Intrauterine Brain Research Articles

B-cell immune deficiency in twin sisters expands the phenotype of MOPDI.

Microcephalic osteodysplastic primordial dwarfism type I (MOPDI) is a very rare and severe autosomal recessive disorder characterized by marked intrauterine growth retardation, skeletal dysplasia, microcephaly and brain malformations. MOPDI is caused by biallelic mutations in RNU4ATAC, a non-coding gene involved in U12-type splicing of 1% of the introns in the genome, which are recognized by their specific splicing consensus sequences. Here, we describe a unique observation of immunodeficiency in twin sisters with mild MOPDI, who harbor a novel n.108_126del mutation, encompassing part of the U4atac snRNA 3' stem-loop and Sm protein binding site, and the previously reported n.111G>A mutation. Interestingly, both twin sisters show mild B-cell anomalies, including low naive B-cell counts and increased memory B-cell and plasmablasts counts, suggesting partial and transitory blockage of B-cell maturation and/or excessive activation of naive B-cells. Hence, the localization of a mutation in stem II of U4atac snRNA, as observed in another RNU4ATAC-opathy with immunodeficiency, that is, Roifman syndrome (RFMN), is not required for the occurrence of an immune deficiency. Finally, we emphasize the importance of considering immunodeficiency in MOPDI management to reduce the risk of serious infectious episodes.

Megalencephaly: Classification, Genetic Causes, and Related Syndromes

AbstractMegalencephaly is a developmental disorder due to an abnormal neuronal proliferation and migration during intrauterine or postnatal brain development that leads to cerebral overgrowth and neurological dysfunction. This cerebral overgrowth may affect the whole encephalon or only a region; when it involves one hemisphere it is referred to as hemimegalencephaly. Megalencephaly presents with a head circumference measurement of 2 standard deviations above the average measure for age. This group of disorders is clinically characterized by early onset and refractory to therapy epilepsy, neurodevelopmental disorders, behavioral problems, and autism spectrum disorder. Syndromic forms of megalencephaly should be considered when associated with other congenital abnormalities. Megalencephaly in fact could be associated with segmental overgrowth and cutaneous/vascular abnormalities (i.e., Proteus syndrome, CLOVES [congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis, and/ or skeletal abnormalities] syndrome, Klippel-Trenaunay syndrome, megalencephaly-capillary malformation-polymicrogyria syndrome , megalencephaly-postaxial polydactyly-polymicrogyria-hydrocephalus syndrome, etc.) or generalized overgrowth (i.e., Weaver or Beckwith-Wiedemann syndrome) as well as with nanism in achondroplasia where megalencephaly is associated with disproportionate short stature, primary skeletal dysplasia, characteristic facies (prominent forehead, flat nasal bridge), narrow chest, and normal intelligence. It is possible to identify three main groups of disorders associated with megalencephaly: idiopathic or benign, metabolic, and anatomic. The idiopathic (benign) form indicates an abnormal increased head circumference in absence of neurological impairment, such as in benign familial megalencephaly. In metabolic megalencephaly (such as in organic acid disorders, metabolic leukoencephalopathies, or lysosomal diseases) there is an increase of different constituents that increase the size of the brain, whereas in the anatomical form there are underlying genetic causes. Neuroimaging is crucial for diagnosis, as it can reveal a generalized brain growth or a segmental one and possible specific frameworks associated. In all these conditions it is necessary to identify possible microdeletion-microduplication by chromosomal arrays.

Gestational age at birth, birth weight, and gestational age when intrauterine brain sparing occurs determines the neonatal outcome in growth-restricted infants born before 32 weeks of gestation: a retrospective cohort analysis.

Preterm birth and fetal growth restriction are the main determinants of perinatal mortality. In the absence of therapeutic interventions, management is restricted to the observation of fetal growth and fetoplacental perfusion to determine the timing of delivery. Fetal circulatory redistribution, known as "brain sparing," represents a sign of fetal hypoxia and has been implemented in algorithms for when to deliver. In the absence of any other option, the nitric oxide donor pentaerythrityl tetranitrate (PETN), which has been shown to improve fetoplacental flow and reduce preterm birth in high-risk patients, is offered to patients as a personal therapy attempt. The aim of this study was to evaluate determinants related to pregnancy, including PETN intake during pregnancy, on immediate neonatal outcomes in a cohort of growth-restricted infants born before 32 completed weeks of gestation. We performed a retrospective cohort study of 98 infants born with a birth weight below the 10th percentile before 32 completed weeks of gestation at our tertiary care center between 2010 and 2019. PETN was offered to all mothers with a history of severe adverse pregnancy outcomes who were at high risk of developing fetal growth restriction as an individual therapy attempt. The mean gestational age at birth was 188.5 days, and the mean birth weight was 549 g, corresponding to a median percentile of three. In 73 (79.3%) cases, brain sparing occurred during pregnancy. A total of 22 (22.4%) neonates were stillborn, 20 died postnatally, and 37.3% developed a severe complication. Multivariable analysis revealed birth weight percentile, gestational age at birth, and gestational age when brain sparing first occurred to be robust predictors of mortality or severe neonatal morbidity. In 39 neonates of mothers taking PETN, this impact of brain sparing was not observed. Our study is the first to demonstrate a significant association between the early occurrence of brain-sparing and severe neonatal outcomes in a cohort of very early preterm, growth-restricted newborns. The data suggest that PETN intake may ameliorate the effect of brain sparing in the affected neonates.

A novel case of 16q22.3 duplication syndrome in a child with overgrowth: case report and literature review

BackgroundDistal chromosome 16 duplication syndrome (also known as 16q partial trisomy) is a very rare genetic disorder recently described in few clinical reports. 16q trisomy is generally associated with a multisystemic phenotype including intrauterine growth restriction (IUGR), brain and cardiac defects, intellectual disability (ID) and an increased risk of both prenatal and postnatal lethality. Smaller copy number variants (CNV) within the 16q region create partial trisomies, which occur less frequently than full trisomy 16q.Case presentationWe present the clinical case of a 12-years-old male with a 16q22.3q24.1 de novo heterozygous duplication whose phenotype was characterized by ID, facial dysmorphisms, stature and weight overgrowth. To date, only five other cases of this syndrome have been reported in scientific literature, and none of them comprised overgrowth.ConclusionsOur case report highlights the great heterogeneity in clinical manifestations and provides new evidence for better defining the phenotypic picture for smaller 16q distal CNVs, suggesting unusual features.

Cobblestone-like brain malformation with a new bi-allelic ADGRG1 (GPR-56) mutation: Fetal imaging-pathology correlation.

Autosomal recessive cobblestone-like cortical malformation of the brain, with no eye or muscle involvement, has been reported in patients with biallelic mutations in ADGRG1 (formerly GPR56) and in other brain surface defects (eg, variants in COL3A1). We reported the intra-uterine brain MRI (iu-MRI), post-mortem MRI (pm-MRI), and neuropathology findings of a new ADGRG1 mutation in a fetus at early gestation. Imaging findings were compared with those of the sibling harboring the same mutation, to provide insights about the evolving morphology of such malformation. A 21-week fetus underwent iu-MRI for a suspected cortical anomaly on ultrasound. After the MRI results, the termination of the pregnancy was carried out. A pm-MRI scan and autopsy were performed. A neuropathology-imaging correlation was achieved. The 5-year old sibling affected by developmental impairment also underwent a brain MRI. Both subjects underwent a genetic investigation. Two patterns of abnormality of the cerebral surface were identified on both fetal MRI: one at the vertex resembling a cobblestone-cortex due to neuronal overmigration into the subarchnoid space and the other in the occipital areas resembling polymicrogyria. These details closely matched the neuropathology findings. MRI findings of the sibling consisted of typical ADGRG1/GPR56-related brain findings showing a polymicrogyric-like cortex, also reported as bilateral frontal-parietal polymicrogyria. A flattened pons and small cerebellar vermis were present in both cases. Genetic testing demonstrated a novel homozygous variant c.1484T>C in the c gene in both cases. Our findings provide further evidence of the overlap of ADGRG1/GPR56-related brain dysgenesis with cobblestone-like cortical malformation of the brain.

Development of the basilar artery system in the human embryonic period

The doctrine of the origin and development of cerebral arteries in the embryonic period of man in the XIX – XXI centuries was formed by I. Tandler (1899, 1902), H. Evans (1911), G.L. Streeter (1908, 1918), G.D. Aronovich (1939), D.N. Padget (1947 – 1972), N.V. Popova-Latkina (1954 – 1975), Y.N. Shapovalov (1963), A.G. Knorre (1967), I. Stanek (1977), B. Carlson (1983), A.V. Gorbunov (1998 – 2022), etc. To date, we have shown that basilar arteries are detected in embryos at 7 weeks of intrauterine development, posterior cerebral arteries with plexiform branching – at 8 weeks of intrauterine life, and persistent trigeminal arteries continue to be detected in prenatal embryos at 8-9 weeks of human prenatal ontogenesis. In prenatal embryos 7-8-9 weeks of prenatal ontogenesis, the basilar artery system provides the needs of the human intrauterine brain.

Case Report and Review: An Unusual Case of Fetal Traumatic Brain Injury

We herein report an unusual case of maternal road traffic accident with blunt trauma to the abdomen at 34 weeks of gestation followed by delivery of severely encephalopathic baby and also a brief review of similar previous reports.The baby had near normal transition, then progressively developed severe encephalopathy and multiple organ dysfunction attributed mainly to the intrauterine traumatic injury. The baby had multiple intra and extra axial bleeds,cerebral edema and diffuse axonal injury, as revealed by the CT scan. The baby was managed conservatively with various neuroprotective strategies similar to management in older children and thus cerebral edema/ hematomas subsided. The baby required ventilatory support, prolonged assisted ventilation/oxygen and the metabolic derangements were managed accordingly. The baby was discharged on oral Levetiracetam, multivitamins and nasogastric tube feeds. Baby was followed up sequentially till day 74 and on physical examination had poor head growth and increased muscle tone of the extremities. Neuroimaging revealed diffuse multicystic leukoencephalomalacia, hydrocephalus ex vacuo with cortical thinning. Intrauterine fetal brain injury is an uncommon incidence which causes mortality and significant morbidity in the child. Neuroimaging of the fetus after trauma to the mother can lead to early diagnosis and anticipation. Early vigorous neuroprotective measures and management may prevent mortality and reduce further brain insult in theseneonates. There is paucity of information on management of such cases thus they should be reported in detail forstudy and future references.

Excitatory and inhibitory neuron imbalance in the intrauterine growth restricted fetal guinea pig brain: Relevance to the developmental origins of schizophrenia and autism.

Neurodevelopmental disorders such as schizophrenia and autism are thought to involve an imbalance of excitatory and inhibitory signaling in the brain. Intrauterine growth restriction (IUGR) is a risk factor for these disorders, with IUGR onset occurring during critical periods of neurodevelopment. The aim of this study was to determine the impact of IUGR on excitatory and inhibitory neurons of the fetal neocortex and hippocampus. Fetal brains (n=2) were first collected from an unoperated pregnant guinea pig at mid-gestation (32days of gestation [dg]; term ∼67dg) to visualize excitatory (Ctip2) and inhibitory (calretinin [CR] and somatostatin [SST]) neurons via immunohistochemistry. Chronic placental insufficiency (CPI) was then induced via radial artery ablation at 30dg in another cohort of pregnant guinea pigs (n=8) to generate IUGR fetuses (52dg; n=8); control fetuses (52dg; n=7) were from sham surgeries with no radial artery ablation. At 32dg, Ctip2- and CR-immunoreactive (IR) cells had populated the cerebral cortex, whereas SST-IR cells had not, suggesting these neurons were yet to complete migration. At 52dg, in IUGR versus control fetuses, there was a reduction in SST-IR cell density in the cerebral cortex (p=.0175) and hilus of the dentate gyrus (p=.0035) but not the striatum (p>.05). There was no difference between groups in the density of Ctip2-IR (cortex) or CR-IR (cortex, hippocampus) neurons (p>0.05). Thus, we propose that an imbalance in inhibitory (SST-IR) and excitatory (Ctip2-IR) neurons in the IUGR fetal guinea pig brain could lead to excitatory/inhibitory dysfunction commonly seen in neurodevelopmental disorders such as autism and schizophrenia.

Impaired in vivo feto-placental development is associated with neonatal neurobehavioral outcomes.

Fetal growth restriction (FGR) is a risk factor for neurodevelopmental problems, yet remains poorly understood. We sought to examine the relationship between intrauterine development and neonatal neurobehavior in pregnancies diagnosed with antenatal FGR. We recruited women with singleton pregnancies diagnosed with FGR and measured placental and fetal brain volumes using MRI. NICU Network Neurobehavioral Scale (NNNS) assessments were performed at term equivalent age. Associations between intrauterine volumes and neurobehavioral outcomes were assessed using generalized estimating equation models. We enrolled 44 women diagnosed with FGR who underwent fetal MRI and 28 infants underwent NNNS assessments. Placental volumes were associated with increased self-regulation and decreased excitability; total brain, brainstem, cortical and subcortical gray matter (SCGM) volumes were positively associated with higher self-regulation; SCGM also was positively associated with higher quality of movement; increasing cerebellar volumes were positively associated with attention, decreased lethargy, non-optimal reflexes and need for special handling; brainstem volumes also were associated with decreased lethargy and non-optimal reflexes; cerebral and cortical white matter volumes were positively associated with hypotonicity. Disrupted intrauterine growth in pregnancies complicated by antenatally diagnosed FGR is associated with altered neonatal neurobehavior. Further work to determine long-term neurodevelopmental impacts is warranted. Fetal growth restriction is a risk factor for adverse neurodevelopment, but remains difficult to accurately identify. Intrauterine brain volumes are associated with infant neurobehavior. The antenatal diagnosis of fetal growth restriction is a risk factor for abnormal infant neurobehavior.

Differential age-dependent development of inter-area brain connectivity in term and preterm neonates

BackgroundAmong preterm infants, higher morbidities of neurological disturbances and developmental delays are critical issues. Resting-state networks (RSNs) in the brain are suitable measures for assessing higher-level neurocognition. Since investigating task-related brain activity is difficult in neonates, assessment of RSNs provides invaluable insight into their neurocognitive development.MethodsThe participants, 32 term and 71 preterm neonates, were divided into three groups based on gestational age (GA) at birth. Cerebral hemodynamic activity of RSNs was measured using functional near-infrared spectroscopy in the temporal, frontal, and parietal regions.ResultsHigh-GA preterm infants (GA ≥ 30 weeks) had a significantly stronger RSN than low-GA preterm infants and term infants. Regression analyses of RSNs as a function of postnatal age (PNA) revealed a steeper regression line in the high-GA preterm and term infants than in the low-GA infants, particularly for inter-area brain connectivity between the frontal and left temporal areas.ConclusionsSlower PNA-dependent development of the frontal–temporal network found only in the low-GA group suggests that significant brain growth optimal in the intrauterine environment takes place before 30 weeks of gestation. The present study suggests a likely reason for the high incidence of neurodevelopmental impairment in early preterm infants.ImpactResting-state fNIRS measurements in three neonate groups differing in gestational age (GA) showed stronger networks in the high-GA preterm infants than in the term and low-GA infants, which was partly explained by postnatal age (PNA).Regression analyses revealed a similar PNA-dependence in the development of the inter-area networks in the frontal and temporal lobes in the high-GA and term infants, and significantly slower development in the low-GA infants.These results suggest that optimal intrauterine brain growth takes place before 30 weeks of gestation. This explains one of the reasons for the high incidence of neurodevelopmental impairment in early preterm infants.

Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case-Control Longitudinal Study in Human Premature Neonates.

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.

Catenin Alpha 2 May Be a Biomarker or Potential Drug Target in Psychiatric Disorders with Perseverative Negative Thinking.

AlphaN-catenin gene CTNNA2 has been implicated in intrauterine brain development, as well as in several psychiatric disorders and cardiovascular diseases. Our present aim was to investigate CTNNA2 gene-wide associations of single-nucleotide polymorphisms (SNPs) with psychiatric and cardiovascular risk factors to test the potential mediating role of rumination, a perseverative negative thinking phenotype in these associations. Linear mixed regression models were run by FaST-LMM within a sample of 795 individuals from the Budakalasz Health Examination Survey. The psychiatric outcome variables were rumination and its subtypes, and ten Brief Symptom Inventory (BSI) scores including, e.g., obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, and paranoid ideation. Cardiovascular outcome variables were BMI and the Framingham risk scores for cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We found nominally significant CTNNA2 associations for every phenotype. Rumination totally mediated the associations of CTNNA2 rs17019243 with eight out of ten BSI scores, but none with Framingham scores or BMI. Our results suggest that CTNNA2 genetics may serve as biomarkers, and increasing the expression or function of CTNNA2 protein may be a potential new therapeutic approach in psychiatric disorders with perseverative negative thinking including, e.g., depression. Generally, an antiruminative agent could be a transdiagnostic and preventive psychopharmacon.

Severe brain trauma to the fetus in a car accident: Literature review and a clinical case

Car accidents are the main cause of trauma during pregnancy. Even a non-severe accident is associated with a high risk of injury and unfavorable outcome for the fetus, especially in the event of placental abruption. Major agents leading to a trauma could also include safety belt and safety airbags. Blunt abdominal trauma during a car accident is associated with such type of intrauterine injury as fetal skull fractures and various intracranial hemorrhages. Despite a common viewpoint on relatively high death rates in this population, it is not infrequent that fetal trauma has a favorable outcome without any clinically significant neurological deficiency.The paper presents an analysis of the main outcomes of intrauterine brain injury and associated factors. As an illustration, we describe a case of a car accident related brain injury to a fetus at 38 week of gestation, with skull fracture, brain contusion, and subarachnoidal, epidural and subdural, parenchymal and intraventricular hemorrhages induced by the safety belt, with the mother being virtually uninjured. After treatment, the patient was discharged from the hospital in a satisfactory state, without clinically significant neurological symptoms and signs. A 8-months follow-up of the infant showed some delay in brain maturation manifesting as benign epileptiform discharges of childhood and magnetic resonance imaging patterns.It is highly likely, that the leading factors ensuring a favorable outcome of a intrauterine severe brain trauma (without fatal trauma to the mother and fetus) are as follows: correct obstetric strategy, late gestational age and absence of a massive parenchymal and/or intraventricular bleeding. After the short-term clinical recovery from a severe intrauterine brain trauma and in addition to it, proper follow-up of the child is essential because of a high risk of long-term cerebral and functional abnormalities, mostly paroxysmal, behavioral and cognitive.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Phasic and tonic alertness in preterm 5-year-old healthy children

ABSTRACT Preterm delivery may interrupt the intrauterine brain development and implies a risk factor for the developing brain. In the long term, most frequently particular forms of attention deficits are described which refer to the basic aspects of attention i.e., arousal or tonic alertness. As this reflects top-down processes, the current study focuses on bottom-up processed phasic alertness in preschool aged preterm children. Additionally, we made a division of response times into decision and movement time to quantify more exactly the contribution of cognitive and motor performance to reaction times. We investigated basic aspects of attention functioning and contrasted phasic and tonic alertness in 31 low-risk healthy preterm (28–36 weeks of gestation) and 22 term children of five to 6 years of age by using a self-designed computerized test. Preterm children exhibited delayed decision and reaction time in the tonic non-cued alertness condition but not in the phasic cued alertness condition compared to term children. Current results suggest that preterm birth, even when clinically relevant symptoms are absent, may have long-term consequences on basic aspects of attention functioning. Results further suggest that preterm children may profit from auditory cues to overcome these deviations, which yield evidence for a clear distinction between impaired top-down and intact bottom-up controlled processes. These findings might provide a promising groundwork for the development of therapeutical interventions and prevention strategies, whose use and impact to support preterm children should be addressed in further investigations.

Twin discordance: a study of volumetric fetal brain MRI and neurodevelopmental outcome.

This study employed magnetic resonance imaging (MRI) to compare brain volumes of discordant twins and examined their neurodevelopment after birth by using a validated exam. A prospective historical cohort study of discordant dichorionic diamniotic (DCDA) or monochorionic diamniotic (MCDA) twin fetuses, who undergone an MRI scan to evaluate growth restriction in the discordant twin (weight < 10th centile) during 6 years period, at a single tertiary center. Twenty-seven twin pairs were included in the volumetric study and 17 pairs were included in the neurodevelopmental outcome examination. The volumes of the supratentorial brain region, both hemispheres, eyes, and the cerebellum were measured by 3D MRI semi-automated volume measurements. Volumes were plotted on normal growth curves and discordance was compared between weight at birth and brain structure volumes. Neurodevelopmental outcome was evaluated using the VABS-II questionnaire at a mean age of 4.9 years. The volume of major brain structures was significantly larger in the appropriate-for-gestational-age twins (AGA) compared to the small-for-gestational-age (SGA) co-twins (p < 0.001). The birth weight discordance was 32.3% (24.9-48.6) and was significantly greater (p < 0.001) than the discordance of the prenatal supratentorial brain (13.6% [5.6-18]), cerebellum volume (21.7% [9.5-30.8]). Further neurodevelopmental outcome evaluation found no significant difference between the AGA twin and the SGA twin. In discordant twins, the smaller twin showed a "brain-preserving effect," which in our study was not associated with a worse neurodevelopmental outcome. The use of MRI in such cases may aid in decision-making and parental consultation. • Weight discordance at birth was significantly greater compared to intrauterine brain volume discordance measured by 3D MRI. • Small-for-gestational-age (SGA) fetuses preserve brain development. • In highly discordant twins, there was no long-term difference in neurodevelopmental outcome at a mean age of 4.9 years.

Clinical and molecular characterization of 12 prenatal cases of Cri-du-chat syndrome.

BackgroundThis study aimed to define the molecular basis for 12 prenatal cases of Cri‐du‐chat syndrome (CdCS) and the potential genotyping‐phenotyping association.MethodsKaryotyping and single nucleotide polymorphism array analyses for copy number variants were performed.ResultsNine cases had 5p terminal deletions and three had 5p interstitial deletions, and these cases had variable deletion sizes with partial overlapping. Phenotypically, besides intrauterine growth restriction (IUGR) and brain as well as heart abnormalities, hypospadias, and lung dysplasia were observed. Potential genetic causes for specific phenotypes in these cases were identified.ConclusionThis study defined the molecular bases for the patients of CdCS, which is important for genetic counseling for these families. The findings of present study expand the clinical features of CdCS in the fetal period, and provided important information for further refining the genotypic–phenotypic correlations for this syndrome.

The seluang fish (Rasbora spp.) diet to improve neurotoxicity of endosulfan-induced intrauterine pup's brain through of oxidative mechanism

Summary Epidemiological evidence suggested the relationship between pesticide exposure and increased risk of autism. In autism, there is a change in the production of neurotransmitters and oxidative stress. Seluang fish has high-protein that has not been investigated for its effects on autism. This study aimed to determine the effect of seluang fish on neurotransmitters and oxidative stress in endosulfan-induced rats intrauterine. This study used pup's rat induced by endosulfan intrauterine. The pregnant rats divided into 2 groups were K0 without endosulfan induced and K1 with endosulfan induced. After 4 weeks, 8 pup's rats of K0 and K1 were sacrificed for blood and brain samples, while 8 pup's rats were given a standard diet (P1) and fed a Seluang fish diet (P2) respectively for 4 weeks. Then examined the parameters of serum and brain serotonin, brain H2O2, SOD, and MDA levels. The results showed that K1had increased brain H2O2 and MDA levels, whereas brain and serum serotonin levels and brain SOD decreased significantly compared to K0. Group P1 and P2 showed decreasing brain H2O2 and MDA levels significantly than K1, brain serotonin levels increased significantly than K1, whereas serum serotonin levels were not significantly different (p = 0.483). Group P1 and P2 were not different significantly in the serum and brain serotonin, and brain SOD levels. The brain H2O2 (p

Optimal Assessment and Quantification of Iodine Nutrition in Pregnancy and Lactation: Laboratory and Clinical Methods, Controversies and Future Directions.

Iodine intake must be boosted during pregnancy to meet the demands for increased production and placental transfer of thyroid hormone essential for optimal foetal development. Failure to meet this challenge results in irreversible brain damage, manifested in severity from neurological cretinism to minor or subtle deficits of intelligence and behavioural disorders. Attention is now being focused on explaining observational studies of an association between insufficient iodine intake during pregnancy and mild degrees of intellectual impairment in the offspring and confirming a cause and effect relationship with impaired maternal thyroid function. The current qualitative categorisation of iodine deficiency into mild, moderate and severe by the measurement of the median urinary iodine concentration (MUIC) in a population of school-age children, as a proxy measure of dietary iodine intake, is inappropriate for defining the degree or severity of gestational iodine deficiency and needs to be replaced. This review examines progress in analytical techniques for the measurement of urinary iodine concentration and the application of this technology to epidemiological studies of iodine deficiency with a focus on gestational iodine deficiency. We recommend that more precise definitions and measurements of gestational iodine deficiency, beyond a spot UIC, need to be developed. We review the evidence for hypothyroxinaemia as the cause of intrauterine foetal brain damage in gestational iodine deficiency and discuss the many unanswered questions, from which we propose that further clinical studies need to be designed to address the pathogenesis of neurodevelopmental impairments in the foetus and infant. Agreement on the testing instruments and standardization of processes and procedures for Intelligence Quotient (IQ) and psychomotor tests needs to be reached by investigators, so that valid comparisons can be made among studies of gestational iodine deficiency and neurocognitive outcomes. Finally, the timing, safety and the efficacy of prophylactic iodine supplementation for pregnant and lactating women needs to be established and confirmation that excess intake of iodine during pregnancy is to be avoided.

Rapid Postnatal Adaptation of Neurodevelopment in Pigs Born Late Preterm

Preterm birth interrupts intrauterine brain growth and maturation and may induce a delay in postnatal neurodevelopment. Such developmental delays can result from the reduced fetal age at birth, together with the clinical compli­cations of preterm birth (e.g., hypoxia, ischemia, and inflammation). We hypothesized that late preterm birth, inducing only mild clinical complications, has minimal effects on brain-related outcomes such as motor function and behavior. Using the pig as a model for late preterm infants, piglets were cesarean delivered preterm (90%, 106 days gestation) or at full term, reared by identical procedures, and euthanized for tissue collection at birth or after 11 days (e.g., term-corrected age for preterm pigs). Clinical variables and both structural and functional brain endpoints were assessed. The preterm pigs were slow to get on their feet, gained less weight (–30%), and had a higher cerebral hydration level and blood-to-cerebrospinal fluid permeability than the term pigs. At term-corrected age (11 days), the absolute weight of the brain and the weights of its regions were similar between 11-day-old preterm and newborn term pigs, and both were lower than in 11-day-old term pigs. Postnatally, physical activity and movements in an open field were similar, except that preterm pigs showed a reduced normalized stride length and increased normalized maximum stride height. Perinatal brain growth is closely associated with advancing postconceptional age in pigs, and late preterm birth is initially associated with impaired brain growth and physical activity. Postnatally, neuromuscular functions mature rapidly and become similar to those in term pigs, even before term-corrected age. Neuromuscular functions and behavior may show rapid postnatal adaptation to late preterm birth in both pigs and infants.