Infant Gut Microbiota Associated with Fine Motor Skills

Background: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. Methods: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. Results: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. Conclusions: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders.This study was granted by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341); Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-02) and partially funded by the European Commission MyNewGut FP7 EU Project (Grant agreement n° 613979). Research post-doctoral fellowship from the Alfonso Martín Escudero Foundation; MyNewGut FP7 EU Project (Grant agreement n° 613979); DynaHEALTH EU Project HORIZON 2020 (Grant agreement n°: 633595-2); Marie Curie post-doctoral fellowship (FP7, no. 329812, NutriOmics); The first author received Pre-Doc scholarships from the Spanish Ministry of Education, Culture and Sports (FPU16/04587). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Visual evoked potentials in offspring born to mothers with overweight, obesity and gestational diabetes

Overweight, obesity, and gestational diabetes (GD) during pregnancy may negatively affect neurodevelopment in the offspring. However, the mechanisms are unclear and objective measures of neurodevelopment in infancy are scarce. We hypothesized that these maternal metabolic pathologies impair cortical visual evoked potentials (cVEPs), a proxy for visual and neuronal maturity. At 3 months of age, visual acuity was significantly poorer in offspring born to GD mothers. At 18 months of age, there were no differences in visual acuity but infants born to GD mothers had significantly longer latencies of cVEPs when measured at 15', and 30' of arc. The group differences at 30' remained significant after confounder adjustment (mean [SD] 121.0 [16.0] vs. 112.6 [7.6] ms in controls, p = 0.007) and the most prolonged latencies were observed in offspring to GD mothers with concurrent overweight (128.9 [26.9] ms, p = 0.002) and obesity (118.5 [5.1] ms, p = 0.020). Infants born to mothers with GD, particularly those with concurrent overweight or obesity, have prolonged latencies of visual evoked potentials at 18 months of age, suggesting that this maternal metabolic profile have a long lasting, non-optimal, effect on infants brain development.This work was supported by Spanish Ministry of Innovation and Science. Junta de AndalucõÂa: Excellence Projects (P06-CTS-02341 [to CC]); Spanish Ministry of Education (Grant no. SB2010- 0025 [to CC]); Spanish Ministry of Economy and Competitiveness (BFU2012-40254- C03-01 [to CC]); Abbott Laboratories, Granada, Spain; Henning and Johan Throne-Holst's foundation (Post Doc scholarship [to SKB])

Effects of Maternal Fish Oil and/or 5-MethylTetrahydrofolate Supplementation during Pregnancy on Offspring Brain Resting-State at 10 Years Old: A Follow-Up Study from the NUHEAL Randomized Controlled Trial

Recent studies have shown that maternal supplementation with folate and long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy may affect children’s brain development. We aimed at examining the potential long-term effect of maternal supplementation with fish oil (FO) and/or 5-methyl-tetrahydrofolate (5-MTHF) on the brain functionality of offspring at the age of 9.5–10 years. The current study was conducted as a follow-up of the Spanish participants belonging to the Nutraceuticals for a Healthier Life (NUHEAL) project; 57 children were divided into groups according to mother’s supplementation and assessed through functional magnetic resonance imaging (fMRI) scanning and neurodevelopment testing. Independent component analysis and double regression methods were implemented to investigate plausible associations. Children born to mothers supplemented with FO (FO and FO + 5-MTHF groups, n = 33) showed weaker functional connectivity in the default mode (DM) (angular gyrus), the sensorimotor (SM) (motor and somatosensory cortices) and the fronto-parietal (FP) (angular gyrus) networks compared to the No-FO group (placebo and 5-MTHF groups, n = 24) (PFWE < 0.05). Furthermore, no differences were found regarding the neuropsychological tests, except for a trend of better results in an object recall (memory) test. Considering the No-FO group, the aforementioned networks were associated negatively with attention and speed-processing functions. Mother’s FO supplementation during pregnancy seems to be able to shape resting-state network functioning in their children at school age and appears to produce long-term effects on children´s cognitive processing.European Union (EU) 212652 007036Commission of the European Community within the 5th Framework Program QLK1-CT-1999-00888European Research Council (ERC) 322605 META-GROWTHSpanish Ministry of Science, Innovation and Universities FJCI-2017-3339

Long-Chain Polyunsaturated Fatty Acids, Homocysteine at Birth and Fatty Acid Desaturase Gene Cluster Polymorphisms Are Associated with Children’s Processing Speed up to Age 9 Years

Both pre- and early postnatal supplementation with docosahexaenoic acid (DHA), arachidonic acid (AA) and folate have been related to neural development, but their long-term effects on later neural function remain unclear. We evaluated the long-term effects of maternal prenatal supplementation with fish-oil (FO), 5-methyltetrahydrofolate (5-MTHF), placebo or FO + 5-MTHF, as well as the role of fatty acid desaturase (FADS) gene cluster polymorphisms, on their offspring’s processing speed at later school age. This study was conducted in NUHEAL children at 7.5 (n = 143) and 9 years of age (n = 127). Processing speed tasks were assessed using Symbol Digit Modalities Test (SDMT), Children Color Trails Test (CCTT) and Stroop Color andWord Test (SCWT). Long-chain polyunsaturated fatty acids, folate and total homocysteine (tHcy) levels were determined at delivery from maternal and cord blood samples. FADS and methylenetetrahydrofolate reductase (MTHFR) 677 C > T genetic polymorphisms were analyzed. Mixed models (linear and logistic) were performed. There were significant differences in processing speed performance among children at different ages (p < 0.001). The type of prenatal supplementation had no effect on processing speed in children up to 9 years. Secondary exploratory analyses indicated that children born to mothers with higher AA/DHA ratio at delivery (p < 0.001) and heterozygotes for FADS1 rs174556 (p < 0.05) showed better performance in processing speed at 9 years. Negative associations between processing speed scores and maternal tHcy levels at delivery were found. Our findings suggest speed processing development in children up to 9 years could be related to maternal factors, including AA/DHA and tHcy levels, and their genetic background, mainly FADS polymorphism. These considerations support that maternal prenatal supplementation should be quantitatively adequate and individualized to obtain better brain development and mental performance in the offspring.European Commission 212652 007036 QLK1-CT-1999-00888European Commission European Commission Joint Research Centre DYNAHEALTH-633595 Lifecycle-733206European Research Council Advanced Grant META-GROWTH ERC-2012AdG 322605Erasmus Plus Programme Early Nutrition eAcademy Southeast Asia 573651EPP-1-2016-1-DE-EPPKA2-CBHE-JPErasmus Plus Programme Capacity Building to Improve Early Nutrition and Health in South Africa 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JPEU Interreg Programme Focus in CD-CE111European Joint Programming Initiative Project NutriPROGRAM and EndObesityGerman Ministry of Education and Research, Berlin 01 GI 0825German Research Foundation (DFG) Ko912/12-1 INST 409/224-1 FUGGElse Kroner-Fresenius-FoundationLMU University Hospital

Maternal prepregnancy body mass index and offspring white matter microstructure: results from three birth cohorts

Prepregnancy maternal obesity is a global health problem and has been associated with offspring metabolic and mental ill-health. However, there is a knowledge gap in understanding potential neurobiological factors related to these associations. This study explored the relation between maternal prepregnancy body mass index (BMI) and offspring brain white matter microstructure at the age of 6, 10, and 26 years in three independent cohorts. Maternal BMI was associated with higher FA and lower MD in multiple brain tracts in offspring aged 10 and 26 years, but not at 6 years of age. Future studies should examine whether our observations can be replicated and explore the potential causal nature of the findings.This work was supported by the European Union’s Horizon 2020 research and innovation program [grant agreement no. 633595 DynaHEALTH] and no. 733206 LifeCycle], the Netherlands Organization for Health Research and Development [ZONMW Vici project 016.VICI.170.200]. The PREOBE cohort was funded by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341) and Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-01). The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Centre, the Erasmus University, and the Netherlands Organization for Health Research and Development (ZonMW, grant ZonMW Geestkracht 10.000.1003). The Northern Finland Birth Cohort 1986 is funded by University of Oulu, University Hospital of Oulu, Academy of Finland (EGEA), Sigrid Juselius Foundation, European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NIH/NIMH (5R01MH63706:02

Efectos de la obesidad y la diabetes materna durante la gestación sobre el neurodesarrollo de los hijos

El desarrollo humano es un proceso altamente complejo, influenciado por un amplio rango de interacciones genéticas y factores ambientales. El periodo de desarrollo embrio-fetal es uno de los más vulnerables en la vida humana. Los cambios que tengan lugar en el ambiente intrauterino van a impactar sobre el desarrollo del nuevo ser, con efectos a largo plazo que alcanzarán no sólo la infancia sino también en la vida adulta, habiéndose establecido claras asociaciones con el desarrollo de enfermedades crónicas no-transmisibles. Se ha comprobado que durante la vida fetal y los primeros años de vida se produce una "programación" e "imprinting" metabólicos tempranos mediados por el estado nutricional y metabólico materno, la alimentación en los primeros 2 años de vida y otros factores ambientales socio-económicos, culturales y demográficos. Numerosos estudios experimentales y epidemiológicos han demostrado que alteraciones durante la vida pre-, peri- y postnatal pueden tener un impacto significativo sobre la salud futura y el desarrollo del niño. Durante la vida precoz existen diversas "ventanas críticas" para el desarrollo cerebral que pueden influir de forma permanente en el neurodesarrollo final del individuo; los efectos de factores ambientales, metabólicos y nutricionales desfavorables durante la gestación pueden determinar diversas alteraciones a largo plazo, incluso cambios en la estructura y función cerebral, merma de las capacidades intelectuales o trastornos de la conducta, lo cual va a tener un gran impacto en la vida del nuevo ser. El presente trabajo se justifica por la falta de evidencia científica acerca del patrón de crecimiento y desarrollo en niños nacidos de madres metabólicamente comprometidas. En el marco del Proyecto PREOBE, estudio de cohorte prospectivo, en el que se reclutaron embarazadas con normopeso (18≤BMI<25), sobrepeso (25≤BMI<30), obesidad (BMI≥30) y aquellas que desarrollaron diabetes gestacional, se ha realizado un seguimiento del crecimiento y neurodesarrollo de los hijos. Los objetivos del presente estudio son: 1) Estudiar las diferencias en la evolución del embarazo, así como la ganancia de peso, y los cambios metabólicos e inmunológicos que van a determinar el tipo de parto y el crecimiento fetal. 2) Determinar cómo la obesidad y/o la diabetes maternas pueden afectar el neurodesarrollo de sus hijos, analizando los cambios evolutivos del desarrollo neuropsicológico durante el primer año y medio de vida. 3) Evaluar los efectos de diferentes polimorfismos genéticos del PPAR-γ Pro12-Ala, tanto en la madre como en sus hijos, sobre el neurodesarrollo de los niños. Los resultados más relevantes muestran que el sobrepeso, la obesidad y la diabetes gestacional maternas se asocian al estado nutricional, la antropometría y composición corporal, y determinan cambios importantes en diferentes biomarcadores.Tesis Univ. Granada. Programa Oficial de Doctorado en: Condicionantes Genéticos, Nutricionales y Ambientales del Crecimiento y DesarrolloEsta memoria de tesis doctoral forma parte del Proyecto de Investigación de Excelencia (Ref. P06-CTS-02341), titulado: "Papel de la Nutrición y la Genética materna sobre la Programación del Desarrollo del Tejido Adiposo Fetal. Búsqueda de Marcadores de Riesgo de Obesidad en Etapas Precoces de la Vida"; Acrónimo: PREOBE ("Programación Precoz de la Obesidad"), subvencionado por la Consejería de Innovación, Ciencia y Empresa, de la Junta de Andalucía y parcialmente por los Laboratorios Abbott Nutrition

The Nutritional Profile of Food Advertising for School-Aged Children via Television: A Longitudinal Approach

The prevalence of childhood obesity continues to increase. Screen time, one of the most documented reasons for the obesogenic environment, enhances childhood obesity, since advertisements for unhealthy food products are still broadcast on channels for children. This is presently one of the main challenges for the government in Spain, since the current laws and obligations are not updated. This study aims to analyze food advertising aimed at children on Spanish television in 2013 and 2018 on children's and general channels to test the effect of laws and obligations over time. In total, we viewed 512 h of the most viewed channels, two children's and two general channels, during the week and on weekends during specific periods of 2013 and 2018. Food advertising was categorized as core, non-core, and other food advertisement (CFA, NCFA, and OFA, respectively) according to the nutritional profile. A total of 2935 adverts were analyzed, 1263 in 2013 and 1672 in 2018. A higher proportion of NCFAs were broadcast on children's channels than in prior years, rising from 52.2% to 69.8% (p 2.5; p < 0.001), due to exposure to adverts for high-sugar and high-fat foods such as cakes, muffins, cookies, and fried and frozen meals rich in fat. In conclusion, the trends of nutritional profiles in food advertising on television are worsening over time, since the prevalence of NCFAs was higher in 2018 than in 2013. Currently, CFAs are not mainly broadcast on children's channels, confirming high-risk exposure to non-core food advertising by watching them. Thus, food advertising laws and obligations should be adapted to increase compliance.This work was supported by the Commission of the European Community’s 7th Framework Programme (FP7/2008-2013), grant agreement no. 212652 (NUTRIMENTHE project), within the 6th Framework Programme, contract no. 007036 (EARNEST project), and supported in part by the Commission of the European Community within the 5th Framework Programme, contract no. QLK1-CT-1999-00888 (NUHEAL project). This publication is the work of the authors and does not necessarily reflect the views of the Commission of the European Community. The funders had no role in the design, analysis or writing of this article.Ye

The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring.

Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI≥25 kg/m2) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113·3 (sd 9·9) v. 117·1 (sd 9·2), P=0·039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114·0 (sd 9·7) v. 121·5 (sd 10·9), P=0·039) and lower receptive, expressive and composite (99·5 (sd 8·6) v. 107·6 (sd 8·3), P=0·004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12·3 (sd 2·0) v. 13·0 (sd 2·1), P=0·037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women

Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial.

During fetal and perinatal periods, many nutrients, such as long-chain polyunsaturated fatty acids [contained in fish oil (FO)] and folate, are important in achieving normal brain development. Several studies have shown the benefits of early nutrition on children's neurocognitive development. However, the evidence with regard to the attention system is scarce. The aim of this study was to analyze the long-term effects of FO, 5-methyltetrahydrofolate (5-MTHF), or FO+5-MTHF prenatal supplementation on attention networks. Participants were 136 children born to mothers from the NUHEAL (Nutraceuticals for a Healthy Life) project (randomly assigned to receive FO and/or 5-MTHF or placebo prenatal supplementation) who were recalled for a new examination 8.5 y later. The response conflict-resolution ability (using congruent and incongruent conditions)), alerting, and spatial orienting of attention were evaluated with behavioral measures (Attention Network Test), electroencephalography/event-related potentials (ERPs), and standardized low-resolution brain electromagnetic tomography (sLORETA). Children born to mothers supplemented with 5-MTHF alone solved the response conflict more quickly than did the placebo and the FO+5-MTHF groups (all P Folate supplementation during pregnancy, rather than FO or FO+5-MTHF supplementation, improves children's ability to solve response conflicts. This advantage seems to be based on the higher activation of the midcingulate cortex, indicating that early nutrition influences the functionality of specific brain areas involved in executive functions. This trial was registered at clinicaltrials.gov as NCT01180933

Cultural effects on neurodevelopmental testing in children from six European countries: an analysis of NUTRIMENTHE Global Database

Cultural background is an important variable influencing neuropsychological performance. Multinational projects usually involve gat