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This study examined the associations between maternal pre-pregnancy BMI and gestational weight gain (GWG) and children’s neuropsychological outcomes at 3 to 5 years of age. A total of 379 women and their children from the Alberta Pregnancy Outcomes and Nutrition (APrON) study participated. Covariate-adjusted robust regressions examined associations between maternal pre-pregnancy BMI, GWG class, interaction terms, and child outcomes. Each unit increase in maternal BMI was linked to a 0.48-point decrement (95% CI: −0.75 to −0.21) in children’s Full Scale IQ. Higher pre-pregnancy BMI was related to poorer performance on the other intelligence indexes (B = −0.35 to −0.47, 95% CIs: −0.75, −0.02) and lower performance on measures of language (B = −0.08 to −0.09, 95% CIs: −0.16, −0.02), motor skills (B = −0.08 to −0.11, 95% CIs: −0.18, −0.01), and executive function (B = −0.09 to −0.16, 95% CIs: −0.26, −0.01). GWG below the recommended range was associated with a 4.04-point decrement (95% CI: 7.89, −0.11) in Full Scale IQ, but better performance on a spatial working memory test (B = 0.27, 95% CI: 0.02, 0.52). GWG above the recommended range was associated with lower language (B = −0.79, 95% CI: −1.52, −0.06) and memory scores (B = −0.93, 95% CI: −1.64, −0.22). Interactions were found between pre-pregnancy BMI and GWG on measures of intelligence and executive function. Maternal pre-pregnancy BMI and GWG are related to children’s performance in various neuropsychological domains and may interact to predict outcomes. Optimizing maternal health and weight prior to conception and during pregnancy may enhance children’s neuropsychological outcomes.

How gut immunity in early life is shaped by birth in relation to delivery mode, intrapartum antibiotic prophylaxis (IAP) and labor remains undetermined. We aimed to address this gap with a study of secretory Immunoglobulin A (SIgA) in the infant gut that also tested SIgA-stimulating pathways mediated by gut microbiota and metabolites. Among 1017 Canadian full-term infants, gut microbiota of fecal samples collected at 3 and 12 months were profiled using 16S rRNA sequencing; C. difficile was quantified by qPCR; fecal metabolites and SIgA levels were measured by NMR and SIgA enzyme-linked immunosorbent assay, respectively. We assessed the putative causal relationships from birth events to gut microbiota and metabolites, and ultimately to SIgA, in statistical sequential mediation models, adjusted for maternal gravida status in 551 infants. As birth mode influences the ability to breastfeed, the statistical mediating role of breastfeeding status and milk metabolites was also evaluated. Relative to vaginal birth without maternal IAP, cesarean section (CS) after labor was associated with reduced infant gut SIgA levels at 3 months (6.27 vs. 4.85 mg/g feces, p < 0.05); this association was sequentially mediated through gut microbiota and metabolites of microbial or milk origin. Mediating gut microbiota included Enterobacteriaceae, C. difficile, and Streptococcus. The milk or microbial metabolites in CS-SIgA mediating pathways were galactose, fucose, GABA, choline, lactate, pyruvate and 1,2-propanediol. This cohort study documented the impact of birth on infant gut mucosal SIgA. It is the first to characterize gut microbe-metabolite mediated pathways for early-life SIgA maturation, pathways that require experimental verification.

Women’s nutritional status during pregnancy can have long-term effects on children’s brains and cognitive development. Folate and choline are methyl-donor nutrients and are important for closure of the neural tube during fetal development. They have also been associated with brain and cognitive development in children. Animal studies have observed that prenatal folate and choline supplementation is associated with better cognitive outcomes in offspring and that these nutrients may have interactive effects on brain development. Although some human studies have reported associations between maternal folate and choline levels and child cognitive outcomes, results are not consistent, and no human studies have investigated the potential interactive effects of folate and choline. This lack of consistency could be due to differences in the methods used to assess folate and choline levels, the gestational trimester at which they were measured, and lack of consideration of potential confounding variables. This narrative review discusses and critically reviews current research examining the associations between maternal levels of folate and choline during pregnancy and brain and cognitive development in children. Directions for future research that will increase our understanding of the effects of these nutrients on children’s neurodevelopment are discussed.

The gut microbiome is hypothesized to play a crucial role in the development of obesity and insulin resistance (IR); the pathways linking the microbiome to IR in pediatrics have yet to be precisely characterized. We aimed to determine the relationship between the gut microbiome composition and metabolic functions and IR in children with obesity. In a cross-sectional study, fecal samples from children with obesity (10–16 years old) were collected for taxonomical and functional analysis of the fecal microbiome using shotgun metagenomics. The homeostatic model assessment for insulin resistance (HOMA-IR) was determined using fasting glucose and insulin. Associations between HOMA-IR and α-diversity measures as well as metabolic pathways were evaluated using Spearman correlations; relationships between HOMA-IR and β-diversity were assessed by permutational multivariate analysis of variance. Twenty-one children (nine males; median: age = 12.0 years; BMI z-score = 2.9; HOMA-IR = 3.6) completed the study. HOMA-IR was significantly associated with measures of α-diversity but not with β-diversity. Children with higher HOMA-IR exhibited lower overall species richness, Firmicutes species richness, and overall Proteobacteria species Shannon diversity. Furthermore, HOMA-IR was inversely correlated with the abundance of pathways related to the biosynthesis of lipopolysaccharides, amino acids, and short-chain fatty acids, whereas positive correlations between HOMA-IR and the peptidoglycan biosynthesis pathways were observed. In conclusion, insulin resistance was associated with decreased microbial α-diversity measures and abundance of genes related to the metabolic pathways. Our study provides a framework for understanding the microbial alterations in pediatric obesity.

Glioblastoma (GBM) is an aggressive tumor with a dismal prognosis. Neural stem-like cells contribute to GBM’s poor prognosis by driving drug resistance and maintaining cellular heterogeneity. GBM neural stem-like cells express high levels of brain fatty acid-binding protein (FABP7), which binds to polyunsaturated fatty acids (PUFAs) ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Similar to brain, GBM tissue is enriched in AA and DHA. However, DHA levels are considerably lower in GBM tissue compared to adult brain. Therefore, it is possible that increasing DHA content in GBM, particularly in neural stem-like cells, might have therapeutic value. Here, we examine the fatty acid composition of patient-derived GBM neural stem-like cells grown as neurosphere cultures. We also investigate the effect of AA and DHA treatment on the fatty acid profiles of GBM neural stem-like cells with or without FABP7 knockdown. We show that DHA treatment increases DHA levels and the DHA:AA ratio in GBM neural stem-like cells, with FABP7 facilitating the DHA uptake. We also found that an increased uptake of DHA inhibits the migration of GBM neural stem-like cells. Our results suggest that increasing DHA content in the GBM microenvironment may reduce the migration/infiltration of FABP7-expressing neural stem-like cancer cells.

Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.

In young children, the relationship between vitamin D and biomarkers of immune function is not well elucidated. The objective was to investigate relationships between vitamin D and immune function in young children. Data were from a cross-sectional study (study 1) of healthy children 1.8–5.9 years (n = 457) and a 12 weeks trial using vitamin D fortified foods (study 2) in healthy 1.8–8.7 years old (n = 77) in Montreal, Canada. Vitamin D status and ex vivo immune function were assessed. In study 1 (male: n = 242; 53%), plasma IL-6, TNFα and CRP were significantly higher (p < 0.05) in children with 25-hydroxyvitamin D (25(OH)D) ≥ 75 nmol/L compared to

We examined the association between maternal vitamin D intake during breastfeeding with their infants’ vitamin D status in infants who did or did not receive vitamin D supplements to determine whether infant supplementation was sufficient. Using plasma from a subset of breastfed infants in the APrON (Alberta Pregnant Outcomes and Nutrition) cohort, vitamin D status was measured by liquid chromatography-tandem mass spectrometry. Maternal and infants’ dietary data were obtained from APrON’s dietary questionnaires. The median maternal vitamin D intake was 665 International Units (IU)/day, while 25% reported intakes below the recommended 400 IU/day. Of the 224 infants in the cohort, 72% were exclusively breastfed, and 90% were receiving vitamin D supplements. Infants’ median 25(OH)D was 96.0 nmol/L (interquartile ranges (IQR) 77.6–116.2), and 25% had 25(OH)D < 75 nmol/L. An adjusted linear regression model showed that, with a 100 IU increase in maternal vitamin D intake, infants’ 25(OH)D increased by 0.9 nmol/L controlling for race, season, mid-pregnancy maternal 25(OH)D, birthweight, and whether the infant received daily vitamin D supplement (β = 0.008, 95% confidence interval (CI) 0.002, 0.13). These results suggest that, to ensure infant optimal vitamin D status, not only do infants require a supplement, but women also need to meet current recommended vitamin D intake during breastfeeding.

This study assessed the long-term effects of dietary vaccenic acid (VA) and elaidic acid (EA) on plasma and splenocyte phospholipid (PL) composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl), obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.

Epidemiological studies have associated high fish oil consumption with decreased risk of breast cancer (BC). n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish and fish oils exert anti-cancer effects. However, few studies have examined the relative efficacy of EPA and DHA alone and in mixtures on BC subtypes. This was the objective of the present review, as this research is a necessity for the translation of findings to human health and disease. The literature suggests that DHA has a greater anti-cancer effect in triple negative BC (TNBC). In estrogen positive (ER+) BC, DHA has a greater effect on cell viability, while both fatty acids have similar effects on apoptosis and proliferation. These effects are associated with preferential uptake of DHA into TNBC lipid rafts and EPA in ER+ BC. EPA:DHA mixtures have anti-cancer activity; however, the ratio of EPA:DHA does not predict the relative incorporation of these two fatty acids into membrane lipids as EPA appears to be preferentially incorporated. In summary, DHA and EPA should be considered separately in the context of BC prevention. The elucidation of optimal EPA:DHA ratios will be important for designing targeted n-3 LCPUFA treatments.

Globally, there were 14.1 million new cancer diagnoses and 8.2 million cancer deaths in 2012. For many cancers, conventional therapies are limited in their successes and an improved understanding of disease progression is needed in conjunction with exploration of alternative therapies. The long chain polyunsaturated fatty acid, docosahexaenoic acid (DHA), has been shown to enhance many cellular responses that reduce cancer cell viability and decrease proliferation both in vitro and in vivo. A small number of studies suggest that DHA improves chemotherapy outcomes in cancer patients. It is readily incorporated into cancer cell membranes and, as a result there has been considerable research regarding cell membrane initiated events. For example, DHA has been shown to mediate the induction of apoptosis/reduction of proliferation in vitro and in vivo. However, there is limited research into the effect of DHA on cell cycle regulation in cancer cells and the mechanism(s) by which DHA acts are not fully understood. The purpose of the current review is to provide a critical examination of the literature investigating the ability of DHA to stall progression during different cell cycle phases in cancer cells, as well as the consequences that these changes may have on tumour growth, independently and in conjunction with chemotherapy.

Study objectives were to examine the impact of feeding a mixture of choline forms, or a diet high in glycerophosphocholine (GPC) on maternal immune function and offspring growth during lactation. Lactating Sprague-Dawley rat dams (n = 6/diet) were randomized to one of three diets, providing 1 g/kg total choline: Control (100% free choline (FC)), Mixed Choline (MC; 50% phosphatidylcholine (PC), 25% FC, 25% GPC), or High GPC (HGPC; 75% GPC, 12.5% PC, 12.5% FC). At 3 weeks, cell phenotypes and cytokine production with Concanavalin A (ConA)-or lipopolysaccharide (LPS)-stimulated splenocytes and mesenteric lymphocytes were measured. Feeding MC or HGPC diets improved pups’ growth compared to Control (+22% body weight, p < 0.05). In spleen, MC-and HGPC-fed dams had higher proportions of cytotoxic (CD8+) T cells expressing CD27, CD71 and CD127, total B cells (CD45RA+) and dendritic cells (OX6+OX62+), and produced less IL-6 and IFN-γ after ConA than Control-fed dams (p < 0.05). MC and HGPC LPS-stimulated splenocytes produced less IL-1β and IL-6 than Control. ConA-stimulated mesenteric lymphocytes from MC and HGPC dams produced more IL-2 and IFN-γ than Control (p < 0.05). In summary, feeding a mixture of choline forms during lactation improved offspring growth and resulted in a more efficient maternal immune response following mitogenic immune challenge.

Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) during the suckling period on the development of the immune system and oral tolerance (OT) in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA) or DHA (N = 8, 0.9% DHA) diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA) treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13) response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05). Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05). Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05). Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT.