Previous studies have suggested that prenatal maternal folate deficiency is associated with reduced prenatal brain growth and psychological problems in offspring. However, little is known about the longer-term impact. The aims of this study were to investigate whether prenatal maternal folate insufficiency, high total homocysteine levels and low vitamin B12 levels are associated with altered brain morphology, cognitive and/or psychological problems in school-aged children. This study was embedded in Generation R, a prospective population-based cohort study. The study sample consisted of 256 Dutch children aged between 6 and 8 years from whom structural brain scans were collected using MRI. The mothers of sixty-two children had insufficient (<8 nmol/l) plasma folate concentrations in early pregnancy. Cognitive development was assessed by the Snijders-Oomen Niet-verbale intelligentietest – Revisie and the NEPSY-II-NL. Psychological problems were assessed at age 6 years using the parent report of the Child Behavior Checklist. Low prenatal folate levels were associated with a smaller total brain volume (B –33·34; 95 % CI –66·7, 0·02; P=050) and predicted poorer performance on the language (B –0·28; 95 % CI –0·52, –0·04; P=0·020) and visuo-spatial domains (B –0·27; 95 % CI –0·50, –0·04; P=0·021). High homocysteine levels (>9·1 µmol/l) predicted poorer performance on the language (B –0·31; 95 % CI –0·56, –0·06; P=0·014) and visuo-spatial domains (B –0·36; 95 % CI –0·60, –0·11; P=0·004). No associations with psychological problems were found. Our findings suggest that folate insufficiency in early pregnancy has a long-lasting, global effect on brain development and is, together with homocysteine levels, associated with poorer cognitive performance.

Neurodevelopment has been linked, among other factors, to maternal and early infant diets. The objective of this review, which is part of the NUTRIMENTHE research project ‘The effect of diet on the mental performance of children’ (www.nutrimenthe.com), was to update current evidence on the effects of nutritional interventions such as iron, folic acid or n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy and/or in early life on the mental performance and psychomotor development of children. In May 2014, we searched MEDLINE and The Cochrane Database of Systematic Reviews for relevant studies published since 2009. The limited updated evidence suggests that iron supplementation of infants may positively influence the psychomotor development of children, although it does not seem to alter their mental development or behaviour. The use of multivitamin-containing folic acid supplements during pregnancy did not benefit the mental performance of the offspring. Evidence from randomised controlled trials (RCT) did not show a clear and consistent benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on childhood cognitive and visual development. Caution is needed when interpreting current evidence, as many of the included trials had methodological limitations such as small sample sizes, high attrition rates, and no intention-to-treat analyses. Taken together, the evidence is still inconclusive. Large, high-quality RCT to assess the effects of supplementation with iron, LCPUFA or folic acid are still needed to further clarify the effects of these, and other nutrients, on neurodevelopment. Recent recommendations from scientific societies are briefly presented.

The aim of this study was to assess the economic benefits of improved cognitive development related to being breast-fed. Breast-feeding rates were assessed in the Avon Longitudinal Study of Parents and Children. Educational attainment was assessed at age 16 years with higher attainment defined as gaining five General Certificate of Secondary Education (GCSE) passes at a high grade. The economic benefit of being breast-fed was calculated in a decision model using a child’s educational attainment and the corresponding expected value of average income in later life. There was a positive association between being breast-fed and achieving higher educational attainment, which remained significant, after adjustment for possible confounders: being breast-fed <6 months yielded an OR of 1·30 (95 % CI 1·13, 1·51) and for ≥6 months yielded an OR of 1·72 (95 % CI 1·46, 2·05), compared with never breast-fed children. On the basis of UK income statistics, the present value of lifetime gross income was calculated to be £67 500 higher for children achieving 5 high-grade GCSE passes compared with not achieving this. Therefore, the economic benefit of being breast-fed <6 months would be £4208 and that for ≥6 months would be £8799/child. The model shows that the increased educational attainment associated with being breast-fed has a positive economic benefit for society, even from small improvements in breast-feeding rates. Within a total UK birth cohort of 800 000/year an increase by 1 % in breast-feeding rates would be worth >£33·6 million over the working life of the cohort. Therefore, breast-feeding promotion is likely to be highly cost-effective and policymakers should take this into consideration.

In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4–18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child’s gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

Although the impact of diet on physical health is an important public health issue, less attention has been devoted to the relationship between nutrition and children’s mental development. The views of parents and teachers about the extent to which diet affects physical and mental development of children were compared in four European countries. An online questionnaire (developed in English and translated) was circulated through a market research agency. Participants were parents or teachers of children aged 4–10 years without learning or behavioural issues. Questionnaires were returned by 1606 parents (401 in England, Germany and Hungary; 403 in Spain) and 403 teachers (100 in each country, except for 103 in Hungary). Teachers were older than parents (35·3 % v. 18·3 % over 45 years; P<0·001) and less likely to smoke (15·9 % v. 26·3 %, P<0·001). There was no difference between the proportions of parents and teachers who felt that a child’s physical development depended very much/extremely (v. moderately/slightly/not at all) on diet (overall 79·8 %). Lower proportions of both groups thought that mental development was very much/extremely influenced by diet (67·4 %). In the regression modelling, believing that physical and mental performance was greatly influenced by diet was significantly and positively associated with living in Hungary, scoring higher on a measure of General Health Interest and (parents only) level of education attained. Differences existed among countries in most views. Lower levels of awareness of the importance of diet for brain development and cognition (compared with physical health outcomes) indicate the potential for educating consumers, especially parents with lower educational attainment.

Head circumference in infants has been reported to predict brain size, total grey matter volume (GMV) and neurocognitive development. However, it is unknown whether it has predictive value on regional and subcortical brain volumes. We aimed to explore the relationship between several head circumference measurements since birth and distributions of GMV and subcortical volumes at later childhood. We examined seventy-four, Caucasian, singleton, term-born infants born to mothers randomised to receive fish oil and/or 5-methyltetrahydrofolate or placebo prenatal supplementation. We assessed head circumference at birth and at 4 and 10 years of age and cognitive abilities at 7 years of age. We obtained brain MRI at 10 years of age, on which we performed voxel-based morphometry, cortical surface extraction and subcortical segmentation. Analyses were controlled for sex, age, height, weight, family status, laterality and total intracranial volume. Prenatal supplementation did not affect head circumference at any age, cognitive abilities or total brain volumes. Head circumference at 4 years presented the highest correlation with total GMV, white matter volume and brain surface area, and was also strongly associated with GMV of frontal, temporal and occipital areas, as well as with caudate nucleus, globus pallidus, putamen and thalamus volumes. As relationships between brain volumes in childhood and several outcomes extend into adulthood, we have found that ages between 0 and 4 years as the optimal time for brain growth; postnatal factors might have the most relevant impact on structural maturation of certain cortical areas and subcortical nuclei, independent of prenatal supplementation.

A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children. It is, however, unknown how different fitness measures relate to shapes of subcortical brain nuclei. We aimed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 (sd 0·2) years from the NUtraceuticals for a HEALthier life project. Cardiorespiratory fitness, muscular strength and speed agility were assessed using valid and reliable tests (ALPHA-fitness test battery). Shape of the subcortical brain structures was assessed by MRI, and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach. Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei. These associations were both positive and negative, indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. Cardiorespiratory fitness was mainly associated with expansions, whereas handgrip was mostly associated with contractions in the structures studied. Future randomised-controlled trials will confirm or contrast our findings, demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function.

Cultural background is an important variable influencing neuropsychological performance. Multinational projects usually involve gathering data from participants from different countries and/or different cultures. Little is known about the influence of culture on neuropsychological testing results in children and especially in European children. The objectives of this study were to compare neuropsychological performance of children from six European countries (Belgium, Germany, Italy, The Netherlands, Poland and Spain) using a comprehensive neuropsychological battery and to apply a statistical procedure to reduce the influence of country/cultural differences in neuropsychological performance. As expected, the results demonstrated differences in neuropsychological performance among children of the six countries involved. Cultural differences remained after adjusting for other confounders related to neuropsychological execution, such as sex, type of delivery, maternal age, gestational age and maternal educational level. Differences between countries disappeared and influence of culture was considerably reduced when standardised scores by country and sex were used. These results highlight the need for developing specific procedures to compare neuropsychological performance among children from different cultures to be used in multicentre studies.

Variants in the human genes of fatty acid (FA) desaturase 1 (FADS1), 2 (FADS2) and 3 (FADS3) are associated with PUFA blood levels. We explored if maternal prenatal supplementation and children’s genetic variation in seventeen SNP of the FADS1, FADS2 and FADS3 gene cluster influence twenty-one of the most relevant cheek cells’ derived FA in glycerophospholipids (GPL-FA). The study was conducted in 147 Spanish and German mother–children pairs participating in the Nutraceuticals for a Healthier Life (NUHEAL) study at 8, 9 and 9·5 years. Linear and mixed model longitudinal regression analyses were performed. Maternal fish-oil (FO) or FO+5-methyltetrahydrofolate (5-MTHF) supplementation during pregnancy was associated with a significant decrease of arachidonic acid (AA) concentrations in cheek cell GPL in the offspring, from 8 to 9·5 years; furthermore, maternal FO+5-MTHF supplementation was associated with higher n-6 docosapentaenoic acid concentrations in their children at age 8 years. FADS1 rs174556 polymorphism and different FADS2 genotypes were associated with higher concentrations of linoleic and α-linolenic acids in children; moreover, some FADS2 genotypes determined lower AA concentrations in children’s cheek cells. It is suggested an interaction between type of prenatal supplementation and the offspring genetic background driving GPL-FA levels at school age. Prenatal FO supplementation, and/or with 5-MTHF, seems to stimulate n-3 and n-6 FA desaturation in the offspring, increasing long-chain PUFA concentrations at school age, but depending on children’s FADS1 and FADS2 genotypes. These findings suggest potential early nutrition programming of FA metabolic pathways, but interacting with children’s FADS polymorphisms.