Impaired Neurological Development Research Articles

The association between anemia and sensorineural hearing loss: A review.

Anemia affects a third of the world's population and contributes to increased morbidity and mortality, decreased work productivity, and impaired neurological development. In recent years, many studies have found a possible association between anemia and sensorineural hearing loss (SNHL), especially in various types of nutritional deficiency and hemoglobin disorders anemia. Anemia may affect hearing through various mechanisms, including affecting microcirculation in the ear, causing tissue hypoxia in the ear, and through inflammatory and oxidative stress pathways. This review aims to comprehensively analyze the association between various types of anemia and SNHL, including possible biological mechanisms, clinical features, and treatment strategies, and clarify the importance of anemia treatment and management in preventing SNHL.

A Case Report of a Patient with Pyruvate Carboxylase Deficiency

Background: Pyruvate carboxylase catalyzes the carboxylation of pyruvate to oxaloacetate, a crucial intermediate of the tricarboxylic acid (TCA) cycle and the initial step in converting pyruvate to glucose (gluconeogenesis). Pyruvate carboxylase deficiency is a rare metabolic disorder characterized by lactic acidosis, failure to thrive, development delay, and recurrent seizures at an early age in severely affected patients. The onset and severity of pyruvate carboxylase deficiency have been classified as severe neonatal (type B), usually fatal, less severe infantile (type A), compatible with survival but with impaired neurologic development, and milder, later onset (type C) with some residual impairment. Clinical manifestations include hypotonia, mixed hypertonia, ataxia, choreoathetosis, microcephaly, and other signs of impaired white matter development. Case Report: A 7-day-old baby with a birth weight of 3kg, born to related parents, presented with clinical symptoms such as lethargy, poor feeding, and grunting since birth. Additionally, he experienced a drop in O2 saturation and cyanosis during his hospitalization. Test results revealed lactic acidosis and hyperammonemia. Furthermore, serum amino acids chromatography- HPLC indicated an increase in lysine and citrulline. The patient succumbed after 16 days due to multi-organ damage. Genetic analysis identified pyruvate carboxylase enzyme deficiency. Conclusion: Pyruvate carboxylase deficiency is a rare inborn error of metabolism that can lead to developmental delay and failure to thrive, typically beginning in the neonatal or early infantile period. The possibility of pyruvate carboxylase deficiency should be considered in any child presenting with lactic acidosis and neurological abnormalities, particularly if associated with hypoglycemia, hyperammonemia, or ketosis.

Sulfate: a neglected (but potentially highly relevant) anion.

Sulfate is an important anion as sulfonation is essential in modulation of several compounds, such as exogens, polysaccharide chains of proteoglycans, cholesterol or cholesterol derivatives and tyrosine residues of several proteins. Sulfonation requires the presence of both the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) and a sulfotransferase. Genetic disorders affecting sulfonation, associated with skeletal abnormalities, impaired neurological development and endocrinopathies, demonstrate the importance of sulfate. Yet sulfate is not measured in clinical practice. This review addresses sulfate metabolism and consequences of sulfonation defects, how to measure sulfate and why we should measure sulfate more often.

Identification of CYFIP2 Arg87Cys Ligands via In Silico and In Vitro Approaches.

The advancement of next-generation sequencing has enabled the identification of specific mutations associated with early infantile epileptic encephalopathies (EIEEs). In EIEE, epileptic spasms and seizures that occur since early childhood lead to impaired neurological development. The CYFIP2 p.Arg87Cys variant was recently related to EIEE. CYFIP2 participates in the Wave Regulatory Complex (WRC), which is related to the regulation of actin dynamics. The variant residue is at the interface between the CYFIP2 protein and WAVE1 protein inside the WRC. Thus, the weakening of this interaction induced by the residue modification, which also causes the flexibilization of the loop 80-110 within the CYFIP2 structure, allows the constant activation of the WCR. This study aimed to identify ligands for CYFIP2 p.Arg87Cys and potential therapy targets using in silico in vitro approaches. Models of different CYFIP2 versions were constructed, and molecular docking analyses were conducted. A total of 3946 ligands from the PDE3 and Drugbank databases were screened, leading to the identification of 11 compounds that selectively bind to the variant protein. The impact of binding in CYFIP2 was also evaluated using a thermal stability assay. These findings contribute to a better understanding of CYFIP2's functional role in pathology and can guide more in vitro experiments, facilitating the development of targeted therapies for CYFIP2-related conditions.

Abstract #1319041: Hyperinsulinism-Hyperammonemia Syndrome in a Toddler With Recurrent Episodes of Loss of Consciousness

Hyperinsulinism-hyperammonemia syndrome (HI/HA) is one of the causes of hyperinsulinemic hypoglycemia in young children, which is responsive to diazoxide and protein restriction. Hypoglycemia of various etiologies in young children can lead to impaired neurological development. Early diagnosis and hence accurate management, is extremely important to prevent significant sequelae. We present a case of HI/HA, showing the importance of implementing the accurate approach for hypoglycemia in reaching the right diagnosis.

Molecular Dynamics of CYFIP2 Protein and Its R87C Variant Related to Early Infantile Epileptic Encephalopathy.

The CYFIP2 protein (cytoplasmic FMR1-interacting protein 2) is part of the WAVE regulatory complex (WRC). CYFIP2 was recently correlated to neurological disorders by the association of the R87C variant with early infantile epileptic encephalopathy (EIEE) patients. In this set of syndromes, the epileptic spasms and seizures since early childhood lead to impaired neurological development in children. Inside the WRC, the variant residue is at the CYFIP2 and WAVE1 protein interface. Thus, the hypothesis is that the R87C modification weakens this interaction, allowing the WRC complex’s constant activation. This work aimed to investigate the impacts of the mutation on the structure of the WRC complex through molecular dynamics simulation. For that, we constructed WRC models containing WAVE1-NCKAP1 proteins complexed with WT or R87C CYFIP2. Our simulations showed a flexibilization of the loop comprising residues 80–110 due to the loss of contacts between internal residues in the R87C CYFIP2 as well as the key role of residues R/C87, E624, and E689 in structural modification. These data could explain the mechanism by which the mutation impairs the stability and proper regulation of the WRC.

Role of colour doppler indices in diagnosing intrauterine growth restriction in high risk pregnancies in second and third trimester

Intrauterine growth restriction (IUGR) is associated with impaired neurological development of child, increased morbidity and increased risk of death during perinatal period. Doppler ultrasound during pregnancy is a useful tool for early detection of IUGR and this helps in early management to prevent further complications associated with IUGR.To study efficacy of color doppler in diagnosing Intrauterine growth restriction in high risk pregnancies in second and third trimester.Diagnostic efficacy study was conducted among 100 subjects with high risk pregnancy presenting in second and third trimester. IUGR was suspected when there was a growth lag of >4 weeks between gestational age and fundal height. Further two-dimensional ultrasound was performed. Bi-parietal diameter, Head circumference, Abdominal circumference, Femur length were noted, estimated fetal weight was calculated. IUGR fetuses were identified if abdominal circumference is<5 percentile and estimated fetal weight was<10 percentile for that gestational age. Vessels studied were Uterine artery, Umbilical artery, Middle cerebral artery, Ductus venosus. The doppler indices studied were RI, PI, S/D, Cerebro-Placental ratio (CPR). Majority were of 22-25 years (52.5%); 53.75% were primigravida; 41.25% presented at 33-37 weeks; 46.25% had gestational hypertension. The overall sensitivity of doppler indices as seen in the present study was good (89.9%) but specificity was only 9.1%. Among the other indices, CPR had the best diagnostic utility with sensitivity=64%; specificity=100% and PPV=100% followed by umbilical artery doppler with sensitivity=55.1%; specificity=81.8% and PPV=96.1%.The overall color doppler indices are highly sensitive in detection of IUGR and lacks the specificity. CPR and Umbilical artery doppler can be used with more reliability.

Novel IBA57 mutations in two chinese patients and literature review of multiple mitochondrial dysfunction syndrome.

Multiple mitochondrial dysfunction syndrome (MMDS) refers to a class of mitochondrial diseases caused by nuclear gene mutations, which usually begins in early infancy and is classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure, as well as early fatality resulted from dysfunction of energy metabolism in multiple systems. So far, six types of MMDS have been identified based on different genotypes, which are caused by mutations in NFU1, BOLA3, IBA57, ISCA2, ISCA1 and PMPCB, respectively. IBA57 encodes a protein involved in the mitochondrial Fe/S cluster assembly process, which plays a vital role in the activity of multiple mitochondrial enzymes. Herein, detailed clinical investigation of 2 Chinese patients from two unrelated families were described, both of them showed mildly delay in developmental milestone before disease onset, the initial symptoms were all presented with acute motor and mental retrogression, and brain MRI showed diffused leukoencephalopathy with cavities, dysplasia of corpus callosum and cerebral atrophy. Exome sequencing revealed three IBA57 variants, one shared variant (c.286T>C) has been previously reported, the remaining two (c.189delC and c.580A>G) are novel. To enhance the understanding of this rare disease, we further made a literature review about the current progress in clinical, genetic and treatment of the disorder. Due to the rapid progress of MMDS, early awareness is crucial to prompt and proper administration, as well as genetic counseling.

Defining drinking water metal contaminant mixture risk by coupling zebrafish behavioral analysis with citizen science

Contaminated drinking water is an important public health consideration in New England where well water is often found to contain arsenic and other metals such as cadmium, lead, and uranium. Chronic or high level exposure to these metals have been associated with multiple acute and chronic diseases, including cancers and impaired neurological development. While individual metal levels are often regulated, adverse health effects of metal mixtures, especially at concentrations considered safe for human consumption remain unclear. Here, we utilized a multivariate analysis that examined behavioral outcomes in the zebrafish model as a function of multiple metal chemical constituents of 92 drinking well water samples, collected in Maine and New Hampshire. To collect these samples, a citizen science approach was used, that engaged local teachers, students, and scientific partners. Our analysis of 4016 metal-mixture combinations shows that changes in zebrafish behavior are highly mixture dependent, and indicate that certain combinations of metals, especially those containing arsenic, cadmium, lead, and uranium, even at levels considered safe in drinking water, are significant drivers of behavioral toxicity. Our data emphasize the need to consider low-level chemical mixture effects and provide a framework for a more in-depth analysis of drinking water samples. We also provide evidence for the efficacy of utilizing citizen science in research, as the broader impact of this work is to empower local communities to advocate for improving their own water quality.

Prenatal Ultrasound Diagnosis of Biometric changes in the Brain of Growth Restricted Fetuses. A Systematic Review of Literature.

Fetal growth restriction (FGR) occurs when the fetus does not reach its intrauterine potential for growth and development as a result of compromise in placental function. It is a condition that affects 5 to 10% of pregnancies and is the second most common cause of perinatal morbidity and mortality. Children born with FGR are at risk of impaired neurological and cognitive development and cardiovascular or endocrine diseases in adulthood. The purpose of the present revision is to perform a literature search for evidence on the detection and assessment by ultrasound of brain injury linked to FGR during fetal life. Using a systematic approach and quantitative evaluation as study methodology, we reviewed ultrasound studies of the fetal brain structure of growth-restricted fetuses with objective quality measures. A total of eight studies were identified. High quality studies were identified for measurement of brain volumes; corpus callosum; brain fissure depth measurements, and cavum septi pellucidi width measurement. A low-quality study was available for transverse cerebellar diameter measurement in FGR. Further prospective randomized studies are needed to understand the changes that occur in the brain of fetuses with restricted growth, as well as their correlation with the changes in cognitive development observed.

Screening of Thyroid Function Test During First Trimester of Pregnancy

Introduction: During pregnancy maternal thyroid dysfunction has been associated with a number of adverseoutcomes, like preterm birth, placental abruption, fetal death and impaired neurological development inthe child. The presence of Thyroid Peroxidase Antibody (TPO-Ab) results miscarriage, preterm birth andmaternal post-partum thyroid disease. Hypothyroidism is closely associated with the presence of ThyroidPeroxidase Antibody. If a pregnant woman is positive for TPO-Ab in early pregnancy, her chances todeveloping thyroid abnormalities.Objective: To find out the level of TPO-Ab and thyroid status in first trimester of pregnancy. Method:Observational cross-sectional Study was designed in Department of Biochemistry, Medical college,Vadodara, Gujarat, India.Sample Size: 200 Normal pregnant women that randomly selected from the first trimesters of pregnancy.The study parameters were - thyroid peroxidase anti-body (TPO-Ab); serum thyroid stimulating hormone(TSH); serum T3 and serum T4.Result: Our study found that 30(15%) pregnant women of first trimester was hypothyroidism (TSH>2.5mIU/l) Out of these 30 females, 9(4.5%) had overt hypothyroidism & 21 (10.5%) had subclinicalhypothyroidism, among these 30 subjects, 26(13%) had found TPO-Ab positive (TPO-Ab >35 IU//mL)there was a significant positive correlation between positive TPO-Ab and serum TSH level of study subjectsand there was a negative correlation between serum TSH and serum T4,T3 level in study subjects.Conclusion: In this study we found 15% prevalence of hypothyroidism (4.5 % overt & 10.5 % subclinical)in first trimester of pregnancy. We found positive TPO-Ab in 13% of pregnant females and all these hadsome thyroid dysfunctions, subclinical or overt hypothyroidism, subclinical being much more common thanovert hypothyroidism.

The Effect of the Sound of Holy Quran on Pain Level of Neonates During Invasive Procedure

Venipuncture and intravenous therapy are painfull procedures when hospitalized. The experience of pain in the neonatal period can lead to impaired neurological, attention, and learning development and also behavioral disorders in children. One of the most pleasanttypes of music is the recitation of the Holy Quran is a complementary therapy for relief pain. Although Breastfeeding was effective for reducing pain but not easy to implemented if nurse or health care proffesionals need space room for intervention and far from their mother. So need study further about nonpharmacological treatment contributes to optimal pain management in neonates. This study aimed to determine the effect of the sound of the holy Quran recitation on pain level neonates undergoing the invasive procedure at Perinatology Care Unit on Al Islam Hospital Bandung. This was a quasi-experimental study conducted on 36 neonates, selected with purposive sampling divided into two groups. Pain level was measured with the Neonatal Infant Pain Scale instrument during venipuncture or intravenous procedure. The Study was conducted since desember 2018 until february 2019. The data were analyzed using Mann whitney. The result showed a significant difference in pain level (p= 0.001) between the intervention and the control groups. The find ings indicated that the sound of Holy Quran recitation could help decrease pain level of neonates during invasive procedure.

A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development

A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development

Fetal heart rhabdomyomatosis: a single-center experience

Objectives: The primary aim of the study was to evaluate the prevalence of fetal heart tumors in a single tertiary referral center over a period of 15 years. The secondary aim was to confirm the presence of tuberous sclerosis complex (TSC) through the evaluation of germline mutation in TSC1/TSC2 and assess the outcomes in affected fetuses and newborns.Methods: A retrospective study was conducted between 2003 and 2017. Fetal echocardiography was performed in the second trimester of pregnancy in the study population. The identification of heart tumors and further follow-up were performed by a pediatric cardiologist. Molecular genetic analysis was conducted on fetuses and children in cases where TSC was suspected.Results: In total, 39,018 fetuses were examined between 2003 and 2017. Heart tumors were detected in nine fetuses and were diagnosed as rhabdomyoma in all cases. We identified mutations in one of the TSC1 or TSC2 genes in all cases with multiple rhabdomyomas (8/9). In all born children (5/9), the genetically confirmed diagnosis of TSC was established, and clinically pathological deposits in the brain were found.Conclusion: Fetal heart tumors are usually represented by rhabdomyomas having a good cardiac prognosis. However, rhabdomyoma is usually the first symptom of TSC with a subsequent brain disorder and impaired neurological development.

Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries.

Anemia affects a third of the world's population and contributes to increased morbidity and mortality, decreased work productivity, and impaired neurological development. Understanding anemia's varied and complex etiology is crucial for developing effective interventions that address the context-specific causes of anemia and for monitoring anemia control programs. We outline definitions and classifications of anemia, describe the biological mechanisms through which anemia develops, and review the variety of conditions that contribute to anemia development. We emphasize the risk factors most prevalent in low- and middle-income countries, including nutritional deficiencies, infection/inflammation, and genetic hemoglobin disorders. Recent work has furthered our understanding of anemia's complex etiology, including the proportion of anemia caused by iron deficiency (ID) and the role of inflammation and infection. Accumulating evidence indicates that the proportion of anemia due to ID differs by population group, geographical setting, infectious disease burden, and the prevalence of other anemia causes. Further research is needed to explore the role of additional nutritional deficiencies, the contribution of infectious and chronic disease, as well as the importance of genetic hemoglobin disorders in certain populations.

A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development

We report a recurrent CNOT1 de novo missense mutation, GenBank: NM_016284.4; c.1603C>T (p.Arg535Cys), resulting in a syndrome of pancreatic agenesis and abnormal forebrain development in three individuals and a similar phenotype in mice. CNOT1 is a transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells in a pluripotent state. These findings suggest that CNOT1 plays a critical role in pancreatic and neurological development and describe a novel genetic syndrome of pancreatic agenesis and holoprosencephaly.

Aluminium release by coated and uncoated fluid-warming devices.

The use of fluid-warming systems is recommended for infusion rates >500ml.h-1 to avoid peri-operative hypothermia. Some fluid-warming devices use disposable aluminium-heated plates for heat transfer, but there is no protective coating to separate the fluid from the heated aluminium surface. It is unknown if this could promote release of aluminium into infusion fluids. We investigated a coated (Fluido compact) and an uncoated (enFlow) fluid-warming device using normal saline or balanced electrolyte solution as infusion fluids, pumped through the heated disposables at flow rates of 2, 4 and 8ml.min-1 for 60min each. Aluminium concentrations in the fluid samples were analysed using graphite furnace atomic absorption spectrometry. With saline the coated and uncoated devices yielded aluminium concentrations below the level of quantification (<128μg.l-1 ). Similarly, balanced electrolyte solution in the coated device yielded aluminium concentrations <128μg.l-1 . However, balanced electrolyte solution in the uncoated device yielded aluminium concentrations of up to 6794 (3465-8002 [1868-7421]) μg.l-1 . Repeating this last study at a flow rate of 2ml.min-1 resulted in quite high aluminium concentrations when the uncoated device was not heated (~1000μg.l-1 ) and higher concentrations after the device was heated. We conclude that using uncoated aluminium plates in fluid-warming systems can lead to a risk of administering potentially harmful concentrations of aluminium when balanced crystalloid solutions are used. The mechanism is unclear, but heat is in part involved. Coating for aluminium within medical devices in direct contact with infusion fluids should be recommended.

INTRAUTERINE GROWTH RETARDATION - A REVIEW ARTICLE

Small for gestational age (SGA) and fetal growth restriction (FGR) is difficult to define exactly. In this pregnancy condition, the fetus does not reach its biological growth potential as a consequence of impaired placental function, which may be because of a variety of factors. Fetuses with FGR are at risk for perinatal morbidity and mortality, and poor long-term health outcomes, such as impaired neurological and cognitive development, and cardiovascular and endocrine diseases in adulthood. At present no gold standard for the diagnosis of SGA/FGR exists. The first aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines. Another aim to summary a number of interventions which are being developed or coming through to clinical trial in an attempt to improve fetal growth in placental insufficiency. Key words: fetal growth restriction (FGR), Small for gestational age (SGA)

INTRAUTERINE GROWTH RETARDATION - A REVIEW ARTICLE

Small for gestational age (SGA) and fetal growth restriction (FGR) is difficult to define exactly. In this pregnancy condition, the fetus does not reach its biological growth potential as a consequence of impaired placental function, which may be because of a variety of factors. Fetuses with FGR are at risk for perinatal morbidity and mortality, and poor long-term health outcomes, such as impaired neurological and cognitive development, and cardiovascular and endocrine diseases in adulthood. At present no gold standard for the diagnosis of SGA/FGR exists. The first aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines. Another aim to summary a number of interventions which are being developed or coming through to clinical trial in an attempt to improve fetal growth in placental insufficiency. Key words: fetal growth restriction (FGR), Small for gestational age (SGA)

Iodine deficiency in women of childbearing age: not bread alone?

Iodine deficiency remains a public health concern, particularly in pregnant women and those planning pregnancy because of the risk of impaired fetal neurological development. Following implementation of strategies to improve iodine intake in Australia, there has been minimal investigation into current iodine status. We aimed to characterise iodine status in a population of women of childbearing-age in Australia. A cross-sectional study was performed in 97 women of childbearing-age attending outpatient clinics at a tertiary hospital in Sydney. Pregnant and postmenopausal women were excluded. Iodine intake was surveyed via questionnaire. Spot urinary iodine (UI) was concurrently measured. The relationships between UI, dietary intake and use of iodine-containing multivitamins/medications were examined. Median UI was 117 ug/L. Forty women (41%) were iodine deficient (UI <100 ug/L). The most commonly consumed source of dietary iodine was bread (29/97, 30% daily). Forty-three women took iodine-containing multivitamins but 18/43 (41.2%) remained deficient. There were no significant associations between UI and diet. There was a smaller proportion of deficient people than in our previous study (125/180 non-pregnant subjects, 69%, vs 41% in this study, p<0.001). The overall population median is now sufficient, however, a significant proportion of this multicultural group are iodine deficient. There are similar proportions of deficiency in those using iodine supplements versus not. Contributors may include ethnicity-related dietary practices, limited awareness or poor adherence to iodine supplements. Despite public health strategies, a significant proportion of women of child-bearing age remained iodine deficient. Further research involving a larger population and contributors to iodine deficiency is warranted.