Central Nervous System Defects Research Articles

Non-cardiac birth defects and long-term risk of cardiovascular hospitalisation

BackgroundPatients with heart defects are at risk of developing cardiovascular disease. Our objective was to determine if non-cardiac birth defects are associated with the risk of cardiovascular hospitalisation.MethodsWe conducted a...

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

Frequency of major congenital malformations in neonates born in three tertiary care hospitals of Pakistan.

Objective: To assess the frequency of major congenital anomalies in newborns delivered in three different hospitals of Pakistan. Study Design: Cross Sectional study. Setting: Department of Pediatrics Hameed Latif Teaching Hospital, Lahore, Ittefaq Hospital Lahore and HITEC-IMS Taxilla. Period: Jan 2023 to November 2023. Methods: 205 neonates who met the inclusion criteria were included in the study from labour room of Hameed Latif Teaching Hospital Lahore, Ittefaq Hospital Lahore and HITEC-IMS Taxilla. Informed consent was obtained from parents. Demographic variables (name of mother, gender, birthweight and gestational age at birth) were recorded. Then neonates were admitted in NICU and evaluated for presence of congenital malformations including cardiovascular system defects, limbs anomalies, genitourinary system, central nervous system and chromosomal anomalies. All data was entered in specially designed performa. Results: We found that overall gestational age was greater than 32 weeks with mean age of 37.190±2.00 weeks. Mean birth weight was 2.938±0.31 Kg. Frequency and %age of patients according to gender was 60% males and 40% females. Major congenital malformation was seen in 2.9% patients. Among infants with major congenital malformations, cardiovascular system defects were seen in 33.3% infants, limb anomalies 16.7%, genitourinary system 16.7% and central nervous system defects were 33.3%. Parents of 67.7% of cases were cousins. It was observed that only 32.3% of the mothers had taken the recommended daily dose of folic acid in antenatal period. Conclusion: Central nervous system and cardiovascular system defects were the most prominent anomalies detected. Prenatal diagnosis may be helpful in decreasing mortality by offering early termination.

Teratogenicity and Reactive Oxygen Species after transient embryonic hypoxia: Experimental and clinical evidence with focus on drugs causing failed abortion in humans

Teratogenicity and Reactive Oxygen Species after transient embryonic hypoxia: Experimental and clinical evidence with focus on drugs with human abortive potential.Reactive Oxygen Species (ROS) can be harmful to embryonic tissues. The adverse embryonic effects are dependent on the severity and duration of the hypoxic event and when during organongenesis hypoxia occurs. The vascular endothelium of recently formed arteries in the embryo is highly susceptible to ROS damage. Endothelial damage results in vascular disruption, hemorrhage and maldevelopment of organs, which normally should have been supplied by the artery. ROS can also induce irregular heart rhythm in the embryo resulting in alterations in blood flow and pressure from when the tubular heart starts beating. Such alterations in blood flow and pressure during cardiogenesis can result in a variety of cardiovascular defects, for example transpositions and ventricular septal defects. One aim of this article is to review and compare the pattern of malformations produced by transient embryonic hypoxia of various origins in animal studies with malformations associated with transient embryonic hypoxia in human pregnancy due to a failed abortion process. The results show that transient hypoxia and compounds with potential to cause failed abortion in humans, such as misoprostol and hormone pregnancy tests (HPTs) like Primodos, have been associated with a similar spectrum of teratogenicity. The spectrum includes limb reduction-, cardiovascular- and central nervous system defects. The hypoxia-ROS related teratogenicity of misoprostol and HPTs, is likely to be secondary to uterine contractions and compression of uterinoplacental/embryonic vessels during organogenesis.

Correlation between contractile properties of quadriceps muscle and functional performance in runners with patellofemoral pain syndrome

Background: Long distance runners commonly complain from patellofemoral pain syndrome (PFPS) that limits their performance and return to sport. Abnormal neuromuscular control of the quadriceps has been demonstrated to cause patellar mal-tracking and hence PFPS. Changes in muscle morphology and neural activity have a role in neuromuscular changes, a key contributor to either primary or secondary injuries. Poor landing mechanics, impaired postural control, as well as changed peripheral muscle activation are all clinical manifestations of neuromuscular control deficiencies caused by central nervous system defects that have a deleterious effect on the contractile characteristics of skeletal muscle. Objectives: The purpose of this study was to investigate the correlation between contractile properties of quadriceps muscle and functional performance in long distance runners with PFPS. Study design: Cross-sectional study. Methods: Thirty runners were recruited form multiple Egyptian clubs. Tensiomyography (TMG) Parameters were assessed regarding Contraction time (Tc), Maximal displacement (Dm), Sustain time (Ts), Relaxion time (Tr) and Delay time (Td) in Rectus femoris (RF), Vastus medialis (VM) and Vastus lateralis (VL) separately and correlated with functional performance; number of repetitions in 30 seconds for anteromedial lunge test, balance and reach test and step-down test. Outcome measures: Functional performance was measured using functional performance tests; anteromedial lunge test, balance and reach test and step-down test. Results: It was found that VM Tc, VL Dm, were moderately positively correlated with anteromedial lunge (r = 0.583, 0.404, p<0.05) respectively. In contrast, RF Tr was negatively correlated with anteromedial lunge (-0.364, p<0.05); VM Ts,Tr,Dm; VL Td were moderately negatively correlated with balance and reach (r = --0.577, -0.388, 0.655 and -0.385, respectively, p<0.05). In contrast, VL Tc was moderately positively correlated with step-down (r = 0.424, p = 0.019). Conclusion: All contractile properties of quadriceps muscle are significantly correlated with functional performance in long distance runners with PFPS. Future studies should address these properties, using proper rehabilitation strategies, to improve performance of runners with PFPS.

FRI387 Reproductive Capacity Of Znhit3 Knockout Mouse Model

Abstract Disclosure: D. Kira: None. Z.A. Hawkins: None. L.P. Chorich: None. S. Brakta: None. L. Gan: None. L.C. Layman: None. Introduction: Zinc finger, HIT domain containing 3 (ZNHIT3), also known as thyroid hormone receptor-interacting protein 3 (TRIP-3), is a 155 amino acid protein with an N-terminus Zinc finger HIT domain (11-42a.a) that is involved in pre-ribosomal RNA processing. It also has a C-terminus short conserved LxxLL binding motif that interacts with the ligand binding domain of the thyroid receptor in the presence of thyroid hormone as a co-activator associated with hepatocyte nuclear factor-4α (HNF-4α). ZNHIT3 is localized to the cytoplasm and the nucleus. Biallelic ZNHIT3 pathogenic variants in the N-terminus have been identified in persons with Progressive encephalopathy with Edema, Hypsarrhythmia, and Optic atrophy (PEHO) syndrome, a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Heterozygous pathogenic variants in ZNHIT3 affecting the C-terminus have been demonstrated in individuals with Mayer-Rokitansky-Küster-Hauser (MRKH). MRKH consists of the congenital absence of the uterus and vagina, either as isolated Mullerian aplasia (type 1) or associated with renal, skeletal, cardiac, and auditory anomalies (type 2). Previous studies of animal models utilizing morpholino injection-induced knockdown and CRISPR editing of znhit3 in zebrafish both showed cerebellar defects and microcephaly. We are not aware of a mouse model of Znhit3.Hypothesis: We hypothesize that the Znhit3 knockout (KO) mouse will demonstrate reproductive abnormalities and an MRKH-related phenotype. Methods: Heterozygous Znhit3 (Znhit3+/-) KO mice were generated by CRISPR. A 1 base deletion was introduced in exon 2, creating a frameshift and a stop codon in exon 3, which leads to a truncated protein. We then crossed male and female Znhit3+/- mice and Znhit3+/- and wild-type Znhit3+/+ (WT) mice. Pups' genotypes were confirmed with DNA sequencing of tail samples. Pups were weighed weekly from age 3 weeks to 16 weeks. Results: Mating 17 pairs of Znhit3+/- mice resulted in a total of 73 pups born, of which 50 were Znhit3+/- and, 23 were WT with a ratio of almost 2:1. No homozygous Znhit3 (Znhit3-/-) KO pups were born. There was no significant difference in weights between Znhit3+/- and WT pups. Conclusion: Heterozygous Znhit3+/- animals appeared to be phenotypically normal with similar weights to WT. However, the Hardy-Weinberg equilibrium (1 homozygous wild-type: 2 heterozygous: 1 homozygous variant) was disrupted, as no Znhit3−/− homozygotes were born, suggesting embryonic lethality. It is possible that central nervous system, cardiac, and/or renal defects could be responsible for this lethality, which will be studied in embryos at E18.5, 15.5, and 12.5. A detailed phenotypic characterization will be performed with regard to reproductive function and MRKH-related organ development. Presentation: Friday, June 16, 2023

Treatment with quercetin increases Nrf2 expression and neuronal differentiation of sub ventricular zone derived neural progenitor stem cells in adult rats.

The presence of neural precursor stem cells (NPSCs) in some parts of the adult brain and the potency of these types of cells with a therapeutic viewpoint, has opened up a new approach for the treatment and recovery of the defects of central nervous system (CNS). Quercetin, as an herbal flavonoid, has been extensively investigated and shown to have numerous restoratives, inhibitory, and protective effects on some cell-lines and disorders. The purpose of this study is to simultaneously investigate the effect of quercetin on the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) gene and the effect on the proliferation and differentiation of NPSCs derived from the subventricular zone (SVZ) of the brain of adult rats. The cell obtained from SVZ cultured for one week and treated with quercetin at the concentrations of 1, 5, and 15μM to evaluate the Nrf2 expression, proliferation and differentiation of NSCs after one week. Cellular and genetic results was performed by RT-PCR, MTT assay test, quantification of images with Image-J and counting. The results indicated that the quercetin increases expression of Nrf2 at concentration above 5μM. Also differentiation and proliferation rate of NSCs is affected by various concentrations of quercetin in a dose-dependent manner. These findings confirmed the dose-dependent effect of quercetin on proliferation and differentiation of cell. In addition, quercetin increased the expression of Nrf2 gene. By combining these two effects of quercetin, this substance can be considered an effective compound in the treatment of degenerative defects in CNS.

Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models.

Protein synthesis is a fundamental process that underpins almost every aspect of cellular functioning. Intriguingly, despite their common function, recessive mutations in aminoacyl-tRNA synthetases (ARSs), the family of enzymes that pair tRNA molecules with amino acids prior to translation on the ribosome, cause a diverse range of multi-system disorders that affect specific groups of tissues. Neurological development is impaired in most ARS-associated disorders. In addition to central nervous system defects, diseases caused by recessive mutations in cytosolic ARSs commonly affect the liver and lungs. Patients with biallelic mutations in mitochondrial ARSs often present with encephalopathies, with variable involvement of peripheral systems. Many of these disorders cause severe disability, and as understanding of their pathogenesis is currently limited, there are no effective treatments available. To address this, accurate in vivo models for most of the recessive ARS diseases are urgently needed. Here, we discuss approaches that have been taken to model recessive ARS diseases in vivo, highlighting some of the challenges that have arisen in this process, as well as key results obtained from these models. Further development and refinement of animal models is essential to facilitate a better understanding of the pathophysiology underlying recessive ARS diseases, and ultimately to enable development and testing of effective therapies.

Scalp Tumor and Hydroureteronephrosis in Patients with Nephronophthisis and Homozygous NPHP1 Deletion.

Homozygous deletion of NPHP1 can lead to isolated nephronophthisis (NPHP) and syndromic disorders. However, the phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1 has not been reported. Clinical data, laboratory results, and genetic testing of 4 NPHP patients were collected. Examination of their eyes, heart, and urinary tract and of their hepatobiliary, skeletal, and central nervous systems was evaluated. Isolated NPHP was observed in 1 case, and syndromic disorders were observed in the other 3 patients. Their syndromic disorders showed NPHP combined with central nervous system defects, eye involvement, scalp tumor, arachnoid cyst, or hydroureteronephrosis. Large homozygous deletions covering the whole NPHP1 gene locus were identified in all 4 patients. We report a novel phenotype of scalp tumor and hydroureteronephrosis in NPHP patients with homozygous deletion of NPHP1, paving an avenue for further research on NPHP1-associated deformity in the skin and the urinary system.

Prenatal Diagnoses of Congenital CNS Anomalies

Background: Congenital anomalies affecting the central nervous system are among the most prevalent. The most common central nervous system anomalies are neural tube defects, which affect roughly 1-2 of every 1000 newborns. Objectives: We detect the accuracy of ultrasound to diagnose CNS abnormalities. Patients and Methods: Descriptive cross-sectional study on 567 patients coming for antenatal care at Sohag Governorate undergoing mid anatomical scan between September 2021 and December 2022. After getting approval from the ethical committee at Sohag University and written consent from each woman. Clinical or post-natal neuroimaging using computed tomography or magnetic resonance imaging validated the prenatal diagnosis in situations where pregnancy progressed and the fetus survived. The total number of miscarriages, stillbirths, and infant deaths was recorded. Results: Diagnostic accuracy of ultrasound in diagnosis of congenital neurological anomalies: 2D&3D US had 100% sensitivity and 100% specificity with positive predictive value 100% and negative predictive value 100% in all parameters. Conclusions: Based on these findings, we can say that ultrasonography is useful for detecting and diagnosing some defects of the fetal central nervous system.

Initial study on quantitative electroencephalographic analysis of bioelectrical activity of the brain of children with fetal alcohol spectrum disorders (FASD) without epilepsy

Fetal alcohol spectrum disorders (FASD) are spectrum of neurodevelopmental conditions associated with prenatal alcohol exposure. The FASD manifests mostly with facial dysmorphism, prenatal and postnatal growth retardation, and selected birth defects (including central nervous system defects). Unrecognized and untreated FASD leads to severe disability in adulthood. The diagnosis of FASD is based on clinical criteria and neither biomarkers nor imaging tests can be used in order to confirm the diagnosis. The quantitative electroencephalography (QEEG) is a type of EEG analysis, which involves the use of mathematical algorithms, and which has brought new possibilities of EEG signal evaluation, among the other things—the analysis of a specific frequency band. The main objective of this study was to identify characteristic patterns in QEEG among individuals affected with FASD. This study was of a pilot prospective study character with experimental group consisting of patients with newly diagnosed FASD and of the control group consisting of children with gastroenterological issues. The EEG recordings of both groups were obtained, than analyzed using a commercial QEEG module. As a results we were able to establish the dominance of the alpha rhythm over the beta rhythm in FASD-participants compared to those from the control group, mostly in frontal and temporal regions. Second important finding is an increased theta/beta ratio among patients with FASD. These findings are consistent with the current knowledge on the pathological processes resulting from the prenatal alcohol exposure. The obtained results and conclusions were promising, however, further research is necessary (and planned) in order to validate the use of QEEG tools in FASD diagnostics.

Risk of birth defects in children conceived with assisted reproductive technology: A meta-analysis.

Although assisted reproductive technology (ART) is extensively used in couples with fertility problems, the risk of birth defects among infants conceived with ART is still a concern. Therefore, to more accurately assess the risk of birth defects after ART treatment, we performed a meta-analysis of all available cohort studies relating to birth defects among infants conceived with ART. We used an established strategy to search the databases of PUBMED, EMBASE, COCHRANE, WEB OF SCIENCE, CNKI, CBM and VIP for studies published between 2008 and 2020. Subgroup analyses and sensitivity analyses were used to examine sources of heterogeneity. Pooled adjusted odds ratios (ORs) were calculated using a fixed effects model. RevMan5.3 was used to draw a forest plot, and Stata14.0 was used to test for publication bias. We included 14 cohort studies from different countries. The infants conceived with ART had a 1.22-fold higher likelihood of birth defects than children born after natural pregnancy(OR = 1.22, 95% CI [1.17, 1.28], P < .05). The prevalence of birth defects after ART treatment was higher in singleton births than in multiple births. In a meta-analysis of data from 6 studies, we found associations between ART and birth defects related to specifics organs: cardiovascular defects, OR = 1.51, 95% CI [1.34-1.69], P < .05; musculoskeletal defects, OR = 1.09, 95% CI [1.03-1.15], P < .05; urogenital defects, OR = 1.24, 95% CI [1.11-1.38], P < .05; central nervous system defects, OR = 1.33, 95% CI [1.14-1.55], P < .05; and orofacial defects, OR = 1.45, 95% CI [1.15-1.83], P < .05. ART treatment does present an increased risk of birth defects. The prevalence of birth defects after ART treatment is lower in multiple births than in singleton births. Further research is required to examine the risks for birth defects after ART treatment.

Edward’s Syndrome-A Case Report

Edward’s syndrome is commonly known as the trisomy 18 syndrome. It is a devastating genetic disorder that can be characterized by multiple congenital anomalies. About 50% babies with this syndrome do not survive beyond one week of age and approximately 95% does not survive past the first year of life. The feature of Edward’s Syndrome involves in craniofacial, skeletal, cardiovascular, central nervous system and genitourinary malformations. The mortality rate among infants with trisomy 18 is high as a result of cardiac and renal malformations, feeding difficulty, sepsis and central nervous system defects. Here we report a neonate with Edward’s syndrome.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (3) : 178-181

Relative prevalence and outcome of fetal posterior fossa abnormality.

To find out the relative incidence and outcome of posterior fossa abnormality (PFA) in terms of survival at birth until 2 years of age. We conducted a prospective study; all fetuses diagnosed with posterior fossa abnormality were followed-up. The outcome was observed with respect to survival, the presence of associated anomalies, the existence of developmental delay after a telephonic interview. Out of 2703 children with congenital anomalies, 921 (34.1%) had a central nervous system defect;76 cases of PFA were fully followed. Dandy-Walker malformation (DWM) was present in 50% (38/76), mega cisterna magna 18.4% (14/76), Blake pouch cyst 13.2% (10/76), vermian hypoplasia (VH) 13.2% (10/76) and arachnoid cyst 5.2% (4/76). The diagnosis was possible before 20 weeks in only 12 (15.8%) cases.The mean gestational age at delivery was 34.7 ± 6.7 weeks. Associated anomalies were seen in 35/76 (46.1%) cases. A total of 35/76 (46.1%) survived after 2 years; there was developmental delay in 9.2% of cases. There is a large variation in the outcome of PFA depending upon the type of anomaly. Associated anomalies are common in VH and DWM, making their prognosis worse.

Features of gestational period and perinatal outcomes in women with insulin resistance

Aim. To study the course of pregnancy and perinatal outcomes in women with insulin resistance. Material and methods. A retrospective and prospective study of 102 women and their newborns who were born in the State Institution “Research Institute of Obstetrics, Gynecology, and Perinatology” for the period 2017-2019 was conducted. All pregnant women were divided into 3 groups according to the level of insulin resistance index (NOMA index). Group I - 42 pregnant women with developmental risk factors for diabetes with an insulin resistance index above 2.84. Group II consisted of 30 subjects with a NOMA index below 2.21, and Group III (n = 30) consisted of healthy pregnant women with a physiological course of pregnancy and labor. Results. Newborns born to women with a NOMA index above 2.84 (pathological insulin resistance) have a high incidence of perinatal complications: central nervous system defects, various degrees of asphyxia, hypotrophy, and immaturity. Conclusion. Insulin resistance in general affects pregnancy and has a negative impact on the course of pregnancy, causing a high incidence of complications such as threatened miscarriage, preeclampsia, chronic placental insufficiency and affecting perinatal outcomes.

Birth Defects among Newborns in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

The incidence of birth defects is 2-3% in the general population but it is increasing. An estimated 303,000 newborns die within 4 weeks of birth every year, worldwide, due to congenital anomalies. The objective of this study was to find out the prevalence of birth defects among newborns in a tertiary care centre. A descriptive cross-sectional study was done in the Department of Obstetrics and Gynaecology and the Department of Paediatrics from 15 June 2016 and 14 June 2019. Ethical approval was obtained from the Institutional Review Committee (Reference number: 142/077/078-IRC). Data of newborns were collected from the hospital records. Convenience sampling method was used. Point estimate and 99% Confidence Interval were calculated. Among 32,695 newborns, birth defects were seen in 169 (0.51%) (0.41-0.61, 99% Confidence Interval). The most common birth defect was musculoskeletal defects seen in 60 (35.50%) newborns followed by central nervous system defect seen in 30 (17.75%) newborns. The prevalence of birth defects among newborns was lower than in other studies done in a similar setting. birth defect; congenital malformation; prevalence.

Risk of birth defects by pregestational type 1 or type 2 diabetes: National Birth Defects Prevention Study, 1997-2011.

Previous studies found consistent associations between pregestational diabetes and birth defects. Given the different biological mechanisms for type 1 (PGD1) and type 2 (PGD2) diabetes, we used National Birth Defects Prevention Study (NBDPS) data to estimate associations by diabetes type. The NBDPS was a study of major birth defects that included pregnancies with estimated delivery dates from October 1997 to December 2011. We compared self-reported PGD1 and PGD2 for 29,024 birth defect cases and 10,898 live-born controls. For case groups with ≥5 exposed cases, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between specific defects and each diabetes type. We calculated crude ORs (cORs) and 95% CIs with Firth's penalized likelihood for case groups with 3-4 exposed cases. Overall, 252 (0.9%) cases and 24 (0.2%) control mothers reported PGD1, and 357 (1.2%) cases and 34 (0.3%) control mothers reported PGD2. PGD1 was associated with 22/26 defects examined and PGD2 was associated with 29/39 defects examined. Adjusted ORs ranged from 1.6 to 70.4 for PGD1 and from 1.6 to 59.9 for PGD2. We observed the strongest aORs for sacral agenesis (PGD1: 70.4, 32.3-147; PGD2: 59.9, 25.4-135). For both PGD1 and PGD2, we observed elevated aORs in every body system we evaluated, including central nervous system, orofacial, eye, genitourinary, gastrointestinal, musculoskeletal, and cardiac defects. We observed positive associations between both PGD1 and PGD2 and birth defects across multiple body systems. Future studies should focus on the role of glycemic control in birth defect risk to inform prevention efforts.

Accuracy and clinical utility of standard postmortem radiological imaging after early second trimester termination of pregnancy

ObjectiveThis study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at <23 weeks’ gestation for congenital fetal malformations in comparison to autopsy. Study designThis a prospective single-center study on fetuses underwent termination of pregnancy for fetal defects. Overall concordance between any radiological exam and autopsy was evaluated. For postmortem MRI only, the following subgroups were analyzed: 1) total agreement; 2) agreement for main findings; 3) agreement for main findings but major relevant additional findings at autopsy; 4) total disagreement. Results174 cases were collected. The overall concordance with autopsy for main findings was 71% (115/163) for postmortem MRI and 99% (173/174) for prenatal ultrasound (US). Postmortem MRI detection rate was high for central nervous system (CNS) defects (98%), gastrointestinal, genitourinary and respiratory defects (100%), while it was poor for cardiovascular and musculoskeletal defects (25% and 42%, respectively). For musculoskeletal abnormalities, the performance of postmortem XR and postmortem CT exams improved the detection rate from 42% for postmortem MRI alone to 92%. ConclusionsPostmortem MRI has a good overall concordance for fetal defects after termination of pregnancy performed at <23 weeks. Along with autopsy, postmortem MRI may be offered for all cases of CNS defects in order to prevent inconclusive exams due to autolysis of the brain tissue, while postmortem CT and postmortem XR are indicated for musculoskeletal defects. In the presence of multiple abnormalities or cardiac defects the couple should be counseled on the poor performance of radiological investigations.

Benzoresorcinol induces developmental neurotoxicity and injures exploratory, learning and memorizing abilities in zebrafish

Benzophenones (BPs) are a class of UV absorber commonly used in skin care products like sunscreens. With its wide range of application, its environmental and human hazards have received much attention in recent days. Previous studies on the toxicity of BPs mainly focused on its endocrine-disrupting effects, but there are limited studies on its neurodevelopment and neurotoxicity. Herein, using the zebrafish model we studied the neurodevelopmental- and neuro-toxicity of benzophenone 1 (BP1) (0.8, 1.0, 1.2, 1.6, and 2.4 μg/mL). As a result, BP1 led to an increase of embryo mortality, a decrease in hatching rate, and an increase in the rate of developmental abnormalities in a concentration-dependent manner. BP1 also caused developmental defects in the central nervous system (CNS) and dopaminergic (DA) neurons. Accordingly, BP1 injured larval zebrafish general locomotion and response to stimuli in light/dark challenge. In adult zebrafish, BP1 exposure (1, 10, 100, 1000 μg/L) caused inhibition of learning and memory abilities in the T-maze tests, and inhibited exploratory behavior and activity in the novel tank diving tests. Further, transcription levels of genes related to neurotoxicity, neurodevelopment, and anxiety revealed that BP1 may affect the development and function of the myelin sheath, inducing structural and functional defects of CNS, manifested as abnormal behaviors such as anxiety. Hence, the current study revealed the neurodevelopmental toxicity and neurotoxicity of BP1, expanded our knowledge about the toxic effects of BP1 on organisms, posing a possible threat to the environment and human health.

Retrospective clinical evaluation of indications for termination of pregnancies due to fetal anomaly

Objective:To assess the indications for termination of pregnancy (TOP) in pregnant patients who were followed up with suspicion of fetal anomaly in a Turkish tertiary referral center.Material and Methods:This retrospective study was carried out in patients who were followed up with suspicion of fetal anomaly between May 2016 and May 2019 at the Perinatology Clinic of Obstetrics and Gynecology Department in Pamukkale University Hospital, which is a tertiary hospital in Denizli province in Turkey. Women were divided into two depending on gestational period: group 1 ≤22 weeks; and group 2 (>23 weeks of gestation).Results:Four hundred and seventeen pregnant women were evaluated and TOP was performed at a mean gestational age of 27.7±6.3 weeks. There were 308 (73.8%) women in group 1 and 109 (26.2%) in group 2. The decision to terminate pregnancy was due to fetal anomaly in 117 (28.1%). The majority of termination pregnancies in group 2 were performed because of multiple malformations and/or central nervous system defects. All chromosomal diseases were detected in group 1.Conclusion:With a good perinatal screening program, fetal anomalies can be diagnosed early. Therefore, early TOP is possible. Thus, pregnancy termination can be made before reaching the life limit.