Fetal Brain Development Research Articles

Anesthetic recommendations for maternal and fetal safety in nonobstetric surgery: a balancing act.

Nonobstetric surgery during pregnancy is associated with maternal and fetal risks. Several physiologic changes create unique challenges for anesthesiologists. This review highlights physiologic changes of pregnancy and presents clinical recommendations based on recent literature to guide anesthetic management for the pregnant patient undergoing nonobstetric surgery. Nearly every anesthetic technique has been safely used in pregnant patients. Although it is difficult to eliminate confounding factors, exposure to anesthetics could endanger fetal brain development. Perioperative fetal monitoring decisions require an obstetric consult based on anticipated maternal and fetal concerns. Given the limitations of fasting guidelines, bedside gastric ultrasound is useful in assessing aspiration risk in pregnant patients. Although there is concern about appropriateness of sugammadex for neuromuscular blockade reversal due its binding to progesterone, preliminary literature supports its safety. These recommendations will equip anesthesiologists to provide safe care for the pregnant patient and fetus undergoing nonobstetric surgery.

Effects of Cumulative Duration of Repeated Anesthesia Exposure on Fetal Brain Development in the Ovine Model

(J Clin Anesth. 2023;85:111050) This study examines the impact of repeated and prolonged exposure to sevoflurane anesthesia on fetal neurodevelopment in pregnant sheep. The rationale behind this research lies in the concern over the possible negative effects of long or repeated exposure to anesthesia during pregnancy on fetal brain development, particularly based on findings in animal studies. The experiment involves exposing pregnant sheep to different anesthesia regimens and conducting neurobehavioral assessments of their offspring. It aims to determine whether repeated exposure results in neurodevelopmental impairments. The study follows ethical guidelines designed to align with principles promoting humane animal research.

Development and validation of a food frequency questionnaire to assess habitual iodine intake among women of childbearing age.

Adequate iodine status is critical for thyroid hormone synthesis, which is essential for foetal brain development. Suboptimal iodine status has been reported in young women across Europe. Although urinary iodine concentration (UIC) is a good indicator of recent exposure, it does not reflect habitual iodine intake. This study aimed to develop and validate an iodine-specific food frequency questionnaire (I-FFQ) to assess habitual intake in Irish women aged 18-50 years. A 47-item interviewer-administered I-FFQ, informed by national food consumption data on Irish women aged 18-35 years, was developed and validated in a study of 100 nonpregnant women using a 4-day weighed food diary (FD) and UIC as the reference methods. Correlation, cross-classification and Bland-Altman analyses were used to assess agreement and bias between the I-FFQ and FD. Validity coefficients were calculated using the method of triads. Median (interquartile range [IQR]) UIC was 82 (49, 139) µg/L. Median (IQR) intakes were 161 (106, 217) and 133 (98, 182) µg/day for the I-FFQ and FD, respectively (p = 0.001). Estimates were moderately correlated (r = 0.434), and the I-FFQ classified 89% of participants into the same or adjacent tertile of intake as the FD. Validity coefficients for the I-FFQ, FD and UIC were 0.542, 0.800 and 0.228, respectively. Though repeatability analyses 10 weeks later (n = 69) showed slight differences in estimates of intake (I-FFQ1: 164 (104, 210) µg/day; I-FFQ2: 132 (67, 237) µg/day), intakes were highly correlated between administrations (r = 0.627, p = 0.001). The I-FFQ provides a reasonable estimate of habitual iodine intake in young women.

Sex-specific associations between placental corticotropin releasing hormone and problem behaviors in childhood

Placental corticotropin-releasing hormone (pCRH) is a neuroactive peptide produced in high concentrations in mid-late pregnancy, during key periods of fetal brain development. Some evidence suggests that higher pCRH exposure during gestation is associated with adverse neurodevelopment, particularly in female offspring. In 858 mother-child dyads from the sociodemographically diverse CANDLE cohort (Memphis, TN), we examined: (1) the slope of pCRH rise in mid-late pregnancy and (2) estimated pCRH at delivery as a measure of cumulative prenatal exposure. When children were 4 years-old, mothers reported on problem behaviors using the Child Behavior Checklist (CBCL) and cognitive performance was assessed by trained psychologists using the Stanford-Binet Intelligence Scales. We fitted linear regression models examining pCRH in relation to behavioral and cognitive performance measures, adjusting for covariates. Using interaction models, we evaluated whether associations differed by fetal sex, breastfeeding, and postnatal neighborhood opportunity. In the full cohort, log-transformed pCRH measures were not associated with outcomes; however, we observed sex differences in some models (interaction p-values≤0.01). In male offspring, an interquartile (IQR) increase in pCRH slope (but not estimated pCRH at delivery), was positively associated with raw Total (β=3.06, 95%CI: 0.40, 5.72), Internalizing (β=0.89, 95%CI: 0.03, 1.76), and Externalizing (β=1.25, 95%CI: 0.27, 2.22) Problem scores, whereas, in females, all associations were negative (Total Problems: β=−1.99, 95%CI: −3.89, −0.09; Internalizing: β=−0.82, 95%CI: −1.42, −0.23; Externalizing: β=−0.56, 95%CI: −1.34, 0.22). No associations with cognitive performance were observed nor did we observe moderation by breastfeeding or postnatal neighborhood opportunity. Our results provide further evidence that prenatal pCRH exposure may impact subsequent child behavior in sex-specific ways, however in contrast to prior studies suggesting adverse impacts in females, steeper mid-gestation pCRH rise was associated with more problem behaviors in males, but fewer in females.

Maternal usage of varying levels of dietary folate affects the postnatal development of cerebellar folia and cortical layer volumes

ABSTRACT Objective The cerebellum has a long, protracted developmental period; therefore, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is an essential nutrient in fetal and postnatal brain development, and its supplementation during pregnancy is widely recommended. This study aimed to describe the effects of maternal folate intake on postnatal cerebellum development. Methods Twelve adult female Rattus norwegicus (6–8 weeks old) rats were randomly assigned to one of four groups and given one of four premixed diets: a standard diet (2 mg/kg), a folate-deficient (folate 0 mg/kg), folate-supplemented (8 mg/kg), or folate supra-supplemented (40 mg/kg). The rats began consuming their specific diets 14 days before mating and were maintained on them throughout pregnancy and lactation. Five pups from each group were sacrificed, and their brains processed for light microscopic examination on postnatal days 1, 7, 21, and 35. The data gathered included the morphology of the cerebellar folia and an estimate of the volume of the cerebellar cortical layer using the Cavalieri method. Results Folia of the folate-supplemented and supra-supplemented groups were thicker and showed extensive branching with sub-lobule formation. The folate-deficient diet group's folia were smaller, had more inter-folial spaces, or fused. When compared to the folate-deficient group, the volumes of the cerebellum and individual cerebellar cortical layers were significantly larger in the folate-supplemented and supra-supplemented groups (p<0.05). Conclusion Folate supplementation during pregnancy and lactation improves the degree and complexity of the cerebellar folia and the volumes of individual cerebellar cortical layers.

Nutrition knowledge among pregnant women in Lebanon: A cross-sectional study.

Women's knowledge of the nutritional guidelines during pregnancy can affect the health and nutritional status of both mother and child. Having good nutritional information related to maternal dietary intake and healthy lifestyles is therefore of great importance. However, there is limited published research that demonstrates pregnant women's knowledge of the nutritional guidelines during pregnancy in Lebanon. To assess the knowledge on food sources and energy recommendations as well as food safety practices and diet-health relationship among women during pregnancy in Lebanon. A cross-sectional study. The study was conducted at prenatal care clinics in Lebanon, and all pregnant women present, regardless of nationality, were invited to complete the self-administered nutrition knowledge questionnaire. The study assessed five different nutrition knowledge domains (food sources of nutrients, dietary behaviors, food safety knowledge, micronutrients for fetal development, and energy requirements and weight gain) and the demographic characteristics of pregnant women who completed a multidimensional online survey based on validated and existing measures. Four-hundred and ten responses were obtained. Approximately half of respondents (47%) held a university degree, for 42% of women this was their first pregnancy, and 71% had a planned pregnancy. Among the different nutrition knowledge domains, the highest levels of knowledge were for the behaviors that can minimize the effect of nausea/vomiting, heartburn, and constipation during pregnancy (63.9%) and the lowest levels of knowledge was for the importance of iodine and omega-3 fatty acids in pregnancy (28.4%). Most of females knew about food safety practices during pregnancy (72.9%) but less than half were knowledgeable about listeriosis contamination (45.9%), and the types of fish that are the safest to select during pregnancy (47.8%). Despite the fact that pregnant women had an adequate level of knowledge in different nutrition-related areas, there was inadequate level of awareness related to critical nutrients and behaviors that can have adverse effects on mother and/or baby. Therefore, there is a need to focus on specific maternal nutrition aspects such as iron-rich foods, listeriosis food contamination, and nutrients that aid in fetal brain and retina development.

General anesthesia for maternal surgery during pregnancy: dogmas, myths and evidence, a narrative review

Up to 1% of pregnant women require general anesthesia and maternal non-obstetric surgery during pregnancy, of which urgent abdominal procedures are most commonly indicated. This narrative review summarizes several dogmas and myths on the management of general anesthesia during pregnancy and the corresponding evidence. While historical studies found delayed gastric emptying during pregnancy, recent evidence concluded that gastric emptying remains nearly normal during the entire pregnancy until the onset of labor. To correctly estimate the aspiration risk, gastric ultrasound should be increasingly performed. Based on the available evidence, the application of cricoid pressure should be discouraged during rapid sequence induction of pregnant women. A cuffed endotracheal tube is traditionally recommended, but laryngeal masks have been used in &gt; 9000 patients undergoing cesarean section without observation of aspiration. All material to manage a difficult airway should be available as difficult intubation remains an ongoing concern in obstetrics. Risk factors for difficult intubation are nonobstetric in nature. Due to the lack of evidence for hemodynamic management, it is not possible to make an evidence-based recommendation. We recommend to adhere to the expert opinion of maintaining maternal blood pressure close to the normal physiologic value by using (15°-)30° left lateral tilt position, intravenous fluids and noradrenaline or phenylephrine. Most recent clinical observational studies suggested to consider laparoscopic over open surgery as a standard treatment for abdominal surgery. While animal studies observed impaired fetal brain development after prenatal anesthesia exposure, this could not be confirmed by an observational clinical study.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation

BackgroundMaternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HypothesisYigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. MethodsPregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. ResultsWe demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. ConclusionOverall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models.

Autism spectrum disorder (ASD) affects 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development.

Divergent growth of the transient brain compartments in fetuses with nonsyndromic isolated clefts involving the primary and secondary palate.

Cleft lip/palate is a common orofacial malformation that often leads to speech/language difficulties as well as developmental delays in affected children, despite surgical repair. Our understanding of brain development in these children is limited. This study aimed to analyze prenatal brain development in fetuses with cleft lip/palate and controls. We examined in utero MRIs of 30 controls and 42 cleft lip/palate fetal cases and measured regional brain volumes. Cleft lip/palate was categorized into groups A (cleft lip or alveolus) and B (any combination of clefts involving the primary and secondary palates). Using a repeated-measures regression model with relative brain hemisphere volumes (%), and after adjusting for multiple comparisons, we did not identify significant differences in regional brain growth between group A and controls. Group B clefts had significantly slower weekly cerebellar growth compared with controls. We also observed divergent brain growth in transient brain structures (cortical plate, subplate, ganglionic eminence) within group B clefts, depending on severity (unilateral or bilateral) and defect location (hemisphere ipsilateral or contralateral to the defect). Further research is needed to explore the association between regional fetal brain growth and cleft lip/palate severity, with the potential to inform early neurodevelopmental biomarkers and personalized diagnostics.

Genotype-phenotype correlation study of structural abnormalities in a fetal brain caused by a novel KDM4B variant.

Fetal ventriculomegaly (VM), a common brain structure malformation detected during prenatal ultrasound diagnosis, is associated with an increased risk of neurodevelopmental disorders (NDDs) after birth. KDM4B encodes a lysine-specific demethylase that interacts with histone H3K23me3. Variations in KDM4B are reportedly associated with human NDDs; however, only 11 such patients have been reported. Herein, we report a fetus with VM and agenesis of the corpus callosum (ACC), which suggests that KDM4B plays an important role in fetal brain development. Fetal skin tissue and parental peripheral venous blood samples were collected. Whole-exome and Sanger sequencing were performed to analyze fetal germline variants. Human 293T cells transfected with wild-type or mutant KDM4B were used for western blotting (WB) to analyze protein expression levels. An insertion variant of KDM4B, NM_015015.3: c.2889_2890insGAGAGCATCACGGTGAGCTGTGGGGTGGGGCAGGGGGCGGGGGGAGGCTGGGAGCACAGTGACAACCTGTACCCC, was identified in the fetal tissue; however, the parents carried the wild-type gene. The WB results indicated significantly reduced expression of the mutant protein, likely owing to decreased stability. The structural abnormalities in the brain of the studied fetus may be attributed to an insertion variant of KDM4B. This study highlights the importance of screening for KDM4B variants and considering potential copy number variations when observing VM or ACC in prenatal ultrasound imaging.

Maternal obesity and autism spectrum disorders in offspring

There is a growing body of evidence from both human epidemiologic and animal studies that maternal obesity and a high-fat diet are associated with autism spectrum disorders (ASDs). They also include cognitive impairment, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes the role of the maternal immune activation hypothesis and the other possible mechanism underlying abnormal fetal brain development, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity and neurodevelopmental and psychiatric morbidity in offspring. Finally, this review summarizes the available targeted strategies that can be designed to curb maternal obesity and the subsequent development of ASDs.

Developmental Windows for Effects of Choline and Folate on Excitatory and Inhibitory Neurotransmission During Human Gestation.

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses. Paired stimuli, S1, S2, were presented 500 msec apart. Higher P50 amplitude in response to S1 (P50S1microV) assesses excitation, and lower P50S2microV assesses inhibition in this paired-stimulus paradigm. Development of inhibition was related solely to maternal choline plasma concentration and folate supplementation at 16 weeks' gestation. Development of excitation was related only to maternal choline at 28 weeks. Higher maternal choline concentrations later in gestation did not compensate for earlier lower concentrations. At 4 years of age, increased behavior problems on the Child Behavior Checklist 1½-5yrs were related to both newborn inhibition and excitation. Incomplete development of inhibition and excitation associated with lower choline and folate during relatively brief periods of gestation thus has enduring effects on child development.

The Effects of General Anesthetics on the Developing Brain of Fetus

The Effects of General Anesthetics on the Developing Brain of Fetus

Investigation of Pogz Gene Variants in Non-Syndromic Autism Spectrum Disorder.

Genetic factors play an important role in the etiopathogenesis of autism spectrum disorder (ASD). The Pogo Transposable Element with ZNF Domain protein (POGZ) gene (MIM*614787) has been reported to be one of the most frequently mutated genes associated with ASD. This study aims to analyze the exonic regions of the POGZ gene in individuals diagnosed with non-syndromic ASD. Fifty-one non-syndromic cases diagnosed with ASD according to the DSM-V diagnostic criteria, aged 2-18 years, were included in the study. The healthy control group consisted of 50 children of similar age groups without neurodevelopmental problems. Amplicons produced using deep intronic primers covering the mRNA-encoded regions of the POGZ gene from at least 50 base pairs were sequenced by Next Generation Sequencing Analysis. No pathogenic or likely pathogenic variants reported in open-access databases (ClinVar, HGMD, etc.) were detected in the case group. In the ASD and healthy control groups, rs113396244, rs11204811, rs779479223, rs772352054, rs3831142, rs112072925, rs227453 and rs142860188 variants were determined. The rs3831142, rs112072925, rs2274535, rs142860188 variants were found statistically significant in the ASD group. The distribution of the cases with detected single nucleotide polymorphisms (SNPs) according to gender was not statistically significant. The variants identified as statistically significant within the patient group are situated in regions that encompass both the HP1-ZNF and DDE domains of the protein. Given the crucial role that the DDE domain plays, particularly in fetal brain development and neurogenesis, these four variants may potentially possess modifying and/or predisposing effects in the context of ASD.

Parental exposure of cannabinoids THC and CBD reduces reproductive rates in Drosophila melanogaster

The FDA discourages women from using marijuana during pregnancy or breastfeeding on the basis that cannabinoids such as THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol) can negatively affect fetal brain development. However, despite increasing accessibility of cannabinoids, their impact on fertility, pregnancy, and reproduction rates has not been well studied. We hypothesized that CBD and THC, would reduce reproductive rates in Drosophila melanogaster. Our experiments were designed to show how cannabinoids might impact hatch rates in Drosophila by exposing them to previously reported concentrations of CBD and THC. We did a hatch assay with the control, THC, and CBD to compare rates of hatching between controls and flies treated with either 0.5 mg/mL THC or 0.5 mg/mL CBD. Compared to control groups, both cannabinoid groups showed a statistically significant decrease in reproductive rates. The control group had a hatch rate of 94.8%, while the CBD and THC groups had hatch rates of 86.2% and 89.6%, respectively. In the THC group, pupae were noted to turn red and die before emerging. While we predicted cannabinoids would reduce reproductive rates, we had expected THC would have the greater impact on reproduction. The results from our experiments indicated that CBD showed a greater reduction on hatching than THC. However, THC caused unusual and unexpected mortalities. This study provides evidence that cannabinoids such as THC and CBD reduce the rate of reproductive success, although the exact mechanism requires further study.

Molecular Targets of Cannabidiol warn against its consumption during pregnancy

People use cannabidiol (CBD), the primary non-psychoactive cannabinoid of cannabis, as a treatment for symptoms that are commonly associated with pregnancy including nausea, pain, and anxiety. Many people believe CBD is safe to take during pregnancy. However, CBD crosses the placenta and affects the activity of protein targets that are expressed in the fetal brain. Cannabidiol alters the activity of ion channels including voltage- gated sodium, potassium, and calcium channels that control the electrical activity of neurons. Abnormal electrical activity could disrupt brain function via changes in axon growth and synapse structure and function. Furthermore, CBD alters the activity of G- protein coupled receptors that are expressed in the fetal brain and are important for axon growth and guidance suggesting that fetal exposure could prevent axons from reaching their correct targets. Indeed, cannabidiol exposure reduces axon growth in vitro and in vivo. This raises the possibility that CBD consumption during pregnancy could disrupt fetal brain development. Recent studies show that oral cannabidiol consumption during pregnancy alters the excitability of the pyramidal neurons of the prefrontal cortex and affects postnatal cognitive function in mouse offspring. Furthermore, fetal CBD exposure increases thermal pain sensitivity in offspring. Gestational cannabidiol exposure affects compulsivity and memory in a different rodent model. Here, we discuss how CBD affects various ion channels and G-protein coupled receptors, the roles of these proteins in neurodevelopment, and evidence that CBD affects brain development.

Neurodevelopmental disorders: 2024 update.

Neurodevelopmental disorders encompass a range of conditions such as intellectual disability, autism spectrum disorder, rare genetic disorders and developmental and epileptic encephalopathies, all manifesting during childhood. Over 1,500 genes involved in various signaling pathways, including numerous transcriptional regulators, spliceosome elements, chromatin-modifying complexes and de novo variants have been recognized for their substantial role in these disorders. Along with new machine learning tools applied to neuroimaging, these discoveries facilitate genetic diagnoses, providing critical insights into neuropathological mechanisms and aiding in prognosis, and precision medicine. Also, new findings underscore the importance of understanding genetic contributions beyond protein-coding genes and emphasize the role of RNA and non-coding DNA molecules but also new players, such as transposable elements, whose dysregulation generates gene function disruption, epigenetic alteration, and genomic instability. Finally, recent developments in analyzing neuroimaging now offer the possibility of characterizing neuronal cytoarchitecture in vivo, presenting a viable alternative to traditional post-mortem studies. With a recently launched digital atlas of human fetal brain development, these new approaches will allow answering complex biological questions about fetal origins of cognitive function in childhood. In this review, we present ten fascinating topics where major progress has been made in the last year.

Fetal-BET: Brain Extraction Tool for Fetal MRI.

Goal: In this study, we address the critical challenge of fetal brain extraction from MRI sequences. Fetal MRI has played a crucial role in prenatal neurodevelopmental studies and in advancing our knowledge of fetal brain development in-utero. Fetal brain extraction is a necessary first step in most computational fetal brain MRI pipelines. However, it poses significant challenges due to 1) non-standard fetal head positioning, 2) fetal movements during examination, and 3) vastly heterogeneous appearance of the developing fetal brain and the neighboring fetal and maternal anatomy across gestation, and with various sequences and scanning conditions. Development of a machine learning method to effectively address this task requires a large and rich labeled dataset that has not been previously available. Currently, there is no method for accurate fetal brain extraction on various fetal MRI sequences. Methods: In this work, we first built a large annotated dataset of approximately 72,000 2D fetal brain MRI images. Our dataset covers the three common MRI sequences including T2-weighted, diffusion-weighted, and functional MRI acquired with different scanners. These data include images of normal and pathological brains. Using this dataset, we developed and validated deep learning methods, by exploiting the power of the U-Net style architectures, the attention mechanism, feature learning across multiple MRI modalities, and data augmentation for fast, accurate, and generalizable automatic fetal brain extraction. Results: Evaluations on independent test data, including data available from other centers, show that our method achieves accurate brain extraction on heterogeneous test data acquired with different scanners, on pathological brains, and at various gestational stages. Conclusions:By leveraging rich information from diverse multi-modality fetal MRI data, our proposed deep learning solution enables precise delineation of the fetal brain on various fetal MRI sequences. The robustness of our deep learning model underscores its potential utility for fetal brain imaging.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice

BackgroundPolyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal–fetal fatty acid metabolism. ObjectiveThis study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. MethodsInsulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/β-catenin/MFSD2a) of the placenta and fetal brain using western blotting. ResultsGDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n–3 PUFA and n–6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n–3 PUFA in the fetal brain. GDM downregulated the Wnt3/β-catenin/MFSD2a signaling pathway, which transfers n–3 PUFA in the placenta and fetal brain. The HF diet increased n–6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n–6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental β-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). ConclusionsMaternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/β-catenin/MFSD2a pathway of the placental–fetal barrier and by affecting maternal fatty acid metabolism.