Changes In Maternal Metabolism Research Articles

Relationship between maternal biological features, environmental factors, and newborn neuromotor development associated with visual fixation abilities

Newborn visual fixation abilities predict future cognitive, perceptive, and motor skills. However, little is known about the factors associated with the newborn visual fixation, which is an indicator of neurocognitive abilities. We analyzed maternal biological and environmental characteristics associated with fine motor skills (visual tracking) in 1 month old infants. Fifty-one infants were tested on visual tracking tasks (Infant Visuomotor Behavior Assessment Scale/ Guide for the Assessment of Visual Ability in Infants) and classified according to visual conducts scores. Differences between groups were compared considering motor development (Alberta Infant Motor Scale) maternal mental health (Edinburgh Postnatal Depression Scale and Hamilton Anxiety Scale); home environment (Affordances in the Home Environment for Development Scale); maternal care (Coding Interactive Behavior); breastmilk composition (total fatty acids, proteins, and cortisol); and maternal metabolic profile (serum hormones and interleukins). Mothers of infants with lower visual fixation scores had higher levels of protein in breastmilk at 3 months. Mothers of infants with better visual conduct scores had higher serum levels of T4 (at 1 month) and prolactin (at 3 months). There were no associations between visual ability and motor development, home environment, or maternal care. Early newborn neuromotor development, especially visual and fine motor skills, is associated with maternal biological characteristics (metabolic factors and breastmilk composition), highlighting the importance of early detection of maternal metabolic changes for the healthy neurodevelopment of newborns.

Traversing Antepartum Wernicke’s Encephalopathy: In-Depth Insights and Strategies

Antepartum Wernicke’s encephalopathy (WE) is a severe neurological disorder caused by a deficiency of thiamine (Vitamin B1), essential for glucose metabolism, and neuronal function. This review aims to provide an in-depth analysis of WE during pregnancy, highlighting its pathophysiology, risk factors, clinical presentation, diagnostic challenges, and management strategies. Thiamine is critical in the Krebs cycle and neurotransmitter production, and its deficiency leads to substantial biochemical disruptions and neuronal damage. Pregnant women are particularly susceptible due to their increased nutritional demands to support fetal growth and maternal metabolic changes, making them prone to thiamine deficiency and its severe neurological consequences. The clinical manifestations of WE include ophthalmoplegia, ataxia, confusion or altered mental state, peripheral neuropathy, and cardiovascular issues. Diagnosing WE during pregnancy is challenging due to its atypical presentation, requiring a high degree of clinical suspicion and awareness of risk factors. Diagnostic limitations include variable clinical symptoms and challenges in interpreting serum thiamine levels and neuroimaging findings. While neuroimaging can show characteristic brain lesions, its utility is limited by variability. Managing WE during pregnancy requires prompt recognition, immediate thiamine supplementation, continued supportive measures, and careful monitoring. Severe or refractory cases may require advanced management strategies. Pharmacological treatments include standardized thiamine administration protocols, guided by clinical guidelines and recommendations. Early detection and management of WE in pregnant women are vital to prevent irreversible neurological damage and improve maternal and fetal outcomes. Adherence to clinical guidelines is crucial to mitigate the impact of this condition.

Host-gut microbiota interactions during pregnancy.

Mammalian pregnancy is characterized by a well-known suite of physiological changes that support fetal growth and development, thereby positively affecting both maternal and offspring fitness. However, mothers also experience trade-offs between current and future maternal reproductive success, and maternal responses to these trade-offs can result in mother-offspring fitness conflicts. Knowledge of the mechanisms through which these trade-offs operate, as well as the contexts in which they operate, is critical for understanding the evolution of reproduction. Historically, hormonal changes during pregnancy have been thought to play a pivotal role in these conflicts since they directly and indirectly influence maternal metabolism, immunity, fetal growth and other aspects of offspring development. However, recent research suggests that gut microbiota may also play an important role. Here, we create a foundation for exploring this role by constructing a mechanistic model linking changes in maternal hormones, immunity and metabolism during pregnancy to changes in the gut microbiota. We posit that marked changes in hormones alter maternal gut microbiome composition and function both directly and indirectly via impacts on the immune system. The gut microbiota then feeds back to influence maternal immunity and metabolism. We posit that these dynamics are likely to be involved in mediating maternal and offspring fitness as well as trade-offs in different aspects of maternal and offspring health and fitness during pregnancy. We also predict that the interactions we describe are likely to vary across populations in response to maternal environments. Moving forward, empirical studies that combine microbial functional data and maternal physiological data with health and fitness outcomes for both mothers and infants will allow us to test the evolutionary and fitness implications of the gestational microbiota, enriching our understanding of the ecology and evolution of reproductive physiology.

Alcohol blunts pregnancy-mediated insulin resistance and reduces fetal brain glucose despite elevated fetal gluconeogenesis, and these changes associate with fetal weight outcomes.

Prenatal alcohol exposure (PAE) impairs fetal growth and neurodevelopment. Although alcohol is well known to alter metabolism, its impact on these processes during pregnancy is largely unexplored. Here, we investigate how alcohol affects maternal-fetal glucose metabolism using our established mouse binge model of PAE. In the dam, alcohol reduces the hepatic abundance of glucose and glycolytic intermediates, and the gluconeogenic enzymes glucose-6-phosphtase and phosphoenolpyruvate carboxykinase. Fasting blood glucose is also reduced. In a healthy pregnancy, elevated maternal gluconeogenesis and insulin resistance ensures glucose availability for the fetus. Glucose and insulin tolerance tests reveal that alcohol impairs the dam's ability to acquire insulin resistance. Alcohol-exposed dams have enhanced glucose clearance (p < .05) in early gestation, after just two days of alcohol, and this persists through late term when fetal glucose needs are maximal. However, maternal plasma insulin levels, hepatic insulin signaling, and the abundance of glucose transporter proteins remain unchanged. In the PAE fetus, the expression of hepatic gluconeogenic genes is elevated, and there is a trend for elevated blood and liver glucose levels. In contrast, fetal brain and placental glucose levels remain low. This reduced maternal fasting glucose, reduced hepatic glucose, and elevated glucose clearance inversely correlated with fetal body and brain weight. Taken together, these data suggest that alcohol blunts the adaptive changes in maternal glucose metabolism that otherwise enhance fetal glucose availability. Compensatory attempts by the fetus to increase glucose pools via gluconeogenesis do not normalize brain glucose. These metabolic changes may contribute to the impaired fetal growth and brain development that typifies PAE.

Bone Mineral Density During and After Lactation: A Comparison of African American and Caucasian Women

During lactation, changes in maternal calcium metabolism are necessary to provide adequate calcium for newborn skeletal development. The calcium in milk is derived from the maternal skeleton through a process thought to be mediated by the actions of parathyroid hormone-related protein (PTHrP) in combination with decreased circulating estrogen concentrations. After weaning, bone lost during lactation is rapidly regained. Most studies of bone metabolism in lactating women have been performed in Caucasian subjects. There are well-documented differences between African American (AA) and Caucasian (C) bone metabolism, including higher bone mineral density (BMD), lower risk of fracture, lower 25-hydroxyvitamin D (25(OH) D), and higher PTH in AA compared to C. In this prospective paired cohort study, BMD and markers of bone turnover were compared in self-identified AA and C mothers during lactation and after weaning. BMD decreased in both AA and C women during lactation, with similar decreases at the lumbar spine (LS) and greater bone loss in the C group at the femoral neck (FN) and total hip (TH), demonstrating that AA are not resistant to PTHrP during lactation. BMD recovery compared to the 2 week postpartum baseline was observed 6 months after weaning, though the C group did not have complete recovery at the FN. Increases in markers of bone formation and resorption during lactation were similar in AA and C. C-terminal telopeptide (CTX) decreased to 30% below post-pregnancy baseline in both groups 6 months after weaning, while procollagen type 1 N-terminal (P1NP) returned to baseline in the AA group and fell to below baseline in the C group. Further investigation is required to determine impacts on long term bone health for women who do not fully recover BMD before a subsequent pregnancy.

P-543 Higher maternal age alters the insulin/IGF system and intracellular lipid metabolism of the endometrium and in the preimplantation embryo – insights from the rabbit model.

Abstract Study question Our aim was to analyse the embryo-maternal-interaction, focusing on the insulin/IGF-system and lipid metabolism on day 6 of pregnancy in reproductive young and old rabbits. Summary answer Advanced maternal age has a decisive effect on maternal and embryonic insulin/IGF-signalling and lipid metabolism, leading to higher embryo loss already during preimplantation period. What is known already The reproductive potential in women declines with age. Molecular and biochemical mechanisms involved in age-related infertility and their impact on embryo-maternal-interaction during early pregnancy are still not completely understood. However, establishment of a successful pregnancy depends on the physiological condition of the mother and a continuous dialogue with the developing embryo. The insulin/IGF-system plays a pivotal role in this embryo-maternal crosstalk, connecting maternal insulin/IGF with embryonic metabolism, cell proliferation and differentiation. Study design, size, duration We used the rabbit as reproductive model to investigate maternal age-related alterations in embryo-maternal-interaction during preimplantation period. Compared to humans, the rabbit shares high similarities in early embryo development, gastrulation and lipid metabolism (DOI: 10.1530/REP-12-0091 and DOI: 10.1093/ajcn/62.2.458S). A total of 50 young (16-20 weeks) and 31 old (&amp;lt;108 weeks) sexually mature, female rabbits were used for analysis at day 6 post coitum. Participants/materials, setting, methods We measured mRNA and protein levels of target genes of the insulin/IGF system and lipid metabolism by quantitative PCR, Western Blot and ELISA. Therefore, maternal blood, endometrium and blastocysts were analysed from reproductive young (16 to 20 weeks) and old (over 108 weeks) rabbits on day 6 of pregnancy. Blastocysts and ovulation points were counted and only blastocysts at the pre-gastrulating stage 1, separated in embryoblast (EB) and trophoblast (TB), were used for further analyses. Main results and the role of chance At day 6 of pregnancy, reproductive old rabbits had a lower amount of embryos. Maternal serum insulin and IGF levels were reduced in reproductive old rabbits, accompanied by a paracrine upregulation of IGF1 and its receptors in the endometrium. Preimplantation blastocysts adapted to hormonal changes by reducing IGF1 and IGF2 levels in both embryonic compartments, EB and TB, while the expression of embryonic IGF receptors was unchanged. Furthermore, an increase of fatty acids metabolism was observed in the ageing endometrium, indicated by the higher level of carnitine palmitoyltransferase I B (CPT1B) and elevated expression of fatty acid binding and transport proteins. These results are in line with lower level of fatty acid synthesis (FASN) in the endometrium from old, gravid rabbits, the key enzyme of fatty acid synthesis. Embryonic fatty acid uptake and b-oxidation were increased in EB and TB, too. The observed changes in embryonic and maternal lipid metabolism are caused by the alterations of the transcription factors cAMP-responsive element binding protein (CREB) and peroxisome proliferator-activated receptor (PPAR) α and γ in endometrium and embryos from reproductive old rabbits. Limitations, reasons for caution Rabbit embryogenesis reflects human development only during blastocysts formation. Therefore, statements are limited to the embryogenesis stages investigated. Wider implications of the findings The results of the current study are in accordance with the common literature, showing that advanced maternal age affects developmental competence of embryos. Our study points out that advanced maternal age alters lipid metabolism and insulin/IGF-signalling, which are two crucial components in embryo-maternal-interaction. Trial registration number not applicable

Pulse wave Doppler ultrasound of umbilical cord in experimentally induced pregnancy toxemia in sheep

Contrary to its widespread use in human cases, the use of Doppler ultrasonography is only recently becoming prevalent in farm animals. This study aimed to determine the effects of maternal metabolic and clinical changes on fetal hemodynamics during pregnancy toxemia with the doppler examination of umbilical cord. In the study twenty ewes with a single healthy fetus were included in the study. At the end of the 120th day of pregnancy, 20 single-bearing pregnant ewes were randomly categorized into two groups. Ewes in the control group were fed to meet all nutritional requirements. On the other contrary, the experimental ewes were fed to meet equivalent to 50 % of the daily needs and then fasted for 96 h. Doppler ultrasonographic examinations of umbilical cord were performed once every two days and once a day during fasting. Beta hydroxybutyric acid (BHBA) concentration was measured by taking blood from sheep on examination days. Pulse systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, pulsatility index (PI), resistance index (RI), and fetal heart rate (FHR) as well as BHBA values and how those parameters has changed over time (time by treatment effect) due to energy deprivation during pregnancy were evaluated using repeated measure analysis of variance. No clinical signs were observed in both toxemia and control groups during restricted feeding. BHBA concentration increased and there was a significant time, time by treatment and main effect of treatment effect between groups. No significant main effect of treatment and time by treatment interaction was observed in the changes of PI, RI, FHR, and systolic/diastolic velocity values over time in both groups. FHR was reduced over time, and there was a significant time effect in FHR in both groups. Although doppler indices didn't increase, both PSV and EDV values increased significantly in the pregnancy toxemia group compared with the controls (Time P = 0.03, time by treatment interaction P < 0.05) and the main effect of treatment P < 0.05). The marked increase in blood velocities (PSV and EDV) in the umbilical cord is probably due to the compensatory functioning for excessive energy deprivation of the fetus. Therefore, PSV and EDV might be a valuable indicator for evaluating the fetus's health status during the management of the PT.

Maternal high fat diets: impacts on offspring obesity and epigenetic hypothalamic programming.

Maternal high-fat diet (HFD) during pregnancy is associated with rapid weight gain and fetal fat mass increase at an early stage. Also, HFD during pregnancy can cause the activation of proinflammatory cytokines. Maternal insulin resistance and inflammation lead to increased adipose tissue lipolysis, and also increased free fatty acid (FFA) intake during pregnancy (˃35% of energy from fat) cause a significant increase in FFA levels in the fetus. However, both maternal insulin resistance and HFD have detrimental effects on adiposity in early life. As a result of these metabolic alterations, excess fetal lipid exposure may affect fetal growth and development. On the other hand, increase in blood lipids and inflammation can adversely affect the development of the liver, adipose tissue, brain, skeletal muscle, and pancreas in the fetus, increasing the risk for metabolic disorders. In addition, maternal HFD is associated with changes in the hypothalamic regulation of body weight and energy homeostasis by altering the expression of the leptin receptor, POMC, and neuropeptide Y in the offspring, as well as altering methylation and gene expression of dopamine and opioid-related genes which cause changes in eating behavior. All these maternal metabolic and epigenetic changes may contribute to the childhood obesity epidemic through fetal metabolic programming. Dietary interventions, such as limiting dietary fat intake <35% with appropriate fatty acid intake during the gestation period are the most effective type of intervention to improve the maternal metabolic environment during pregnancy. Appropriate nutritional intake during pregnancy should be the principal goal in reducing the risks of obesity and metabolic disorders.

EVALUATION OF OGCT AS SCREENING AND DIAGNOSTIC TOOL FOR GESTATIONAL DIABETES MELLITUS

Pregnancy induces progressive changes in maternal carbohydrate metabolism. As pregnancy advances insulin resistance and diabetogenic stress due to placental hormones necessitate compensatory increase in insulin secretion. Gestational diabetes mellitus developed as a result in this situation. In respect to complications, GDM and pre GDM women are having equal magnitude.High prevalence ethnically proven population with T2DM is strongly recommended to universal Screening. 2 hrs Blood suagr level above 140 mg/dl is worldwide criteria for gestational diabetes mellitus. Pregnant women with GDM are having poor pregnancy outcome with increasing incidence of pre eclampsia, lower segment caesarean section and macrosomia.

The value of lipid metabolites 9,10-DOA and 11,12-EET in prenatal diagnosis of fetal heart defects

AimsTo explore the maternal metabolic changes of fetal congenital heart disease (FCHD), and screen metabolic markers to establish a practical diagnostic model. MethodsMaternal peripheral serum from 17 FCHD and 63 non-FCHD pregnant were analyzed by Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS). ResultsIn the FCHD and the non-FCHD, 132 metabolites were identified, including 35 differential metabolites enriched in the purine, caffeine, primary bile acid, and arachidonic acid metabolism pathway. Finally, the screened (+/-)9,10-dihydroxy-12Z-octadecenoic acid (AUC = 0.888) and 11,12-epoxy-(5Z,8Z,11Z)-icosatrienoic acid (AUC = 0.995) were incorporated into the logistic regression model. The AUC value of the two-metabolite model was 1.0, superior to proline (AUC = 0.867), uric acid (AUC = 0.789), glutamine (AUC = 0.705), and taurine (AUC = 0.923) previously reported. The clinical decision curve analysis (DCA) showed the highest clinical net benefit of the model, and internal validation by bootstrap shows the robustness of the model (Brier Score = 0.005). ConclusionFor the prenatal diagnosis of CHD, our findings are of great clinical significance. As an additional screening procedure, the identification model might be used to detect.

Western diet-induced shifts in the maternal microbiome are associated with altered microRNA expression in baboon placenta and fetal liver.

Maternal consumption of a high-fat, Western-style diet (WD) disrupts the maternal/infant microbiome and contributes to developmental programming of the immune system and nonalcoholic fatty liver disease (NAFLD) in the offspring. Epigenetic changes, including non-coding miRNAs in the fetus and/or placenta may also underlie this risk. We previously showed that obese nonhuman primates fed a WD during pregnancy results in the loss of beneficial maternal gut microbes and dysregulation of cellular metabolism and mitochondrial dysfunction in the fetal liver, leading to a perturbed postnatal immune response with accelerated NAFLD in juvenile offspring. Here, we investigated associations between WD-induced maternal metabolic and microbiome changes, in the absence of obesity, and miRNA and gene expression changes in the placenta and fetal liver. After ~8-11 months of WD feeding, dams were similar in body weight but exhibited mild, systemic inflammation (elevated CRP and neutrophil count) and dyslipidemia (increased triglycerides and cholesterol) compared with dams fed a control diet. The maternal gut microbiome was mainly comprised of Lactobacillales and Clostridiales, with significantly decreased alpha diversity (P = 0.0163) in WD-fed dams but no community-wide differences (P = 0.26). At 0.9 gestation, mRNA expression of IL6 and TNF in maternal WD (mWD) exposed placentas trended higher, while increased triglycerides, expression of pro-inflammatory CCR2, and histological evidence for fibrosis were found in mWD-exposed fetal livers. In the mWD-exposed fetus, hepatic expression levels of miR-204-5p and miR-145-3p were significantly downregulated, whereas in mWD-exposed placentas, miR-182-5p and miR-183-5p were significantly decreased. Notably, miR-1285-3p expression in the liver and miR-183-5p in the placenta were significantly associated with inflammation and lipid synthesis pathway genes, respectively. Blautia and Ruminococcus were significantly associated with miR-122-5p in liver, while Coriobacteriaceae and Prevotellaceae were strongly associated with miR-1285-3p in the placenta; both miRNAs are implicated in pathways mediating postnatal growth and obesity. Our findings demonstrate that mWD shifts the maternal microbiome, lipid metabolism, and inflammation prior to obesity and are associated with epigenetic changes in the placenta and fetal liver. These changes may underlie inflammation, oxidative stress, and fibrosis patterns that drive NAFLD and metabolic disease risk in the next generation.

Maternal Lipid Metabolism Is Associated With Neonatal Adiposity: A Longitudinal Study.

Pregnancy is characterized by progressive decreases in glucose insulin sensitivity. Low insulin sensitivity resulting in hyperglycemia is associated with higher neonatal adiposity. However, less is known regarding lipid metabolism, particularly lipid insulin sensitivity in pregnancy and neonatal adiposity. Because higher maternal prepregnancy body mass index is strongly associated with both hyperlipidemia and neonatal adiposity, we aimed to examine the longitudinal changes in basal and clamp maternal lipid metabolism as contributors to neonatal adiposity. Twelve women planning a pregnancy were evaluated before pregnancy, in early (12-14 weeks), and late (34-36 weeks) gestation. Body composition was estimated using hydrodensitometry. Basal and hyperinsulinemic-euglycemic clamp glucose and glycerol turnover (GLYTO) were measured using 2H2-glucose and 2H5-glycerol and substrate oxidative/nonoxidative metabolism with indirect calorimetry. Total body electrical conductivity was used to estimate neonatal body composition. Basal free-fatty acids decreased with advancing gestation (P = 0.0210); however, basal GLYTO and nonoxidative lipid metabolism increased over time (P = 0.0046 and P = 0.0052, respectively). Further, clamp GLYTO and lipid oxidation increased longitudinally over time (P = 0.0004 and P = 0.0238, respectively). There was a median 50% increase and significant positive correlation during both basal and clamp GLYTO from prepregnancy through late gestation. Neonatal adiposity correlated with late pregnancy basal and clamp GLYTO (r = 0.6515, P = 0.0217; and r = 0.6051, P = 0.0371). Maternal prepregnancy and late pregnancy measures of basal and clamp lipid metabolism are highly correlated. Late pregnancy basal and clamp GLYTO are significantly associated with neonatal adiposity and account for ~40% of the variance in neonatal adiposity. These data emphasize the importance of maternal lipid metabolism relating to fetal fat accrual.

Immunometabolic adaptation and immune plasticity in pregnancy and the bi-directional effects of obesity.

Mandatory maternal metabolic and immunological changes are essential to pregnancy success. Parallel changes in metabolism and immune function make immunometabolism an attractive mechanism to enable dynamic immune adaptation during pregnancy. Immunometabolism is a burgeoning field with the underlying principle being that cellular metabolism underpins immune cell function. With whole body changes to the metabolism of carbohydrates, protein and lipids well recognised to occur in pregnancy and our growing understanding of immunometabolism as a determinant of immunoinflammatory effector responses, it would seem reasonable to expect immune plasticity during pregnancy to be linked to changes in the availability and handling of multiple nutrient energy sources by immune cells. While studies of immunometabolism in pregnancy are only just beginning, the recognised bi-directional interaction between metabolism and immune function in the metabolic disorder obesity might provide some of the earliest insights into the role of immunometabolism in immune plasticity in pregnancy. Characterised by chronic low-grade inflammation including in pregnant women, obesity is associated with numerous adverse outcomes during pregnancy and beyond for both mother and child. Concurrent changes in metabolism and immunoinflammation are consistently described but any causative link is not well established. Here we provide an overview of the metabolic and immunological changes that occur in pregnancy and how these might contribute to healthy versus adverse pregnancy outcomes with special consideration of possible interactions with obesity.

Fetal sex and maternal fasting glucose affect neonatal cord blood-derived endothelial progenitor cells

BackgroundMaternal cardiovascular risk factors (CVRF) in pregnancy, i.e., obesity and hyperglycemia, transmit to the fetus and affect placental and fetal endothelial function. Moreover, a sex dimorphism in endothelial function and susceptibility towards CVRF exists already in utero. Endothelial colony-forming cells (ECFC) are circulating endothelial progenitors highly present in neonatal cord blood and sensitive to CVRF. This study investigated whether fetal sex or subtle maternal metabolic changes within healthy range alter fetal ECFC outgrowth.MethodsOutgrowth of ECFC from cord blood of male (n = 31) and female (n = 26) neonates was analyzed after healthy pregnancies and related to fetal sex and maternal metabolic parameters.ResultsMale ECFC grew out earlier (−20.57% days; p = 0.031) than female. Although all women were non-diabetic, higher levels of fasting plasma glucose (FPG) at midpregnancy increased the time required for colony outgrowth (OR: 1.019; p = 0.030), which, after stratifying for fetal sex, was significant only in the males. Gestational weight gain and BMI did not affect outgrowth. Colony number was unchanged by all parameters.ConclusionsFetal sex and maternal FPG within normal range alter ECFC function in utero. A role of ECFC in postnatal angiogenesis and vasculogenesis has been suggested, which may be affected by altered outgrowth dynamics.ImpactThis study is the first to report that a sexual dimorphism exists in ECFC function, as cells of female progeny require a longer period of time until colony outgrowth than ECFC of male progeny.Our data show that ECFC function is highly sensitive and affected by maternal glucose levels even in a normal, non-diabetic range.Our data raise the question of whether maternal plasma glucose in pregnancy should be considered to play a critical role even in the non-diabetic setting.

Gestational Insulin Resistance Is Mediated by the Gut Microbiome–Indoleamine 2,3-Dioxygenase Axis

Normal gestation involves a reprogramming of the maternal gut microbiome (GM) that contributes to maternal metabolic changes by unclear mechanisms. This study aimed to understand the mechanistic underpinnings of the GM-maternal metabolism interaction. The GM and plasma metabolome of CD1, NIH-Swiss, and C57 mice were analyzed with the use of 16S rRNA sequencing and untargeted liquid chromatography-mass spectrometry throughout gestation. Pharmacologic and genetic knockout mouse models were used to identify the role of indoleamine 2,3-dioxygenase (IDO1) in pregnancy-associated insulin resistance (IR). Involvement of gestational GM was studied with the use of fecal microbial transplants (FMTs). Significant variation in GM alpha diversity occurred throughout pregnancy. Enrichment in gut bacterial taxa was mouse strain and pregnancy time point specific, with the species enriched at gestation day 15/19 (G15/19), a point of heightened IR, being distinct from those enriched before or after pregnancy. Metabolomics revealed elevated plasma kynurenine at G15/19 in all 3 mouse strains. IDO1, the rate-limiting enzyme for kynurenine production, had increased intestinal expression at G15, which was associated with mild systemic and gut inflammation. Pharmacologic and genetic inhibition of IDO1 inhibited kynurenine levels and reversed pregnancy-associated IR. FMT revealed that IDO1 induction and local kynurenine level effects on IR derive from the GM in both mouse and human pregnancy. GM changes accompanying pregnancy shift IDO1-dependent tryptophan metabolism toward kynurenine production, intestinal inflammation, and gestational IR, a phenotype reversed by genetic deletion or inhibition of IDO1. (Gestational Gut Microbiome-IDO1 Axis Mediates Pregnancy Insulin Resistance; EMBL-ENA ID: PRJEB45047. MetaboLights ID: MTBLS3598).

Pathophysiology and risk factors of peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a potentially fatal form of idiopathic heart failure with variable prevalence across different countries and ethnic groups. The cause of PPCM is unclear, but environmental and genetic factors and pregnancy-associated conditions such as pre-eclampsia can contribute to the development of PPCM. Furthermore, animal studies have shown that impaired vascular and metabolic function might be central to the development of PPCM. A better understanding of the pathogenic mechanisms involved in the development of PPCM is necessary to establish new therapies that can improve the outcomes of patients with PPCM. Pregnancy hormones tightly regulate a plethora of maternal adaptive responses, including haemodynamic, structural and metabolic changes in the cardiovascular system. In patients with PPCM, the peripartum period is associated with profound and rapid hormonal fluctuations that result in a brief period of disrupted cardiovascular (metabolic) homeostasis prone to secondary perturbations. In this Review, we discuss the latest studies on the potential pathophysiological mechanisms of and risk factors for PPCM, with a focus on maternal cardiovascular changes associated with pregnancy. We provide an updated framework to further our understanding of PPCM pathogenesis, which might lead to an improvement in disease definition.

Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes.

The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams’ systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review.

Low-molecular-weight heparin (LMWH) is commonly used for preventing or treating venous thromboembolic disease (VTE) during pregnancy. The physiological changes in maternal metabolism have led to discussions on optimal LMWH dosing strategy and possible need for monitoring. The aim of this systematic review is to summarize and discuss whether LMWH dose adjustment according to anti-Xa provides superior effectiveness and safety compared with weight adjusted or fixed dosed LMWH in pregnant women. A systematic literature search was performed in PubMed, Embase, and Scopus on September 26, 2020. The study is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Effectiveness was defined as episodes of thrombosis and safety as bleeding episodes. In total, 33 studies were included: 4 randomized controlled studies and 29 cohort studies. Prophylactic dosing strategies employing weight dosed, fixed dosed, or anti-Xa adjusted LMWH dosing performed equal in effectiveness and safety. In pregnant women with VTE or high thromboembolic risk, therapeutic weight-adjusted LMWH and weight plus anti-Xa-adjusted LMWH provided equal results in terms of effectiveness and safety. Pregnant women with mechanical heart valves (MHVs) received therapeutic anti-Xa-adjusted LMWH with four out of seven studies presenting mean peak anti-Xa within target ranges. Still, pregnant women with MHV experienced both thrombosis and bleeding with anti-Xa in target. Based on the results of this systematic review, current evidence does not support the need for anti-Xa monitoring when using LMWH as thromboprophylaxis or treatment during pregnancy. Nonetheless, the need for anti-Xa monitoring in pregnant women with MHV may need further scrutiny.

Relation between maternal lipid profile and pregnancy complications and perinatal outcomes

Background: Pregnant experiences physiological changes in maternal lipid metabolism to support fetal development. In some cases a misadaptation occurs and exceeds the physiological range and dyslipidemia is recognized, some pregnancies pacing without alterations and in pregnancies pacing without compilations. Objective: determine the relation between maternal lipid profile and pregnancy complications and perinatal. Patients and Methods: A Prospective study conducted on 164 pregnant throughout the period May 2018 – October 2019. Methodology: Pregnant were assessed clinically, obstetrically & tested for lipid profile during 2nd & 3rd-trimester, for detecting any maternal or neonatal complications. Results: 28 pregnant developed maternal complications [GHTN (3.66%), Pre-eclampsia (2.44%), GDM (3.05%), IHCP (1.83%), PTL (4.27%), PTB (3.05%) & ROM (4.78 %)]. Lipid profile parameters in complicated cases during 2nd/3rd trimester for TC, TG, LDL & HDL were 189.3±4.8/243.2±4.8 mg/dl, 271.0±8.4/251.2±8. 4 mg/dl, 110. 8±5.6/114.2±5.6 mg/dl) & 60.4±1.8/61.2±1.9 mg/dl). We observed every mg/dl elevation in maternal third-trimester TG concentration was associated with an increased risk of GDM (P= 0.009), GHTN (P= 0.00), preeclampsia (P= 0.001) and IHCP (P= 0.005). Every mg/dl increase in 3rd trimester TG concentration was associated with an increased risk for SGA, LGA & macrosomia. In contrary, every mg/dl increase in 3rd trimester TG concentration was associated with decreased risk for Low Apgar score. Conclusion: maternal dyslipidemia is a risk factor & associated with developing & occurrence on maternal complication during pregnancy & effect neonatal outcome. Testing lipid profile during second & third trimesters can early predict certain disorders associated with pregnancy.

Does Altered Cellular Metabolism Underpin the Normal Changes to the Maternal Immune System during Pregnancy?

Pregnancy is characterised by metabolic changes that occur to support the growth and development of the fetus over the course of gestation. These metabolic changes can be classified into two distinct phases: an initial anabolic phase to prepare an adequate store of substrates and energy which are then broken down and used during a catabolic phase to meet the energetic demands of the mother, placenta and fetus. Dynamic readjustment of immune homeostasis is also a feature of pregnancy and is likely linked to the changes in energy substrate utilisation at this time. As cellular metabolism is increasingly recognised as a key determinant of immune cell phenotype and function, we consider how changes in maternal metabolism might contribute to T cell plasticity during pregnancy.