Filaggrin Mutation Status and Prevention of Atopic Dermatitis with Maternal Probiotic Supplementation.

The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive  effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.

Melatonin supplementation in obese mothers reduces hypothalamic inflammation and enhances thermogenesis in mice progeny.

Maternal obesity might induce obesity and metabolic alterations in the progeny. The study aimed to determine the effect of supplementing obese mothers with Mel (Mel) on thermogenesis and inflammation. C57BL/6 female mice (mothers) were fed from weaning to 12 weeks control diet (C, 17% kJ as fat) or a high-fat diet (HF, 49% kJ as fat) and then matted with male mice fed the control diet. Melatonin (10 mg/kg daily) was supplemented to mothers during gestation and lactation, forming the groups C, CMel, HF, and HFMel (n = 10/group). Twelve-week male offspring were studied (plasma biochemistry, immunohistochemistry, protein, and gene expressions at the hypothalamus - Hyp, subcutaneous white adipose tissue - sWAT, and interscapular brown adipose tissue - iBAT). Comparing HFMel vs. HF offspring, fat deposits and plasmatic proinflammatory markers decreased. Also, HFMel showed decreased Hyp proinflammatory markers and neuropeptide Y (anabolic) expression but improved proopiomelanocortin (catabolic) expression. Besides, HFMel sWAT adipocytes changed to a beige phenotype with-beta-3 adrenergic receptor and uncoupling protein-1 activation, concomitant with browning genes activation, triggering the iBAT thermogenic activity. In conclusion, compelling evidence indicated the beneficial effects of supplementing obese mothers with Mel on the health of their mature male offspring. Mel led to sWAT browning-related gene enhancement, increased iBAT thermogenis, and mitigated hypothalamic inflammation. Also, principal component analysis of the data significantly separated the untreated obese mother progeny from the progeny of treated obese mothers. If confirmed in humans, the findings encourage a future guideline recommending Mel supplementation during pregnancy and breastfeeding.

Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice.

Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor ß (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.

Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age.

BACKGROUND: We previously reported in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze. METHODS: We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25-75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25-75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age. RESULTS: Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25-75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment. CONCLUSIONS: Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci. Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603.

Sex-Dependent Variations in Hypothalamic Fatty Acid Profile and Neuropeptides in Offspring Exposed to Maternal Obesity and High-Fat Diet.

Maternal obesity and/or high-fat diet (HF) consumption can disrupt appetite regulation in their offspring, contributing to transgenerational obesity and metabolic diseases. As fatty acids (FAs) play a role in appetite regulation, we investigated the maternal and fetal levels of FAs as potential contributors to programmed hyperphagia observed in the offspring of obese dams. Female mice were fed either a control diet (CT) or HF prior to mating, and fetal and maternal blood and tissues were collected at 19 days of gestation. Elevated levels of linoleic acid were observed in the serum of HF dams as well as in the serum of their fetuses. An increased concentration of eicosadienoic acid was also detected in the hypothalamus of female HF-O fetuses. HF-O male fetuses showed increased hypothalamic neuropeptide Y (Npy) gene expression, while HF-O female fetuses showed decreased hypothalamic pro-opiomelanocortin (POMC) protein content. Both male and female fetuses exhibited reduced hypothalamic neurogenin 3 (NGN-3) gene expression. In vitro experiments confirmed that LA contributed to the decreased gene expression of Pomc and Ngn-3 in neuronal cells. During lactation, HF female offspring consumed more milk and had a higher body weight compared to CT. In summary, this study demonstrated that exposure to HF prior to and during gestation alters the FA composition in maternal serum and fetal serum and hypothalamus, particularly increasing n-6, which may play a role in the switch from POMC to NPY neurons, leading to increased weight gain in the offspring during lactation.

Maternal inulin alleviates high-fat diet-induced lipid disorder in offspring by epigenetically modulating hypothalamus feeding circuit-related genes.

Increasing evidence supports the existence of fetal-originated adult diseases. Recent research indicates that the intrauterine environment affects the fetal hypothalamic energy intake center. Inulin is a probiotic that can moderate metabolic disorders, but whether maternal inulin intervention confers long-term metabolic benefits to lipid metabolism in offspring in their adult lives and the mechanism involved are unknown. Here, we used a maternal overnutrition model that was induced by excess energy intake before and during pregnancy and lactation and maternal inulin intervention was performed during pregnancy and lactation. The hypothalamic genome methylation in offspring was analyzed using a methylation array. The results showed that maternal inulin treatment modified the maternal high-fat diet (HFD)-induced increases in body weight, adipose tissue weight, and serum insulin and leptin levels and decreases in serum adiponectin levels. Maternal inulin intervention regulated the impairments in hypothalamic leptin resistance, induced the methylation of Socs3, Npy, and Il6, and inhibited the methylation of Lepr in the hypothalamus of offspring. In conclusion, maternal inulin intervention modifies offspring lipid metabolism, and the underlying mechanism involves the methylation of genes in the hypothalamus feeding circuit.

Effect of the enhancing nutrition and antenatal infection treatment (ENAT) intervention on birth weight in Ethiopia: a cluster randomized controlled trial.

BACKGROUND: The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) intervention was implemented in Ethiopia to improve newborn birth weight (BW) by strengthening the contents and quality of antenatal care (ANC), especially point-of-care testing for maternal infections. This study examined the effect of the ENAT intervention on birth weight. METHODS: We conducted a cluster randomized controlled trial of 22 clusters (health centers), randomized equally between 11 intervention and 11 control clusters. This study enrolled and followed pregnant women from ANC booking to the end of pregnancy or loss to follow-up. The primary outcome was mean BW, and the incidence of low birth weight (LBW) was the secondary outcome. We presented univariate comparisons of outcomes between the intervention and control arms for mean BW and LBW. Multilevel analyses using random effects models were performed to adjust for clustering and individual-level covariates. RESULTS: We enrolled and followed up 4,868 and 4,821 pregnant women in the intervention and control arms, respectively, from March 2021-July 2022. During follow-up, 3445 pregnant women in the intervention and 3192 in the control delivered in the health centers, and BW measurements of their babies were recorded within 48 h. The mean BW was 3,152 g (standard deviation (SD) = 339.8 g) in the intervention and 3,044 g (SD = 353.8 g) in the control arms (mean difference, 108 g; 95% confidence interval (CI): 91.3-124.6; P = 0.000). Adjusting for clustering and several covariates, the mean BW remained significantly higher in the intervention arm than in the control arm (adjusted ß coef., 114.3; p = 0.011). The incidence of LBW was 4.7% and 7.3% in the intervention and control arms, respectively. The adjusted risk of LBW was significantly lower by 36% in the intervention arm than in the control arm (adjusted relative risk, 0.645; p = 0.027). CONCLUSION: This study provided sufficient evidence of the effectiveness of the ENAT intervention in improving birth weight in the study population. The intervention demonstrated that an increase in birth weight can be attained by availing point-of-care testing, strengthening infection prevention, and maternal nutrition within the ANC platform of public health facilities in a low-income setting. TRIAL REGISTRATION: Registered at Pan African Clinical Trial Registry (PACTR) database dated 09/05/2023, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25493 . The unique identification number for the registry is PACTR202305694761480.

Taurine supplementation reduces adiposity and hepatic lipid metabolic activity in adult offspring following maternal cafeteria diet.

Maternal taurine supplementation has been shown to exert protective effects following a maternal obesogenic diet on offspring growth and metabolism. However, the long-term effects of maternal cafeteria diet on adiposity, metabolic profile, and hepatic gene expression patterns following supplementation of taurine in adult offspring remains unclear. In this study, we hypothesized that exposure to maternal taurine supplementation would modulate the effects of maternal cafeteria diet by reducing adiposity and hepatic gene expression patterns involved in lipid metabolism in adult offspring. Female Wistar rats were fed a control diet, control diet supplemented with 1.5% taurine in drinking water, cafeteria diet (CAF) or CAF supplemented with taurine (CAFT) from weaning. After 8 weeks, all animals were mated and maintained on the same diets during pregnancy and lactation. After weaning, all offspring were fed with control chow diet until the age of 20 weeks. Despite similar body weights, CAFT offspring had significantly lower fat deposition and body fat when compared with CAF offspring. Microarray analysis revealed that genes (Akr1c3, Cyp7a1, Hsd17b6, Cd36, Acsm3, and Aldh1b1) related to steroid hormone biosynthesis, cholesterol metabolism, peroxisome proliferator-activated receptor signaling pathway, butanoate metabolism, and fatty acid degradation were down-regulated in CAFT offspring. The current study shows that exposure to maternal cafeteria diet promoted adiposity and taurine supplementation reduced lipid deposition and in both male and female offspring and led to alterations in hepatic gene expression patterns, reducing the detrimental effects of maternal cafeteria diet.

Obese mothers supplemented with melatonin during gestation and lactation ameliorate the male offspring's pancreatic islet cellular composition and beta-cell function.

Melatonin supplementation to obese mothers during gestation and lactation might benefit the pancreatic islet cellular composition and beta-cell function in male offspring adulthood. C57BL/6 females (mothers) were assigned to two groups (n = 20/each) based on their consumption in control (C 17% kJ as fat) or high-fat diet (HF 49% kJ as fat). Mothers were supplemented with melatonin (Mel) (10 mg/kg daily) during gestation and lactation, or vehicle, forming the groups (n = 10/each): C, CMel, HF, and HFMel. The male offspring were studied, considering they only received the C diet after weaning until three months old. The HF mothers and their offspring showed higher body weight, glucose intolerance, insulin resistance, and low insulin sensitivity than the C ones. However, HFMel mothers and their offspring showed improved glucose metabolism and weight loss than the HF ones. Also, the offspring's higher expressions of pro-inflammatory markers and endoplasmic reticulum (ER) stress were observed in HF but reduced in HFMel. Contrarily, antioxidant enzymes were less expressed in HF but improved in HFMel. In addition, HF showed increased beta-cell mass and hyperinsulinemia but diminished in HFMel. Besides, the beta-cell maturity and identity gene expressions diminished in HF but enhanced in HFMel. In conclusion, obese mothers supplemented with melatonin benefit their offspring's islet cell remodeling and function. In addition, improving pro-inflammatory markers, oxidative stress, and ER stress resulted in better glucose and insulin levels control. Consequently, pancreatic islets and functioning beta cells were preserved in the offspring of obese mothers supplemented with melatonin.

Maternal High-Fat Diet Controls Offspring Kidney Health and Disease.

A balanced diet during gestation is critical for fetal development, and excessive intake of saturated fats during gestation and lactation is related to an increased risk of offspring kidney disease. Emerging evidence indicates that a maternal high-fat diet influences kidney health and disease of the offspring via so-called renal programming. This review summarizes preclinical research documenting the connection between a maternal high-fat diet during gestation and lactation and offspring kidney disease, as well as the molecular mechanisms behind renal programming, and early-life interventions to offset adverse programming processes. Animal models indicate that offspring kidney health can be improved via perinatal polyunsaturated fatty acid supplementation, gut microbiota changes, and modulation of nutrient-sensing signals. These findings reinforce the significance of a balanced maternal diet for the kidney health of offspring.

Neuronal Differentiation and Outgrowth Effect of Thymol in Trachyspermum ammi Seed Extract via BDNF/TrkB Signaling Pathway in Prenatal Maternal Supplementation and Primary Hippocampal Culture.

Reviving the neuronal functions in neurodegenerative disorders requires the promotion of neurite outgrowth. Thymol, which is a principal component of Trachyspermum ammi seed extract (TASE), is reported to have neuroprotective effects. However, the effects of thymol and TASE on neuronal differentiation and outgrowth are yet to be studied. This study is the first report investigating the neuronal growth and maturation effects of TASE and thymol. Pregnant mice were orally supplemented with TASE (250 and 500 mg/kg), thymol (50 and 100 mg/kg), vehicle, and positive controls. The supplementation significantly upregulated the expression of brain-derived neurotrophic factor (BDNF) and early neuritogenesis markers in the pups' brains at post-natal day 1 (P1). Similarly, the BDNF level was significantly upregulated in the P12 pups' brains. Furthermore, TASE (75 and 100 µg/mL) and thymol (10 and 20 µM) enhanced the neuronal polarity, early neurite arborization, and maturation of hippocampal neurons in a dose-dependent manner in primary hippocampal cultures. The stimulatory activities of TASE and thymol on neurite extension involved TrkB signaling, as evidenced by attenuation via ANA-12 (5 µM), which is a specific TrkB inhibitor. Moreover, TASE and thymol rescued the nocodazole-induced blunted neurite extension in primary hippocampal cultures, suggesting their role as a potent microtubule stabilizing agent. These findings demonstrate the potent capacities of TASE and thymol in promoting neuronal development and reconstruction of neuronal circuitry, which are often compromised in neurodegenerative diseases and acute brain injuries.

Leucine supplementation in maternal high-fat diet alleviated adiposity and glucose intolerance of adult mice offspring fed a postweaning high-fat diet.

BACKGROUND: Combined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated. METHODS: Female mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring. RESULTS: HFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho ß, and its downstream targets, proliferator-activated receptor-γ co-activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring. CONCLUSIONS: Leucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.

Maternal nutrition and effects on offspring vascular function.

Maternal nutrition during pregnancy may have profound effects on the developing fetus and impact risk for cardiovascular disease later in life. Here, we provide a narrative review on the impact of maternal diet during pregnancy on offspring vascular function. We review studies reporting effects of maternal micronutrient (folic acid, iron) intakes, high-fat diets, dietary energy restriction, and low protein intake on offspring endothelial function. We discuss the differences in study design and outcomes and potential underlying mechanisms contributing to the vascular phenotypes observed in the offspring. We further highlight key gaps in the literature and identify targets for future investigations.

Elateriospermum tapos Yogurt Supplement in Maternal Obese Dams during Pregnancy Modulates the Body Composition of F1 Generation.

Maternal obesity is a key predictor of childhood obesity and a determining factor for a child's body composition. Thus, any form of maternal nutrition during the gestational period plays a vital role in influencing the growth of the fetus. Elateriospermum tapos (E. tapos) yogurt has been found to comprise many bioactive compounds such as tannins, saponins, α-linolenic acid, and 5'-methoxy-bilobate with apocynoside I that could cross the placenta and exhibit an anti-obesity effect. As such, this study aimed to investigate the role of maternal E. tapos yogurt supplementation on offspring body composition. In this study, 48 female Sprague Dawley (SD) rats were induced with obesity using a high-fat diet (HFD) and were allowed to breed. Upon confirmation of pregnancy, treatment was initiated with E. tapos yogurt on the obese dams up to postnatal day 21. The weaning offspring were then designated into six groups according to their dam's group (n = 8) as follows; normal food and saline (NS), HFD and saline (HS), HFD and yogurt (HY), HFD and 5 mg/kg of E. tapos yogurt (HYT5), HFD and 50 mg/kg of E. tapos yogurt (HYT50), and HFD and 500 mg/kg of E. tapos yogurt (HYT500). The body weight of the offspring was accessed every 3 days up to PND 21. All the offspring were euthanized on PND 21 for tissue harvesting and blood sample collection. The results showed that both male and female offspring of obese dams treated with E. tapos yogurt showed growth patterns similar to NS and reduced levels of triglycerides (TG), cholesterol, LDL, non-HDL, and leptin. Liver enzymes such as ALT, ALP, AST, GGT, and globulin, and renal markers such as sodium, potassium, chloride, urea, and creatinine levels significantly reduced (p < 0.05) in the offspring of E. tapos yogurt-treated obese dams with the normal histological architecture of the liver, kidney, colon, RpWAT, and visceral tissue that is comparable to NS. In toto, E. tapos yogurt supplementation of obese dams exerted an anti-obesity effect by preventing intergenerational obesity by reversing HFD-induced damage in the fat tissue of the offspring.

Fortified balanced energy-protein supplementation during pregnancy and lactation and infant growth in rural Burkina Faso: A 2 × 2 factorial individually randomized controlled trial.

BACKGROUND: Optimal nutrition is crucial during the critical period of the first 1,000 days from conception to 2 years after birth. Prenatal and postnatal supplementation of mothers with multimicronutrient-fortified balanced energy-protein (BEP) supplements is a potential nutritional intervention. However, evidence on the long-term effects of BEP supplementation on child growth is inconsistent. We evaluated the efficacy of daily fortified BEP supplementation during pregnancy and lactation on infant growth in rural Burkina Faso. METHODS AND FINDINGS: A 2 × 2 factorial individually randomized controlled trial (MISAME-III) was implemented in 6 health center catchment areas in Houndé district under the Hauts-Bassins region. From October 2019 to December 2020, 1,897 pregnant women aged 15 to 40 years with gestational age <21 completed weeks were enrolled. Women were randomly assigned to the prenatal intervention arms receiving either fortified BEP supplements and iron-folic acid (IFA) tablets (i.e., intervention) or IFA alone (i.e., control), which is the standard of care during pregnancy. The same women were concurrently randomized to receive either of the postnatal intervention, which comprised fortified BEP supplementation during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention), or the postnatal control, which comprised IFA alone for 6 weeks postpartum (i.e., control). Supplements were provided by trained village-based project workers under direct observation during daily home visits. We previously reported the effect of prenatal BEP supplementation on birth outcomes. The primary postnatal study outcome was length-for-age z-score (LAZ) at 6 months of age. Secondary outcomes were anthropometric indices of growth (weight-for length and weight-for-age z-scores, and arm and head circumferences) and nutritional status (prevalence rates of stunting, wasting, underweight, anemia, and hemoglobin concentration) at 6 months. Additionally, the longitudinal prevalence of common childhood morbidities, incidence of wasting, number of months of exclusive breastfeeding, and trajectories of anthropometric indices from birth to 12 months were evaluated. Prenatal BEP supplementation resulted in a significantly higher LAZ (0.11 standard deviation (SD), 95% confidence interval (CI) [0.01 to 0.21], p = 0.032) and lower stunting prevalence (-3.18 percentage points (pp), 95% CI [-5.86 to -0.51], p = 0.020) at 6 months of age, whereas the postnatal BEP supplementation did not have statistically significant effects on LAZ or stunting at 6 months. On the other hand, postnatal BEP supplementation did modestly improve the rate of monthly LAZ increment during the first 12 months postpartum (0.01 z-score/month, 95% CI [0.00 to 0.02], p = 0.030), whereas no differences in growth trajectories were detected between the prenatal study arms. Furthermore, except for the trend towards a lower prevalence of underweight found for the prenatal BEP intervention at 6 months (-2.74 pp, 95% CI [-5.65 to 1.17], p = 0.065), no other secondary outcome was significantly affected by the pre- or postnatal BEP supplementation. CONCLUSIONS: This study provides evidence that the benefits obtained from prenatal BEP supplementation on size at birth are sustained during infancy in terms of linear growth. Maternal BEP supplementation during lactation may lead to a slightly better linear growth towards the second half of infancy. These findings suggest that BEP supplementation during pregnancy can contribute to the efforts to reduce the high burden of child growth faltering in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03533712.

Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes.

Maternal obesity during pregnancy adversely impacts offspring health, predisposing them to chronic metabolic diseases characterized by insulin resistance, dysregulated macronutrient metabolism, and lipid overload, such as metabolic-associated fatty liver disease (MAFLD). Choline is a semi-essential nutrient involved in lipid and one-carbon metabolism that is compromised during MAFLD progression. Here, we investigated under high-fat (HF) obesogenic feeding how maternal choline supplementation (CS) influenced the hepatic lipidome of mouse offspring. Our results demonstrate that maternal HF+CS increased relative abundance of a subclass of phospholipids called plasmalogens in the offspring liver at both embryonic day 17.5 and after 6 weeks of postnatal HF feeding. Consistent with the role of plasmalogens as sacrificial antioxidants, HF+CS embryos were presumably protected with lower oxidative stress. After postnatal HF feeding, the maternal HF+CS male offspring also had higher relative abundance of both sphingomyelin d42:2 and its side chain, nervonic acid (FA 24:1). Nervonic acid is exclusively metabolized in the peroxisome and is tied to plasmalogen synthesis. Altogether, this study demonstrates that under the influence of obesogenic diet, maternal CS modulates the fetal and postnatal hepatic lipidome of male offspring, favoring plasmalogen synthesis, an antioxidative response that may protect the mouse liver from damages due to HF feeding.

Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet.

SCOPE: Perinatal maternal moderately high-fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n-3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning. METHODS AND RESULTS: Female Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high-fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics. CONCLUSIONS: Gestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long-term outcomes.

Long-chain n-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner.

This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague-Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.

Maternal obesity damages the median eminence blood-brain barrier structure and function in the progeny: the beneficial impact of cross-fostering by lean mothers.

Maternal obesity is an important risk factor for obesity, cardiovascular, and metabolic diseases in the offspring. Studies have shown that it leads to hypothalamic inflammation in the progeny, affecting the function of neurons regulating food intake and energy expenditure. In adult mice fed a high-fat diet, one of the hypothalamic abnormalities that contribute to the development of obesity is the damage of the blood-brain barrier (BBB) at the median eminence-arcuate nucleus (ME-ARC) interface; however, how the hypothalamic BBB is affected in the offspring of obese mothers requires further investigation. Here, we used confocal and transmission electron microscopy, transcript expression analysis, glucose tolerance testing, and a cross-fostering intervention to determine the impact of maternal obesity and breastfeeding on BBB integrity at the ME-ARC interface. The offspring of obese mothers were born smaller; conversely, at weaning, they presented larger body mass and glucose intolerance. In addition, maternal obesity-induced structural and functional damage of the offspring's ME-ARC BBB. By a cross-fostering intervention, some of the defects in barrier integrity and metabolism seen during development in an obesogenic diet were recovered. The offspring of obese dams breastfed by lean dams presented a reduction of body mass and glucose intolerance as compared to the offspring continuously exposed to an obesogenic environment during intrauterine and perinatal life; this was accompanied by partial recovery of the anatomical structure of the ME-ARC interface, and by the normalization of transcript expression of genes coding for hypothalamic neurotransmitters involved in energy balance and BBB integrity. Thus, maternal obesity promotes structural and functional damage of the hypothalamic BBB, which is, in part, reverted by lactation by lean mothers.NEW & NOTEWORTHY Maternal dietary habits directly influence offspring health. In this study, we aimed at determining the impact of maternal obesity on BBB integrity. We show that DIO offspring presented a leakier ME-BBB, accompanied by changes in the expression of transcripts encoding for endothelial and tanycytic proteins, as well as of hypothalamic neuropeptides. Breastfeeding in lean dams was sufficient to protect the offspring from ME-BBB disruption, providing a preventive strategy of nutritional intervention during early life.

Multiple modifiable maternal, household and health service factors are associated with maternal nutrition and early breastfeeding practices in Burkina Faso.

Low coverage of effective nutrition interventions in many high-burden countries, due to service provision and demand factors, result in poor uptake of recommended practices and nutrition outcomes. We examined the factors that influence maternal nutrition and early breastfeeding practices and determined the extent that the key factors could improve these practices in two regions in Burkina Faso. We used household survey data among pregnant (n = 920) and recently delivered women (n = 1840). Multivariable regression analyses were conducted to identify the determinants of a diverse diet and iron-folic acid (IFA) supplement consumption, weight monitoring during pregnancy and early initiation of breastfeeding (EIBF). Population attributable risk analysis was used to estimate how much the outcomes can be improved under optimal conditions of interventions that address the modifiable determinants. During pregnancy, 21% of women achieved minimum diet diversity (MDD-W), 70% consumed 90+ IFA tablets and 65% were weighed 4+ times; EIBF was 40%. Nutrition knowledge was associated with MDD-W (odds ratio [OR]: 3.2), 90+ IFA (OR: 1.5) and EIBF (OR: 1.9). Positive social norms and family support were associated with 90+ IFA (OR: 1.5). Early and 4+ ANC visits were associated with 90+ IFA (OR: 1.5 and 10) and 4+ weight monitoring (OR: 6.2). Nutrition counselling was associated with 90+ IFA (OR: 2.5) and EIBF (OR: 1.5). Under optimal programme conditions, 41% of women would achieve MDD-W, 93% would consume 90+ IFA, 93% would be weighed 4+ times and 57% would practice EIBF. Strengthening the delivery and uptake of interventions targeted at these modifiable factors has the potential to improve maternal nutrition practices.