Project description:The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.
Project description:Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development.
Project description:Importance:Strategies to prevent autism in children exposed to antiepileptic drugs (AEDs) during pregnancy are important. Objective:To explore whether folic acid supplementation and folate status in pregnancy are associated with reduced risk of autistic traits owing to in utero AED exposure. Design, Setting, and Participants:The population-based, prospective Norwegian Mother and Child Cohort Study approached Norwegian-speaking women attending routine ultrasonographic examinations from June 1999 through December 31, 2008 (163?844 of 277?702 women refused). No exclusion criteria were applied beyond language. Questionnaires during and after pregnancy, analysis of blood samples, and linkage to the Medical Birth Registry of Norway were performed. Children aged 18 to 36 months of women with available information on use of AEDs and of folic acid supplementation (n?=?104?946) were included in the analysis from March 1, 2016, through June 13, 2017. Exposures:Maternal folic acid supplementation 4 weeks before to 12 weeks after conception. Plasma folate concentration was analyzed at gestational weeks 17 to 19. Main Outcomes and Measures:Autistic traits were evaluated using the Modified Checklist for Autism in Toddlers and Social Communication Questionnaire. Odds ratios (ORs) for autistic traits in children by maternal use vs nonuse of folic acid supplements were adjusted for maternal health and socioeconomic factors. Folate concentrations and folic acid doses were associated with the degree of autistic traits. Results:The overall mean (SD) age of the 104?946 mothers of participating children was 29.8 (4.6) years, with complete information available for analysis in 103 868. Mean (SD) age of women with epilepsy who received AED treatment was 29.4 (4.9); women with epilepsy who did not receive AED treatment, 29.1 (4.9); and without epilepsy, 29.8 (4.6) years. In the 335 children exposed to AEDs, the risk for autistic traits was significantly higher at 18 months of age (adjusted OR [AOR], 5.9; 95% CI, 2.2-15.8) and 36 months of age (AOR, 7.9; 95% CI, 2.5-24.9) when their mothers had not used folic acid supplements compared with children of mothers who had used supplements. Among women without epilepsy, the corresponding risks were lower at 18 months of age (AOR, 1.3; 95% CI, 1.2-1.4) and 36 months of age (AOR, 1.7; 95% CI, 1.5-1.9); among the 389 children of women with untreated epilepsy, the corresponding risks were not significant at 18 months of age (AOR, 1.0; 95% CI, 0.4-3.0) and 36 months of age (AOR, 2.5; 95% CI, 0.4-16.6). Degree of autistic traits was inversely associated with maternal plasma folate concentrations (??=?-0.3; P?=?.03) and folic acid doses (??=?-0.5; P?<?.001). Concentrations of AEDs were not associated with the degree of autistic traits. Conclusions and Relevance:Risk of autistic traits in children exposed to AEDs in utero may be mitigated by periconceptional folic acid supplementation and folate status. Fertile women using AEDs should take folic acid supplements continuously.
Project description:Introduction:Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring. A wealth of observational studies have reported on both obstetric outcomes and complications, including pre-eclampsia, gestational diabetes, mode and timing of delivery. Many foetal and childhood outcomes are also linked to vitamin D status, including measures of foetal size, body composition and skeletal mineralization, in addition to later childhood outcomes, such as asthma. Sources of data:Synthesis of systematic and narrative reviews. Areas of agreement and controversy:The findings are generally inconsistent in most areas, and, at present, there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. In most areas, the evidence tends towards maternal vitamin D being of overall benefit, but often does not reach statistical significance in meta-analyses. Growing points and areas timely for developing research:The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily. High-quality randomized placebo-controlled trials, such as the UK-based MAVIDOS trial, will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes.
Project description:BackgroundIron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it may also improve other maternal and birth outcomes.ObjectivesTo assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention.Search methodsWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 July 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (2 July 2012) and contacted relevant organisations for the identification of ongoing and unpublished studies.Selection criteriaRandomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy.Data collection and analysisWe assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy.Main resultsWe included 60 trials. Forty-three trials, involving more than 27,402 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo.Overall, women taking iron supplements were less likely to have low birthweight newborns (below 2500 g) compared with controls (8.4% versus 10.2%, average risk ratio (RR) 0.81; 95% confidence interval (CI) 0.68 to 0.97, 11 trials, 8480 women) and mean birthweight was 30.81 g greater for those infants whose mothers received iron during pregnancy (average mean difference (MD) 30.81; 95% CI 5.94 to 55.68, 14 trials, 9385 women). Preventive iron supplementation reduced the risk of maternal anaemia at term by 70% (RR 0.30; 95% CI 0.19 to 0.46, 14 trials, 2199 women) and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women). Although the difference between groups did not reach statistical significance, women who received iron supplements were more likely than controls to report side effects (25.3% versus 9.91%) (RR 2.36; 95% CI 0.96 to 5.82, 11 trials, 4418 women), particularly at doses 60 mg of elemental iron or higher. Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130g/L during pregnancy and at term. Twenty-three studies were conducted in countries that in 2011 had some malaria risk in parts of the country. In some of these countries/territories, malaria is present only in certain areas or up to a particular altitude. Only two of these reported malaria outcomes. There is no evidence that iron supplementation increases placental malaria. For some outcomes heterogeneity was higher than 50%.Authors' conclusionsPrenatal supplementation with daily iron are effective to reduce the risk of low birthweight, and to prevent maternal anaemia and iron deficiency in pregnancy. Associated maternal side effects and particularly high Hb concentrations during pregnancy at currently used doses suggest the need to update recommendations on doses and regimens for routine iron supplementation.
Project description:Pregnancy requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Despite increasing knowledge, data is lacking on the transition of pre-pregnancy endometrial lymphocytes to a pregnancy state. Here, we immunophenotyped lymphocytes from endometrium (MMC), term decidua parietalis (DPMC), and PBMC for direct comparison. We found that the immune cell composition of MMC and DPMC clearly differ from each other, with less NK-cells, and more NKT-cells and T-cells in DPMC. An increased percentage of central memory and effector memory T-cells, and less naive T-cells in DPMC indicates that decidual T-cells are more experienced than endometrial T-cells. The increased percentage of CD4+CD25highCD127- Treg in DPMC, including differentiated Treg, is indicative of a more experienced and tolerogenic environment during pregnancy. The Th cell composition of both MMC and DPMC was different from PBMC, with a preference for Th1 over Th2 in the uterine environment. Between MMC and DPMC, percentages of Th cell subsets did not differ significantly. Our results suggest that already before pregnancy a tightly controlled Th1/Th2/Th17 balance is present. These findings create opportunities to further investigate the underlying immune mechanism of pregnancy complications using menstrual blood as a source for endometrial lymphocytes.
Project description:Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated the effect of maternal naringin supplementation during pregnancy on the offspring's cerebral redox status. Pregnant Wistar rats were divided into control and naringin groups and supplemented from gestational day 15 to gestational day 21. On postnatal days 1, 7, and 21, offspring were euthanized, and the prefrontal cortex, hippocampus, striatum, and cerebellum dissected. On postnatal day 1, maternal naringin supplementation positively modulated the pups' brain redox status. On postnatal day 7, a pro-oxidative milieu was observed in the offspring's striatum and cerebellum in a sex-dependent manner, even though the prefrontal cortex and hippocampus were not negatively affected. Besides, the alterations observed on postnatal day 7 did not persist up to weaning. Our findings demonstrated that the effect induced by naringin supplementation in the brain redox status differed according to the period of development in which naringin was consumed since the beneficial effects usually found in the adult rodents became detrimental when the supplementation was applied during pregnancy.
Project description:The maternal immune system engages in a fine balancing act during pregnancy by simultaneously maintaining immune tolerance to the fetus and immune responses to protect against invading organisms. Pregnancy is an intricately orchestrated process where effector immune cells with fetal specificity are selectively silenced. This requires a sustained immune suppressive state not only by expansion of maternal Foxp3+ regulatory T cells (Tregs) but also by leaning the immune clock toward a Th2 dominant arm. The fetus, known as a semi-allograft or temporary-self, leads to remission of autoimmune hepatitis during pregnancy. However, this tolerogenic immune state reverts back to a Th1 dominant arm, resulting in post-partum flare of AIH. Various hormones play a significant role in endocrine-immune axis during pregnancy. The placenta functions as a barrier between the maternal immune system and the fetus also plays a pivotal role in creating a tolerogenic environment during pregnancy. We review the evidence of immune tolerance during pregnancy and immune escape at post-partum period, focusing on patients with autoimmune hepatitis.