopment. Uncertainty still remains, after years of intensive and extensive research on the association between dietary supplementations of iron and FA in pregnancy, respectively, on neurodevelopmental scores later on. According to previous intervention studies and observations, available evidence suggests that (1) iron supplementation has positive effects when the iron-deficiency anemia is clinically suggestive and confirmed by blood biochemistry, and (2) when the supplementation with FA, even if protracted, is maintained within recommended dosages [1, 2]. Based on these observations, newer well-designed studies in developing countries are required to better understand the effects and needs in settings where poor nutrition is common.

LC-PUFA (Long Chain Poly-Unsaturated Fatty Acid

Prenatal docosahexaenoic acid effect on maternal-infant DHA-equilibrium and fetal neurodevelopment: a randomized clinical trial

Comments: This randomized, longitudinal, double-blind, single-center trial, conducted at the University of Kansas Medical Center (USA), aimed to examine the rate of maternal-infant docosahexaenoic acid (DHA) equilibrium at delivery and its effect on fetal heart rate variability (HRV) score and fetal autonomic brain age score (fABAS) at 32 and 36 weeks gestation. Three hundred pregnant women have been randomly supplemented with200 or 800 mg of DHA during pregnancy until delivery and blood samples of 262 maternal-infant dyads have been collected at delivery. Power computations have indicated that 125 participants per group may provide 88% power. Participants who received a higher dose of DHA were more likely to achieve maternal-infant DHA equilibrium at delivery. Moreover, there is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. However, within this sample, the equilibrium status was not related to fetal neurodevelopment.

Omega-3 fatty acid dietary supplements consumed during pregnancy and lactation and child neurodevelopment: a systematic review

Comments: The authors performed a systematic review to evaluate the impacts of omega-3 fatty acid supplementation before and during pregnancy and lactation on cognitive development in children. Finally, 33 articles have been included. According to their conclusions, omega-3 fatty acid supplementation during pregnancy may be beneficial for neurodevelopment in children. However, there was insufficient and heterogeneous evidence to make a specific recommendation about routine supplementation with omega-3 fatty acids before and during pregnancy and breastfeeding.

Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: a randomized, triple-blinded, controlled clinical trial

Comments: This triple-blind, randomized, controlled clinical trial compared neurocognitive function in 2,565 Malawian children with uncomplicated severe acute malnutrition, age range 6–59 months, treated with 3 different ready-to-use therapeutic food (RUTF):RUTF made with reduced amounts of linoleic acid (LA) without added DHA (HORUTF),first arm; added DHA (DHA-HORUTF), second arm; and standard RUTF (SRUTF, third arm). The results showed that DHA-HORUTF achieved superior global Malawi Developmental Assessment Tool (MDAT) z-scores than children who consumed SRUTF. This study provides the first direct evidence that reduction in LA and addition of DHA in RUTF enhances cognition in children with severe acute malnutrition.

General Comments: We have selected 3 studies with heterogeneous results. Indeed, in the first RCT, maternal DHA equilibrium status was not related to fetal neurodevelopment, while the other 2 studies may support that omega-3 supplementation during gestation and childhood may positively influence brain development and cognitive function. Waiting for larger trials, we may consider the various individual polymorphisms of individual fatty acids, to explain the differences of results according to genetics. Nevertheless, nonnegative results have been found in association with LC-PUFA supplementations in terms of cognitive achievement. On the whole, the results from these investigations and other studies suggest reconsidering the effects of the whole pattern of FA, not limited to longer-chain PUFA, considering the peculiar, favorable observations at long term of breastfeeding and human milk composition, inclusive of the whole FA pattern, on developmental scores.

Toxicity

The benefits of fish intake: results concerning prenatal mercury exposure and child outcomes from the ALSPAC pre birth cohort

Comments: This review used data collected by the Avon Longitudinal Study of Parents and Children (ALSPAC) [3, 4], in a relatively industrialized area in south-west of England, to assess the influence of maternal consumption of mercury-containing foods during pregnancy on child cognitive development. The investigators have summarized the results of 12 papers that have used data from the ALSPAC. Estimates of fetal mercury exposures have been compared with various cognitive outcomes measured during the child’s development, such as preschool cognition assessment (vocabulary, social activity), school-age cognition assessment (IQ full-scale, IQ verbal, IQ performance),and 6 measures of behavior. Positive and significant associations with prenatal mercury levels were shown for total and performance IQ, mathematical/scientific reasoning, and birthweight in fish-consuming versus non-fish-consuming mothers. Seafood Contains several dietary factors, first of all PUFAs, but also others, such as iodine and amino acids, that may contribute to neurodevelopment, beyond the potential negative effects of metal’s contamination

Impact of dietary mercury intake during pregnancy on the health of neonates and children: a systematic review

Comments: The investigators conducted a systematic review to examine the relationships between maternal exposure to methylmercury with diet during gestation and the health of the offspring up to 8 years of age. It is widely agreed that maternal high mercury levels during pregnancy relate to lower scores in various neuropsychological and developmental tests. Nevertheless, consistent with the findings from the ALSPAC study, mercury toxicity may be attenuated by other crucial nutrients in the maternal diet, such as PUFAs.

Interaction of prenatal bisphenols, maternal nutrients, and toxic metal exposures on neurodevelopment of 2-year-olds in the APrON cohort

Comments: The authors investigated 394 mother-child pairs to examine the total bisphenol-A(BPA) and bisphenol-S (BPS) concentrations of metals and maternal nutrient status on child cognitive development at 2 years of age. All samples and data were extracted from mothers and children participating in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Results showed that only higher maternal exposure of cadmium, in particular from canned fish [5], was significantly associated with lower motor scores but it did not modify the relationships between bisphenols and neurodevelopment in the present cohort. Furthermore, maternal selenium status was a significant effect-measure modifier of the relationship between maternal bisphenols and child motor development, appearing protective against the adverse effects of bisphenols.

General Comments: Through many years observational studies have increasingly considered the effects of toxic element intake during pregnancy on child cognition. The main dietary sources of toxic elements are usually represented by water, rice grain and other cultivated grains, vegetables, chicken, soil, and marine organisms, especially fish and seafood from coastal areas, associated with industrial discharge [6, 7]. On the other side, the role of whole foods and their dietary patterns as far neuroprotection should be considered too. Examples are represented by fish (as in the ALSPAC study) with its whole composition, compared with the potential negative effects of mercury, as well as other examples of negative (such as cadmium) and positive(such as selenium) contributors in neuroprotection.

References

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