Search Results (645)

Background/Objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body’s ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. Results: A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation. Full article

Background/Objectives: To collect evidence from studies that explored the associations between serum vitamin D (25[OH]D) concentrations/status and the presence of depressive/anxiety symptoms in the ante- and/or postnatal periods (PROSPERO-CRD42023390895). Methods: Studies that assessed serum 25[OH]D concentrations in adult women during the ante/postnatal periods and those that used valid instruments to identify the experience/severity of depressive/anxiety symptoms were included. Independent researchers performed the identification/selection of studies, data extraction, risk of bias (RoB) assessment, and bibliometric analysis steps. Results: Of the total of 6769 eligible records, 15 cohort studies [high (n = 3), moderate (n = 7), and low (n = 5) RoB], nine cross-sectional studies [moderate (n = 3) and low (n = 6) RoB], and one case-control study [moderate RoB] were included (n = 25). Depression (n = 24) and anxiety (n = 4) symptoms were assessed. A significant difference in antenatal serum 25[OH]D concentrations between the groups of women with and without depression was identified (mean difference: −4.63 ng/mL; 95% confidence interval [95% CI]: −8.88; −0.38). Postnatal serum 25[OH]D concentrations were found to be, on average, −2.36 ng/mL (95% CI: −4.59; −0.14) lower in women with postnatal depression than in those without. Maternal antenatal anxiety was associated with significantly lower concentrations/deficiency of 25[OH]D in only one included study. Conclusions: Based on very low/low-quality evidence, it was observed that reduced serum 25[OH]D concentrations in the ante- and postnatal period are associated with the presence of ante- and postnatal depressive symptoms, respectively. Low/deficient antenatal serum 25[OH]D concentrations may not be related to the presence of anxiety symptoms before childbirth. Well-designed longitudinal studies are needed to explore the estimated pooled effect of these associations. Full article

Preeclampsia, a hypertensive disorder during pregnancy, frequently correlates with adverse neurological outcomes in offspring, including cognitive impairments, autism spectrum disorder, depressive disorder, attention deficit hyperactivity disorder, and cerebral palsy. Despite these known consequences, the understanding of neuronal damage in the offspring of preeclamptic mothers remains insufficient. Here, we review the neuronal abnormalities resulting from maternal preeclampsia exposure, which include disrupted neurogenesis, loss of neuronal cell integrity, accumulation of cellular debris, decreased synaptogenesis and myelination, and increased neurite growth stimulated by maternal preeclampsia serum. The underlying mechanisms potentially driving these effects involve microglial activation, inflammatory responses, and reduced angiogenesis. Intervention strategies aimed at improving fetal neuronal outcomes are also discussed, encompassing pharmacological treatments such as pravastatin, tadalafil, and melatonin, as well as non-pharmacological approaches like dietary modifications, maternal exercise, and standard care for children. These interventions hold promise for clinical application, offering avenues to address early neuronal abnormalities and prevent the onset of long-term neurological disorders. Full article

Background: Childhood vitamin A deficiency leads to increased morbidity and mortality. Human milk is the only source of vitamin A for exclusively breastfed infants. Dried Moringa oleifera leaf powder (moringa) is a good food source of provitamin A and other carotenoids. Its effect during lactation on human milk vitamin A and carotenoid content is unclear. Objectives: Our objective was to investigate the effect of maternal moringa consumption on human milk retinol and carotenoid concentrations and maternal and infant vitamin A status. Methods: We conducted a 3-month pilot single-blinded cluster-randomized controlled trial in breastfeeding mother–infant pairs (n = 50) in Kenya. Mothers received corn porridge with (20 g/d) or without moringa with complete breast expressions and maternal and infant serum collected at enrollment (infant <30 days old) and 3 months. Milk was analyzed for retinol and selected carotenoids; maternal/infant serum was analyzed for retinol binding protein (RBP). Results: 88% (n = 44) pairs completed milk and serum samples. Four mothers (9%) had vitamin A deficiency (RBP <0.07 µmol/L); 11 (25%) were vitamin A insufficient (VAI; RBP <1.05 µmol/L). Alpha-carotene concentration in milk was higher in the moringa than the control group at baseline (p = 0.024) and at exit (least squares means, LSM, 95%CI µg/mL 0.003, 0.003–0.004 moringa vs. 0.002, 0.001–0.003 control, n = 22/cluster; p = 0.014). In mothers with VAI, alpha-carotene was higher in the moringa group than controls at exit (LSM, 95%CI µg/mL 0.005, 0.003–0.009 moringa, n = 3, vs. 0.002, 0.000–0.004 control, n = 8, p = 0.027) with no difference at baseline. Milk carotenoids did not correlate with vitamin A status (serum RBP) in infants or mothers. Conclusions: Maternal moringa consumption did not impact concentration of milk vitamin A and resulted in limited increase in milk carotenoids in this cohort. Full article

Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized. Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS. Methods: A single-center, retrospective study was carried out. All patients were treated between 2012 and 2019. A total of 73 patients had all the endocrine and obstetric data available. Pre-pregnancy hormone levels (total testosterone-T, androstenedione-AD, DHEAS (dehydroepiandrosterone sulfate), SHBG (sex-hormone-binding globulin), and TSH (thyroid-stimulating hormone) were collected, and T/SHBG, AD/SHBG, DHEAS/SHBG, T/AD indexes were calculated and compared. Results: When miscarriage was present in the history, significantly elevated pre-pregnancy AD levels were observed. Higher pre-pregnancy AD level was noted in PCOS patients delivering female newborns as compared to males. Additionally, a higher T/AD ratio was associated with subsequent preterm delivery, but significance was lost after age adjustment. Maternal age at delivery had a significant negative correlation with pre-pregnancy DHEAS levels and DHEAS/SHBG ratio. Pre-pregnancy SHBG displayed a significant negative correlation, while pre-pregnancy androgen/SHBG ratios exhibited positive correlations with both birth weight and birth weight percentile. Conclusions: Based on our data, AD and the T/AD ratio emerge as distinctive factors in certain outcomes, implying a potential specific role of altered 17-β-HSD (17β-hydroxysteroid dehydrogenase) enzyme activity, possibly influencing offspring outcomes. The pre-pregnancy T/SHBG ratio exhibits a potentially stronger correlation with fetal growth potential compared to SHBG alone. DHEAS and maternal age at delivery are strongly correlated in PCOS patients. Full article

Background: The phenotypic spectrum of ANO5 muscle disease ranges widely from elevated creatine kinase (CK) levels in the serum of asymptomatic individuals to progressive muscular dystrophy. Due to overlapping clinical features among muscular dystrophies, the diagnosis of ANO5 muscle disease is established by molecular genetic tests. Early diagnosis is crucial for the clinical management of symptoms and to mitigate cardiac and musculoskeletal complications. Methods: Quad-joint analysis was performed on whole genome sequencing (WGS) data obtained from an 18-year-old female with mild myalgia and elevated CK and her unaffected parents and sister. The phenotype-driven analysis was performed to prioritize genomic alterations related to the phenotype. The zygosity-based analysis investigated compound heterozygous and de novo status for all variants. Results: The quad-joint WGS analysis revealed a novel pathogenic heterozygous variant, ANO5:c.1770_1773del (p.Phe593Metfs*15), that was paternally inherited. A second and known pathogenic heterozygous variant, ANO5:c.148C>T (p.Arg50*), was also present that was maternally inherited. The genome finding led to the diagnosis of autosomal recessive ANO5 muscle disease and an early personalized clinical management for the patient regarding her cardiac and musculoskeletal health. Conclusions: This is the first report of the ANO5:c.1770_1773del variant in the literature. This report highlights the spectrum of ANO5 muscle disease and describes the role of quad-joint WGS in the early diagnosis and preventive clinical management of ANO5 muscle disease. Full article

Preeclampsia (PE) is a complex and multifaceted obstetric syndrome characterized by several distinct molecular subtypes. It complicates up to 5% of pregnancies and significantly contributes to maternal and newborn morbidity, thereby diminishing the long-term quality of life for affected women. Due to the widespread dissatisfaction with the effectiveness of existing approaches for assessing PE risk, there is a pressing need for ongoing research to identify newer, more accurate predictors. This study aimed to investigate early changes in the maternal serum proteome and associated signaling pathways. The levels of 125 maternal serum proteins at 11–13 weeks of gestation were quantified using liquid chromatography–multiple reaction monitoring mass spectrometry (LC-MRM MS) with the BAK-125 kit. Ten serum proteins emerged as potential early markers for PE: Apolipoprotein M (APOM), Complement C1q subcomponent subunit B (C1QB), Lysozyme (LYZ), Prothrombin (F2), Albumin (ALB), Zinc-alpha-2-glycoprotein (AZGP1), Tenascin-X (TNXB), Alpha-1-antitrypsin (SERPINA1), Attractin (ATRN), and Apolipoprotein A-IV (APOA4). Notably, nine of these proteins have previously been associated with PE in prior research, underscoring the consistency and reliability of our findings. These proteins play key roles in critical molecular processes, including complement and coagulation cascades, platelet activation, and insulin-like growth factor pathways. To improve the early prediction of PE, a highly effective Support Vector Machine (SVM) model was developed, analyzing 19 maternal serum proteins from the first trimester. This model achieved an area under the curve (AUC) of 0.91, with 87% sensitivity and 95% specificity, and a hazard ratio (HR) of 13.5 (4.6–40.8) with p < 0.001. These findings demonstrate that serum protein-based SVM models possess significantly higher predictive power compared to the routine first-trimester screening test, highlighting their superior utility in the early detection and risk stratification of PE. Full article

A maternal diet rich in dietary fiber, such as β-glucan, plays a crucial role in the offspring’s acquisition of gut microbiota and the subsequent shaping of its microbiome profile and metabolome. This in turn has been shown to aid in neurodevelopmental processes, including early microglial maturation and immunomodulation via metabolites like short chain fatty acids (SCFAs). This study aimed to investigate the effects of oat β-glucan supplementation, solubilized by citric acid hydrolysis, from gestation to adulthood. Female C57BL/6J mice were orally supplemented with soluble oat β-glucan (ObG) or carboxymethyl cellulose (CMC) via drinking water at 200 mg/kg body weight during breeding while the control group received 50 mg/kg body weight of carboxymethyl cellulose. ObG supplementation increased butyrate production in the guts of both dams and 4-week-old pups, attributing to alterations in the gut microbiota profile. One-week-old pups from the ObG group showed increased neurodevelopmental markers similar to four-week-old pups that also exhibited alterations in serum markers of metabolism and anti-inflammatory cytokines. Notably, at 8 weeks, ObG-supplemented pups exhibited the highest levels of spatial memory and cognition compared to the control and CMC groups. These findings suggest a potential enhancement of neonatal neurodevelopment via shaping of early-life gut microbiome profile, and the subsequent increased later-life cognitive function. Full article

Background: Preeclampsia is a leading cause of pregnancy-related maternal and fetal morbidity and mortality. Although its precise cause and prevention remain unclear, risk factors such as overweight and inadequate nutrient intake (e.g., calcium, folic acid, and vitamin D) are known to increase its incidence. Recent research has focused on the genetic predisposition to preeclampsia, identifying polymorphisms that may affect enzyme or receptor function. This study aims to review existing literature examining the relationship between genetic polymorphisms, BMI (body mass index), and nutrient levels in preeclampsia to develop more actionable therapeutic strategies. Methods: A systematic review was conducted to analyze studies on the nutrigenetic relationship between BMI, micronutrients, and preeclampsia. Results: A total of 17 studies investigating 12 genes related to BMI and 10 studies exploring 3 genes in relation to micronutrient levels were included in the analysis. Several polymorphisms associated with preeclampsia were found to be influenced by maternal BMI or serum vitamin levels. The interactions between certain gene variants and these factors suggest that both BMI and micronutrient status may modify the risk of developing preeclampsia in genetically predisposed individuals. Conclusions: Our findings emphasize the potential for reanalyzing existing data by categorizing based on genotype and nutrient levels. This approach could yield more personalized dietary and therapeutic recommendations for managing preeclampsia. In the future, genetic information may support the development of tailored nutritional counseling during pregnancy to mitigate preeclampsia risk. Full article

Background/Objective: Infertility affects an estimated 40–50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11–1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 μmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66–1.01, p = 0.06), and 1 μg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33–1.02, p = 0.056). DHEAS levels <6.5 μmol/L had an OR 3.86 (95% CI 1.10–13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18–10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75–11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89–10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40–7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02–6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too. Full article

Background: The prevalence of overweight (OW), obesity (OB), and gestational diabetes mellitus (GDM) has been increasing worldwide in recent years. Adipolin is a new adipokine with reduced circulating levels in obesity and type 2 diabetes mellitus (T2DM). Objectives: Our prospective case-control study aimed to evaluate the maternal serum levels of adipolin and adiponectin, metabolic parameters, and anthropometric characteristics at the time of oral glucose tolerance test (OGTT) in pregnant women with a pre-pregnancy body mass index (BMI) ≥ 25 Kg/m² and correlate them with newborn adipolin, adiponectin levels, and anthropometric characteristics of the newborns, and secondly to evaluate pregnancy outcomes. Material and Methods: After the OGTT results, we had 44 OW/OB pregnant women with GDM, 30 OW/OB pregnant women without GDM, and 92 lean healthy (LH) pregnant women. Data were analyzed by ANOVA and correlation tests, with a p-value < 0.05 considered significant. Results: We found no differences between adipolin values of the OW/OB pregnant women with GDM and the LH group (p > 0.99), OW/OB without GDM and the LH group (p = 0.56), and between OW/OB groups (p = 0.57). OW/OB pregnant women with GDM had a higher rate of gestational hypertension compared with the LH group (p < 0.0001). Newborns from OW/OB pregnant women with GDM were more frequently diagnosed with jaundice (p = 0.02), and they required more frequent admission to the neonatal intensive care unit (NICU) for treatment of respiratory distress (p = 0.01) compared with newborns from LH mothers. Conclusions: Our study revealed that the serum levels of adipolin in the second trimester among the group of OW/OB pregnant women with GDM, matched for age and BMI with OW/OB pregnant women without GDM, were not significantly different. This suggests that adipolin may not play an essential role in the occurrence of GDM in these patients. Despite good glycemic control during pregnancy, OW/OB pregnant women with GDM and their newborns tend to have more complications (gestational hypertension, jaundice, NICU admission) than LH pregnant women and their newborns, highlighting the importance of weight control before pregnancy. Full article

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease. Full article

Decidualization of the uterine endometrium is a critical process for embryo implantation in mammals, primarily occurring on gestational day 8 in pregnant mice. However, the interplay between the maternal gut microbiome, metabolism, and the uterus at this specific time point remains poorly understood. This study employed a multi-omics approach to investigate the metabolic, gut microbiome, and transcriptomic changes associated with early pregnancy (gestational day 8 (E8)) in mice. Serum metabolomics revealed a distinct metabolic profile at E8 compared to controls, with the differential metabolites primarily enriched in amino acid metabolism pathways. The gut microbial composition showed that E8 mice exhibited higher alpha-diversity and a significant shift in beta-diversity. Specifically, the E8 group displayed a decrease in pathogenic Proteobacteria and an increase in beneficial Bacteroidetes and S24-7 taxa. Transcriptomics identified myriads of distinct genes between the E8 and control mice. The differentially expressed genes were enriched in pathways involved in alanine, aspartate, and glutamate metabolism, PI3K-Akt signaling, and the PPAR signaling pathway. Integrative analysis of the multi-omics data uncovered potential mechanistic relationships among the differential metabolites, gut microbiota, and uterine gene expression changes. Notably, the gene Asns showed strong correlations with specific gut S24-7 and metabolite L-Aspartatic acid, suggesting its potential role in mediating the crosstalk between the maternal environment and embryo development during early pregnancy. These findings provide valuable insights into the complex interplay between the maternal metabolome, the gut microbiome, and the uterine transcriptome in the context of early pregnancy, which may contribute to our understanding of the underlying mechanisms of embryo implantation and development. Full article

Low fertility is the main cause of the low productivity in beef cattle and is mainly associated with a lack of conception after fertilization. The establishment of early pregnancy in cattle is a complex physiological process, and embryo implantation is crucial for the successful establishment of pregnancy. Exosomal miRNAs play an important role in regulating mammalian embryo implantation and development. This study used synchronous estrus technology to extract exosomes from bovine serum at 0, 14, and 21 days of early pregnancy and analyzed the expression profile of exosomal miRNAs through RNA-seq technology. We identified 472 miRNA precursor sequences and 367 mature miRNA sequences in the three sample groups, with the majority of the miRNAs having high abundance. Differentially expressed miRNAs (DEmiRNAs) were screened, and 20 DEmiRNAs were obtained. The differential expression analysis results show that compared to day 0, there were 15 DEmiRNAs in the serum on day 14 and 5 on day 21 of pregnancy. Compared to the 14th day of pregnancy, there were eight DEmiRNAs in the serum on the 21st day of pregnancy. Bioinformatics analysis shows that the target genes of DEmiRNAs regulated the signaling pathways closely related to early pregnancy, including the VEGF, NF-κB, and MAPK signaling pathways. In addition, the newly discovered miRNAs were bta-miR-3604, bta-miR-2889, bta-miR-3432a, and bta-miR-409b. These results provide a theoretical reference for screening the molecular markers for early pregnancy establishment and maternal recognition of pregnancy (MRP) in cattle and new ideas for shortening the calving interval in cows. Full article

Toxoplasmosis, caused by Toxoplasma gondii, poses a significant threat to sheep flocks, affecting reproductive performance and meat quality, and leading to economic losses. This study aimed to evaluate the correlation between anti-T. gondii IgG antibodies in the serum and colostrum of naturally infected ewes and to assess passive immunity in newborn lambs. Blood and colostrum samples were collected from 162 ewes and 182 lambs across 20 sheep farms in Paraíba, Brazil. Samples were tested for anti-T. gondii and anti-Neospora caninum IgG using indirect fluorescence antibody tests (IFATs), with titers ≥ 1:64 considered positive. Among the ewes, 45.1% tested positive for anti-T. gondii IgG in serum, with titers ranging from 1:64 to 1:16,384. The colostrum from 94.6% of the ewes also tested positive, although 74% had higher titers in their serum than in their colostrum. Concordance between serum and colostrum was high, with a kappa coefficient of 0.950. Lamb serum showed a perfect agreement with maternal colostrum (kappa = 0.962), demonstrating effective passive transfer of antibodies. This study confirms that colostrum is a reliable matrix for detecting anti-T. gondii antibodies and assessing passive immunity in lambs. The high concordance between serum, colostrum, and lamb titers suggests that IFATs on colostrum can be a practical tool for monitoring maternal antibody transfer, contributing to the better management of T. gondii infections in sheep flocks. Full article