Dietary Supplementation with Rumen-Protected Arginine or N-Carbamylglutamate Enhances Fetal Liver Development in Nutrient-Restricted Pregnant Hu Ewes.

This study was conducted in nutrient-restricted pregnant Hu ewes to determine whether rumen-protected arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation affects fetal liver growth and development. From 35 d to 110 d of gestation, 32 Hu ewes were randomly divided into four groups: a control group (100% of the National Research Council (NRC) requirements), a nutrient-restricted group (50% of the NRC requirements), and two treatment groups (ARG and NCG, 50% of the NRC requirements, supplemented with 20 g/day RP-Arg or 5 g/day NCG, respectively). Fetal body weights, fetal liver growth performance, the capability of antioxidation, and the expression of the mRNA and proteins of apoptosis-related genes in the fetal liver were determined and analyzed at 110 d of gestation. The dry matter, water, fat, protein, and ash components of the fetal livers in the RG group were found to be lower than in the CG group, and these components were significantly higher in the NCG group than in the RG group (p < 0.05). A decrease in DNA, RNA, and protein concentrations and contents, as well as in protein/DNA ratios, was observed in the RG group in comparison to the CG group (p < 0.05). Compared with the RG group, the NCG group had higher concentrations of DNA, RNA, and protein, as well as higher protein/DNA ratios (p < 0.05). The RG group had lower concentrations of cholinesterase, nitric oxide, nitric oxide synthase, superoxide dismutase, alanine aminotransferase, and total protein than the CG group (p < 0.05). The RG group had higher levels of glutathione peroxidase, maleic dialdehyde, and aspartate aminotransferase than the CG group (p < 0.05). In the RG group, the mRNA and protein expression of p53 and Bax was significantly increased (p < 0.05) compared with the CG group, and the gene expression of FasL and Bcl-2, the ratio of Bcl-2 to Bax, and the protein expression of Bcl-2 in the RG group were lower (p < 0.05) than in the CG group. It appears that RP-Arg and NCG supplementation during pregnancy could influence fetal liver growth and development. A nutrition-based therapeutic intervention to alleviate reduced fetal growth can be developed based on this study, which has demonstrated that maternal undernutrition during pregnancy induces the maldevelopment of the fetal liver.

Effect of preconception multiple micronutrients vs. iron-folic acid supplementation on maternal and birth outcomes among women from developing countries: a systematic review and meta-analysis.

Background: Maternal malnutrition affects the somatic growth of the fetus and subsequent adverse events during infancy and childhood period. Though trials have been conducted on multiple micronutrient (MMN) supplements initiated during the preconception period, there is no collated evidence on this. Materials and methods: We performed a systematic review of published trials with the application of Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The searches were conducted until 30 September 2023. Meta-analysis was performed using Review Manager 5 software. The primary objective was to compare the effect of preconception MMN vs. iron-folic acid (IFA) supplementation on newborn anthropometric parameters at birth. Results: Of the 11,832 total citations retrieved, 12 studies with data from 11,391 participants [Intervention = 5,767; Control = 5,624] were included. For the primary outcome, there was no significant difference in the birth weight [MD, 35.61 (95% CI, -7.83 to 79.06), p = 0.11], birth length [MD, 0.19 (95% CI, -0.03 to 0.42), p = 0.09], and head circumference [MD, -0.25 (95% CI, -0.64 to -0.14), p = 0.22] between the MMN and control groups. For all the secondary outcomes [except for small for gestational age (SGA) and low birth weight (LBW)], the difference between the MMN and control groups was not significant. The GRADE evidence generated for all the outcomes varied from "very low to moderate certainty." Conclusion: A "very low certainty" of evidence suggests that MMN supplementation may not be better than routine IFA supplementation in improving newborn anthropometric parameters (weight, length, and head circumference). The adverse events resulting from the supplementation were not significant. We need better quality uniformly designed RCTs before any firm recommendation can be made.Systematic review registration: identifier (CRD42019144878: https://www.crd.york.ac.uk/prospero/#searchadvanced).

Astaxanthin and DHA Supplementation Modulates the Maternal Undernutrition-induced Impairment of Cognitive Behavior and Synaptic Plasticity in Adult Life of Offspring's -Exploring the Molecular Mechanism.

Maternal nutrition was recognized as a significant part of brain growth and maturation in most mammalian species. Timely intervention with suitable nutraceuticals would provide long-term health benefits. We aim to unravel the molecular mechanisms of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated undernourished dams at their gestational, lactational, and at both the time point with Astaxanthin (AsX) and Docosahexaenoic acid (DHA), and their pups were used as experimental animals. We evaluated the cognitive function by subjecting the pups to behavioral tests in their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and uncoupling protein-2 (UCP2) gene expression in pups born to undernourished dams in their adult life, which AsX and DHA modulated. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) tasks in offspring's. The expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control and AsX-DHA treated groups at CA1, CA2, CA3, and DG. AsX and DHA supplementation upregulated BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished rats, which are involved in intracellular signaling cascades like Ras, PI3K, and PLC. The results of our study give new insights into neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing maternal undernutrition-induced cognitive impairment in offspring's.

The effect of maternal undernutrition on adverse obstetric outcomes among women who attend antenatal care in Gedeo zone public hospitals, cohort study design.

BACKGROUND: Undernutrition refers to an overall deficiency of nutrients due to an inadequate intake of a well-balanced diet. Undernourishment during pregnancy is an important contributor to maternal morbidity and mortality. It remains a persistent problem in developing countries, where women usually fall behind men in having access to food, health care, and education. Despite the high prevalence of maternal undernourishment, its direct impact on obstetric outcomes has not been studied in developing countries, including Ethiopia. OBJECTIVE: This study aimed to assess the effect of maternal undernutrition on adverse obstetric outcomes in Gedeo zone public hospitals. METHOD: A cohort study design was employed in Gedeo zone public hospitals from June 30, 2022, to February 28, 2023. This study included 721 pregnant women, 237 were exposed group whereas 484 were non-exposed. A systematic random sampling technique was used to select a non-exposed group and the exposed group was selected consecutively. Both groups were followed for 7 months, from 16 weeks of gestation to 24 h of delivery. The pretested interviewer-administered questionnaire and checklist were used. EpiData 4.4.1.2.version was used for data entry and analyzed using Stata version 16 software. A modified Poisson regression model with robust standard errors was used to determine relative risk, and the statistical association was declared at a p-value ≤ 0.05. Finally, the findings were reported in figures, tables, and words. RESULT: The incidence of adverse obstetrics outcomes among undernourished and normally nourished mothers was hypertensive disorder during pregnancy (HDDP) (7.49% vs. 3.19%), antepartum haemorrhage (7.49% vs. 3.19%), obstructed labor (1.53% vs. 3.49%), premature rupture of the membrane (2.5% vs. 3.33%), preterm labor (6.52% vs. 6.93%), instrumental vaginal delivery (1.8% vs. 4.3%), postpartum haemorrhage (5.95% vs. 3.88%), and sepsis (3.74% vs. 1.94%). The risk of adverse obstetric outcomes among undernourished women was hypertensive disorder during pregnancy (HDDP) (aRR) = 4.07, 95%CI: 2.53-6.55), antepartum haemorrhage (APH) (aRR = 5.0, 95% CI: 2.08-12.72), preterm labor (aRR = 1.8, 95%CI: 1.23-2.62), operative delivery (aRR = 1.24, 95%C: 0.87-1.78), postpartum haemorrhage (aRR = 3.02, 95%CI: 1.91-4.79), and sepsis/chrioaminitis (aRR = 3.55, 95%CI: 1.83-6.89) times higher than normally nourished women. CONCLUSION: The incidence rates of hypertensive disorder during pregnancy (HDDP), antepartum haemorrhage, postpartum haemorrhage, and sepsis were higher among undernourished women than normally nourished women. Undernourished women during pregnancy have an increased risk of adverse obstetrics outcomes including hypertensive disorder during pregnancy, antepartum, preterm labor, operative delivery, postpartum haemorrhage, and sepsis/chorioamnionitis.

Hand Washing Practice and Food Insecurity are Associated With Undernutrition of Breastfeeding Mothers in Rural Ethiopia: A Cross-sectional Study.

Background: Breastfeeding mothers are prone to undernutrition. However, factors contributing to maternal undernutrition are not exhaustively understood. Hence, this study aimed to determine prevalence of undernutrition among breastfeeding mothers and identify associated factors. Methods: A cross-sectional study was conducted among 606 breastfeeding mothers from selected rural districts in Oromia and Sidama regional states of Ethiopia. Data were collected through an interviewer-administered questionnaire. Nutritional status was assessed using body mass index (BMI) and mid-upper-arm-circumference (MUAC). Logistic regression analysis was used to identify factors associated with maternal undernutrition. Results: One out of ten breastfeeding mothers was found undernourished as determined by BMI (12.6%) and MUAC (10.7%). Mothers who did not practice hand washing after cleaning children's bottom were 2 and 3 times more likely to be undernourished compared to their counters, as measured by BMI (AOR = 2.29, P = .002) and MUAC (AOR = 3.03, P < .001), respectively. Mothers living in mildly or moderately food insecure households (AOR = 2.37, P = .019) were more than two times more likely to be undernourished as determined by MUAC. Mothers who breastfed children in the age range of 9 to 11 (AOR = 2.79, P = .025) or 12 to 23 (AOR = 2.57, P = .018) months were more than two and half times more likely to be undernourished as determined by BMI. Conclusions: Maternal undernutrition is a medium-level public health problem in rural districts of Oromia and Sidama regional states in Ethiopia. The lack of hand washing practice after cleaning a child's bottom, household food insecurity and higher child age increased the odds of maternal undernutrition. Mothers should prioritize and improve their nutritional care as the age of their breastfed child increases. Nutrition programs in rural districts of Ethiopia should also aim to improve personal hygiene practices and food insecurity integrated with implementation researches to evaluate program's impact on nutritional status of breastfeeding mothers.

Timing of maternal nutrient restriction during mid- to late-gestation influences net umbilical uptake of glucose and amino acids in adolescent sheep.

Previous research demonstrated that maternal nutrient restriction during mid- to late-gestation influenced net umbilical uptakes of glucose and amino acids in sheep. However, it is unclear how the timing and duration of nutrient restriction during mid- to late-gestation influences net uterine, uteroplacental, and fetal flux of glucose and amino acids. On day 50 of gestation, 41 adolescent ewe lambs carrying singletons were randomly assigned to one of six dietary treatments: 1) 100% of nutrient requirements from days 50 to 90 of gestation (CON; n = 7); 2) 60% of nutrient requirements (RES; n = 7) from days 50 to 90 of gestation; 3) 100% of nutrient requirements from days 50 to 130 of gestation (CON-CON; n = 6); 4) 100% of nutrient requirements from days 50 to 90 of gestation and 60% of nutrient requirements from days 90 to 130 of gestation (CON-RES; n = 7); 5) 60% of nutrient requirements from days 50 to 90 of gestation and 100% of nutrient requirements from days 90 to 130 of gestation (RES-CON; n = 7); or 6) 60% of nutrient requirements from days 50 to 130 of gestation (RES-RES; n = 7). On day 90 (n = 14) and day 130 (n = 27), intraoperative procedures were performed to evaluate uteroplacental blood flows, collect blood samples, and then ewes were euthanized. Net uterine, uteroplacental, and umbilical fluxes of glucose and amino acids were calculated by multiplying blood flow by the arterial-venous concentration difference. Data from days 90 and 130 were analyzed separately using ANOVA in SAS. Maternal nutrient restriction during mid-gestation increased (P = 0.04) net umbilical glucose uptake but, maternal nutrient restriction during late-gestation decreased (P = 0.02) net umbilical glucose uptake. Net umbilical essential amino acid uptake decreased (P = 0.03) with nutrient restriction during mid-gestation; however, net umbilical uptakes of Phe (P = 0.02), Thr (P = 0.05), Met (P = 0.09), and His (P = 0.08) increased or tended to increase after nutrient restriction during late-gestation. These data demonstrate that net umbilical glucose and amino acid uptakes were influenced by the timing of nutrient restriction during mid- to late-gestation. Elevated net umbilical glucose uptake after mid-gestational nutrient restriction was sustained throughout late-gestation, independent of late-gestational feeding level. Long-term adaptations in umbilical glucose uptake may have implications for prenatal and postnatal growth and development of the offspring.

Maternal undernutrition during gestation can lead to decreased fetal growth, decreased uteroplacental blood flow, and changes in nutrient supply to the fetus. However, it is unclear how the timing (mid-gestation vs. late-gestation) and duration (40 d vs. 80 d) of nutrient restriction influence nutrient supply to the fetus during mid- to late-gestation. Pregnant ewe lambs fed a pelleted diet to meet 100% of nutritional requirements or 60% of nutritional requirements during mid-gestation alone (days 50 to 90) or during mid- and late-gestation (days 50 to 130). At the end of mid-gestation and late-gestation, the net nutrient supply between the maternal, placental, and fetal compartments was measured. The results indicated that the timing of nutrient restriction influenced the net nutrient supply to the fetus but, the duration of nutrient restriction did not. Nutrient restriction during mid-gestation increased glucose to the fetus but nutrient restriction during late-gestation decreased glucose to the fetus. The opposite response occurred for fetal essential amino acid supply where nutrient restriction during mid-gestation decreased essential amino acid supply to the fetus but increased for several essential amino acids during late-gestational nutrient restriction. The timing of maternal undernutrition during mid- to late-gestation can affect the amount of nutrients delivered to the fetus and thus, could potentially impact postnatal growth and development.

Cocoa Shell Extract Reduces Blood Pressure in Aged Hypertensive Rats via the Cardiovascular Upregulation of Endothelial Nitric Oxide Synthase and Nuclear Factor (Erythroid-Derived 2)-like 2 Protein Expression.

Cocoa shell is a by-product of cocoa manufacturing. We obtained an aqueous extract (CSE) rich in polyphenols and methylxanthines with antioxidant and vasodilatory properties. We aimed to evaluate the effects of CSE supplementation in aged hypertensive rats on blood pressure and the mechanism implicated. Eighteen-month-old male and female rats exposed to undernutrition during the fetal period who developed hypertension, with a milder form in females, were used (MUN rats). Systolic blood pressure (SBP; tail-cuff plethysmography) and a blood sample were obtained before (basal) and after CSE supplementation (250 mg/kg; 2 weeks, 5 days/week). Plasma SOD, catalase activity, GSH, carbonyls, and lipid peroxidation were assessed (spectrophotometry). In hearts and aortas from supplemented and non-supplemented age-matched rats, we evaluated the protein expression of SOD-2, catalase, HO-1, UCP-2, total and phosphorylated Nrf2 and e-NOS (Western blot), and aorta media thickness (confocal microscopy). MUN males had higher SBP compared with females, which was reduced via CSE supplementation with a significant difference for group, sex, and interaction effect. After supplementation with plasma, GSH, but not catalase or SOD, was elevated in males and females. Compared with non-supplemented rats, CSE-supplemented males and females exhibited increased aorta e-NOS and Nrf2 protein expression and cardiac phosphorylated-Nrf2, without changes in SOD-2, catalase, HO-1, or UCP-2 in cardiovascular tissues or aorta remodeling. In conclusion, CSE supplementation induces antihypertensive actions related to the upregulation of e-NOS and Nrf2 expression and GSH elevation and a possible direct antioxidant effect of CSE bioactive components. Two weeks of supplementation may be insufficient to increase antioxidant enzyme expression.

DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation.

This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requirements during the 8.5-month gestational period, DNA methylation in the fetal liver was analyzed with reduced representation bisulfite sequencing (RRBS). The promoters and gene bodies in the LN fetuses were hypomethylated compared to HN fetuses. Pathway analysis showed that the genes with DMR in the exon/intron in the LN group were associated with pathways involved in Cushing syndrome, gastric acid secretion, and aldosterone synthesis and secretion. Promoter hypomethylation in the LN group was frequently observed in genes participating in various signaling pathways (thyroid hormone, Ras/Rap1, PIK3-Akt, cAMP), fatty acid metabolism, and cholesterol metabolism. The promoter hypomethylated genes ALPL and GNAS were upregulated in the LN group, whereas the promoter hypermethylated genes GRB10 and POR were downregulated. The intron/exon hypomethylated genes IGF2, IGF2R, ACAD8, TAT, RARB, PINK1, and SOAT2 were downregulated, whereas the hypermethylated genes IGF2BP2, NOS3, and NR2F1 were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver.

Barriers to adequate nutrition in pregnant adolescent Colombian females.

Pregnant adolescent females face nutritional challenges. The nutritional demands of a growing fetus, when added to the requirements for growing adolescent bodies, are risk factors for undernutrition. An adolescent expectant mother's nutritional status therefore affects both the mother's and the child's future growth, development, and potential development of diseases later in life. In Colombia, the rate of female adolescent pregnancies is higher than neighboring countries and the global average. The most recent data suggest that approximately 21 % of all pregnant adolescent females in Colombia are underweight, 27 % suffer from anemia, 20 % suffer from vitamin D deficiency, and 19 % suffer from vitamin B12 deficiency. Contributing factors to these nutritional deficiencies during pregnancy may be the region in which the female lives, the female's ethnicity, and the female's socioeconomic and educational status. In rural parts of Colombia, limitations regarding access to prenatal care and food choices that include animal source proteins may also contribute to nutritional deficiencies. To help remedy this, recommendations include encouraging nutrient dense food sources with higher protein content, eating one additional meal per day, and taking a prenatal vitamin throughout the pregnancy. Making healthy eating choices can be difficult for adolescent females with limited resources and education; therefore, it is recommended that discussions about nutrition begin at the first prenatal visit for optimum benefits. These factors should be considered for the development of future health policies and interventions in Colombia and other low-income and middle-income countries where pregnant adolescent females may be experiencing similar nutritional deficiencies.

MicroRNA and mRNA sequencing analyses reveal key hepatic metabolic and signaling pathways responsive to maternal undernutrition in full-term fetal pigs.

Maternal undernutrition is highly prevalent in developing countries, leading to severe fetus/infant mortality, intrauterine growth restriction, stunting, and severe wasting. However, the potential impairments of maternal undernutrition to metabolic pathways in offspring are not defined completely. In this study, 2 groups of pregnant domestic pigs received nutritionally balanced gestation diets with or without 50% feed intake restriction from 0 to 35 gestation days and 70% from 35 to 114 gestation days. Full-term fetuses were collected via C-section on day 113/114 of gestation. MicroRNA and mRNA deep sequencing were analyzed using the Illumina GAIIx system on fetal liver samples. The mRNA-miRNA correlation and associated signaling pathways were analyzed via CLC Genomics Workbench and Ingenuity Pathway Analysis Software. A total of 1189 and 34 differentially expressed mRNA and miRNAs were identified between full-nutrition (F) and restricted-nutrition (R) groups. The correlation analyses showed that metabolic and signaling pathways such as oxidative phosphorylation, death receptor signaling, neuroinflammation signaling pathway, and estrogen receptor signaling pathways were significantly modified, and the gene modifications in these pathways were associated with the miRNA changes induced by the maternal undernutrition. For example, the upregulated (P<.05) oxidative phosphorylation pathway in R group was validated using RT-qPCR, and the correlational analysis indicated that miR-221, 103, 107, 184, and 4497 correlate with their target genes NDUFA1, NDUFA11, NDUFB10 and NDUFS7 in this pathway. These results provide the framework for further understanding maternal malnutrition's negative impacts on hepatic metabolic pathways via miRNA-mRNA interactions in full-term fetal pigs.

Curcumin intake during lactation suppresses oxidative stress through upregulation of nuclear factor erythroid 2-related factor 2 in the kidneys of fructose-loaded female rat offspring exposed to maternal protein restriction.

BACKGROUND: A high-fructose diet causes the progression of chronic kidney disease. Maternal malnutrition during pregnancy and lactation increases oxidative stress, leading to chronic renal diseases later in life. We investigated whether curcumin intake during lactation could suppress oxidative stress and regulate NF-E2-related factor 2 (Nrf2) expression in the kidneys of fructose-loaded female rat offspring exposed to maternal protein restriction. METHODS: Pregnant Wistar rats received diets containing 20% (NP) or 8% (LP) casein and 0 or 2.5 g "highly absorptive curcumin" /kg diet containing-LP diets (LP/LP or LP/Cur) during lactation. At weaning, female offspring received either distilled water (W) or 10% fructose solution (Fr) and were divided into four groups: NP/NP/W, LP/LP/W, LP/LP/Fr, and LP/Cur/Fr. At week 13, glucose (Glc), triacylglycerol (Tg), and malondialdehyde (MDA) levels in the plasma, macrophages number, fibrotic area, glutathione (GSH) levels, glutathione peroxidase (GPx) activity, protein expression levels of Nrf2, heme oxygenase-1 (HO-1), and superoxide dismutase 1 (SOD1) in the kidneys were examined. RESULTS: The plasma levels of Glc, TG, and MDA, the number of macrophages, and the percentage of fibrotic area in the kidneys of the LP/Cur/Fr group were significantly lower than those of the LP/LP/Fr group. The expression of Nrf2 and its downstream molecules HO-1 and SOD1, GSH levels, and GPx activity in the kidneys of the LP/Cur/Fr group were significantly higher than those of the LP/LP/Fr group. CONCLUSIONS: Maternal curcumin intake during lactation may suppress oxidative stress by upregulating Nrf2 expression in the kidneys of fructose-loaded female offspring exposed to maternal protein restriction.

Thermoneutrality effects on developmental programming of obesity.

Developmental programming studies using mouse models have housed the animals at human thermoneutral temperatures (22°C) which imposes constant cold stress. As this impacts energy homeostasis, we investigated the effects of two housing temperatures (22°C and 30°C) on obesity development in male and female offspring of Control and FR dams. Pregnant mice were housed at 22°C (cold-exposed, CE) or 30°C (thermoneutrality, TN) room temperature. At gestational age e10, mice were fed either an ad libitum diet (Control) or were 30% food-restricted (FR) to produce low birth weight newborns. Following delivery, all dams were fed an ad libitum diet and maternal mice continued to nurse their own pups. At 3 weeks of age, offspring were weaned to an ad libitum diet and housed at similar temperatures as their mothers. Body weights and food intake were monitored. At 6 months of age, body composition and glucose tolerance test were determined, after which, brain and adipose tissue were collected for analysis. FR/CE and FR/TN offspring exhibited hyperphagia and were significantly heavier with increased adiposity as compared to their respective Controls. There was sex-specific effects of temperature in both groups. Male offspring at TN were heavier with increased body fat, though the food intake was decreased as compared to CE males. This was reflected by hypertrophic adipocytes and increased arcuate nucleus satiety/appetite ratio. In contrast, female offspring were not impacted by housing temperature. Thus, unlike female offspring, there was a significant interaction of diet and temperature evident in the male offspring with accentuated adverse effects evident in FR/TN males.

Effects of Maternal Nutrient Restriction and Melatonin Supplementation on Cardiomyocyte Cell Development Parameters Using Machine Learning Techniques.

The objective of the current study was to examine the effects of maternal feed restriction and melatonin supplementation on fetal cardiomyocyte cell development parameters and predict binucleation and hypertrophy using machine learning techniques using pregnant beef heifers. Brangus heifers (n = 29) were assigned to one of four treatment groups in a 2 × 2 factorial design at day 160 of gestation: (1) 100% of nutrient requirements (adequately fed; ADQ) with no dietary melatonin (CON); (2) 100% of nutrient requirements (ADQ) with 20 mg/d of dietary melatonin (MEL); (3) 60% of nutrient requirements (nutrient-restricted; RES) with no dietary melatonin (CON); (4) 60% of nutrient requirements (RES) with 20 mg/d of dietary melatonin (MEL). On day 240 of gestation, fetuses were removed, and fetal heart weight and thickness were determined. The large blood vessel perimeter was increased in fetuses from RES compared with ADQ (p = 0.05). The total number of capillaries per tissue area exhibited a nutrition by treatment interaction (p = 0.01) where RES-MEL increased capillary number compared (p = 0.03) with ADQ-MEL. The binucleated cell number per tissue area showed a nutrition by treatment interaction (p = 0.010), where it was decreased in RES-CON vs. ADQ-CON fetuses. Hypertrophy was estimated by dividing ventricle thickness by heart weight. Based on machine learning results, for the binucleation and hypertrophy target variables, the Bagging model with 5 Decision Tree estimators and 3 Decision Tree estimators produced the best results without overfitting. In the prediction of binucleation, left heart ventricular thickness feature had the highest Gin importance weight followed by fetal body weight. In the case of hypertrophy, heart weight was the most important feature. This study provides evidence that restricted maternal nutrition leads to a reduction in the number of cardiomyocytes while melatonin treatment can mitigate some of these disturbances.

Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain monoamine profiles.

Dietary folic acid augmentation during gestation reduces neurodevelopmental disorder risk in offspring; however, it is still unclear if excessive maternal folic acid intake can impair brain function in offspring. We examined if excessive folic acid intake throughout gestation altered the behavior of male offspring under poor nutrition during early gestation (E5.5-E11.5). Dams were divided into four groups: control (CON, 2 mg folic acid/kg of food), excessive folic acid fortification (FF, 10 mg folic acid/kg of food), undernutrition (UN, 40% food reduction from E5.5-E11.5), and excessive folic acid fortification plus undernutrition (UN-FF). Excess maternal folic acid fortification induced hyperactivity in the open-field and lower anxiety-like behavior in the elevated plus maze at 9 weeks of age. These behavioral changes were accompanied by reduced dopamine in the prefrontal cortex (PFC), norepinephrine in the amygdala, and 5-hydroxytryptamine (5-HT) in the dorsal midbrain (DM), PFC, and amygdala where 5-HT neurons project from the DM. Furthermore, canonical discriminant analysis, including dopamine and DOPAC concentrations in the PFC, norepinephrine concentrations in the PFC, amygdala, and pons, and 5-HT and 5-HIAA concentrations in the amygdala and DM, correctly classified 73.5% of the offspring in CON, FF, UN, and UN-FF groups. The first discriminant function mainly classified groups based on nutritional status, whereas the second function mainly classified groups based on folic acid intake. Our study suggests that combined transformations of brain monoamine profiles by maternal undernutrition and excess folic acid intake is involved in the behavioral alteration of offsprings.

Effect of integrated nutrition-sensitive and nutrition-specific intervention package on maternal malnutrition among pregnant women in Rwanda.

Maternal undernutrition remains a major public health concern in Rwanda despite significant gains and progress. An integration of nutrition-specific and nutrition-sensitive interventions was implemented in five districts of Rwanda to improve maternal and child nutrition. The package included nutrition education and counselling, promotion of agricultural productivity, promotion of financial literacy/economic resilience and provision of Water, Hygiene and Sanitation services. However, there is limited evidence about the effect of such interventions in reducing maternal undernutrition. A postintervention quasi-experimental study was conducted among pregnant women to determine the effect of the integrated intervention on their nutritional status. It was carried out in two intervention districts, namely Kicukiro and Kayonza, and two control districts, namely Gasabo and Gisagara between November 2020 and June 2021. Five hundred and fifty-two women were recruited for the intervention arm, while 545 were recruited for the control arm. Maternal undernutrition was defined as either having low mid-upper arm circumference (<23 cm) during delivery or low body mass index (<18.5 kg/m2 ) in the first trimester or both. A multivariable logistic regression model was used to assess the effect of the integrated interventions. The prevalence of maternal undernutrition was significantly lower in the intervention group compared with the control group (4.7% vs. 18.2%; p < 0.001). After controlling the potential confounders, the risk of maternal undernutrition was 77.0% lower in the intervention group than in the control group [adjusted odds ratio= 0.23; 95% confidence interval = 0.15-0.36; p < 0.001]. Further studies are therefore recommended to establish causation and inform the potential scale-up of these interventions nationally in Rwanda.

Maternal Underweight and Its Association with Composite Index of Anthropometric Failure among Children under Two Years of Age with Diarrhea in Bangladesh.

Malnutrition in women has been a long-standing public health concern, with serious effects on child survival and development. Maternal body mass index (BMI) is an important maternal nutritional indicator. There are few published studies although child anthropometric failures do not occur in isolation and identifying children with single versus several co-occurring failures can better capture cases of growth failure in combination: stunting, wasting, and underweight. In the context of multiple anthropometric failures, traditional markers used to assess children's nutritional status tend to underestimate overall undernutrition. Using the composite index of anthropometric failure (CIAF), we aimed to assess the association between maternal undernutrition and child undernutrition among children with diarrhea under the age of two and to investigate the correlates. Using 1431 mother-child dyads from the Antibiotic for Children with Diarrhea (ABCD) trial, we extracted children's data at enrollment and on day 90 and day 180 follow-ups. ABCD was a randomized, multi-country, multi-site, double-blind, placebo-controlled clinical trial. The Bangladesh site collected data from July 2017 to July 2019. The outcome variable, CIAF, allows combinations of height-for-age, height-for-weight, and weight-for-age to determine the overall prevalence of undernutrition. The generalized estimating equation was used to explore the correlates of CIAF. After adjusting all the potential covariates, maternal undernutrition status was found to be strongly associated with child undernutrition using the CIAF [aOR: 1.4 (95% CI: 1.0, 1.9), p-value = 0.043] among the children with diarrhea under 2 years old. Maternal higher education had a protective effect on CIAF [aOR: 0.7 (95% CI: 0.5, 0.9), p-value = 0.033]. Our study findings highlight the importance of an integrated approach focusing on maternal nutrition and maternal education could affect a reduction in child undernutrition based on CIAF.

Maternal-placental-fetal drug metabolism is altered by late gestation undernutrition in the pregnant ewe.

BACKGROUND: Maternal undernutrition during pregnancy disrupts both fetal growth and development with perturbations to certain physiological processes within the maternal-fetal-placental unit, including metabolic function. However, it is unknown if hypoglycemia during pregnancy alters maternal-fetal-placental drug metabolism as mediated by cytochrome P450 (CYP) enzymes. Despite this, hypoglycemia reduces CYP enzyme activity in non-pregnant animals. We therefore hypothesised that in a sheep model of hypoglycemia induced by late gestation undernutrition (LGUN), maternal-fetal-placental CYP activity would be reduced, and that fetal glucose infusion (LGUN+G) would rescue reduced CYP activity. METHODS: At 115d gestation (term, 150d), ewes were allocated to control (100% metabolic energy requirement (MER); n = 11), LGUN (50% MER; n = 7) or LGUN+G (50% MER + fetal glucose infusion; n = 6) and maintained on their diets until post-mortem. Maternal-fetal-placental CYP activity assays were performed at 131-133d gestation. Microsomes were isolated from placenta and fetal liver collected at 139-142d gestation and incubated with CYP-specific probe drugs. Metabolite concentrations were measured using Liquid Chromatography - tandem mass spectrometry (LC-MS/MS). RESULTS: CYP2C19 and CYP3A were undetectable in placenta or fetal liver, and CYP1A2 was undetectable in the fetal liver. Placental-specific CYP1A2 and CYP2D6 activity and hepatic-specific CYP2D6 activity were unaffected by LGUN. Maternal-fetal-placental CYP1A2 activity was reduced in response to LGUN in the maternal compartment only. CONCLUSIONS: Reduced maternal-fetal-placental CYP1A2 activity, but not placental-specific CYP1A2 activity, may lead to the developing fetus being exposed to increased concentrations of CYP1A2-specific substrates and suggests further consideration of drug dosing is required in instances of late gestation maternal undernutrition.

Effects of intrauterine growth restriction during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses.

OBJECTIVE: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. METHODS: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. RESULTS: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). CONCLUSION: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

Calorie- and Protein-Deficient Diets Despite Adequate Dietary Diversity among Pregnant Women in a Low-Income Urban Area in Delhi, India.

We interviewed 221 antenatal women in the second or third trimester of pregnancy attending a primary care antenatal clinic at a low-income area in Delhi, India, during 2019-20. The Minimum Dietary Diversity-Women (MDD-W) score for 10 food groups was calculated using the open recall method during a 24-h recall period. The median MDD-W score was 6 (IQR 4-7). Low dietary diversity (MDD-W <5) was observed in 65 (29.4%) participants. Low SES and higher age (≥25 years) were statistically significant predictors of lower dietary diversity, but it was unrelated to parity. Furthermore, protein deficit was observed in 185 (83.7%) and calorie deficit in 210 (95%) participants.

Adult rats from undernourished dams show sex-dependent impaired expression in taste papillae and hypothalamus of genes responsible for sweet and fat detection and signalling.

AIM: Individuals undernourished in utero or during early life are at high risk of developing obesity and metabolic disorders and show an increased preference for consuming sugary and fatty food. This study aimed at determining whether impaired taste detection and signalling in the lingual epithelium and the brain might contribute to this altered pattern of food intake. METHODS: The preference for feeding fat and sweet food and the expression in circumvallate papillae and hypothalamus of genes coding for sweet and fat receptors and transducing pathways were evaluated in adult rats born to control or calorie-restricted dams. Expression in the hypothalamus and the brain's reward system of genes involved in the homeostatic and hedonic control of food intake was also determined. RESULTS: Male and female undernourished animals exhibited increased expression in taste papillae and hypothalamus of T1R1, T1R2, CD36, gustducin, TRMP5 and PLC-ß2 genes, all of which modulate sweet and fat detection and intracellular signalling. However, the severity of the effect was greater in females than in males. Moreover, male, but not female, undernourished rats consumed more standard and sweetened food than their control counterparts and presented increased hypothalamic AgRP and NPY mRNAs levels together with enhanced dopamine transporter and dopamine receptor D2 expression in the ventral tegmental area. CONCLUSIONS: Maternal undernutrition induces sex-specific changes in food preferences and gene expression in taste papillae, hypothalamus and brain reward regions. The gene expression alterations in the male offspring are in line with their preference for consuming sugary and fatty food.