Cognition (N&G 2024)

Cognition

Introduction

The chapter includes articles published from July 1, 2022 up to June 30, 2023, focusing on the connections between infant and children nutrition and cognition. Original articles on nutrition and cognition comprising randomized controlled trials (RCTs), observational studies, and reviews have been selected. The selected articles fall into two macroareas, subdivided into two main categories, subdivided in turn into further topics:

1. Mother-infant dyad, subdivided into macronutrients, iodine, vitamin B12, other nutrients, and gut microbiome

2. Infants and children, subdivided into dietary habits and food and nutrients. 

The studies concerning intrauterine life and lactation stage, respectively, are mostly concentrated
to maternal dietary intakes of single nutrients, but growing interest is taking place for maternal intakes of macronutrients and dietary habits. These studies are also growing in the postlactational stages, from the start of complementary feeding onward up to later pediatric ages (comprehensive of adolescence). This approach is consistent with the general issues of sustainability, considering diet a correlate of lifestyle, setting, socioeconomic conditions, and local resources as part of the exposome, the sum of external factors that, in association with gene-related predisposition, is a major determinant of growth and development during childhood.

We have reported the selected papers by using a rather homogeneous approach to underline differences in topic, effects (for RCTs) and/or associations (for prospective and observational studies and reviews), settings, approach, and results on developmental parameters as separated outcome, in order to allow a clearer interpretation of the results while contextualizing the research in an appropriate way.

The specific comments will follow any section, while a short final overview will summarize the possible evolution steps of the research in nutrition and development.

Mother-Infant Dyad
Macronutrients

Neurodevelopment, vision and auditory outcomes at age 2 years in offspring of
participants in the ‘Women

Macronutrient: lipids
Setting: rural Democratic Republic of the Congo, Guatemala, India, and Pakistan
Effect: no
Study: RCT
Treatment/methods: Maternal lipid-based nutrient supplement initiated preconceptionally (arm 1,n = 217), at 12 weeks of gestation (arm 2, n = 230), or not (arm 3, n = 220); intervention stopped at delivery.

Age-related effects: Prenatal maternal nutrition supplementation was not associated with any neurodevelopmental outcomes at age 2 years. Maternal education, family environment, and length-for-age Z-score at 24 months predicted early child development.

The association between maternal ultra-processed food consumption during
pregnancy and child neuropsychological development: a population-based birth
cohort study

Macronutrient/food: ultra-processed food (UPF)
Setting: Spain
Association: partial
Study: prospective cohort study
Treatment/methods: Food frequency questionnaire during weeks 12 and 32 of gestation. The NOVA classification was used to identify UPFs. Child neuropsychological development was assessed with the Bayley Scales of Infant and Toddler Development and the McCarthy Scales of Children’s Abilities.

Age-related associations: Adverse association between maternal consumption of UPF during pregnancy and verbal functioning in early childhood (4–5 years of age)

Processed foods and diet quality in pregnancy may affect child neurodevelopment
disorders: a narrative review

Macronutrients/food: ultra-processed food (UPF)
Setting: the United Kingdom, Europe, the United States (mostly)
Associations: yes
Study: review
Treatment/methods: PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Scholar databases were
searched for original articles.
Age-related associations: Child cognitive development was negatively impacted by a maternal diet with many UPFs, saturated fats, and total sugars (especially those added or hidden in packaged carbonated beverages). Conversely, a Mediterranean diet led to better neurodevelopment, particularly verbal intelligence and executive functions, in middle childhood.

Prenatal exposure to trans fatty acids and head growth in fetal life and
childhood: triangulating confounder-adjustment and instrumental variable
approaches

Macronutrient: lipids/trans-fatty acids (TFAs)
Setting: the Netherlands
Association: partial
Study: prospective cohort study
Treatment/methods: Maternal plasma TFA concentration was assessed using gas chromatography in midgestation. Offspring head circumference (HC) was measured in the second and third trimesters using ultrasonography; childhood brain morphology was assessed using magnetic resonance imaging at age 10 years.

Age-related associations: A higher gestational TFA level was associated with a smaller fetal HC in the third trimester and lower fetal HC growth rate from the second to the third trimester. No association between prenatal TFA exposure and nonverbal IQ at age 6 years. No association between prenatal exposure to TFAs and fetal HC in the second trimester or global brain volume at age 10 years.

Circulating levels of short-chain fatty acids during pregnancy and infant
neurodevelopment

Macronutrient: lipids/short-chain fatty acids (SCFAs)
Setting: Spain
Associations: yes
Study: prospective cohort study (ECLIPSES)
Treatment/methods: Serum SCFA concentrations were assessed in the first and third trimester of pregnancy by liquid chromatography with tandem mass spectrometry; infant cognitive development and temperament have been assessed by Bayley Scales of Infant Development-III and the Early Infancy Temperament Questionnaire.

Age-related associations: Lower serum levels of acetic, butyric, and isobutyric acid, mainly during the first trimester, were related to better language and psychomotor development and, in the case of butyric acid, better intensity behavior in infants. Medium levels of propionic acid were related to better scores for development, mood, and temperament, at 40 days of age.

The impact of maternal high-fat diet on offspring neurodevelopment

Macronutrients: fats
Setting: animal studies (RCTs and observations)
Effects: unclear
Study: review (partly systematic)

Treatment/methods: Recent findings from rodent models and from human studies have been reviewed to study the potential effect of maternal high-fat diet (mHFD) on neurodevelopment of the offspring, including both male and female animals in biological studies; therefore, most recent publications started describing female phenotype as well.

Age-related effects: The effect of mHFD on brain remains underinvestigated, particularly on females. Most of the intervention research is performed on animal models and we are in pressing need of human studies.

Comments: Within this area of growing interest, the unique RCT selected comes from developing countries, showing no effect of a prenatal maternal nutrition supplementation of lipids with any neurodevelopmental outcomes at age 2 years, while environmental factors accounted for most of the observed differences. The results suggest the need to consider confounders even in settings where malnutrition is a common condition and any type of supplementation is usually considered as positive. The authors conclude that “a multisectoral approach is needed to maximize opportunities to improve children’s early development.” Two observational studies (one as review) from rich, well-developed settings underline negative associations between the maternal consumption of ultra-processed foods (UPFs) in pregnancy and later developmental measures in middle childhood. A poor environmental setting cannot be excluded from observational studies, in a cause-reverse relationship, mainly due the lower cost of UPF compared to whole, fresh foods. Finally, two observational papers on fatty acids have been included, out of the usual long-chain polyunsaturated fatty acids (LC-PUFA) issue, and focused on trans-fatty acids (TFA, showing negative associations even at long term) and short-chain fatty acids (SCFA, positive associations for propionic acid at short term), respectively, and developmental achievements. Experimentally, the role of total fat intakes is controversial and possibly underinvestigated as far as brain development. On the whole, more research on the role of fats and supposed “minor” fatty acid families is actually needed on the role in neurodevelopment, besides the overinvestigated role of PUFA and LC-PUFA.

Iodine

A scoping review of iodine and fluoride in pregnancy in relation to maternal
thyroid function and offspring neurodevelopment

Micronutrients: iodine and fluoride
Setting: Europe, Asia (mostly)
Associations: unclear
Study: scoping review

Treatment/methods: Scoping review of the literature on iodine and fluoride exposure during pregnancy and their individual effects on thyroid function and offspring neurodevelopment. Just one study has been found associating both the exposures.
Age-related associations: Fluoride intake might interfere with iodine status and adversely affect thyroid function during a critical intrauterine period of brain development, but more studies are needed, for sure.

Prenatal iodine supplementation and early childhood neurodevelopment:
the PoppiE trial – study protocol for a multicentre randomised controlled trial

Micronutrient: iodine
Setting: Australia
Effects: ongoing study up to 24 months of age
Study: RCT
Treatment/methods: A total of 754 women (377 per group) less than 13 weeks’ gestation with an iodine intake of ≥165 μg per day from food have been randomized to receive either a low iodine (20 μg per day) multivitamin and mineral supplement or an identical supplement containing 200 μg per day (amount commonly used in prenatal supplements in Australia), from enrolment until delivery. Neurodevelopment of infant will be assessed using the Cognitive Scale of the Bayley-IV and behavioral and emotional development of infants using the Infant Toddler Social Emotional Assessment.

Age-related effects: Ongoing study, effects on children of 24 months of age

Comments: The role of iodine (I) deficiency in maternal thyroid function and offspring neurodevelopment is well known. Effects of iodine on cognition are however underestimated, particularly in well-developed countries. The first review highlights the possible interference of fluoride (F) on maternal iodine status, with a consequent adverse association with the thyroid function during a critical prenatal period of brain growth. Since both iodine and fluoride may be prescribed to pregnant women, further data are needed to define recommendations for iodine intake and fluoride exposure for pregnant women. The second article is a protocol of an RCT trial to evaluate maternal iodine supplementation during pregnancy and its role on early childhood neurodevelopment. The study is the first RCT to investigate childhood neurodevelopmental outcomes following reduced prenatal iodine supplementation in an iodine-sufficient population living in Australia.

Vitamin B12 and Related Compounds

Association between maternal choline, fetal brain development, and child
neurocognition: systematic review and meta-analysis of human studies

Micronutrient: choline
Setting: mostly well-developed countries
Effects/association: yes
Study: systematic review and meta-analysis
Treatment/methods: A total of 30 articles have been selected (including case-control studies, RCT, and observational studies) addressing neural tube defects (NTDs) and associations between prenatal and early postnatal choline intake, brain development, and neurocognitive function of children.
Age-related effects/associations: Low maternal choline intake/circulating serum total choline in early pregnancy was associated with a 36% higher odds ratio for NTDs. In general, RCTs providing up to 1 g choline per day to women during the second part

Maternal choline supplementation: a potential therapy for developmental
manganese exposure?

Micronutrient: choline
Setting: animal studies
Effects: partial
Study: RCT
Treatment/methods: Starting at gestational day 3, pregnant dams were given standard diet or diet with additional choline throughout gestation and lactation until offsprings were weaned. Pups were exposed orally to 0 or 50 mg Mn/kg per day during early postnatal life. In adulthood, animals were tested in the five-choice serial reaction time task and the Montoya staircase task, to assess impulsivity, focused and selective attention, behavioral reactivity to errors or omission of an expected reward, and sensorimotor function.

Age-related effects: The maternal choline supplementation (MCS) was partially effective in protecting against Mn-induced deficits, particularly in the domains of attentional function and behavioral reactivity (at 12–24 hours after birth). Collectively, these findings demonstrate that MCS may hold promise as nutritional intervention to protect against the neurotoxic impacts of elevated Mn exposure. These findings, taken with evidence from other studies demonstrating the benefit of MCS to offspring and the fact that ∼90% of women consume less than the adequate intake of choline, inform the recommendation that MCS should be considered for pregnant women.

Associations between maternal folate status and choline intake during pregnancy
and neurodevelopment at 3–4 years of age in the Alberta Pregnancy Outcomes and
Nutrition (APrON) study

Micronutrient: folate and choline
Setting: Canada
Associations: no
Study: prospective cohort study (APrON)

Treatment/methods: Maternal-child pairs (n = 309) from the APrON study have been enrolled. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall. Their children’s neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence – Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children – Second Edition.
Age-related associations: Maternal folate status and choline intake during the second trimester of pregnancy were not associated with children’s intelligence, language, memory, or motor outcomes at 3–4 years of age; however, their interaction may have an influence on children’s executive functions.

Maternal vitamin B12 status during pregnancy and early infant neurodevelopment:
the ECLIPSES study

Micronutrient: Vitamin B12
Setting: Spain
Associations: yes
Study: prospective cohort study (ECLIPSES)
Treatment/methods: A total of 434 mother-infant pairs from the ECLIPSES study have been enrolled, to examine maternal vitamin B12 status at the beginning and end of pregnancy and the neurodevelopmental outcomes of infants 40 days postpartum using the Bayley Scales of Infant Development-III (BSID-III, cognitive, language, and motor skills).
Age-related associations: Medium maternal first-trimester vitamin B12 levels (312 to 408 pg/mL, tertile 2) were associated with better neonatal performance in the motor, gross motor, language, and cognitive skills with respect to tertile 1 (<312 pg/mL), at 40 days after birth. The probability of obtaining a neonatal motor, gross motor, and receptive language score >75th percentile was significantly higher also in the tertile 2 group.

Comment: Neural tube defects (NTDs) still occur among some women who consume 400 μg of folic acid for prevention. Since intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs, we have considered together papers on B12, folate, and choline. Within this context, a positive influence on neurodevelopment is biologically plausible.

In the first paper, the authors underline the association between maternal choline
intake and child neurocognition/neurodevelopment. Despite limitations of available
trials and observational studies, higher maternal choline intakes may be associated
with better child achievements and should be considered in pregnancy and lactation
since because most young women are not achieving the reference intake of choline.
Furthermore, maternal choline supplementation shows neuroprotective effects too in rodent model. The last two studies reported here show limited associations of maternal folate and choline intake in the second trimester of gestational age (GA) and positive effects of moderately higher maternal vitamin B12 levels in the first trimester of GA on neurocognitive functions at either long (3–4 years ages) or short (40 days) term, respectively. A higher degree in homogeneity study designs is recommendable, to derive practical suggestions on time of intakes and outcomes to suggest appropriate dietary recommendations to mothers in pregnancy.

Other Nutrients

Maternal vitamin D levels during pregnancy and offspring psychiatric outcomes: a
systematic review

Micronutrient: vitamin D
Setting: mostly developed countries
Associations: partial
Study: systematic review

Treatment/methods: Systematic searches have been conducted using MEDLINE, Embase, PsychINFO, and Web of Science for studies to examine the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and offspring neuropsychiatric and psychiatric outcomes. Twenty-nine studies have been included.
Age-related effects: A small amount of evidence shows associations between prenatal vitamin D deficiency and autism spectrum disorders. When studies with larger sample sizes and stricter definitions of vitamin D deficiency were considered, positive associations of vitamin D deficiency were found for attention deficit/hyperactivity disorder and schizophrenia.

Neuroprotective role of lactoferrin during early brain development and injury
through lifespan

Micronutrient: lactoferrin
Setting: mostly animal studies
Associations: yes, for biologic plausibility
Study: narrative review

Treatment/methods: In this narrative review, the role of several nutrients during neurodevelopment has been investigated, particularly focusing on lactoferrin in experimental studies, underlying its presence in human milk and the biological plausibility on brain functions.
Speculation: New evidence, mostly on experimental basis, indicates that early neuroprotective
pathways modulated by lactoferrin could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes. At present, the study supports speculations about functional effects of lactoferrin on the immune response (the same as vitamin D, for instance) on neurodevelopment too.

Comments: In the narrative review on vitamin D, 29 studies have been considered and the author found positive associations of low maternal vitamin D levels with attention deficit/
hyperactivity disorder and schizophrenia in the offspring. The findings could have important implications for public health, as vitamin D deficiency can be readily prevented with vitamin supplements. The second narrative review underlines the potential role of lactoferrin during a period of high cerebral vulnerability, speculating on effects to ensure optimal neurodevelopment, to be confirmed in humans too. Since there is general agreement on the positive effects of either vitamin D or lactoferrin on immune responses, positive effects of both compounds on brain development could support the hypothesis of a shared collaborations between two main integrated networks, that is, the immune and the nervous system, respectively, possibly deriving from a close origin at the level of embryonic tissues.

Gut Microbiome.

Maternal anxiety, depression and stress affects offspring gut microbiome diversity
and bifidobacterial abundances

Nutrient related: infant microbiome
Setting: well-developed area (California)
Associations: yes
Study: longitudinal study

Treatment/methods: In the pre- and postnatal period, maternal stress, anxiety, and depression have been assessed with standardized instruments (the OASIS, PHQ, and PSS, respectively) and maternal inflammatory cytokine levels analyzed. Offspring microbiome have been characterized by using full length 16S sequencing on infant stool samples.

Age-related associations: The diversity and composition of the infant stool microbiome between 5 and 13 months of age are associated with maternal anxiety, depression, and stress metric levels both during pregnancy and the postpartum.

Mechanisms of maternal diet-induced obesity affecting the offspring brain and
development of affective disorders

Nutrient related: infant microbiome

Setting: animal experiments and humans mostly in well-developed countries (North Europe, Australia)

Associations: yes
Study: review (at preclinical and clinical level)

Treatment/methods: Overview of preclinical and clinical studies investigating mechanisms of maternal diet–induced obesity and association between maternal obesity, microbiome, and altered behavioral outcomes in children

Age-related associations: Current literature supports preclinical evidence that the maternal microbiota is associated with offspring development and behavior. Clinical studies have shown associations between childhood maltreatment with altered neurobiology and behaviour. The gut microbiome may act as a key modifiable, and therefore treatable feature of the relationship between maternal obesity and the offspring and infant brain function.

Comments: These selected studies focused on maternal and infant/offspring microbiome composition and possible associations with development. Specific microbial taxa involved in maintaining proper brain and immune function are lower in those born to mothers with mental health disorders, and, at the same time, a direct modification of the maternal microbiota seems to be associated with metabolic and/or mood disorders in the offspring. Once more, the collaboration between an immune-related system (microbiota composition) and brain function may be hypothesized.

Infants and Children
Dietary Habits

Children with lower ratings of executive functions have a greater response to the
portion size effect

Nutrient related: portion size
Setting: well developed (Pennsylvania)
Associations: yes
Study: prospective longitudinal study
Treatment/methods: Parental ratings of child executive functions (EFs) from the Behavior Rating Inventory of Executive Function 2 (BRIEF2) and children’s measured food intake across four meals to assess intake in response to increasing portion size

Age-related associations: EFs moderated the portion size effect such that lower, including Behavioral (BRI) and Emotional (ERI), indices were associated with increases in intake as portions increased. As amount of food increased, children in the lowest functioning tertiles increased intake by 35% and 36%, respectively, compared to children in the higher tertiles, at 7–8 years of age, independent of child and parent weight status. Accordingly, an intervention on EF behaviors could help children to moderate excess intake in response to large portions of energy-dense foods.

Is adherence to the Mediterranean diet associated with good sleep duration in
primary-school children?

Nutrient related: Mediterranean diet (MD)
Setting: Italy
Effects: yes

Study: cross-sectional study
Treatment/methods: The “adherence to the MD” in association with the quality of sleep has been poorly investigated in children from the primary school. In Italian primary school children, the association has been indagated through questionnaires administered to mothers and derived from the Italian version of the KidMed index.

Age-related associations: For children with a good sleep duration, the odds ratio of a poor-to-moderate adherence to the MD was very low, with an average score of 0.282 (95% CI, 0.109–0.681, p <0.05), at 6 years of age.

Are dietary patterns related to cognitive performance in 7-year-old children?
Evidence from a birth cohort in Friuli Venezia Giulia, Italy

Nutrient related: dietary patterns (DPs)
Setting: Italy
Effect: partial
Study: cross-sectional study

Treatment/methods: Dietary patterns were identified through a principal component factor analysis based on 37 nutrients from children’s 3-day dietary records. The Wechsler Intelligence Scale of Children (WISC-IV) test provided measures of cognitive performance, including the full-scale intelligence quotient (FSIQ) and single index scores.

Age-related associations: No significant relationships were observed with the FSIQ score; positive associations were found between the “Seafood” DP and Verbal Comprehension Index or Perceptual Reasoning Index. The “Meat and Potatoes” and “Dairy Products” DPs were inversely associated with the Verbal Comprehension Index and Processing Speed Index scores, respectively, in children aged 7 years.

Unfavorable behaviors in children run in packs! Dietary and non-dietary
modulators of attentional capacity

Nutrient related: breakfast
Setting: Germany
Association: partial
Study: cross-sectional study (CogniDROP intervention study)

Treatment/methods: Children performed a simple computerized Visual Attention Task and an-
swered a questionnaire about behavioral patterns, i.e., skipping breakfast on a school day, frequency of physical activity (PA) outside school, and nighttime sleep.
Age-related associations: Almost 11% of children, at 10–11 years of age, (grade 5–6 of school in Germany) left home in the morning without breakfast, more than 9.5% of children reported poor sleep quality, 24.9% slept less than the recommended 9 h, and girls were insufficiently physically active. Sleep duration, bedtime, and PA correlated with skipping breakfast. Better sleep quality was positively related to reaction time in the Visual Attention Task. Skipping breakfast in the morning seems to be associated with other unfavorable habits.

Comments: Dietary patterns and associations with neurodevelopment and behavior are an
emerging area of interest, according to the interpretation that we do not eat foods,
but whole foods, varying in composition, and within the wide diversity of local dietary
patterns. Food form and tradition, based on local resources, are consistent also with
the concept of sustainable nutrition. Adequate portion size at meals, eating breakfast,
adherence to healthy local models of diet such as the Mediterranean diet, and eating fish show associations with favourable scores of functional developmental achievements, including good sleeping habits. Reverse causality cannot obviously be excluded, based on prospective and cross-sectional studies (considering parents’ socioeconomic status, instruction achievement, and lifestyle).

Foods and Nutrients

Macronutrient intake during infancy and neurodevelopment in preschool children
from the EDEN mother-child cohort

Nutrient: macronutrient
Setting: France
Effect: no
Study: prospective cohort study (EDEN study)
Treatment/methods: Macronutrient intake was assessed by 3-day food records at 12 months of age. Neurodevelopment was assessed using the French version of the Ages and Stages Questionnaire (ASQ) and the French version of the Wechsler Preschool and Primary Scale of Intelligence – Third Edition.

Age-related associations: Macronutrient intake at 12 months was not associated with neurodevelopmental scores in children at 3 and 5–6 years. No association was found between polyunsaturated fatty acid intake and overall neurodevelopmental scores, after accounting for multiple testing.

Nutrient trajectories during infancy and their associations with childhood
neurodevelopment

Nutrient: trajectories of macronutrient intake
Setting: Singapore
Effects: partial
Study: prospective cohort study (GUSTO study)
Treatment/methods: One-day food records were collected to assess dietary intakes, while Bayley Scales of Infant and Toddler Development-III and Kaufman Brief Intelligence Test-2 were conducted to assess child neurodevelopment.
Age-related associations: Protein, total fat, and carbohydrate intake trajectories from 6 to 12 months of infancy had significant but heterogeneous and even opposing associations with childhood language and motor development, while dietary fiber intake trajectory was positively associated with fine motor development at age 24 months. Total energy trajectory showed no significant associations with neurodevelopment outcomes. No associations were found between nutrient trajectories and neurodevelopment outcomes at 54 months of age.

Defining the relationship of gut microbiota, immunity, and cognition in early life –
a narrative review

Nutrient: microbiota
Setting: narrative review (experimental and human studies)
Effects: yes
Study: review

Treatment/methods: A comprehensive literature search was conducted in March 2022 across data bases including Google Scholar, PubMed, EMBASE, and Cochrane.

Age-related effects: Gut microbes influence neurogenesis, myelin formation, and immune and cognitive functions. While limited, evidence shows how gut microbiota affects innate and adaptive immunity as well as cognition. This review underlines the need for increased awareness of gut microbiota’s role in health, particularly given the observed impacts during the first 1,000 days of life.

New perspectives on the associations between blood fatty acids, growth
parameters, and cognitive development in global child populations

Nutrients: fatty acids
Associations: yes
Setting: global, focusing on low- and middle-income countries – Africa, Asia
Study: narrative review
Treatment/methods: Comparison of polyunsaturated fatty acid (PUFA) levels between global child populations; PUFAs and growth parameters; PUFAs and cognitive development; highly unsaturated fatty acids, growth parameters, and cognitive development
Age-related associations: It would be beneficial to utilize a unified approach to collect and measure fatty acids, focusing on levels of those predictive of, or indicating, malnutrition. The observed data could reflect the children’s nutritional status and also aid in the direct comparison between values in comparative studies. The observations could help to develop appropriate interventions to reverse essential fatty acid deficiency during sensitive developmental periods, with the aim to promote proper growth and cognition throughout childhood, adolescence, and adulthood.

Comments: The selected studies reflect the absolute need (in this case) to collect data on the role of macronutrient intakes, microbiota, and fatty acids at a global level (in either well developed and developing countries). The intakes here collected concern the most relevant nutrients and nutrient-related topics (macronutrients, microbiome, and long-chain fatty acids). We should ensure the access to intakes of major nutrients able] to sustain growth and neurodevelopmental achievements for all children throughout the world. The heterogeneity and the paucity of data and associations now available indicate to concentrate efforts toward this direction. As final observation, the last paper reported here reinforces the hypothesis of a close relationship between the immune function and cognition in the first stages of life, with a mediatory effect of the infant microbiome.

Overview: Independent roles of single nutrients, compounds, foods, and dietary patterns starting from the maternal-fetal/infant dyad up to later childhood on cognitive functions represent hot topics. Available data are mainly derived from well-developed, rich, Western countries, but more knowledge from developing countries is needed to plan effective nutritional strategies. Most study designs are highly heterogeneous, whichever the setting, preventing to draw conclusive remarks. To disentangle the role of nutrients and/or diet on cognition in a short time, the usual sentence, “more data are needed from well-done RCTs with adequate sample size,” should be supported, or even overcome, by newer methodological and analytical approaches such as those derived from machine learning models.