The impact of Ramadan fasting on oxidative stress levels in the second trimester of pregnancy.

BACKGROUND: The primary objective of this study was to assess the effect of fasting during Ramadan on maternal oxidative stress levels and foetal development; pregnant women with uncomplicated, singleton pregnancies in the second trimester. METHODS: During the month of Ramadan, 23 March 2023 to 20 April 2023, 50 fasting and 50 non-fasting healthy pregnant women were enrolled in this prospective study. The fasting hours were about 14 h per day in that season. Pregnant women in the second trimester were enrolled in the study. Total antioxidant status (TAS), total oxidant status (TOS) and the oxidative stress index (OSI) were measured from maternal serum samples taken on a fasting day at the end of Ramadan. To evaluate the impact of Ramadan on the foetus, Doppler ultrasonography was performed in the beginning and then at the end of Ramadan in all participants and was used for the following measurements: Increase of biparietal diameter, femur length, estimated foetal body weight, amniotic fluid index and umbilical artery systolic/diastolic ratio. To discern differences between distinct cohorts, independent t-tests and Mann-Whitney's U-tests were employed based on the data distribution. A p value threshold of less than .05 was established to determine statistical significance. RESULTS: TAS level was found to be significantly lower in the group that fasted for more than 15 days compared to the non-fasting group that did not fast (p = .003), but no significant differences were found between the groups in terms of TOS and OSI (p < .05). Obstetric ultrasound parameters showed no significant differences between the two groups (p < .05). CONCLUSIONS: The present study suggests that fasting during the second trimester of pregnancy does not substantially impact maternal or foetal health, as indicated by most oxidative stress markers and foetal parameters studied. However, the observed reduction in the TAS levels in the fasting group warrants further investigation.

Ramadan is the holy month for the Islamic World. During Ramadan, a pregnant woman is exempt from fasting if she believes that fasting would endanger her own health or that of the foetus.The significance of oxidative stress in pregnancy is widely recognised as it is thought to play a role in conditions such as preeclampsia, gestational diabetes and preterm labour. However, the effect of fasting during Ramadan on maternal oxidative stress and foetal development remains unclear.During Ramadan, no adverse foetal effects were observed in fasting pregnant women compared to non-fasting pregnant women. The total antioxidant status (TAS) levels were significantly reduced in the fasting group, suggesting an adaptive metabolic response or influence of fasting duration. Lower TAS levels may not only be attributed to fasting during Ramadan but also to changes in dietary habits and lifestyle factors (e.g. physical activity and sleep).

Grb7, Grb10 and Grb14, encoding the growth factor receptor-bound 7 family of signalling adaptor proteins have overlapping functions in the regulation of fetal growth and post-natal glucose metabolism.

BACKGROUND: The growth factor receptor bound protein 7 (Grb7) family of signalling adaptor proteins comprises Grb7, Grb10 and Grb14. Each can interact with the insulin receptor and other receptor tyrosine kinases, where Grb10 and Grb14 inhibit insulin receptor activity. In cell culture studies they mediate functions including cell survival, proliferation, and migration. Mouse knockout (KO) studies have revealed physiological roles for Grb10 and Grb14 in glucose-regulated energy homeostasis. Both Grb10 KO and Grb14 KO mice exhibit increased insulin signalling in peripheral tissues, with increased glucose and insulin sensitivity and a modestly increased ability to clear a glucose load. In addition, Grb10 strongly inhibits fetal growth such that at birth Grb10 KO mice are 30% larger by weight than wild type littermates. RESULTS: Here, we generate a Grb7 KO mouse model. We show that during fetal development the expression patterns of Grb7 and Grb14 each overlap with that of Grb10. Despite this, Grb7 and Grb14 did not have a major role in influencing fetal growth, either alone or in combination with Grb10. At birth, in most respects both Grb7 KO and Grb14 KO single mutants were indistinguishable from wild type, while Grb7:Grb10 double knockout (DKO) were near identical to Grb10 KO single mutants and Grb10:Grb14 DKO mutants were slightly smaller than Grb10 KO single mutants. In the developing kidney Grb7 had a subtle positive influence on growth. An initial characterisation of Grb7 KO adult mice revealed sexually dimorphic effects on energy homeostasis, with females having a significantly smaller renal white adipose tissue depot and an enhanced ability to clear glucose from the circulation, compared to wild type littermates. Males had elevated fasted glucose levels with a trend towards smaller white adipose depots, without improved glucose clearance. CONCLUSIONS: Grb7 and Grb14 do not have significant roles as inhibitors of fetal growth, unlike Grb10, and instead Grb7 may promote growth of the developing kidney. In adulthood, Grb7 contributes subtly to glucose mediated energy homeostasis, raising the possibility of redundancy between all three adaptors in physiological regulation of insulin signalling and glucose handling.

Fetal Growth Following Electronic Cigarette Use in Pregnancy.

Electronic cigarette (e-cig) use in pregnancy is common, but potential effects on fetal development are largely unknown. This study's goal was to examine the association between e-cig exposure and fetal growth. Data were extracted from medical charts in this single-site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used e-cigs throughout pregnancy and non-e-cig user controls. Fetal size measurements from second- and third-trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for e-cig exposure compared to controls. By the third trimester, the femur length difference was 28.5 points, with the fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal e-cig exposure, becoming larger and impacting more parameters with increasing gestation. While additional studies are warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following e-cig exposure in pregnancy and suggests that e-cigs may not be a "safer" alternative to combustible cigarette smoking in pregnancy.

Evaluation of Polyphenol Intake in Pregnant Women from South-Eastern Spain and the Effect on Anthropometric Measures at Birth and Gestational Age.

During pregnancy, controlling nutrition is crucial for the health of both mother and foetus. While polyphenols have positive health effects, some studies show harmful outcomes during pregnancy. This study evaluated polyphenol intake in a cohort of mother-child pairs and examined its effects on foetal anthropometric parameters. Polyphenol intake was assessed using food frequency questionnaires (FFQs) and 24-h dietary recalls, and analysed with the Phenol-Explorer database. Gestational age and birth measurements were retrieved from medical records. Statistical analyses validated dietary records and assessed polyphenol impact using multivariate generalised linear models. The study found that mean gestational age was 39.6 weeks, with a mean birth weight of 3.33 kg. Mean total polyphenol intake by FFQ was 2231 mg/day, slightly higher than 24-h recall data. Flavonoids and phenolic acids constituted 52% and 37% of intake, respectively, with fruits and legumes as primary sources. This study highlights the use of FFQs to estimate polyphenol intake. Furthermore, the study found associations between polyphenol consumption and anthropometric parameters at birth, with the effects varying depending on the type of polyphenol. However, a more precise evaluation of individual polyphenol intake is necessary to determine whether the effects they produce during pregnancy may be harmful or beneficial for foetal growth.

The characterization of developmental toxicity in fetal offspring induced by acetaminophen exposure during pregnancy.

OBJECTIVE: Acetaminophen (APAP), an antipyretic and analgesic commonly used during pregnancy, has been recognized as a novel environmental contaminant. Preliminary evidence suggests that prenatal acetaminophen exposure (PAcE) could adversely affect offspring's gonadal and neurologic development, but there is no systematic investigation on the characteristics of APAP's fetal developmental toxicity. METHODS: Pregnant mice were treated with 100 or 400 mg/kg∙d APAP in the second-trimester, or 400 mg/kg∙d APAP in the second- or third-trimester, or different courses (single or multiple) of APAP, based on clinical regimen. The effects of PAcE on pregnancy outcomes, maternal/fetal blood phenotypes, and multi-organ morphological and functional development of fetal mice were analyzed. RESULTS: PAcE increased the incidence of adverse pregnancy outcomes and altered blood phenotypes including aminotransferases, lipids, and sex hormones in dams and fetuses. The expression of key functional genes in fetal organs indicated that PAcE inhibited hippocampal synaptic development, sex hormone synthesis, and osteogenic and chondrogenic development, but enhanced hepatic lipid synthesis and uptake, renal inflammatory hyperplasia, and adrenal steroid hormone synthesis. PAcE also induced marked pathological alterations in the fetal hippocampus, bone, kidney, and cartilage. The sensitivity rankings of fetal organs to PAcE might be hippocampus/bone > kidney > cartilage > liver > gonad > adrenal gland. Notably, PAcE-induced multi-organ developmental toxicity was more considerable under high-dose, second-trimester, and multi-course exposure and in male fetuses. CONCLUSION: This study confirmed PAcE-induced alterations in multi-organ development and function in fetal mice and elucidated its characteristics, which deepens the comprehensive understanding of APAP's developmental toxicity.

Maternal exposure to ambient particulate matter on the growth of twin fetuses after in vitro fertilization.

BACKGROUND: While ambient air pollution has been associated with fetal growth in singletons, its correlation among twins is not well-established due to limited research in this area. METHODS: The effects of exposure to PM2.5 particulate matter and its main components during pregnancy on birth weight and the incidence of large for gestational age (LGA) were investigated in 6177 twins born after in vitro fertilization at the Center for Reproductive Medicine of Shanghai Ninth People's Hospital (Shanghai, China) between 2007 and 2021. Other birth weight-related outcomes included macrosomia, low birth weight, very low birth weight, and small for gestational age (SGA). The associations of PM2.5 exposure with birth weight outcomes were analyzed using linear mixed-effect models and random-effect logistic regression models. Distributed lag models were incorporated to estimate the time-varying associations. RESULTS: The findings revealed that an interquartile range (IQR) increase (18 µg/m3) in PM2.5 exposure over the entire pregnancy was associated with a significant increase (57.06 g, 95 % confidence interval [CI]: 30.91, 83.22) in the total birth weight of twins. The effect was more pronounced in larger fetuses (34.93 g, 95 % CI: 21.13, 48.72) compared to smaller fetuses (21.77 g, 95 % CI: 6.94, 36.60) within twin pregnancies. Additionally, an IQR increase in PM2.5 exposure over the entire pregnancy was associated with a 34 % increase in the risk of LGA (95 % CI: 11 %, 63 %). Furthermore, specific chemical components of PM2.5, such as sulfate (SO42-), exhibited effect estimates comparable to the PM2.5 total mass. CONCLUSION: Overall, the findings indicate that exposures to PM2.5 and its specific components are associated with fetal overgrowth in twins.

Nutraceuticals in Pregnancy: A Special Focus on Probiotics.

The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development.

Fetal and obstetrics manifestations of mitochondrial diseases.

During embryonic and neonatal development, mitochondria have essential effects on metabolic and energetic regulation, shaping cell fate decisions and leading to significant short- and long-term effects on embryonic and offspring health. Therefore, perturbation on mitochondrial function can have a pathological effect on pregnancy. Several shreds of evidence collected in preclinical models revealed that severe mitochondrial dysfunction is incompatible with life or leads to critical developmental defects, highlighting the importance of correct mitochondrial function during embryo-fetal development. The mechanism impairing the correct development is unknown and may include a dysfunctional metabolic switch in differentiating cells due to decreased ATP production or altered apoptotic signalling. Given the central role of mitochondria in embryonic and fetal development, the mitochondrial dysfunction typical of Mitochondrial Diseases (MDs) should, in principle, be detectable during pregnancy. However, little is known about the clinical manifestations of MDs in embryonic and fetal development. In this manuscript, we review preclinical and clinical evidence suggesting that MDs may affect fetal development and highlight the fetal and maternal outcomes that may provide a wake-up call for targeted genetic diagnosis.

Predicting newborn birth outcomes with prenatal maternal health features and correlates in the United States: a machine learning approach using archival data.

BACKGROUND: Newborns are shaped by prenatal maternal experiences. These include a pregnant person's physical health, prior pregnancy experiences, emotion regulation, and socially determined health markers. We used a series of machine learning models to predict markers of fetal growth and development-specifically, newborn birthweight and head circumference (HC). METHODS: We used a pre-registered archival data analytic approach. These data consisted of maternal and newborn characteristics of 594 maternal-infant dyads in the western U.S. Participants also completed a measure of emotion dysregulation. In total, there were 22 predictors of newborn HC and birthweight. We used regularized regression for predictor selection and linear prediction, followed by nonlinear models if linear models were overfit. RESULTS: HC was predicted best with a linear model (ridge regression). Newborn sex (male), number of living children, and maternal BMI predicted a larger HC, whereas maternal preeclampsia, number of prior preterm births, and race/ethnicity (Latina) predicted a smaller HC. Birthweight was predicted best with a nonlinear model (support vector machine). Occupational prestige (a marker similar to socioeconomic status) predicted higher birthweight, maternal race/ethnicity (non-White and non-Latina) predicted lower birthweight, and the number of living children, prior preterm births, and difficulty with emotional clarity had nonlinear effects. CONCLUSIONS: HC and birthweight were predicted by a variety of variables associated with prenatal stressful experiences, spanning medical, psychological, and social markers of health and stress. These findings may highlight the importance of viewing prenatal maternal health across multiple dimensions. Findings also suggest that assessing difficulties with emotional clarity during standard obstetric care (in the U.S.) may help identify risk for adverse newborn outcomes.

Investigating the IGF axis as a pathway for intergenerational effects.

Early nutritional and growth experiences can impact development, metabolic function, and reproductive outcomes in adulthood, influencing health trajectories in the next generation. The insulin-like growth factor (IGF) axis regulates growth, metabolism, and energetic investment, but whether it plays a role in the pathway linking maternal experience with offspring prenatal development is unclear. To test this, we investigated patterns of maternal developmental weight gain (a proxy of early nutrition), young adult energy stores, age, and parity as predictors of biomarkers of the pregnancy IGF axis (n = 36) using data from the Cebu Longitudinal Health and Nutrition Survey in Metro Cebu, Philippines. We analyzed maternal conditional weight measures at 2, 8, and 22 years of age and leptin at age 22 (a marker of body fat/energy stores) in relation to free IGF-1 and IGFBP-3 in mid/late pregnancy (mean age = 27). Maternal IGF axis measures were also assessed as predictors of offspring fetal growth. Maternal age, parity, and age 22 leptin were associated with pregnancy free IGF-1, offspring birth weight, and offspring skinfold thickness. We find that free IGF-1 levels in pregnancy are more closely related to nutritional status in early adulthood than to preadult developmental nutrition and demonstrate significant effects of young adult leptin on offspring fetal fat mass deposition. We suggest that the previously documented finding that maternal developmental nutrition predicts offspring birth size likely operates through pathways other than the maternal IGF axis, which reflects more recent energy status.

Impact of Ionizing Radiation Exposure on Placental Function and Implications for Fetal Programming.

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential.

The fetal programming effect of maternal immune activation (MIA) on the offspring's immune system.

The first 1000 days of life is a critical period of development in which adverse circumstances can have long-term consequences for the child's health. Maternal immune activation is associated with increased risk of neurodevelopmental disorders in the child. Aberrant immune responses have been reported in individuals with neurodevelopmental disorders. Moreover, lasting effects of maternal immune activation on the offspring's immune system have been reported. Taken together, this indicates that the effect of maternal immune activation is not limited to the central nervous system. Here, we explore the impact of maternal immune activation on the immune system of the offspring. We first describe the development of the immune system and provide an overview of reported alterations in the cytokine profiles, immune cell profiles, immune cell function, and immune induction in pre-clinical models. Additionally, we highlight recent research on the impact of maternal COVID-19 exposure on the neonatal immune system and the potential health consequences for the child. Our review shows that maternal immune activation alters the offspring's immune system under certain conditions, but the reported effects are conflicting and inconsistent. In general, epigenetic modifications are considered the mechanism for fetal programming. The available data was insufficient to identify specific pathways that may contribute to immune programming. As a consequence of the COVID-19 pandemic, more research now focuses on the possible health effects of maternal immune activation on the offspring. Future research addressing the offspring's immune response to maternal immune activation can elucidate specific pathways that contribute to fetal immune programming and the long-term health effects for the offspring.

Ultrasonography for the detection of pregnancy and study of embryonic and fetal development in camels, buffaloes, and sheep: Techniques, equations, and limitations.

New technologies for detecting pregnancy shortly after mating/insemination and identifying gestational age are essential for speeding up the reproductive cycle and ensuring high reproductive efficiency in livestock farming. Ultrasonography can successfully identify pregnancy and determine gestational age in many domestic animals. On the other hand, many herds of camel and buffalo and flocks of sheep are aware of the day of service, making it difficult to appropriately manage pregnant animals. This study provides a review of the literature on various techniques for ultrasonographically diagnosing pregnancy in camels, buffaloes, and sheep, focusing on the most appropriate times to use each technique, the earliest opportunity to diagnose pregnancy, and the possibility of using various parts of the fetus to create mathematical equations to determine gestational age. Some limitations of ultrasonography in pregnancy diagnosis were identified and significant pregnancy events in dromedaries were discussed, including left-horn and twin pregnancies. The data presented here will prove essential for researchers, farmers, and countries that rely heavily on these animals for providing meat, milk, cosmetics, and other animal products to enhance reproduction and production efficiency.

Impacts of prenatal environmental exposures on fetal-placental-maternal bile acid homeostasis and long-term health in offspring.

During pregnancy, the maternal body undergoes a series of adaptative physiological changes, leading to a slight increase in serum bile acid (BA) levels. Although the fetal liver can synthesize BAs since the first trimester through the alternative pathway, the BA metabolic system is immature in the fetus. Compared to adults, the fetus has a distinct composition of BA pool and limited expression of BA synthesis enzymes and transporters. Besides, the "enterohepatic circulation" of BAs is absent in fetus. Thus, fetal BAs need to be transported to the mother through the placenta for further metabolism and excretion, and maternal BAs can also be transported to the fetus. That is what we call the "fetal-placental-maternal BA circulation". Various BA transporters and nuclear receptors are essential for maintaining the balance of this BA circulation to ensure normal fetal development. However, prenatal adverse environments can alter fetal BA metabolism, resulting in intrauterine developmental abnormalities and susceptibility to a variety of adult chronic diseases. This review summarizes the current understanding of the fetal-placental-maternal BA circulation and discusses the effects of prenatal adverse environments on this particular BA circulation, aiming to provide a theoretical basis for exploring early prevention and treatment strategies for BA metabolism-associated adverse pregnancy outcomes and long-term impairments.

Assessment of fetal development during mid and late term pregnancies by standard B-Mode ultrasonography in Shetland ponies.

Transrectal and transabdominal ultrasonography is an established method to monitor pregnancy, fetal growth and wellbeing in different species. Growth charts with multiple bio-morphometric parameters to estimate days of gestation and days before parturition exist in small companion animals, sheep and goats, riding type horses and large ponies but not in small horse breeds like Shetland ponies. The aim of this study was to apply fetal biometric assessment and detailed description of physiologic fetal development to mid and late term pregnancies in Shetland mares and to generate reference data for clinical practice and for future research. Fetal parameters were collected starting on day 101 of pregnancy in five Shetland mares. The fetal biometric parameters determined consisted of aortic diameter, eye diameter, combined rib and intercostal distance (CRID), stomach length and width and different heart morphology parameters in sagittal and frontal plane. Additionally, fetal activity and organ development in terms of differentiation and changes in echogenicity were recorded. Considering reliably assessable parameters, fetal CRID was the best predictor for gestational age with ± 13.6 days and fetal aortic diameter the most accurate for prediction of days until parturition with ± 16.2 days.

Prenatal developmental toxicity studies of allyl alcohol in rats and rabbits.

Allyl alcohol (C3H6O; prop-2-en-1-ol; CAS RN 107-18-6; EINECS 203-470-7) is used as an intermediate/monomer in polymerization reactions producing chemicals/optical resins or as a coupling/cross-linking agent for unsaturated polyester and alkyd resins. Human exposure to allyl alcohol (AA) is restricted to workplace manufacturing facilities where it is used in enclosed systems, which limits release and impact on environmental receptors. To address regulatory questions about possible developmental toxicity, two OECD Guideline studies were conducted. A rat developmental toxicity study found fetal and maternal toxicity, in the form of resorptions and decreased body weight and food consumption, but no teratogenic effects. A rabbit developmental toxicity study was subsequently conducted upon request by the European Chemical Agency in 2011 under the REACH program and likewise reported maternal toxicity in the form of reductions in body weight gain and food consumption, but neither fetal toxicity or teratogenic effects. The results of both studies are presented and compared in this paper. Based on our review of the collective results of these studies, AA is considered non-teratogenic, yet does elicit increased post-implantation loss and reduced fetal body weight, possibly resulting from concomitant maternal toxicity. Based on the results of these studies, a maternal and developmental toxicity No Observed Adverse Effect Level of 10 mg/kg/day was apparent for both species.

The ontogeny of human fetal trabecular bone architecture occurs in a limb-specific manner.

Gestational growth and development of bone is an understudied process compared to soft tissues and has implications for lifelong health. This study investigated growth and development of human fetal limb bone trabecular architecture using 3D digital histomorphometry of microcomputed tomography data from the femora and humeri of 35 skeletons (17 female and 18 male) with gestational ages between 4 and 9 months. Ontogenetic data revealed: (i) fetal trabecular architecture is similar between sexes; (ii) the proximal femoral metaphysis is physically larger, with thicker trabeculae and greater bone volume fraction relative to the humerus, but other aspects of trabecular architecture are similar between the bones; (iii) between 4 and 9 months gestation there is no apparent sexual or limb dimorphism in patterns of growth, but the size of the humerus and femur diverges early in development. Additionally, both bones exhibit significant increases in mean trabecular thickness (and for the femur alone, bone volume fraction) but minimal trabecular reorganisation (i.e., no significant changes in degree of anisotropy, connectivity density, or fractal dimension). Overall, these data suggest that in contrast to data from the axial skeleton, prenatal growth of long bones in the limbs is characterised by size increase, without major reorganizational changes in trabecular architecture.

Cord blood vitamin E and lipids in infants born small for gestational age.

Vitamin E is associated with the regulation of lipid metabolism. Our previous study revealed an inverse relationship between birth weight and cord blood vitamin E levels, suggesting a potential link between vitamin E and fetal growth. The aim of this study was to determine the association between vitamin E with fetal growth and lipids. In this investigation, a study involving 146 mother-infant pairs was performed. Cord plasma concentrations of vitamin E and lipids were measured. Our findings showed that cord plasma vitamin E levels were elevated in small for gestational age (SGA) infants, and higher vitamin E levels were associated with an increased risk of SGA (OR = 2.239, 95% CI 1.208, 4.742). Additionally, among lipid levels, higher cord plasma triglyceride (TG) levels were associated with increased risks of SGA (OR = 97.020, 95% CI 5.137, 1832.305), whereas after adjusting for confounding factors, the risk became no longer statistically significant. We also found a positive correlation between cord blood vitamin E concentrations and lipid levels. CONCLUSION:  elevated cord blood vitamin E concentrations may be associated with a higher risk of SGA and are positively correlated with lipid levels, suggesting a potential role for vitamin E in fetal lipid metabolism. WHAT IS KNOWN: • Vitamin E is associated with the regulation of lipid metabolism. • Vitamin E is inversely related to birth weight. WHAT IS NEW: • Elevated cord blood vitamin E concentrations may be associated with a higher risk of SGA and positively correlated with lipid levels.

Evaluation of rat and rabbit embryofetal development studies with pharmaceuticals: the added value of a second species.

Embryofetal development (EFD) studies are performed to characterize risk of drugs in pregnant women and on embryofetal development. In line with the ICH S5(R3) guideline, these studies are generally conducted in one rodent and one non-rodent species, commonly rats and rabbits. However, the added value of conducting EFD studies in two species to risk assessment is debatable. In this study, rat and rabbit EFD studies were evaluated to analyze the added value of a second species. Information on rat and rabbit EFD studies conducted for human pharmaceuticals submitted for marketing authorization to the European Medicines Agency between 2004 and 2022 was collected from the database of the Dutch Medicines Evaluation Board, along with EFD studies conducted for known human teratogens. In total, 369 compounds were included in the database. For 55.6% of the compounds similar effects were observed in rat and rabbit EFD studies. Discordance was observed for 44.6% of compounds. Discordance could often be explained based on occurrence of maternal toxicity or the compound's mechanism of action. For other compounds, discordance was considered of limited clinical relevance due to high exposure margins or less concerning EFD toxicity. For 6.2%, discordance could not be explained and was considered clinically relevant. Furthermore, for specific therapeutic classes, concordance between rat and rabbit could vary. In conclusion, in many cases the added value of conducting EFD studies in two species is limited. These data could help identify scenarios in which (additional) EFD studies could be waived or create a weight-of-evidence model to determine the need for (additional) EFD studies.

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.

BACKGROUND: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. OBJECTIVE: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. METHODS: Germ-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. RESULTS: Maternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-ß-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. CONCLUSIONS: The presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.