Maternal one-carbon metabolism during the periconceptional period and human foetal brain growth: A systematic review

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (>17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (<7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases

Acquired Vitamin B12 Deficiency in Newborns: Positive Impact on Newborn Health through Early Detection

The early diagnosis of and intervention in vitamin B12 deficiency in exclusively breastfed infants by mothers with low vitamin B12 is crucial in preventing possible irreversible neurologic damage, megaloblastic anemia, and failure to thrive. We assess the usefulness of the early detection of asymptomatic B12 deficiency related to acquired conditions and highlight the importance of monitoring serum vitamin B12 levels during pregnancy. We describe demographic, clinical, dietary, and biochemical data, including the evolution of a vitamin B12 deficiency's functional biomarkers. We enrolled 12 newborns (5 males) with an age range of 1-2 months old that were exclusively breastfed and asymptomatic. These cases were referred to our metabolic unit due to alterations in expanded newborn screening: high levels of methylmalonic acid and/or total homocysteine (tHcy). All mothers were under a vegetarian diet except three who had abnormal B12 absorption, and all presented low or borderline serum B12 level and high plasma levels of tHcy. Supplementation with oral vitB12 re-established the metabolic homeostasis of the mothers. In infants, therapy with an intramuscular injection of 1.0 mg hydroxocobalamin led to the rapid normalization of the metabolic pattern, and a healthy outcome was observed. Acquired B12 deficiency should be ruled out before proceeding in a differential diagnosis of cobalamin metabolism deficits, methylmalonic acidemia, and homocystinuria.info:eu-repo/semantics/publishedVersio

Determining the nutrition habits of the mothers of gifted children during the pregnancy: A retrospective study

Amaç: Bu araştırmada, üstün zekâlı çocuğu olan annelerin gebelik dönemindeki beslenme al ışkanlıklarının araştırılması ve kontrol grubu ile karşılaştırılması amaçlanmıştır. Gereç ve Yöntemler: Retrospektif ve ta- nımlayıcı nitelikteki bu çalışmaya 48’i üstün zekâlı ve 46’sı kontrol olan 94 çocuk ve anne çifti dâhil edilmiştir. Demografik bilgiler, beslenme alışkan- lıkları ve fiziksel aktivite durumları anket formu ile sorgulanmıştır. Bulgu- lar: Üstün zekâ ve kontrol grubundaki çocukların yaş ortalamaları sırasıyla 9,3±1,9 ve 10,3±1,4 yıldır. Annelerin eğitim durumları arasında anlamlı fark görülmezken (p=0,125), meslek dağılımlarının anlamlı olarak farklı olduğu; kontrol grubu annelerinin %58,7’sinin ev hanımı, üstün zekâ grubu annele- rinin %47,9’unun memur veya özel sektör çal ışanı olduğu belirlenmiştir (p=0,035). Annenin gebelikteki fiziksel aktivite durumu ile çocu ğun üstün zekâlı olması arasında anlamlı bir ilişki bulunmamıştır (p=0,580). Gebelikte balık, çay, kahve ve su tüketimi; ya ğ tercihi, iyotlu/iyotsuz tuz kullan ımı gibi faktörler ve besin desteği kullanımı ile zekâ arasında anlamlı bir ilişki gözlenmemiştir (p>0,05). Gebelikte bir besine aşırı istek duyma oranı her iki grupta da benzer olup üstün zekâ grubunda besinlere kar şı tiksinti duyma oranı, kontrol grubuna göre anlaml ı olarak daha dü şük bulunmu ştur (p=0,039). En fazla istek duyulan besinler başta erik olmak üzere diğer mey- veler olurken en fazla tiksinti duyulan besinler tavuk, so ğan ve çay olarak kaydedilmiştir. Sonuç: Soyut bir kavram olan zekây ı etkileyen faktörlerin belirlenmesi oldukça karma şık ve zorlay ıcıdır. Annenin gebelikteki bes- lenme durumu ve alışkanlıklarının çocuğun zekâ düzeyi üzerindeki etkile- rini net olarak belirlemek için daha kapsaml ı, kontrollü ve uzun süreli çalışmalar gereklidir.Objective: In this study, it was aimed to investigate the nu- tritional habits of mothers with gifted children during pregnancy and to com- pare them with the control group. Material and Methods: This retrospective and descriptive study included 94 child and mother couples, 48 of whom were gifted and 46 of whom were controls. Demographic infor- mation, nutritional habits and physical activity status were questioned with a questionnaire. Results: The mean ages of the children in the gifted and control groups were 9.3±1.9 and 10.3±1.4 years, respectively. While there was no significant difference between the education levels of the mothers (p=0.125), the occupational distributions were significantly different; It was determined that 58.7% of the mothers of the control group were housewives, and 47.9% of the mothers of the gifted group were civil servants or private sector employees (p=0.035). There was no significant relationship between the physical activity status of the mother during pregnancy and the child being in the gifted group (p=0.580). No significant relationship was ob- served between factors such as fish, tea, coffee and water consumption; oil preference, use of iodized/non-iodized salt and the use of nutritional sup- plements during pregnancy and intelligence (p>0.05). The rate of excessive craving for any food during pregnancy was similar in both groups, and the rate of food disgust in the gifted group was found to be significantly lower than the control group (p=0.039). While the most desired foods were other fruits, especially plums, the most disgusting foods were recorded as chicken, onions and tea. Conclusion: Determining the factors affecting intelligence, which is an abstract concept, is quite complex and challenging. More com- prehensive, controlled and long-term studies are needed to more clearly de- termine the effects of the mother’s nutritional status and habits during pregnancy on the child’s intelligence level

Biological Risks and Neurodevelopment in Young North Indian Children

Background. Children growing up in poverty face multiple biological and psychosocial risks, some of which are primarily found in low to middle income countries. Unfavourable biological circumstances, such as inadequate nutrition and childhood illnesses put children at risk for compromised development. Early child development is a precursor for later cognitive functioning and may have lasting consequences for academic achievement and lifelong quality of life. There is a need to identify modifiable risk factors for poor development in order to break the vicious cycle of poverty and poor development. Objectives. The objectives of the current thesis are threefold. First, to examine the effect of two recommended daily allowances of vitamin B12 and/or folic acid for six months on neurodevelopment. Second, to identify other relevant risk factors for poor neurodevelopment in young North Indian children; and, finally, to assess the feasibility of the screening tool Ages and Stages Questionnaire 3rd ed. (ASQ-3) administered by field supervisors to collect reliable data on neurodevelopment in this North Indian field setting. Methods. In a randomized double blind trial, children six to 30 months were given vitamin B12 and/or folic acid or placebo daily for six months. At the end of the study, we measured neurodevelopment in 422 children by ASQ-3 administered directly with the child. During the six months study period, we collected data on childhood illnesses bi-weekly. Information regarding socioeconomic status was collected at baseline, and information regarding stimulation and learning opportunities was collected at end study. Applying linear and logistic regression models, we measured the effect of vitamin B12 and/or folic acid on neurodevelopment, and identified other predictors of developmental status. We also assessed the psychometric properties of the ASQ-3 in the current setting. Results. Compared to placebo, children who received both vitamin B12 and folic acid had 0.45 (95% CI 0.19, 0.73) and 0.28 (95% CI 0.02, 0.54) higher SD-units in the domains of gross motor and problem solving functioning, respectively. The effect was highest in selected subgroups consisting of stunted children, those with evidenceof folate and vitamin B12 deficiency and in those who were younger than 24 months at the end of the study. With the exception of a significant improvement in gross motor scores by vitamin B12 alone, supplementation of either vitamin alone had no effect on any of the outcomes measures. In the multiple regression models, we were able to explain 30.6% of the variation in the total ASQ-3 score. Height for age and weight for height z-scores were positively associated with the total ASQ-3 score, while the number of days with diarrhea was negatively correlated. Variables defined as stimulation and learning opportunities explained most of the variation (25.9%). Our results also indicate that it is possible to collect reliable data on neurodevelopment in this field setting using ASQ-3. Conclusion. Vitamin B12 and folate deficiency, stunting and prolonged diarrhea illness may be important modifiable biological risks adverse neurodevelopment in young children in the current setting. Adequate stimulation and responsive care are crucial for healthy development. Interventions targeting young children growing up in poverty in LMIC should integrate various modifiable risk factors including nutrition, hygiene and early child stimulation to maximize developmental potential in children

Exposición prenatal a manganeso y a arsénico y efectos en el desarrollo neuropsicológico en niños y niñas participantes en la cohorte INMA

Introducción: El manganeso (Mn) es un elemento esencial, indispensable para el desarrollo durante la etapa fetal. Por su parte, el arsénico (As) es un tóxico para el ser humano, siendo su forma inorgánica (iAs) la considerada más tóxica. La principal vía de exposición a ambos compuestos en población general es a través de la dieta. Una vez es absorbido, el iAs es biotransformado en ácido monometilarsónico (MMA) y ácido dimetilarsínico (DMA). Diversos estudios epidemiológicos han relacionado la exposición prenatal a estos metales con efectos adversos en el desarrollo neuropsicológico durante la infancia, aunque la evidencia actual no es concluyente. Además, la mayoría de estos estudios se han realizado en áreas con una alta exposición ambiental a estos compuestos, por lo que la evidencia en zonas con menores niveles en el ambiente, incluyendo agua y alimentos, es todavía escasa. El objetivo general de la presente tesis es estudiar la relación entre la exposición prenatal a Mn y a As y la aparición de efectos adversos en el desarrollo neuropsicológico infantil en los participantes de dos cohortes materno-infantiles, así como evaluar los factores asociados a dichas exposiciones. Metodología: este trabajo forma parte del proyecto multicéntrico de cohortes Infancia y Medio Ambiente (INMA). La población de estudio fue de 807, 1017 y 1179 pares madre-hijo/a de las cohortes de Gipuzkoa y Valencia (2004-2008), según el estudio. Durante el primer trimestre del embarazo se recogieron muestras de suero y orina en las que se analizaron las concentraciones de Mn y As total (TAs) y sus metabolitos (MMA, DMA, As inorgánicos [iAs] y arsenobetaína [AB]), respectivamente. El desarrollo neuropsicológico de los niños y niñas se evaluó mediante las Escalas de Desarrollo Infantil de Bayley (BSID) al año de edad y a través de las Escalas de Habilidades Infantiles McCarthy (MSCA) a los 4-5 años de edad. Se recogió información sociodemográfica, de estilos de vida y dietética mediante cuestionarios, así como otros biomarcadores maternos (ferritina sérica y zinc (Zn) urinario, entre otros). La eficiencia de metilación del As se determinó a través de los porcentajes de los metabolitos y utilizando el análisis de componentes principales. Se utilizaron modelos de regresión lineal multivariante para evaluar los factores asociados a las variables de exposición, así como para evaluar la relación entre la exposición prenatal a Mn, a As y sus metabolitos, así como la eficiencia en la metilación del As y las puntuaciones en las pruebas neuropsicológicas. Finalmente se examinó la linealidad de las relaciones y se exploró la posible modificación del efecto relacionada con diversas variables. Resultados: la media geométrica (MG) e intervalo de confianza del 95% (IC95%) de las concentraciones de Mn en suero durante el primer trimestre del embarazo fue de 1,50 µg/L (1,48-1,53). El único factor dietético asociado (relación directa) a estas concentraciones fue el consumo de frutos secos. Las madres trabajadoras presentaron menores concentraciones de Mn en suero. Por su parte, la MG (IC95%) de las concentraciones de TAs, AB, ∑As (suma de DMA, MMA e iAs), DMA, MMA e iAs en orina fue de 35,55 (33,10-38,19), 20,17 (18,34-22,19), 7,74 (7,41-8,09), 6,82 (6,52-7,14), 0,34 (0,32-0,36) y 0,33 (0,31-0,35) μg/g creatinina, respectivamente. El consumo de arroz se asoció de forma directa con las concentraciones urinarias de todos los metabolitos de As, excepto con la AB. De la misma manera, el consumo de pescado se asoció positivamente con las concentraciones de todos los metabolitos evaluados excepto con el MMA y el iAs. Otros factores asociados con las concentraciones de ciertas especies de As fueron el área de estudio, el país de origen de la madre, la clase social parental y el índice de masa corporal materno (IMC). Respecto a la eficiencia en la metilación del As durante el embarazo, las medianas (IC del 95%) del porcentaje de metabolitos de As fueron 89,7 (89,3-90,2) para %DMA, 5,1 (4,8-5,3) para %MMA y 4,7 (4,5-5,0) para %iAs. Las mujeres nacidas en Latinoamérica y aquellas con un mayor IMC presentaron una mejor metilación del iAs (indicado por mayor %DMA y menor %MMA y %iAs). En este estudio de cohortes multicéntrico no se encontró asociación entre la exposición prenatal a Mn y el desarrollo mental (β [IC95%] = −0,39 [−2,73 a 1,95]), ni con el desarrollo psicomotor (β [IC95%] = −0.92 [−3,48 a 1,65]) de los niños y niñas al año de edad. Respecto a la exposición prenatal a As, en el presente trabajo se observó una relación negativa entre las concentraciones urinarias de MMA durante el primer trimestre del embarazo y las puntuaciones de las escalas general, verbal, cuantitativa, de memoria, de función ejecutiva y de memoria de trabajo del MSCA a los 4-5 años de edad (por ejemplo, β [IC95%] = −1,37 [−2,33 a −0,41] para la escala general). Además, el %MMA se asoció de manera negativa con la subescala de memoria. Finalmente, se observó que los niños y niñas cuyas madres presentaron concentraciones más bajas de Mn, Zn y ferritina obtuvieron puntuaciones más bajas en varias escalas de MSCA con una eficiencia de metilación decreciente. Conclusiones: Los niveles de Mn, As y sus metabolitos analizados en nuestra población son más bajos que los observados en la mayoría de los estudios publicados. Ciertos factores dietéticos, de estilo de vida y ambientales influyen tanto en las concentraciones de Mn y de especies de As, así como en la eficiencia de metilación del As en nuestra población. Este estudio no muestra asociación entre los niveles maternos prenatales de Mn y el desarrollo neuropsicológico al año del nacimiento. No obstante, sí se ha observado una asociación inversa entre las concentraciones de MMA y el desarrollo neuropsicológico de los niños y niñas a los 4-5 años de edad. Además, los niveles maternos de Mn, Zn y ferritina modificaron la asociación entre la eficiencia de metilación del As y las puntuaciones de MSCA.Introduction: Manganese (Mn) is an essential element that is indispensable for correct development during the foetal stage. Arsenic (As) is toxic to humans, its inorganic form (iAs) being considered the most toxic. The main route of exposure to both compounds in the general population is through diet. Once absorbed, iAs is biotransformed into monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Several epidemiological studies have linked prenatal exposure to these metals to adverse effects on neuropsychological development during childhood, although the current evidence is inconclusive. Moreover, most of these studies have been conducted in areas with high environmental exposure to these compounds and evidence in areas with lower levels in the environment, including food and water, is still scarce. The general aim of the present thesis is to study the relationship between prenatal exposure to Mn and As and the occurrence of adverse effects on child neuropsychological development in participants from two maternal-infant cohorts, as well as to evaluate the factors associated with these exposures. Methods: This study is part of the multicentre cohort-based INMA (Infancia y Medio Ambiente [Environment and Childhood]) project. The study population was 807, 1017 and 1179 mother– child pairs from the Gipuzkoa and Valencia cohorts (2004-2008), according to the study. During the first trimester of pregnancy, serum and urine samples were collected and analysed to determine the concentrations of Mn and total As (TAs) and its metabolites (monomethylarsonic acid [MMA], dimethylarsinic acid [DMA], inorganic As [iAs] and arsenobetaine [AB]), respectively. The children's neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 1 year of age and the McCarthy Scales of Children's Abilities (MSCA) at 4-5 years of age. Sociodemographic, lifestyle and dietary information was collected by questionnaires, together with other maternal biomarkers (serum ferritin and urinary zinc [Zn], among others). The As methylation efficiency was determined through metabolite percentages and using principal component analysis. Multivariate linear regression models were used to evaluate factors associated with exposure variables, as well as to assess the relationship between prenatal exposure to Mn, to As and its metabolites, and As methylation efficiency and neuropsychological test scores. Finally, the linearity of the relations and the possible effect modification related to several variables was explored. Results: The geometric mean (GM) and 95% confidence interval (95%CI) of serum Mn concentrations during the first trimester of pregnancy was 1.50 µg/L (1.48-1.53). The only dietary factor associated with these concentrations was the consumption of nuts. Working mothers had lower serum Mn concentrations. The GM (95% CI) of TAs, AB, ∑As (sum of DMA MMA and iAs), DMA, MMA and iAs concentrations in urine were 35.55 (33.10-38.19), 20.17 (18.34-22.19), 7.74 (7.41-8.09), 6.82 (6.52-7.14), 0.34 (0.32-0.36) and 0.33 (0.31-0.35) μg/g creatinine, respectively. Rice consumption was directly associated with urinary concentrations of all As metabolites except AB. Similarly, fish consumption was positively associated with concentrations of all the metabolites assessed except MMA and iAs. Other factors associated with the concentrations of certain As species were study area, maternal country of origin, parental social class and maternal body mass index (BMI). Regarding As methylation efficiency during pregnancy, the medians (95%CI) of the percentage of As metabolites were 89.7 (89.3- 90.2) for %DMA, 5.1 (4.8-5.3) for %MMA and 4.7 (4.5-5.0) for %iAs. Women born in Latin America and those with a higher BMI had better iAs methylation (indicated by higher %DMA and lower %MMA and %iAs). In this multicentre cohort study, no association was found between prenatal Mn exposure and mental development (β [95% CI] = −0.39 [−2.73, 1.95]) or with psychomotor development (β [95% CI] = −0.92 [−3.48, 1.65]) of children at one year of age. Regarding prenatal As exposure, in the present work, a negative relationship was observed between urinary MMA concentrations during the first trimester of pregnancy and scores on the general, verbal, quantitative, memory, executive function and working memory scales of the MSCA at 4-5 years of age (e.g. β [95% CI] = −1.37 [−2.33, −0.41] for the general scale). In addition, %MMA was negatively associated with the memory subscale. Finally, it was observed that children whose mothers had lower concentrations of manganese, zinc and ferritin scored lower on several MSCA scales with decreasing methylation efficiency. Conclusions: The levels of Mn, As and its metabolites analysed in our population are lower than those observed in most of the studies published to date. Certain dietary, lifestyle and environmental factors influence both the concentrations of Mn and As species and the As methylation efficiency in our population. This study shows no association between prenatal maternal Mn levels and neuropsychological development at one year after birth. However, an inverse association between MMA concentrations and the neuropsychological development of children aged 4-5 years has been observed. In addition, maternal Mn, Zn and ferritin levels modified the association between As methylation efficiency and MSCA scores

Benefit and risk assessment of fish in the Norwegian diet - Scientific Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

Source at https://vkm.no/.In 2006, VKM published “A comprehensive assessment of fish and other seafood in the Norwegian diet”. The assessment supported the recommendation from Norwegian Health authorities to eat more fish both for dinner and on sandwiches. In an update of the assessment in 2014 VKM concluded that “the benefits from fish consumption clearly outweigh the negligible risk presented by current levels of contaminants and other undesirable substances in fish”. Because of new knowledge available, the Norwegian Food Safety Authority requested a new benefit and risk assessment of fish in the Norwegian diet in 2019. In the assignment, they asked VKM to answer the following questions: Which health consequences will it have for the Norwegian population if they: Continue with the same fish consumption levels as of today Increase the consumption of fish to match the recommendations given by the Norwegian Directorate of Health </uli

Benefit and risk assessment of fish in the Norwegian diet - Scientific Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

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A Personalized Medicine Approach to the Diagnosis and Management of Autism Spectrum Disorder

This collection of articles provides an overview of the current and future methods for applying a personalized medicine approach to the diagnosis, management, and treatment of autism spectrum disorder

Developing Brains

This volume in the Early Childhood in Focus series aims to present an overview of the most significant areas of neurodevelopmental research, starting in the first section with sufficient basic explanation of the brain and how it functions for the research to be understood by people with little or no previous knowledge of the field. The second section gives an overview of the developmental processes involved as the child’s brain grows and matures in constant interaction with the environment, from conception through to adulthood. For children to reach their full potential, supporting the healthy development of their brains is paramount and the powerful effects of early environments, both physical and social, can no longer be ignored. The third section of this volume focuses on these influences