Central Nervous System Anomalies Research Articles

Profile of various congenital anomalies in fetus detected during antenatal period among high risk mothers by Ultrasonography at Tertiary Care Centre, South Gujarat

Background: With the improvement of basic maternal and child health care services, the deaths due to malnutrition and infections are on a descending trend and due to westernization and lifestyle modifications, perinatal deaths due to anomalies are in ascending trend. Aim & Objectives: The purpose of this study was to estimate the antenatal proportion of congenital anomalies, types, pattern of anomalies and factors associated with anomalies in Tertiary Care Centre, South Gujarat. Settings and Design: Cross-sectional study in Department of Fetal Medicine of New Civil Hospital, Surat. Methods and Material: Sample size was 435. First 10 consecutive high-risk ANC patients, who were referred to Fetal Medicine department from Obstetrics and Gynecology department per day were selected. Data was collected during September 2021 to February 2022. Statistical analysis used: Frequencies, proportions and tests of significance was applied for testing the association of socio-demographic variables, clinical variables etc on presence or absence of congenital anomalies. Results: Proportion of different types of congenital anomalies in high risk pregnant mother was 17.2%. There was significant association between presence of congenital anomalies with history of irregular menstruation (p value: 0.001, OR: 5.19, [CI: 1.76-15.27]) and inadequate amniotic fluid (p value: 0.00, OR: 14.5[CI: 7.23-29.06]). Among total detected anomalies in Ultrasonography scanning, most common anomalies were Cardio-vascular system anomalies (36.4%) and Central Nervous System anomalies (24%). Conclusions: Congenital anomalies were present in about 17 % of high risk antenatal mothers.

Prenatal diagnosis and molecular cytogenetic characterization of fetuses with central nervous system anomalies using chromosomal microarray analysis: a seven-year single-center retrospective study

Few existing reports have investigated the copy number variants (CNVs) in fetuses with central nervous system (CNS) anomalies. To gain further insights into the genotype–phenotype relationship, we conducted chromosomal microarray analysis (CMA) to reveal the pathogenic CNVs (pCNVs) that were associated with fetal CNS anomalies. We enrolled 5,460 pregnant women with different high-risk factors who had undergone CMA. Among them, 57 subjects with fetal CNS anomalies were recruited. Of the subjects with fetal CNS anomalies, 23 were given amniocentesis, which involved karyotype analysis and CMA to detect chromosomal abnormalities. The other 34 cases only underwent CMA detection using fetal abortive tissue. In this study, we identified five cases of chromosome aneuploid and nine cases of pCNVs in the fetuses, with a chromosomal aberration detection rate of 24.56% (14/57). In the 23 cases that were given both karyotype and CMA analysis, one case with trisomy 18 was detected by karyotyping. Moreover, CMA revealed a further three cases of pCNVs, including the 1p36.33p36.31, 7q11.23, and 1q21.1q21.2 microdeletions, with a 13.04% (3/23) increase in CMA yield over the karyotype analysis. Additionally, three cases of trisomy 13, one case of trisomy 21, and six cases of pCNVs were detected in the other 34 fetuses where only CMA was performed. Furthermore, a higher chromosomal aberration detection rate was observed in the extra CNS anomaly group than in the isolated CNS anomaly group (40.91% vs 14.29%). In conclude, several pathogenic CNVs were identified in the fetuses with CNS anomalies using CMA. Among the detected CNVs, ZIC2, GNB1, and NSUN5 may be the candidate genes that responsible for fetal CNS anomalies. Our findings provides an additional reference for genetic counseling regarding fetal CNS anomalies and offers further insight into the genotype–phenotype relationship.

Congenital Anomalies in Yemeni Newborns: A Retrospective Study at a Tertiary Care Hospital in Sana’a City

Background: Congenital anomalies (CAs) are major causes of morbidity and mortality among newborns worldwide. Therefore, the present study aimed to determine the prevalence and types of CAs in Sana’a city, Yemen.
 Methods: This retrospective, cross-sectional study was conducted among newborns admitted to Al-Thawra Modern General Hospital in Sana’a from January to December 2017. Data were collected from 1100 medical records of newborns, besides data about their mothers, using a predesigned data collection sheet. Data were then analyzed, and the results were presented as frequencies and proportions.
 Results: Of 1100 newborns, 164 (14.9%; 95% confidence interval: 12.9–17.1) newborns had CAs. Of these, 74.4% had single-system CAs, and 25.6% had multiple-system CAs. Gastrointestinal tract anomalies (43.9%) were the most frequent CAs, followed by anomalies of the central nervous system (CNS) (18.9%), musculoskeletal system (17.1%), chromosomes (15.2%) and cardiovascular system (14%). However, orofacial anomalies of cleft lip and cleft palate (2.4%) were the least frequent CA, followed by urogenital anomalies (8.5%). Esophageal atresia (33.3%) and imperforated anus (25%) were the most frequent gastrointestinal CAs. On the other hand, meningocele (35.4%) was the most frequent CNS anomaly. Of musculoskeletal anomalies, limb defects were the most frequent (96.4%), while achondroplasia was observed among 3.6% of newborns with CAs. Congenital heart disease was the most frequent cardiovascular anomaly (95.7%), while dextrocardia was observed among 4.3% of newborns. Hypospadias (57.2%) was the most frequent urogenital anomaly, followed by ureteropelvic junction obstruction (21.5%). More than half of newborns with CAs died, while 35.4% of them were discharged from hospital without correction of CAs. On the other hand, CAs were corrected for 11.6% of newborns before discharge.
 Conclusion: The prevalence of CAs among Yemeni newborns is relatively high and can be observed in more than one in ten newborns. The majority of CAs usually affect a single system, most frequently affecting the gastrointestinal tract, followed by the CNS, musculoskeletal system, chromosomes and cardiovascular system. Half of newborns with CAs usually die in hospital before discharge. Therefore, it is necessary to educate parents and conduct regular antenatal screening by a pediatrician to detect these anomalies and manage them appropriately and in a timely manner.

Small pituitary volume and central nervous system anomalies in Fanconi Anemia.

Fanconi anemia (FA) is a genomic instability disorder associated with congenital abnormalities, including short stature and the presence of central nervous system anomalies, especially in the hypothalamic-pituitary area. Thus, differences in pituitary size could associate with the short stature observed in these patients. Our aim was to evaluate whether central nervous system abnormalities and pituitary gland volume correlate with height and hormone deficiencies in these patients. In this cross-sectional exploratory study 21 patients diagnosed with FA between 2017 and 2022 in a Spanish Reference Center were investigated. Magnetic resonance imaging (MRI) was performed and pituitary volume calculated and corelated with height and other endocrine parameters. The percentage of abnormalities in our series was 81%, with a small pituitary (pituitary volume less than 1 SD) being the most frequent, followed by Chiari malformation type 1. The median value of pituitary volume was -1.03 SD (IQR: -1.56, -0.36). Short stature was found in 66.7% [CI95% 43-85.4]. Total volume (mm3) increases significantly with age and in pubertal stages. There were no differences between volume SD and pubertal stage, or the presence of endocrine deficiencies. No correlations were found between pituitary volume and the presence of short stature. The intraclass correlation index (ICC) average for volume was 0.85 [CI95% 0.61-0.94] indicating a good-to-excellent correlation of measurements. Central nervous system anomalies are part of the FA phenotype, the most frequent after pituitary hypoplasia being posterior fossa abnormalities, which may have clinical repercussions in the patient. It is therefore necessary to identify those who could be candidates for neurosurgical intervention. The size of the pituitary gland is smaller in these patients, but this does not seem to be related to hormone deficiency and short stature or exposure to a low dose of total body irradiation.

Exploring the phenotypic spectrum and osteopenia mechanisms in Yunis-Varón syndrome

PurposeBiallelic variants in FIG4 or VAC14 are associated with Yunis-Varón syndrome (YVS), which is characterized by multisystem involvement including skeletal findings, craniofacial dysmorphisms and central nervous system anomalies. Pathogenic variants in those same genes have also been associated with a predominantly neurological phenotype and with nonsyndromic conditions, such as Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. By describing 5 new cases of FIG4-associated YVS and reviewing the literature, we better delineate the clinical phenotype associated with loss of function of those genes. We also explore osteopenia mechanisms by assessing bone physiologic parameters in a mouse model. MethodsExome sequencing or Sanger sequencing was performed in 5 unrelated individuals. Bone histomorphometry was performed in Fig4plt/plt mice and compared with wild type. Relevant literature from the last 10 years was reviewed. ResultsAll individuals presented a phenotype overlapping the typical YVS and the brain anomalies and neurologic syndrome. Clinical features included developmental delay, structural brain malformations, and skeletal anomalies, such as osteopenia. Biallelic FIG4 variants were identified in each individual. In mice, bone histomorphometry parameters suggested that osteopenia might be secondary to reduced bone formation rather than increased bone degradation. ConclusionThis study contributes to a better understanding of the phenotypic variability caused by pathogenic variants in FIG4 or VAC14 and suggests an important overlap between previously described phenotypes. The brain anomalies and neurologic syndrome is likely in the same spectrum as classical YVS. Further studies are still needed to clarify the effects of partial loss-of-function (hypomorphic) variants and to identify genotype-phenotype correlations.

Foetal Autopsy: A Cross-sectional Study of 41 Cases at a Tertiary Care Centre in Kuppam, Andhra Pradesh, India

Introduction: Perinatal mortality includes both late foetal deaths and early neonatal deaths. The perinatal mortality rate in India was 23/1000 live births for the year 2016, with congenital anomalies being the major cause of perinatal mortality. Thus, foetal autopsy plays an important role in identifying various types of congenital anomalies, determining the cause of foetal death, and thereby helping in counselling the parents. Aim: To identify various causes of foetal death and determine the most prevalent cause of foetal death. Materials and Methods: The present cross-sectional study was conducted in the Department of Pathology, PES Institute of Medical Sciences and Research (rural tertiary care referral Institute), Kuppam, Andhra Pradesh, India, from January 2018 to December 2022. Autopsies were performed according to a standard protocol and categorised using the Cunningham and Hollier classification. The data were entered into Microsoft (MS) Excel 2007 and further analysed using Statistical Package for the Social Sciences (SPSS) software version 26.0. Results: The maternal age ranged from 19-36 years with a mean±Standard Deviation (SD) of 24.1±3.37 years. Out of the 41 cases, 29 (70.73%) cases were terminated, and 12 (29.26%) cases had intrauterine foetal death. The majority of cases were in the second trimester, with 37 (90.24%) cases, followed by 4 (9.75%) cases in the third trimester. Foetal causes constituted the majority of cases, 23 (56.09%), followed by placental causes, 12 (29.26%) and maternal causes, 6 (14.63%). Conclusion: The present study concluded that congenital anomalies constituted the most prevalent cause of foetal death, with central nervous system anomalies being the most common. This information helps clinicians in early intervention and counselling parents to avoid similar outcomes in subsequent pregnancies.

Goldenhar syndrome: An ephialte for the anesthesiologist – What we saw was just the tip of the iceberg

Goldenhar syndrome, also called oculoauriculovertebral dysplasia, is characterized by craniofacial, central nervous system, cardiac, renal, and vertebral anomalies. It occurs due to the faulty unilateral development of vertebral arches. Patients presenting for surgery are usually in the pediatric age group. General anesthesia is the preferred mode of anesthesia considering the type of surgery, age of the patient, and vertebral anomaly in this patient group. The first and foremost consideration while anesthetizing these patients is the anticipated difficult airway. Frequently encountered airway abnormalities in these patients are micrognathia, retrognathia, mandibular dysplasia, craniovertebral anomalies leading to limited neck flexion and cervical spine instability, decreased thyromental distance, fascial asymmetry, cleft lip and palate, high arched palate, dental abnormalities, and temporomandibular joint abnormalities. Difficult airways often come disguised as syndromes, and thorough pre-operative evaluation along with preparation for the worst scenarios is a must. We have a myriad of alternative airway management equipment at our disposal. Adequate knowledge is a must for their best use.

Evaluation of Fetal Central Nervous System Anomalies Diagnosed Prenatally: Prenatal and Postnatal Outcomes

Evaluation of Fetal Central Nervous System Anomalies Diagnosed Prenatally: Prenatal and Postnatal Outcomes

Up-regulation of miR-10a-5p expression inhibits the proliferation and differentiation of neural stem cells by targeting Chl1.

Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like ( Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p ( Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.

Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.

Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. Thirty studies were included (n=1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2=72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2=74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2=41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2=56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2=68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

The effect of hypertension in pregnancy and central nervous system anomalies on fetal brain development

Objectives: The aim of this study was to investigate whether maternal hypertension affects fetal brain maturation, and to examine whether treatment with magnesium sulfate has a protective effect on the fetal brain. Methods: A total of 26 fetuses, including 11 dead fetuses of pregnant women who were found to have hypertension and whose pregnancy was terminated due to this reason, and 15 fetuses who did not have this risk factor but died for various reasons as the control group, were included in the study. Brain tissue samples were evaluated for the presence of morphological and histopathological changes, as well as apoptotic cells. The morphologies of the samples were examined in sections stained with hematoxylin-eosin (H&E), and apoptosis was examined with light microscopy by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: In the control group, it was observed that the brain tissue had a morphological structure compatible with the development weeks. In the hypertension group, there were no bleeding foci and brain tissues mostly preserved morphological features similar to control patients. While edema was detected in 45.4% of the infants in the hypertension group, no edema was observed in 54.6%. In the hypertension group, Grade 1 necrosis was observed in 63.6% of the samples, Grade 2 necrosis was observed in 9.1%, and no necrosis was observed in 27.3% of the samples. Conclusions: Based on the findings of this study, it can be concluded that maternal hypertension increases neurological maturation by causing vasodilation in the fetal brain, increasing blood flow, and decreasing cell death.

Prenatal exome sequencing analysis in fetuses with central nervous system anomalies.

To evaluate the utility of prenatal exome sequencing (pES) in fetuses with central nervous system (CNS) abnormalities. This was a retrospective cohort study of fetuses identified to have CNS abnormality on prenatal ultrasound and/or magnetic resonance imaging. All fetuses were first analyzed by chromosomal microarray analysis (CMA). Fetuses with a confirmed aneuploidy or causal pathogenic copy-number variant (CNV) on CMA did not undergo pES analysis and were excluded, while those with a negative CMA result were offered pES testing. Of the 167 pregnancies included in the study, 42 (25.1%) were identified to have a pathogenic or likely pathogenic (P/LP) variant. The diagnostic rate was significantly higher in fetuses with a non-isolated CNS abnormality than in those with a single CNS abnormality (35.7% (20/56) vs 14.5% (8/55); P = 0.010). Moreover, when a fetus had three or more CNS abnormalities, the positive diagnostic rate increased to 42.9%. A total of 25/42 (59.5%) cases had de-novo mutations, while, in the remaining cases, mutations were inherited and carried a significant risk of recurrence. Families whose fetus carried a P/LP mutation were more likely to choose advanced pregnancy termination than those with a variant of uncertain significance, secondary/incidental finding or negative pES result (83.3% (25/30) vs 41.3% (38/92); P < 0.001). pES improved the identification of genetic disorders in fetuses with CNS anomalies without a chromosomal abnormality or CNV identified on CMA, regardless of the number of CNS anomalies and presence of extracranial abnormality. We also demonstrated that pES findings can significantly impact parental decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A Newborn Spina Bifida Case Report

In North America, over seventy thousand cases of disability are attributed to central nervous system anomalies, with the majority of these cases resulting from neural tube defects. Among these defects, meningomyelocele is the most commonly observed condition. Meningomyelocele is characterized by the protrusion of spinal structures outside the skin, leading to deficits in motor function of the lower limbs and challenges related to urinary and fecal elimination. The severity of these clinical symptoms can vary depending on the location of the defect along the neural tube.&#x0D; The root cause of meningomyelocele is associated with the incomplete closure of the neural tube during fetal development. In our specific case, the diagnosis of spina bifida was made prenatally by the perinatology clinic, and the family received comprehensive information about the condition well before the delivery. Despite being informed, the family made the decision to proceed with the birth, and necessary arrangements were made to support this choice. Following the delivery, the newborn underwent an examination confirming the presence of spina bifida, in line with the previous ultrasound diagnosis.

The Prevalence and Pattern of Congenital Anomalies Among Neonates Admitted in a Tertiary Care Hospital in the Andaman and Nicobar Islands: A Retrospective Study.

Introduction Congenital anomalies (CAs) constitute a significant determinant of neonatal mortality in India, and past studies have elucidated their diverse clinical presentations across different geographic regions. Given the limited availability of region-specific data in our locale, this study was initiated to elucidate the prevalence and phenotypic manifestations of congenital anomalies in live births within the distinctive setting of the Andaman and Nicobar Islands, India. Methods This retrospective observational study was conducted at the Department of Pediatrics of the Andaman and Nicobar Islands Institute of Medical Sciences (ANIIMS), located in Port Blair, during a defined one-year period extending from June 2022 to May 2023. All live births presenting with congenital anomalies within this stipulated timeframe were systematically enrolled in the study, and data was meticulously extracted from their respective medical records. The study data was methodically collated and organized utilizing the EpiData software (EpiData Association, Odense, Denmark), followed by a comprehensive descriptive analysis executed through the application of the PSPP software (GNU Project, Boston, MA). Results Among the 1661 neonates admitted during the study's defined period, a total of 61 neonates (3.7%) were identified as having congenital anomalies. Among these anomalies, cardiovascular anomalies were found to be the most prevalent, succeeded by gastrointestinal and central nervous systemanomalies. Notably, major congenital anomalies were discerned in 20 out of 61 neonates, constituting approximately 33% of the neonatal population with anomalies. Neonates afflicted with congenital anomalies displayed a mortality rate of 11.5%. Conclusion The effects of congenital anomalies on individuals, families, and the society are far-reaching. Early identification and timely referraland intervention are the key factors in decreasing the mortality and morbidity associated with congenital anomalies.

Three-Year Post-Neonatal Intensive Care Unit Health Care Utilization Among Infants with Congenital Anomalies

ObjectiveTo describe three-year post-NICU healthcare utilization among children with congenital anomalies discharged home from a level IV NICU Study DesignRetrospective chart review of children with congenital anomalies enrolled in a prior prospective cohort study from 2016-2020. We assessed hospital readmission rate, number of surgeries, and durable medical equipment (DME) use by type of anomaly. ResultsAmong 166 infants enrolled in the original study, 158 survived to NICU discharge. One-third of the cohort had a genetic anomaly. Six out of 158 patients (4%) died before age three. More than half the children were readmitted within the first two years of life and a third were readmitted in the third year of life. Readmissions were highest for those with multiple, musculoskeletal (MSK), and central nervous system (CNS) anomalies, and lowest for abdominal wall defects. About half the children underwent surgeries and this proportion remained constant over the 3-year time. Sixty-two percent of patients received DME at discharge, with gastrostomy tubes (G-tubes) being the most common. G-tubes were still present in 75% of the patients at three years of age. ConclusionChildren with congenital anomalies are at risk for increased healthcare utilization during early childhood. Those with multiple anomalies, a genetic syndrome, MSK, and CNS anomalies and those discharged with DME are at highest risk while those with abdominal wall defects are at lowest risk. Provider awareness, high-quality discharge training, parent psychological support, greater assimilation of families in the NICU, and telehealth may be some strategies to better support these families.

A novel epidermal nevus syndrome associated with congenital pulmonary airway malformation

Epidermal nevus syndromes involve a group of disorders characterized by the type of epidermal nevus and are associated with an extracutaneous abnormality. Most epidermal nevus syndromes involve skin lesions associated with central nervous system, ocular or skeletal anomalies. We report a previously undescribed type of epidermal nevus syndrome in a preterm infant. The face and mouth were remarkable for large exophytic verrucous lesions and extensive pedunculated tumors involving the scalp. The infant was additionally affected by type 3 Congenital Pulmonary Airway Malformation (CPAM). Microscopic examination of the skin lesions revealed multiple layers of immature epithelium and the complete absence of adnexal structures. Chromosomal microarray analysis demonstrated no abnormalities. Family history was significant for numerous maternal relatives with multiple first and second trimester pregnancy losses. The distribution of lesions in this patient was characteristic of postzygotic mosaicism. We believe this case may represent a new histological subtype of epidermal nevi associated with a CPAM lesion. Future molecular research may indicate whether this disorder may be categorized as a distinct entity.

SAT139 Non-insulinoma Pancreatogenous Hypoglycemia Syndrome In A Patient With 1p36 Deletion Syndrome

Abstract Disclosure: E.D. Auckley: None. M.A. Arosemena: None. L. Philipson: None. Background: 1p36 deletion syndrome comprises a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. There has been no report of associated hypoglycemia with this syndrome. Nesidioblastosis, also known as non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), is understood as a rare condition defined by diffuse pancreatic hypertrophy with subsequent hyperinsulinemic hypoglycemia. Diagnosis requires serologic workup consistent with endogenous hyperinsulinemic hypoglycemia, intraarterial calcium stimulation positive for inappropriately elevated insulin secretion, and imaging studies without identified masses. Clinical Case: A 21-year-old female with 1p36 deletion syndrome (seizure disorder, cerebral palsy, vision loss and heart failure) was admitted to the hospital due to persistent falls. On admission vital signs were within normal limits, and physical exam revealed a thin non-verbal patient without significant other findings. During hospitalization and prolonged fasting periods of approximately 14-18 hours related to poor appetite she developed several episodes of hypoglycemia with serum glucose as low as 57 mg/dl. As patient was non-verbal at baseline, symptoms of hypoglycemia such as sweating, lightheadedness or shakiness were not confirmed. Even when she started to eat, hypoglycemic events continued to occur. Dextrose containing fluids (Dextrose 5% and later 10%) were added to try to maintain blood sugars within the normal range. Nevertheless, she continued to develop hypoglycemia. Endocrinology service was consulted and recommended to obtain a critical sample. A critical sample revealed serum glucose of 59 mg/dl, insulin level of 20.6 mcU/mL, proinsulin of 33 pmol/L, and beta-hydroxybutyrate of &amp;lt;0.10 mmol/L. Insulin antibodies was negative. Adrenal insufficiency was unlikely due to a normal 9 am cortisol level of 13.7 ug/dl. Due to the presence of hyperinsulinemic hypoglycemia further workup was conducted. A CT of the abdomen with a pancreatic protocol and 68Ga-DOTATATE PET/CT scan was negative for a pancreatic mass. Endoscopic ultrasound did not reveal a clear pancreatic mass either. This was followed by a calcium stimulation test which showed a two-fold increase in insulin levels in all 3 catheterized pancreatic territories. In the absence of a discrete mass, non-surgical management was recommended. For hypoglycemia management patient was started on octreotide injections with resolution of hypoglycemia. Prior to discharge she was switched to lanreotide and was discharged to continue monthly lanreotide injections. Conclusion: To our knowledge, this is the first case reported of NIPHS in a patient with a mutation in 1p36 deletion. Hyperinsulinism in the setting of diabetes has been reported in this syndrome1 but to our knowledge no cases of hypoglycemia with NIPHS have been reported. Presentation: Saturday, June 17, 2023

Agenesis of the corpus callosum: What to tell expecting parents?

Agenesis of the corpus callosum (ACC) is one of the most common brain malformations, with an incidence estimated to range from 0.5 to 70 in 10,000 among the general population. Prenatal diagnosis is made via ultrasound; however, fetal MRI is useful to confirm or exclude the presence of associated cerebral abnormalities-mostly cortical malformations-that may affect postnatal prognosis. When no additional central nervous system (CNS) or extra CNS anomalies are identified and no genetic cause is found, an isolated ACC is diagnosed. Overall, in cases of ACC, an underlying genetic cause can be identified in up to 12.5% with chromosomal microarray (CMA) and up to 47% with whole exome sequencing (WES). In cases where ACC is the only anomaly detected, the yield of WES is 30%. Postnatal outcomes are variable and depend on whether the condition is isolated or not. In truly isolated ACC, outcomes range from normal in 65% of cases through mild to severe neurodevelopmental impairments in 35% of cases. An interdisciplinary team of medical experts is key in guiding parents toward informed decision-making in pregnancies complicated by ACC. Considering current and expected advancements in genetic testing and imaging technologies in upcoming years, we herein summarize current recommendations for the management and prenatal counseling of expecting parents of fetuses with ACC. Our review pertains primarily to expecting parents of fetuses with complete ACC.

Effectiveness and Safety of Prenatal Valacyclovir for Congenital Cytomegalovirus Infection: Systematic Review and Meta-analysis

ABSTRACT One of the most common causes of infection-related fetal malformations is congenital cytomegalovirus (CMV), which affects approximately 0.5% to 2% of newborns. Several approaches have been investigated for screening, prevention, and treatment; one drug that shows activity against CMV is valacyclovir, and prenatal administration of this drug has been investigated in the context of preventing fetal disorders due to CMV. Although studies and clinical trials have been done regarding the safety and effectiveness of valacyclovir, clinical attitudes regarding universal CMV screening and prenatal valacyclovir treatment have yet to change. This article is a systematic review and meta-analysis of the safety and effectiveness of prenatal valacyclovir in CMV-infected pregnancies. Inclusion criteria included pregnancies with CMV infection diagnosed through serology, with a primary outcome of incidence of congenital CMV confirmed by polymerase chain reaction from amniocentesis. Secondary outcomes included symptomatic infection (rash, jaundice, microcephaly, seizures, hepatosplenomegaly, hearing loss, visual loss, retinitis, and central nervous system anomalies), asymptomatic infection, perinatal death, pregnancy termination, fetal anomaly, or severe symptoms. Adverse events related to the administration of valacyclovir were also recorded. Because relatively few studies were available for inclusion, the authors were unable to assess publication bias, but other risk of bias was assessed using standard tools. Final analysis included 8 studies and 620 pregnant women with CMV in 2 randomized controlled trials and 6 observational studies. One randomized controlled trial focused on valacyclovir treatment for CMV infection acquired in early pregnancy, and the other assessed valacyclovir treatment between 34 and 38 weeks' gestation to reduce risk of CMV within 1 year of delivery. The latter of the 2 studies was not included in pooled data synthesis because of inclusion criteria differences. Three studies focused on valacyclovir treatment for confirmed maternal CMV infection; pooled data analysis showed that valacyclovir-treated pregnancies had lower risk of congenital CMV (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.21–0.64; P &lt; 0.001). When contracted in the first trimester, risk of vertical transmission was lower in those who were treated with valacyclovir (OR, 0.34; 95% CI, 0.15–0.74; P = 0.001); however, there was no effect observed in those with CMV in the periconceptual period. Analysis additionally showed that prenatal valacyclovir treatment was more likely to result in asymptomatic children (OR, 2.98; 95% CI, 1.18–7.55; P = 0.021), but no other significant perinatal differences were observed. These results show that treatment of CMV with prenatal valacyclovir reduces the risk of congenital CMV and its associated complications. Limitations of this analysis include the heterogeneity of inclusion and measurement criteria, as well as small samples to assess perinatal outcomes. Risks associated with the drug were small, and adverse events resolved after patients discontinued valacyclovir. The findings are consistent with previous research showing the benefit of valacyclovir. Further research should assess perinatal outcomes associated with valacyclovir treatment, as well as the role of valacyclovir in secondary versus primary infection. In particular, larger randomized controlled trials should be implemented to determine the association of valacyclovir treatment with the risk of fetal structural anomalies, symptomatic infection, and neurocognitive impairment.

A method framework of automatic localization and quantitative segmentation for the cavum septum pellucidum complex and the cerebellar vermis in fetal brain ultrasound images.

Early detection of central nervous system (CNS) anomalies in human embryos through prenatal screening is crucial for timely intervention and improved patient outcomes. Fetal brain mid-sagittal ultrasound images (FBMUIs) play a pivotal role as a diagnostic tool for detecting structural abnormalities. However, the automatic localization and quantitative segmentation of complex anatomical structures such as the corpus callosum-cavum septum pellucidum complex (CCC) and cerebellar vermis (CV) in FBMUIs present significant challenges. To address this issue, we propose an integrated framework that combines anatomical knowledge with computer vision techniques. Our framework comprises four steps: (I) generation of average templates for CCC and CV local images using a variational autoencoder (VAE); (II) localizing the CCC by using the "Initial Localization-Accurate Localization-Result Detection" strategy, followed by segmenting it based on morphological characteristics using the "Initial Contour Fitting-Contour Iteration" strategy; (III) applying a similar strategy as CCC localization and CV segmentation; and (IV) leveraging spatial and morphological characteristics to achieve accurate localization and segmentation. Our CCC and CV localization and segmentation methods were validated by using 140 FBMUIs from various perspectives. The accuracy and effectiveness of our approach were demonstrated through data statistics and comparative analysis. Currently, clinical trials are being conducted on our method at Shengjing Hospital of China Medical University. Our proposed integrated framework presents a novel solution for the automatic localization and quantitative segmentation of the CCC and CV in FBMUIs. It shows promise for early diagnosis of CNS anomalies in human embryos, offering significant clinical implications.