Dichotomous effect of dietary fiber in pediatrics: a narrative review of the health benefits and tolerance of fiber.

Dietary fibers are associated with favorable gastrointestinal, immune, and metabolic health outcomes when consumed at sufficient levels. Despite the well-described benefits of dietary fibers, children and adolescents continue to fall short of daily recommended levels. This gap in fiber intake (i.e., "fiber gap") might increase the risk of developing early-onset pediatric obesity and obesity-related comorbidities such as type 2 diabetes mellitus into adulthood. The structure-dependent physicochemical properties of dietary fiber are diverse. Differences in solubility, viscosity, water-holding capacity, binding capability, bulking effect, and fermentability influence the physiological effects of dietary fibers that aid in regulating appetite, glycemic and lipidemic responses, and inflammation. Of growing interest is the fermentation of fibers by the gut microbiota, which yields both beneficial and less favorable end-products such as short-chain fatty acids (e.g., acetate, propionate, and butyrate) that impart metabolic and immunomodulatory properties, and gases (e.g., hydrogen, carbon dioxide, and methane) that cause gastrointestinal symptoms, respectively. This narrative review summarizes (1) the implications of fibers on the gut microbiota and the pathophysiology of pediatric obesity, (2) some factors that potentially contribute to the fiber gap with an emphasis on undesirable gastrointestinal symptoms, (3) some methods to alleviate fiber-induced symptoms, and (4) the therapeutic potential of whole foods and commonly marketed fiber supplements for improved health in pediatric obesity.

Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Association of Human Milk Fatty Acid Composition with Maternal Cardiometabolic Diseases: An Exploratory Prospective Cohort Study.

Background: Human milk fatty acids derive from maternal diet, body stores, and mammary synthesis and may reflect women's underlying cardiometabolic health. We explored whether human milk fatty acid composition was associated with maternal cardiometabolic disease (CMD) during pregnancy and up to 5 years postpartum. Materials and Methods: We analyzed data from the prospective CHILD Cohort Study on 1,018 women with no preexisting CMD who provided breast milk samples at 3-4 months postpartum. Milk fatty acid composition was measured using gas-liquid chromatography. Maternal CMD (diabetes or hypertension) was classified using questionnaires and birth records as no CMD (reference outcome group; 81.1%), perinatal CMD (developed and resolved during the perinatal period; 14.9%), persistent CMD (developed during, and persisted beyond, the perinatal period; 2.9%), and incident CMD (developed after the perinatal period; 1.1%). Multinomial logistic regression was used to model associations between milk fatty acid composition (individual, summary, ratios, and patterns identified using principal component analysis) and maternal CMD, adjusting for pre-pregnancy anthropometry and race/ethnicity. Results: Medium-chain saturated fatty acids (MC-SFA), lauric (C12:0; odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.60-0.89) and myristic acid (C14:0; OR = 0.80, 95% CI = 0.66-0.97), and the high MC-SFA principal component pattern (OR = 0.86, 95% CI = 0.76-0.96) were inversely associated with perinatal CMD. Long-chain polyunsaturated fatty acids adrenic acid (C22:4n-6) was positively associated with perinatal (OR = 1.21, 95% CI = 1.01-1.44) and persistent CMD (OR = 1.56, 95% CI = 1.08-2.25). The arachidonic (C20:4n-6)-to-docosahexaenoic acid (C22:6n-3) ratio was inversely associated with incident CMD (OR = 0.52, 95% CI = 0.28-0.96). Conclusions: These exploratory findings highlight a potential novel utility of breast milk for understanding women's cardiometabolic health.

Pre-labor and post-labor cesarean delivery and early childhood adiposity in the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study.

BACKGROUND/OBJECTIVES: Delivery by cesarean section (CS) compared to vaginal delivery has been associated with increased risk of overweight in childhood. Our study examined if the presence or absence of labor events in CS delivery altered risk of overweight in early childhood (1-5 years) compared to vaginal delivery and if this association differed according to infant sex. SUBJECTS/METHODS: The study included 3073 mother-infant pairs from the CHILD Cohort Study in Canada. Data from birth records were used to categorize infants as having been vaginally delivered, or delivered by CS, with or without labor events. Age and sex adjusted weight-for-length (WFL) and body mass index (BMI) z scores were calculated from height and weight data from clinic visits at 1, 3 and 5 years and used to classify children as overweight. Associations between delivery mode and child overweight at each timepoint were assessed using regression models, adjusting for relevant confounding factors including maternal pre-pregnancy BMI. Effect modification by infant sex was tested. RESULTS: One in four infants (24.6%) were born by CS delivery; 13.0% involved labor events and 11.6% did not. Infants born by CS without labor had an increased odds of being overweight at age 1 year compared to vaginally delivered infants after adjustment for maternal pre-pregnancy BMI, maternal diabetes, smoking, infant sex and birthweight-for-gestational age (aOR 1.68 [95% CI 1.05-2.67]). These effects did not persist to 3 or 5 years of age and, after stratification by sex, were only seen in boys (aOR at 1 year 2.21 [95% CI 1.26-3.88]). CONCLUSION AND RELEVANCE: Our findings add to the body of evidence that CS, in particular CS without labor events, may be a risk factor for overweight in early life, and that this association may be sex-specific. These findings could help to identify children at higher risk for developing obesity.

Maternal pre-pregnancy weight status and gestational weight gain in association with child behavior: The mediating role of prenatal systemic inflammation.

BACKGROUND AND AIMS: Maternal pre-pregnancy obesity and excessive gestational weight gain (EGWG) may predispose children to behavioral problems through increased prenatal inflammation. We investigated the association between maternal body mass index (BMI) and gestational weight gain (GWG), and child behavioral problems (primary aim), and the mediating role of prenatal inflammation (secondary aim). METHODS: We used self-reported pre-pregnancy BMI and estimated-GWG data (N = 1137) from a longitudinal cohort study. Maternal serum C-reactive protein (CRP) was measured in the 3rd-trimester. Parent-reported Child Behavior Checklist (CBCL) was used to assess child internalizing and externalizing behaviors at 3-years-of-age. We used analysis of covariance (ANCOVA), multiple linear regression, and mediation analyses for data analysis. RESULTS: Maternal obesity (F = 21.98, df 3836), EGWG (F = 6.53, df 2764), and their combination (F = 18.51, df 3764) were associated with the 3rd trimester CRP, but not child behavior in the whole sample. Maternal underweight was associated with withdrawal problems in all children (ß = 0.56, 95%CI, 0.11,1.00) and aggressive behaviors in female children (ß = 2.59, 95%CI, 0.28,4.91). Obesity had a significant association with externalizing behaviors in female children after controlling for maternal CRP (ß = 3.72, 95%CI, 0.12,7.32). Both inadequate and EGWG were associated with somatic complaints in male children (ß = 0.50, 95%CI, 0.05,0.95; ß = 0.36, 95%CI, 0.01,0.71, respectively). Combined obesity/EGWG was associated with externalizing (ß = 6.12, 95%CI, 0.53,11.70) and aggressive (ß = 4.23, 95%CI, 0.90,7.56) behaviors in female children. We found no significant effects through CRP. CONCLUSIONS: Maternal pre-pregnancy BMI and GWG showed sex-specific associations with child behavioral problems. Prenatal CRP, although increased in obesity and EGWG, did not mediate these associations.

The metabolic load-capacity model and cardiometabolic health in children and youth with obesity.

BACKGROUND: The metabolic load-capacity index (LCI), which represents the ratio of adipose to skeletal muscle tissue-containing compartments, is potentially associated with cardiometabolic diseases. OBJECTIVES: To examine the associations between the LCI and cardiometabolic risk factors in children and youth with obesity. METHODS: This is a cross-sectional study including 10-18 years-old participants with a BMI of ≥95th . LCI by air-displacement plethysmography (ADP) was calculated as fat mass divided by fat-free mass, and LCI by ultrasound (US) as subcutaneous adipose tissue divided by skeletal muscle thickness. Sex-specific medians stratified participants into high versus low LCI. Single (inflammation, insulin resistance, dyslipidemia and hypertension) and clustered cardiometabolic risk factors were evaluated. Linear and logistic regression models tested the associations between these variables, adjusted for sexual maturation. RESULTS: Thirty-nine participants (43.6% males; 59% mid-late puberty) aged 12.5 (IQR: 11.1-13.5) years were included. LCI by ADP was positively associated with markers of inflammation and dyslipidemia; having a higher LCI predicted dyslipidemia in logistic regression. Similarly, LCI by US was positively associated with markers of dyslipidemia and blood pressure. In mid-late pubertal participants, LCI by US was positively associated with markers of insulin resistance and inflammation. CONCLUSIONS: Participants with unfavourable cardiometabolic profile had higher LCI, suggesting its potential use for predicting and monitoring cardiometabolic health in clinical settings.

Maternal Iron and Vitamin D Status during the Second Trimester Is Associated with Third Trimester Depression Symptoms among Pregnant Participants in the APrON Cohort.

BACKGROUND: The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed. OBJECTIVES: This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals. METHODS: The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained. RESULTS: Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (ß: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (ß: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (ß: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 µg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (ß: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 µg/L) and vitamin D (25(OH)D <75 nmol/L) (ß: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients. CONCLUSIONS: A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy.

The importance of the timing of microbial signals for perinatal immune system development.

Background: Development and maturation of the immune system begin in utero and continue throughout the neonatal period. Both the maternal and neonatal gut microbiome influence immune development, but the relative importance of the prenatal and postnatal periods is unclear. Methods: In the present study, we characterized immune cell populations in mice in which the timing of microbiome colonization was strictly controlled using gnotobiotic methodology. Results: Compared to conventional (CONV) mice, germ-free (GF) mice conventionalized at birth (EC mice) showed few differences in immune cell populations in adulthood, explaining only 2.36% of the variation in immune phenotypes. In contrast, delaying conventionalization to the fourth week of life (DC mice) affected seven splenic immune cell populations in adulthood, including dendritic cells and regulatory T cells (Tregs), explaining 29.01% of the variation in immune phenotypes. Early life treatment of DC mice with Limosilactobacillus reuteri restored splenic dendritic cells and Tregs to levels observed in EC mice, and there were strain-specific effects on splenic CD4+ T cells, CD8+ T cells, and CD11c+ F4/80+ mononuclear phagocytes. Conclusion: This work demonstrates that the early postnatal period, compared to the prenatal period, is relatively more important for microbial signals to influence immune development in mice. Our findings further show that targeted microbial treatments in early life can redress adverse effects on immune development caused by the delayed acquisition of the neonatal gut microbiome.

Maternal Pre-Pregnancy BMI and Gestational Weight Gain Are Associated with Preschool Children's Neuropsychological Outcomes in the APrON Cohort.

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.

Corrigendum: Egg-phosphatidylcholine attenuates T-cell dysfunction in high-fat diet fed male Wistar rats.

[This corrects the article DOI: 10.3389/fnut.2022.811469.].

A Physiologically Relevant Dose of 50% Egg-Phosphatidylcholine Is Sufficient in Improving Gut Permeability while Attenuating Immune Cell Dysfunction Induced by a High-Fat Diet in Male Wistar Rats.

BACKGROUND: Obesity is associated with increased intestinal permeability and a diminished immune response. Phosphatidylcholine (PC), a form of choline found in eggs, has been shown to beneficially modulate T-cell response in the context of obesity when provided as the sole form of choline in the diet. OBJECTIVE: This study aimed to determine the impact of varying doses of PC as part of a high-fat diet (HFD) on immune cell function and intestinal permeability. METHODS: Male Wistar rats 4 wk of age were randomly assigned to consume 1 of 6 diets for 12 wk containing the same amount of total choline but differing in the forms of choline: 1-control low-fat (CLF, 20% fat, 100% free choline [FC]); 2-control high-fat (CHF, 50% fat, 100% FC); 3-100% PC (100PC, 50% fat, 100% egg-PC); 4-75% PC (75PC, 50% fat, 75% egg-PC+25% FC); 5-50% PC (50PC, 50% fat, 50% egg-PC+50% FC); and 6-25% PC (25PC; 50% fat, 25% egg-PC+75% FC). Intestinal permeability was measured by fluorescein isothiocyanate-dextran. Immune function was assessed by ex vivo cytokine production of splenocytes and cells isolated from the mesenteric lymph node (MLN) after stimulation with different mitogens. RESULTS: Feeding the CHF diet increased intestinal permeability compared with the CLF diet, and doses of PC 50% or greater returned permeability to levels similar to that of the CLF diet. Feeding the CHF diet lowered splenocyte production of interleukin (IL)-1ß, IL-2, IL-10, and tumor necrosis factor-alpha, and MLN production of IL-2 compared with the CLF group. The 50PC diet most consistently significantly improved cytokine levels (IL-2, IL-10, tumor necrosis factor-alpha) compared with the CHF diet. CONCLUSIONS: Our results show that a dose of 50% of total choline derived from egg-PC can ameliorate HFD-induced intestinal permeability and immune cell dysfunction.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study.

BACKGROUND: Developmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts. OBJECTIVES: This study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex. METHODS: The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models. RESULTS: The risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 µg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males. CONCLUSIONS: Relationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals.

Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort.

BACKGROUND: There is inconsistent evidence regarding the sex-specific associations between prenatal phthalate exposure and children's neurodevelopment. This could be due to differences in the phthalate exposures investigated and the neurodevelopmental domains assessed. OBJECTIVE: To evaluate the associations between prenatal phthalate exposure and sex-specific outcomes on measures of cognition, language, motor, executive function, and behaviour in children 2 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. METHODS: We evaluated the associations between prenatal phthalate exposure and sex-specific neurodevelopmental outcomes in children at 2 years of age using data from 448 mothers and their children (222 girls, 226 boys). Nine phthalate metabolites were measured in maternal urine collected in the second trimester of pregnancy. Children's cognitive, language, and motor outcomes were assessed using the Bayley Scales of Infant Development - Third Edition (Bayley-III). Parents completed questionnaires on children's executive function and behavior, the Behavior Rating Inventory of Executive Function- Preschool Version (BRIEF-P) and Child Behavior Checklist (CBCL), respectively. Sex-stratified robust multivariate regressions were performed. RESULTS: Higher maternal concentrations of ΣDEHP and its metabolites were associated with lower scores on the Bayley-III Cognitive (ß's from -11.8 to -0.07 95% CI's from -21.3 to -0.01), Language (ß's from -11.7 to -0. 09, 95% CI's from -22.3 to -0.02) and Motor (ß's from -10.9 to -0.07, 95% CI from -20.4 to -0.01) composites in boys. The patterns of association in girls were in the opposite direction on the Cognitive and Language composites; on the Motor composite they were in the same direction as boys, but of reduced strength. Higher concentrations of ΣDEHP and its metabolites were associated with higher scores (i.e., more difficulties) on all measures of executive function in girls: inhibitory self-control (B's from 0.05 to 0.11, 95% CI s from -0.01 to 0.15), flexibility (B's from 0.04 to 0.11, 95% CI s from 0.01 to 0.21) and emergent metacognition (B's from -0.01 to 0.06, 95% CIs from -0.01 to 0.20). Similar patterns of attenuated associations were seen in boys. Higher concentrations of ΣDEHP and its metabolites were associated with more Externalizing Problems in girls and boys (B's from 0.03 to 6.82, 95% CIs from -0.08 to 12.0). Two phthalates, MMP and MBP, had sex-specific adverse associations on measures of executive function and behaviour, respectively, while MEP was positively associated with boys' cognitive, language, and motor performance. Limited associations were observed between mixtures of maternal phthalates and sex-specific neurodevelopmental outcomes. CONCLUSIONS: Maternal prenatal concentrations of DEHP phthalates were associated with sex specific difference on measures of cognition and language at 2 years of age, specifically, poorer outcomes in boys. Higher exposure to DEHP was associated with poorer motor, executive function, and behavioural outcomes in girls and boys but the strength of these associations differed by sex. Limited associations were noted between phthalate mixtures and child neurodevelopment.

In parenteral nutrition-fed piglets, fatty acids vary by lipid emulsion and tissue sampled.

BACKGROUND: Children with intestinal failure without liver disease may be given soy-based lipid emulsion (SLE) or mixed lipid emulsion (MLE; containing soy, medium-chain triglyceride, olive, and/or fish oils). Both differ in essential fatty acid content: MLE has added arachidonic acid (AA) and docosahexaenoic acid (DHA). The aim of this study, in neonatal piglets, was to compare serum and tissue fatty acid composition when the emulsions were given at unrestricted doses. METHODS: We compared SLE (n = 15) and MLE (n = 15) at doses of 10-15 g/kg/day in parenteral nutrition (PN). On day 14 we collected serum and tissues. Using gas-liquid chromatography, percentage fatty acids were measured in serum, brain, and liver phospholipid. Comparisons were made to reference values from litter-matched controls (n = 8). RESULTS: Comparing median values, linoleic acid (LA) was lower for MLE vs SLE in serum (-27%), liver (-45%), and brain (-33%) (P < 0.001). AA was lower for MLE in serum (-25%), liver (-40%), and brain (-10%). DHA was higher for MLE in serum (+50%), liver (+200%), and brain (+10%). AA levels were lower for MLE vs control piglets in serum (-81%), liver (-63%), and brain (-9%). DHA levels were higher in serum (+41%), liver (+38%), and brain (+19%). CONCLUSION: This study in piglets has shown that, at unrestricted doses, MLE treatment is associated with low serum and tissue AA compared with SLE and healthy litter-matched controls. Although not yet proven, low tissue AA levels may have functional consequences, and these data support current practice avoiding MLE dose restriction.

Maternal co-exposure to mercury and perfluoroalkyl acid isomers and their associations with child neurodevelopment in a Canadian birth cohort.

BACKGROUND: Perfluoroalkyl acids (PFAAs) within the broader class of per- and polyfluoroalkyl substances (PFAS) are present in human serum as isomer mixtures, but epidemiological studies have yet to address isomer-specific associations with child development and behavior. OBJECTIVES: To examine associations between prenatal exposure to 25 PFAAs, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) isomers, and child neurodevelopment among 490 mother-child pairs in a prospective Canadian birth cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. To consider the influence of a classic neurotoxicant, total mercury (THg), based on its likelihood of co-exposure with PFAAs from common dietary sources. METHODS: Maternal blood samples were collected in the second trimester and child neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III). Linear or curvilinear multiple regression models were used to examine associations between exposures and neurodevelopment outcomes. RESULTS: Select PFAAs were associated with lower Cognitive composite scores, including perfluoroheptanoate (PFHpA) (ß = -0.88, 95% confidence interval (CI): -1.7, -0.06) and perfluorododecanoate (PFDoA) (ß = -2.0, 95% CI: -3.9, -0.01). Non-linear relationships revealed associations of total PFOS (ß = -4.4, 95% CI: -8.3, -0.43), and linear-PFOS (ß = -4.0, 95% CI: -7.5, -0.57) and 1m-PFOS (ß = -1.8, 95% CI: -3.3, -0.24) isomers with lower Language composite scores. Although there was no effect modification, including THg interaction terms in PFAA models revealed negative associations between perfluorononanoate (PFNA) and Motor (ß = -3.3, 95% CI: -6.2, -0.33) and Social-Emotional (ß = -3.0, 95% CI: -5.6, -0.40) composite scores. DISCUSSION: These findings reinforce previous reports of adverse effects of maternal PFAA exposure during pregnancy on child neurodevelopment. The unique hazards posed from isomers of PFOS justify isomer-specific analysis in future studies. To control for possible confounding, mercury co-exposure may be considered in studies of PFAAs.

The Programming Effect of Plant-Based DHA, Along with Equivalent AA, on Immune System and Oral Tolerance Development in Six-Week Allergy Prone BALB/c Pups.

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (AA) on oral tolerance (OT) development in allergy-prone infants is less known. OBJECTIVES: We aim to determine the effects of early life DHA supplementation (1% of total fat, from novel canola oil), along with AA, on OT toward ovalbumin (ova, egg protein) in allergy-prone BALB/c pups at 6-wk. METHODS: Breastfeeding dams (n ≥ 10/diet) were fed DHA+AA (1% DHA, 1% AA wt/wt of total fat) or control (0% DHA, 0% AA) suckling period diet (SPD) during which pups consumed dam's milk. At 3-wk, pups from each SPD group were assigned to either the control or DHA+AA weaning diet. For OT, pups from each diet group were either orally fed ova or placebo daily from 21-25 d. Systemic immunization to ova was induced through intraperitoneal injections before euthanizing 6-wk pups. Ova-specific immunoglobulin (ova-Ig) and splenocytes ex-vivo cytokine response to different stimuli were analyzed using a 3-factor analysis of variance. RESULTS: OT-induced suppression was seen in ova-stimulated splenocyte ex-vivo response, where ova-tolerized pups showed significantly lower total immunoglobulin (Ig)G, IgG1, interleukin (IL)-2 and IL-6 production than sucrose (placebo) pups. DHA+AA SPD was associated with 3 times lower plasma concentrations of ova-IgE (P = 0.03) than controls. DHA+AA weaning diet resulted in lower T helper type-2 cytokines (IL-4 and IL-6) with ova stimulation than controls, which may benefit OT. DHA+AA SPD resulted in significantly higher T cell cytokine response [IL-2, interferon-gamma, (IFNγ) and IL-1ß] to anti-CD3/CD28 stimulation than controls. The splenocytes stimulated with lipopolysaccharide produced lower inflammatory cytokines (IFNγ, tumor necrosis factor-alpha, IL-6, and C-X-C motif ligand 1), which may be because of lower CD11b+CD68+ splenocytes proportion in pups from DHA+AA SPD than control (all P < 0.05). CONCLUSIONS: DHA and AA in early life may influence OT in allergy-prone BALB/c mouse offspring, as they effectively promote T helper type-1 immune responses.

The distribution of dietary choline intake and serum choline levels in Australian women during pregnancy and associated early life factors.

BACKGROUND: Maternal dietary choline has a central role in foetal brain development and may be associated with later cognitive function. However, many countries are reporting lower than recommended intake of choline during pregnancy. METHODS: Dietary choline was estimated using food frequency questionnaires in pregnant women participating in population-derived birth cohort, the Barwon Infant Study (BIS). Dietary choline is reported as the sum of all choline-containing moieties. Serum total choline-containing compounds (choline-c), phosphatidylcholine and sphingomyelin were measured using nuclear magnetic resonance metabolomics in the third trimester. The main form of analysis was multivariable linear regression. RESULTS: The mean daily dietary choline during pregnancy was 372 (standard deviation (SD) 104) mg/day. A total of 236 women (23%) had adequate choline intake (440 mg/day) based on the Australian and New Zealand guidelines, and 27 women (2.6%) took supplemental choline ([Formula: see text] 50 mg/dose) daily during pregnancy. The mean serum choline-c in pregnant women was 3.27 (SD 0.44) mmol/l. Ingested choline and serum choline-c were not correlated (R2) = - 0.005, p = 0.880. Maternal age, maternal weight gain in pregnancy, and a pregnancy with more than one infant were associated with higher serum choline-c, whereas gestational diabetes and environmental tobacco smoke during preconception and pregnancy were associated with lower serum choline-c. Nutrients or dietary patterns were not associated with variation in serum choline-c. CONCLUSION: In this cohort, approximately one-quarter of women met daily choline recommendations during pregnancy. Future studies are needed to understand the potential impact of low dietary choline intake during pregnancy on infant cognition and metabolic intermediaries.

Regulation of immune function in healthy adults: one-stop guide on the role of dietary fatty acids, gut microbiota-derived short chain fatty acids, and select micronutrients in combination with physical activity.

The immune system requires an adequate supply of nutrients, although current dietary recommendations may not account for optimal immune function in healthy adults. Nutrient inadequacies due to the growing influence of the western diet pose a risk for immune dysfunction. This review aims to determine the beneficial effects of supplementing dietary fats, nutrients that modulate gut microbiota, and specific micronutrients on systemic immune functions (concentrations of plasma cytokines, antibodies, and acute phase proteins) during health and acute inflammatory conditions, including COVID-19. We discussed micronutrients (selenium, zinc, and vitamin D) with compelling evidence supporting immunomodulatory properties. Additionally, the synergistic effects of physical activity and dietary interventions on systemic immune markers are explored. Briefly, evidence suggests that dietary consumption of monounsaturated (oleic and palmitoleic acids) and omega-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic acids) promotes anti-inflammatory properties. Food sources (fiber, prebiotics, probiotics, omega-3) and patterns (Mediterranean diet) increase the production of short-chain fatty acids, beneficially altering gut microbiota composition, which subsequently enhances the immunomodulatory properties of circulating immune cells. A positive synergistic role of nutrient supplementation (omega-3 and fiber) and physical activity on circulating C-reactive protein and interleukin-6 levels has been observed. Lastly, omega-3 supplementation during COVID-19 infection may reduce circulating C-reactive protein and pro-inflammatory cytokines and improves pain and fatigue symptoms. This review highlights recent findings that support the beneficial role of specific nutrients in promoting systemic immune function in healthy adults. However, to establish specific dietary recommendations to support optimal immune function, more research is required. Key takeaway: Increasing dietary fats (fish and olive oils) and specific micronutrients may positively impact systemic immune function in healthy adults. Evidence suggests that these nutrients promote immunomodulatory properties useful in resolving acute infection.