Postnatal Supplementation Research Articles

Maternal zinc supplementation improves hepatitis B antibody responses in infants but decreases plasma zinc level.

The World Health Report identifies zinc deficiency as one of the major causes of disease in developing countries, and infants are at particular risk. We aimed to investigate the effect of maternal zinc supplementation on the infant's immune function in a population at risk of deficiency. In a randomized, double-blind placebo-controlled trial, mothers were supplemented either with 20mg/day of elemental zinc (n=20) or placebo (n=19) at the beginning of second trimester, which continued until 6months postpartum. Indicators of the infants' immune function measured included interleukin (IL)-7, thymic size and response to hepatitis B vaccination. Infants born from mothers receiving zinc supplements during pregnancy and postpartum had significantly lower plasma zinc (p<0.05) but marginally higher IL-7 and antibody responses to hepatitis B vaccination (p<0.10) than infants born from mothers not receiving zinc. Maternal zinc supplementation showed no negative impact on copper status of mothers or their infants. Maternal zinc supplementation did not influence infant thymic size, but cord blood IL-7 was found positively associated with thymus size at 1month of age (r=0.392) and with hepatitis B vaccine response at 6months of age (r=0.386). Prenatal and postnatal zinc supplementation marginally improved T cell-dependent antibody responses in infants along with IL-7, a cytokine involved in human T cell development and maintaining homeostasis.

Long-Term Supplementation with Beta Serum Concentrate (BSC), a Complex of Milk Lipids, during Post-Natal Brain Development Improves Memory in Rats.

We have previously reported that the supplementation of ganglioside-enriched complex-milk-lipids improves cognitive function and that a phospholipid-enriched complex-milk-lipid prevents age-related cognitive decline in rats. This current study evaluated the effects of post-natal supplementation of ganglioside- and phospholipid-enriched complex-milk-lipids beta serum concentrate (BSC) on cognitive function in young rats. The diet of male rats was supplemented with either gels formulated BSC (n = 16) or blank gels (n = 16) from post-natal day 10 to day 70. Memory and anxiety-like behaviors were evaluated using the Morris water maze, dark–light boxes, and elevated plus maze tests. Neuroplasticity and white matter were measured using immunohistochemical staining. The overall performance in seven-day acquisition trials was similar between the groups. Compared with the control group, BSC supplementation reduced the latency to the platform during day one of the acquisition tests. Supplementation improved memory by showing reduced latency and improved path efficiency to the platform quadrant, and smaller initial heading error from the platform zone. Supplemented rats showed an increase in striatal dopamine terminals and hippocampal glutamate receptors. Thus BSC supplementation during post-natal brain development improved learning and memory, independent from anxiety. The moderately enhanced neuroplasticity in dopamine and glutamate may be biological changes underlying the improved cognitive function.

PTH-227 Early post-natal environment and supplementation of b. lactis ncc2818 exert a sustained influence on the developing immune system and on gut microbial co-metabolism in the pig

<h3>Introduction</h3> The young piglet is a valuable model for human infants in studies designed to identify interactions between the developing immune system, metabolism and the microbiome in early life. The early postnatal environment, including factors such as weaning and acquisition of the gut microbiota, has been causally linked to the development of later immunological diseases such as allergy and autoimmunity. Here, we show that early-life environment influences development of metabolic and immune phenotype as well as the gut microbiota in a porcine model. <h3>Method</h3> Piglets were removed to an isolator facility 24 h after birth, formula fed until 21d at which point they were weaned. Animals were gender and litter-matched to the control group or supplemented with the human probiotic<i>Bifidobacterium lactis </i>NCC2818 from 1d. Animals were sacrificed at 35d and the experiment was repeated with a second batch of piglets under identical husbandry conditions. Metabolic profiling of serum and urine at 35d was carried out using ¹H Nuclear Magnetic Resonance spectroscopy (NMR). Intestinal barrier function was assessed using immunofluorescence histology and immunoglobulin and cytokine production from various immunological sites was quantified. 16s pyrosequencing was conducted on colonic content and mucosal scrapings. <h3>Results</h3> The immediate environment during the first 24 h of life influenced the early microbiota, with animals from different batches having significantly different colonic bacteria and urinary metabolic profiles at 35d. Despite the underlying differences between the experimental batches, the administration of <i>Bifidobacterium lactis</i>NCC2818 in the diet significantly affected the metabolic phenotype, mucosal cytokine and immunogobulin production, and increased expression of intestinal tight cell junction proteins. Importantly, changes in composition of the microbiota were insufficient to explain the effect of the probiotic on these parameters. <h3>Conclusion</h3> We demonstrate that the environment during the first day of life influences development of the microbiota, metabolic phenotype and immune parameters and suggest that nutritional intervention at this early stage of life could be beneficial for at-risk infants who have suffered aberrant initial intestinal colonisation caused by, for example, caesarean or premature birth. <h3>Disclosure of interest</h3> None Declared.

A critical period for omega-3 nutritional supplementation in the development of the rodent visual system

Retinocollicular connections form precise topographical maps that are normally completed through the selective elimination of misplaced axons and the stabilization of topographically ordered axon terminals during early development. Omega-3 fatty acids, acquired exclusively through the diet, and its main metabolite, docosahexaenoic acid (DHA), are involved in brain development and synaptic maturation. We have previously shown that the nutritional restriction of omega-3/DHA results in abnormal retinocollicular topographical fine-tuning. Therefore, we studied the role of omega-3 fatty acids nutritional supplementation and the developmental time windows during which this postnatal supplementation would restore normal topographical maps in the visual system. Female rats and their litters were chronically fed with either control (soy oil) or restricted omega-3 (coconut oil) diets. Fish oil supplementation was introduced between either postnatal day (PND) 7-13, PND7-28 or PND21-42. At PND13, PND28 or PND42, animals received an anterograde eye injection of a neuronal tracer to visualize retinocollicular axons. Confirming previous observations we found that an omega-3/DHA deficiency resulted in an abnormally high innervation density of retinal axons at the visual layers of the superior colliculus (SC). Although a short-term fish oil supplementation between PND7-13 could not restore normal retinocollicular topography, an extended treatment between PND7-28 completely recovered normal innervation densities of retinotectal axons. However, a late onset supplementation protocol, between PND28-42, was no longer effective in the restoration of the abnormal topographical pattern induced by an early omega-3 nutritional malnutrition. The results suggest a critical period for omega3/DHA dietary intake for the proper development of visual topographical maps.

The Effect of Early Life Methyl Donor Supplementation on Obesity Development

Nearly 50% of women with a normal pre‐pregnancy body mass index gain more weight than recommended during their pregnancy. This excessive gestational weight gain (GWG) significantly increases the risk for the development of obesity in the offspring. Excessive GWG can be modeled in animals by feeding pregnant dams a high fat diet, leading to increased maternal weight gain and obesity‐promoting phenotypes in the offspring. Using a mouse model of excessive GWG, we have documented in the offspring an increased preference for sucrose and fat, increased expression of genes that underlie reward‐related behaviors, and both global and gene specific decreases in DNA methylation. These changes in reward‐related neural circuitry may contribute to the increased risk for the development of obesity in the offspring by altering the animal's response to highly palatable, energy dense foods. We have observed that supplementation during pregnancy can reverse some of the phenotypes that result from maternal high fat diet consumption. It is unknown whether postnatal (adolescent) methyl donor supplementation (MDS) can reverse these phenotypes. To determine this, offspring from dams fed either a high fat diet (HFD) or control diet during gestation were fed a methyl donor supplemented diet during adolescence. It has been determined that postnatal MDS significantly decreases body weight and abdominal fat pad weight in both male and female adult HFD offspring, and does not alter body weights of control diet offspring. Continued assessment of obesity development, preference for palatable foods, metabolic phenotypes, and expression changes of genes underlying homeostatic and hedonic feeding will elucidate whether early postnatal nutritional interventions can be utilized as a therapy to offset adult obesity risk.

Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure

Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long–Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects.

Vitamin B12 supplementation during pregnancy and postpartum improves B12 status of both mothers and infants but vaccine response in mothers only: a randomized clinical trial in Bangladesh.

Poor vitamin B12 (B12) status is associated with adverse outcomes in pregnancy and infancy. Little is known about effects of B12 supplementation on immune function. The present study aimed to evaluate effects of pre- and postnatal B12 supplementation on biomarkers of B12 status and vaccine-specific responses in mothers and infants. In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, age 18-35 years, hemoglobin <110 g/L, 11-14 weeks pregnant) were randomized to receive 250 μg/day B12 or a placebo throughout pregnancy and 3-month postpartum along with 60 mg iron + 400 μg folate. Women were immunized with pandemic influenza A (H1N1) vaccine at 26- to 28-week gestation. Blood from mothers (baseline, 72-h post-delivery, 3-month postpartum), newborns and infants (3-month) was analyzed for hemoglobin, B12, methylmalonic acid (MMA), total homocysteine (tHcy), ferritin and serum transferrin receptor, C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP). Vitamin B12 was also assessed in breast milk. H1N1-specific antibodies were determined in plasma and colostrum/breast milk. At baseline, 26% women were B12 deficient (<150 pmol/L), 40% had marginal status (150-220 pmol/L), 43% had elevated MMA (>271 nmol/L), and 31% had elevated tHcy (>10 μmol/L). Supplementation increased B12 in plasma, colostrums and breast milk (p < 0.05) and lowered MMA in neonates, mothers and infants at 3 months (p < 0.05). B12 supplementation significantly increased H1N1-specific IgA responses in plasma and colostrums in mothers and reduced proportion of infants with elevated AGP and CRP compared with placebo. Supplementation with 250 μg/day B12 during pregnancy and lactation substantially improved maternal, infant and breast milk B12 status. Maternal supplementation improved H1N1 vaccine-specific responses in mothers only and may alleviate inflammatory responses in infants.

Early probiotics to prevent childhood metabolic syndrome: A systematic review

To conduct a systematic review of studies on early probiotic supplementation to prevent childhood metabolic syndrome (MS). Using the Cochrane systematic review strategy we searched PubMed, EMBASE, CENTRAL, CINAHL, and the conference proceedings of the Pediatric American Society meetings and trial registries in December 2014. Randomised controlled trials (RCTs) and non RCTs of probiotic supplementation to the mother and/or infant for a minimum duration of 4 wk were selected. Of these, studies that reported on MS or its components (obesity, raised blood pressure, hyperglycemia, dyslipidemia) in children between 2-19 years were to be eligible for inclusion in the review. Risk of bias (ROB) in selected RCTs and quality assessment of non-RCT studies were to be assessed by the Cochrane ROB assessment table and New Castle Ottawa scale. There were no studies on early probiotic administration for prevention of childhood MS (CMS). Follow up studies of two placebo controlled RCTs (n = 233) reported on the effects of early probiotics on one or more components of MS in children aged 2-19 years. Meta-analysis of those two studies could not be performed due to differences in the patient population, type of outcomes studied and the timing of their assessment. Assessment of childhood metabolic outcomes was not the primary objective of these studies. The first study that assessed the effects of prenatal and postnatal supplementation of Lactobacillus rhamnosus GG on body mass index till 10 years, did not report a significant benefit. In the second study, Lactobacillus paracasei 19 was supplemented to healthy term infants from 4-13 mo. No significant effect on body mass index, body composition or metabolic markers was detected. Current evidence on early probiotic administration to prevent CMS is inadequate. Gaps in knowledge need to be addressed before large RCTs can be planned.

Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity.

Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA), are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores, and a limited nutritional provision of DHA after birth. In addition to long- term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants, and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long term goal of improving morbidity and mortality in this at risk population.

Probiotics' preventive effect on pediatric food allergy: a meta-analysis of randomized controlled trials.

To investigate the preventive effect of probiotics on pediatric food allergy. From MEDLINE bibliographical database, we searched and reviewed all randomized controlled trials on the preventive effects of probiotics on pediatric food allergies up to September 2013 and excluded the studies that do not meet inclusion criteria and extracted the data. Meta-analysis for the results of homogenous studies was performed using RevMan 5.0 and the co-effect was pooled by using fixed-effects model of relative risk (RR) ratios. Ten trials published between 2007 and 2012 including 2701 cases were included. Meta-analysis based on included data showed that the preventive effect of prenatal and postnatal probiotic supplementation on food allergies was not significant with the RR=0.88 (95% CI: 0.76-1.03). Present evidences cannot show in unequivocal terms that prenatal and postnatal probiotic supplementation will prevent food allergic diseases.

Benefícios e riscos dos suplementos medicamentosos fluoretados do mercado brasileiro

Since the use of any medicine should be based on evidence of its benefits and risks, the aim of this study was to evaluate the information contained in the leaflets provided with pre- and post-natal fluoride supplements found in the Brazilian market. Also, it was discussed the anticaries benefit and risk of dental fluorosis resulting from the use of these medications. The sample consisted of information leaflets of medications available on the Brazilian market, with 2 being for pre- and 6 post-natal use. The variables indication, contra-indication and dosage described in the leaflets were analyzed and compared with both the recommendations made by Brazilian and International institutions on the use of these medications, and with the present knowledge about how fluoride controls caries. It was found that there was incoherence between the indications and contra-indications in the information leaflets and the recommendations of institutions as regards these medications. Furthermore, the information was not consistent with present scientific knowledge about the benefits and risks of these medications. In addition, all the medications are formulated with a mixture of calcium salts and fluoride, suggesting that even if the use of these medications were important for control of caries, the fluoride present would not be bioavailable to exert its effect. It was concluded that it is necessary to perform a complete revision of Brazilian standardization of the pre- and post-natal use of fluoride supplements, in view of the inconsistencies found in the information leaflets of products for sale, whether in terms of their possible anticaries effect or risk of dental fluorosis.

Maternal supplementation of α-linolenic acid in normal and protein-restricted diets modulate lipid metabolism, adipose tissue growth and leptin levels in the suckling offspring.

Lipid quantity and quality have been shown to affect serum cholesterol, adipose and serum leptin levels during prenatal and postnatal dietary supplementation of adult rats. Maternal protein deficiency during pregnancy and lactation also affects polyunsaturated fatty acid (PUFA) levels in the offspring. The aim of the present study was to analyze the effect of α-linolenic acid (ALA; n-3) on n-3 PUFA accretion, lipid profile, leptin levels and adipose growth in normal and protein-restricted (deficient) dams and their suckling pups. Garden cress oil rich in ALA (32%) was supplemented in the normal and protein-restricted (10%) diets and fed to rats for 8 weeks prior to gestation and during lactation. PUFA, cholesterol, triglycerides, leptin levels and retroperitoneal white adipose tissue weight (WAT) of the dams and the pups were analyzed at 3 weeks after delivery. The serum cholesterol levels were remarkably decreased (p < 0.01), and the n-3 PUFA levels were markedly increased (p < 0.05) in the pups of lactating normal and protein-deficient dams supplemented with ALA. Triglycerides were unaltered in the dams and the pups of different dietary groups. Serum leptin levels and relative WAT weights were lower (p < 0.01) in the pups of the ALA-supplemented normal and protein-deficient dams. Maternal supplementation of ALA in normal and protein-restricted diets modulates n-3 PUFA levels, cholesterol, leptin levels and also adipose growth in the suckling offspring.

Perinatal α-linolenic acid availability alters the expression of genes related to memory and to epigenetic machinery, and the Mecp2 DNA methylation in the whole brain of mouse offspring

Many animal and human studies indicated that dietary ω-3 fatty acids could have beneficial roles on brain development, memory, and learning. However, the exact mechanisms involved are far from being clearly understood, especially for α-linolenic acid (ALA), which is the precursor for the ω-3 elongation and desaturation pathways. This study investigated the alterations induced by different intakes of flaxseed oil (containing 50% ALA), during gestation and lactation, upon the expression of genes involved in neurogenesis, memory-related molecular processes, and DNA methylation, in the brains of mouse offspring at the end of lactation (postnatal day 19, P19). In addition, DNA methylation status for the same genes was investigated. Maternal flaxseed oil supplementation during lactation increased the expression of Mecp2, Ppp1cc, and Reelin, while decreasing the expression of Ppp1cb and Dnmt3a. Dnmt1 expression was decreased by postnatal flaxseed oil supplementation but this effect was offset by ALA deficiency during gestation. Mecp2 DNA methylation was decreased by maternal ALA deficiency during gestation, with a more robust effect in the lactation-deficient group. In addition, linear regression analysis revealed positive correlations between Mecp2, Reelin, and Ppp1cc, between Gadd45b, Bdnf, and Creb1, and between Egr1 and Dnmt1, respectively. However, there were no correlations, in any gene, between DNA methylation and gene expression. In summary, the interplay between ALA availability during gestation and lactation differentially altered the expression of genes involved in neurogenesis and memory, in the whole brain of the offspring at the end of lactation. The Mecp2 epigenetic status was correlated with ALA availability during gestation. However, the epigenetic status of the genes investigated was not associated with transcript levels, suggesting that either the regulation of these genes is not necessarily under epigenetic control, or that the whole brain model is not adequate for the exploration of epigenetic regulation in the context of this study.

Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces peanut allergen-induced hypersensitivity responses in mice

Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we provided ad libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized/challenged with peanut extract, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for total plasma IgE levels. At termination (10 weeks of age), splenic T lymphocyte population subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by PCR array. Mice given the probiotic-supplemented diet had significantly enhanced probiotic fecal counts compared to controls at 3, 6, 8 and 10 weeks. Moreover, mice fed the probiotic-supplemented diet had enhanced splenic naturally occurring T regulatory cell populations, and reduced splenic gene expression of allergic mediator IL-13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection to hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses.

Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces ovalbumin allergen-induced hypersensitivity responses in mice (HYP7P.305)

Abstract Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) mucosal immunity, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we fed a probiotic-supplemented or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized with egg allergen ovalbumin, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for ovalbumin and total plasma IgE levels. At termination, splenic T helper population subtypes were determined by FACS analysis and gene expression by PCR array. At 21 days of age, pups suckled by lactating dams fed the probiotic supplemented diet had significantly enhanced Lactobacillus acidophilus fecal counts compared to controls. Moreover, mice fed the probiotic supplemented diet had enhanced splenic naturally occurring and induced regulatory T cell populations, enhanced TGFβ gene expression and reduced expression of allergic mediator IL13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection from hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses.

Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces ovalbumin allergen-induced hypersensitivity responses in mice

Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we provided ad libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized/challenged with egg allergen ovalbumin, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for ovalbumin-IgE and total plasma IgE levels. At termination, splenic T helper cell lymphocyte population subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by PCR array. At 21 days of age, pups suckled by lactating dams fed the probiotic supplemented diet had significantly enhanced Lactobacillus acidophilus fecal counts compared to controls. Moreover, mice fed the probiotic supplemented diet had enhanced splenic naturally occurring and induced regulatory T cell populations, enhanced TGFβ gene expression and reduced expression of allergic mediator IL13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection from hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses.

Vitamin B12 Deficiency in Pregnancy and Lactation: Is there a Need for Pre and Post-natal Supplementation?

This article reviews vitamin B12 (B12) status and deficiency during pregnancy and lactation, its effect on pregnancy, and the health of the offspring, with the aim to underscore the need for a sustainable strategy to improve maternal and infant vitamin B12 status of low and middle income countries. Vitamin B12 is a basic nutrient required for maintenance of normal erythropoiesis, cell reproduction, nucleoprotein and myelin synthesis. B12 deficiency is associated with adverse pregnancy outcomes and neurodevelopmental morbidity during infancy. Very few studies have indicated that B12 deficiency may contribute to altered immune responses in animals and humans. Additionally, no studies have shown modulation of infant motor development in response to maternal B12 supplementation. Despite the high global prevalence of B12 deficiency and its serious effects on pregnant women and offspring, there is still no consensus on the cut-off of biochemical markers (indicator of B12 deficiency) to correctly diagnose B12 deficiency in mother-infant dyad. Also, the optimum dose of B12 to normalize B12 status of mother-infant pairs in a deficient population is not known yet. In addition, markers of other functions such as neurodevelopment, immune response that may be affected by vitamin B12 deficiency should be measured to determine if they respond to supplementation. Thus, there is an urgent need to conduct more trials to find out the optimum dose, to investigate whether intervention with such pre-and post natal vitamin B12 supplementation would improve maternal, neonatal and child health outcomes in population at risk, giving emphasis on neurological processes, immune functions and epigenetic modifications. Other strategies including food based approach also require evidence based results which will help to understand effectiveness of a targeted and well-designed intervention among this population.

Glial localization of antiquitin: Implications for pyridoxine‐dependent epilepsy

A high incidence of structural brain abnormalities has been reported in individuals with pyridoxine-dependent epilepsy (PDE). PDE is caused by mutations in ALDH7A1, also known as antiquitin. How antiquitin dysfunction leads to cerebral dysgenesis is unknown. In this study, we analyzed tissue from a child with PDE as well as control human and murine brain to determine the normal distribution of antiquitin, its distribution in PDE, and associated brain malformations. Formalin-fixed human brain sections were subjected to histopathology and fluorescence immunohistochemistry studies. Frozen brain tissue was utilized for measurement of PDE-associated metabolites and Western blot analysis. Comparative studies of antiquitin distribution were performed in developing mouse brain sections. Histologic analysis of PDE cortex revealed areas of abnormal radial neuronal organization consistent with type Ia focal cortical dysplasia. Heterotopic neurons were identified in subcortical white matter, as was cortical astrogliosis, hippocampal sclerosis, and status marmoratus of the basal ganglia. Highly elevated levels of lysine metabolites were present in postmortem PDE cortex. In control human and developing mouse brain, antiquitin immunofluorescence was identified in radial glia, mature astrocytes, ependyma, and choroid plexus epithelium, but not in neurons. In PDE cortex, antiquitin immunofluorescence was greatly attenuated with evidence of perinuclear accumulation in astrocytes. Antiquitin is expressed within glial cells in the brain, and its dysfunction in PDE is associated with neuronal migration abnormalities and other structural brain defects. These malformations persist despite postnatal pyridoxine supplementation and likely contribute to neurodevelopmental impairments.

Effects of Bifidobacterial Supplementation to Pregnant Women and Infants in the Prevention of Allergy Development in Infants and on Fecal Microbiota

Probiotic administration may be a useful method for preventing allergies in infants; however, there have been controversial results about the efficacy. We investigated the effects of bifidobacterial supplementation on the risk of developing allergic diseases in the Japanese population. In an open trial, we gave Bifidobacterium breve M-16V and Bifidobacterium longum BB536 prenatally to 130 mothers beginning 1 month prior to delivery and postnatally to their infants for 6 months. Another 36 mother-infant pairs served as controls and did not receive the bifidobacterial supplementation. Development of allergic symptoms in the infants was assessed at 4, 10 and 18 months of age. Fecal samples were collected from the mothers and infants. The risk of developing eczema/atopic dermatitis (AD) during the first 18 months of life was significantly reduced in infants in the probiotic group (OR: 0.231 [95% CI: 0.084-0.628] and 0.304 [0.105-0.892] at 10 and 18 months of age, respectively). Pyrosequencing analyses indicated an altered composition of the fecal microbiota at 4 months for infants who developed eczema/AD at 4 and 10 months of age. The proportion of Proteobacteria was significantly lower (P = 0.007) in mothers at the time of delivery who received the supplementation when compared with the control group and was positively correlated (r = 0.283, P = 0.024) with that of infants at 4 months of age. No adverse effects were related to the use of probiotics. These data suggest that the prenatal and postnatal supplementation of bifidobacteria is effective in primary preventing allergic diseases. Some limited changes in the composition of fecal microbiota by the bifidobacterial supplementation were observed.

Effects of Energy and Macronutrient Intake on Cognitive Function Through the Lifespan

Abstract This paper reviews effects of both insufficient and excessive energy and macronutrient intake on cognition over the lifespan, including the prenatal period, infancy, childhood, and adulthood. In the brain, the hippocampus is particularly vulnerable to both protein malnutrition and energy undernutrition in utero or infancy, resulting in impaired neurogenesis and deficits in memory and spatial learning, reduced anxiety and increased impulsivity, reflected in impairments of neurotransmitter systems. Conversely, higher protein intake is associated with improved motor development but not mental development, whereas breastfeeding benefits mental development. Nevertheless, pre- and post-natal protein-energy supplementation has been shown to improve cognition in later childhood, and in adulthood, above energy alone. Similarly, n-3 essential fatty acid intake during pregnancy may have long-lasting effects on children’s cognitive abilities. However, over-nutrition, particularly during gestation, may lead to metabolic programming that increases risk of cognitive impairment. In undernourished school children, breakfasts can benefit cognitive performance. In normally nourished children, benefits of breakfast are less clear; nevertheless, acutely, breakfasts lower in glycaemic index can benefit memory, whereas higher glycaemic breakfasts may improve vigilance. This difference depends on the impact of the carbohydrate on cortisol release. In adolescents and adults, moderate carbohydrate loads can benefit cognition, provided that glucoregulation is efficient. Protein intake may benefit memory by restraining task-related cortisol release. Chronically high intake of saturated fats may contribute to cognitive decline, whereas n-3 fatty acids, and perhaps reduced energy intake, may be protective. With aging populations, dietary prediction of cognition in adults is a key area for research.