Fetal Central Nervous System Malformations Research Articles

Pathogenic/likely pathogenic copy number variations and regions of homozygosity in fetal central nervous system malformations.

To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations. A cohort of 539 fetuses with CNS malformations diagnosed by ultrasound/MRI was retrospectively analyzed between January 2016 and December 2019. All fetuses were analyzed by chromosomal microarray analysis (CMA). Three cases with ROHs detected by CMA were subjected to whole-exome sequencing (WES). The fetuses were divided into two groups according to whether they had other structural abnormalities. The CNS phenotypes of the two groups were further classified as simple (one type) or complicated (≥ 2 types). (1) A total of 35 cases with P/LP CNVs were found. The incidence of P/LP CNVs was higher in the extra-CNS group [18.00% (9/50)] than in the isolated group [5.32% (26/489)] (P < 0.01), while there was no significant difference between the simpletype and complicated-type groups. (2) In the simple-type group, the three most common P/LP CNV phenotypes were holoprosencephaly, Dandy-Walker syndrome, and exencephaly. There were no P/LP CNVs associated with anencephaly, microcephaly, arachnoid cysts, ependymal cysts, or intracranial hemorrhage. (3) Only four cases with ROHs were found, and there were no cases of uniparental disomy or autosomal diseases. The P/LP CNV detection rates varied significantly among the different phenotypes of CNS malformations, although simple CNS abnormalities may also be associated with genetic abnormalities.

Potential Neurologic Side Effects of Oral Isotretinoin: A Case of Peripheral Neuropathy

Oral isotretinoin is a well-known, effective medication used in the treatment of severe cystic acne. While efficacious, the potential side effects of isotretinoin are often discussed and may cause concern for patients. Although most side effects of this medication are mild, other more concerning adverse effects have been reported. Of note, isotretinoin has the potential to affect the central nervous system (CNS), causing headaches, pseudotumor cerebri, and fetal CNS malformations. In contrast, the effects on the peripheral nervous system are not well documented. The objective of this case report is to present an instance of oral isotretinoin leading to foot drop in an adolescent patient.

Accuracy of ultrasonography in diagnosis of fetal central nervous system malformation

BACKGROUNDPrenatal examination is an important measure for the screening and diagnosis of fetal malformations.AIMTo investigate the accuracy of ultrasonography in the diagnosis of fetal central nervous system (CNS) malformations.METHODSOne hundred and thirteen pregnant women suspected of having fetal CNS malformations were examined at our hospital from December 2018 to October 2020 using two-dimensional ultrasonography and three-dimensional ultrasonography, respectively. RESULTSAccording to the pathological results, there were 79 cases of CNS malformations and 34 cases of non-CNS malformations among the 113 pregnant women suspected of having fetal CNS malformation. Fifty-one cases of CNS malformation and 26 cases of non-CNS malformation were detected by two-dimensional ultrasonography, and 73 cases of CNS malformation and 30 cases of non-CNS malformation were detected by three-dimensional ultrasonography. The diagnostic sensitivity (92.41%) and accuracy (91.15%) of three-dimensional ultrasonography were higher than those of two-dimensional ultrasonography (64.56% and 68.14%, respectively) (P = 0.000). The specificity of three-dimensional ultrasonography (88.24%) was higher than that of two-dimensional ultrasonography (76.47%); however, the difference was not significant (P = 0.203). CONCLUSIONThree-dimensional ultrasonography has high application value in the diagnosis of fetal CNS malformations. In addition, the image quality is clear, and the diagnostic sensitivity and accuracy are high.

Brain views that benefit from three-dimensional ultrasound.

Fetal central nervous system malformations are among the most common congenital anomalies. Whereas simple axial views are sufficient for basic fetal brain examination, other important views are essential for a more detailed examination, which are sometimes challenging to obtain. Three-dimensional ultrasound can be helpful in obtaining standardized and reproducible images of many difficult fetal brain views. The aim of the present review is to explore the most recent evidence on the utility and technique of three-dimensional ultrasound in the examination of the fetal brain, with particular emphasis on the brain views that benefit from three-dimensional ultrasound. The article describes the various techniques of acquisition and analyses of three-dimensional ultrasound volumes of the fetal brain and their usefulness in the assessment of normal and abnormal fetal brain anatomy. Three-dimensional ultrasound has also permitted the application of many new technologies, such as artificial intelligence and deep machine learning. Recently, thanks to high-quality three-dimensional ultrasound, fetal cortical development can be assessed quantitatively and reliably. Three dimensional ultrasound can help as a complementary tool to two-dimensional ultrasound in the assessment of the fetal brain development and malformations. In addition, it paves the way for the application of promising technologies in the evaluation of fetal brain. A video summarizing the findings of the article. The video illustrates the various approaches and techniques applied for the examination of the fetal brain using three-dimensional ultrasound. Furthermore, the advantages and future perspectives of the application of three-dimensional ultrasound in the examination of the fetal brain are discussed, http://links.lww.com/COOG/A74.

Application of Ultrasonic Doppler Technology Based on Wavelet Threshold Denoising Algorithm in Fetal Heart Rate and Central Nervous System Malformation Detection

This paper discusses the clinical value of standardized early pregnancy ultrasound structure screening in the diagnosis of fetal central nervous system (CNS) malformations. In this paper, 6902 cases (8336 fetuses) of 11～13+ 6 weeks of gestation (5468 cases of singleton pregnancy and 1434 cases of twin pregnancy) underwent standardized early pregnancy ultrasound structure screening. While tracking the pregnancy process and clinical outcome, we found that 13 cases of CNS malformations (10 cases of single pregnancy, 3 cases of twin pregnancy) were detected by prenatal ultrasound in 6902 cases (8336 fetuses) 11～13+ 6 weeks of gestation including 5 cases of exposed brain malformations. There were 4 cases of children with cerebral sickle disease, 2 cases of forebrain without splitting, 1 case of meningocele, and 1 case of open spina bifida. There were 4 cases with other structural abnormalities and 3 cases with abnormal karyotype. Follow-up results of 13 fetuses indicated that except for 3 cases of twin malformed fetuses who continued to be pregnant after selective reduction, ultrasound results of the remaining fetuses were consistent with autopsy results after the induction of labor. For this reason, it can be concluded that standardized ultrasound structural screening during early pregnancy can detect fetal CNS malformations early and has important clinical value in reducing the birth rate of malformed fetuses and guiding obstetric treatment.

Termination of pregnancy following prenatally diagnosed central nervous system malformations.

To analyze fetal cerebral malformations with late termination of pregnancy (TOP) and to evaluate the rate of cases that could have been detected earlier using international recommended requirements of sonographic examination of the fetal central nervous system (CNS). Cases of singleton pregnancies above 18 + 0weeks of gestation ending in late TOP due to fetal CNS malformations between 2002 and 2011 were retrospectively reviewed. The cases were divided into isolated and non-isolated cerebral malformations. Prevalence and timing of TOP were assessed relative to the identified malformations. During this 10-year period, 212 (20.8%) out of 1017 late TOPs were performed in pregnancies with fetal cerebral malformations. 59 cases were excluded because of chromosomal anomalies. 86 (56.2%) of the remaining 153 cases were isolated cerebral malformations while 67 (43.8%) were non-isolated. TOP after viability (≥ 24 + 0weeks of gestation) was performed in 61.4% (94/153). Substantial morbidity (n = 80; 52.3%) and mental retardation (n = 33, 38.4%) made up the leading prognostic groups. In about 80% of detectable anomalies, diagnosis of CNS malformation could have been made earlier by following international guidelines of fetal CNS examination at second trimester scan. General implementation of ultrasound screening in maternity care can significantly reduce the number of late TOPs in Germany.

Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology

Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations, which are outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we infect pregnant rhesus macaques and investigate the impact of persistent ZIKV infection on uteroplacental pathology, blood flow, and fetal growth and development. Despite seemingly normal fetal growth and persistent fetal-placenta-maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic effects on placental oxygen reserve accompanied by significantly decreased oxygen permeability of the placental villi. The observation of abnormal oxygen transport within the placenta appears to be a consequence of uterine vasculitis and placental villous damage in ZIKV cases. In addition, we demonstrate a robust maternal-placental-fetal inflammatory response following ZIKV infection. This animal model reveals a potential relationship between ZIKV infection and uteroplacental pathology that appears to affect oxygen delivery to the fetus during development.

Typical lesions in the fetal nervous system: correlations between fetal magnetic resonance imaging and obstetric ultrasonography findings.

Central nervous system (CNS) malformations play a role in all fetal malformations. Ultrasonography (US) is the best screening method for identifying fetal CNS malformations. A good echographic study depends on several factors, such as positioning, fetal mobility and growth, the volume of amniotic fluid, the position of the placenta, the maternal wall, the quality of the apparatus, and the sonographer’s experience. Although US is the modality of choice for routine prenatal follow-up because of its low cost, wide availability, safety, good sensitivity, and real-time capability, magnetic resonance imaging (MRI) is promising for the morphological evaluation of fetuses that otherwise would not be appropriately evaluated using US. The aim of this article is to present correlations of fetal MRI findings with US findings for the major CNS malformations.

Fetal central nervous system malformations: a ten year review of prenatal consultations at a tertiary care center (P4.150)

Fetal central nervous system malformations: a ten year review of prenatal consultations at a tertiary care center (P4.150)

Outcome of prenatally diagnosed central nervous system malformations in a tertiary center in Singapore

Background: Central nervous malformations are associated with major morbidity and mortality in infants and children. Knowledge of the data about their outcome and neurodisability will help in perinatal counseling and aid in parental decision-making. Objective: To study the fetal and neonatal characteristics of prenatally diagnosed central nervous system (CNS) malformations and the neurodevelopmental outcome of the survivors over 5years. Methods: Maternal and neonatal records of prenatally diagnosed CNS malformations were retrospectively reviewed over five years (January 2005 till December 2009). The relevant fetal and neonatal data were collected from the database maintained by the birth defect registry. The long-term neurodevelopment data was obtained from case records. Results: There were 116 cases of fetal structural CNS malformations. Termination of pregnancy or fetal deaths occurred in 80/116 (69%) of cases, of which 68% had Neural tube defects (NTD). There were 36 live births, of which six infants died of anencephaly and were not included in the study. Among 30 live births 17% of infants needed ventilator support and 17% had neurosurgical intervention. On follow up 37% of the cohort had neurodevelopmental delay, 10% died, 30% had normal neurodevelopmental outcome and 23% defaulted on follow-up. Conclusions: In two-thirds of the fetuses of prenatally diagnosed CNS malformations, termination of pregnancy or fetal death occurred. Nearly half of the survivors who were followed up had a composite outcome of death or global neurodevelopmental delay and need for support services.

Prenatal MRI: Is it still useful in the clinical management of fetal central nervous system malformations diagnosed by ultrasound?

Purpose: To evaluate the role of magnetic resonance imaging in the diagnosis of central nervous system abnormalities and to report its additional and differential value being used as a second line diagnostic procedure.

Zika Virus: Implications for Public Health.

The World Health Organization has declared the current Zika virus (ZIKV) epidemic a public health emergency of international concern. Lack of vaccines and reliable diagnostic tests, broad geographical distribution of mosquito species that can transmit the virus, and absence of population immunity in newly affected countries are causes for concern. Although most infected persons are asymptomatic, ZIKV has been associated with a rise in cases of neurological complications and fetal central nervous system malformations. This defines such an arbovirus as something whose transmission should be prevented. This review summarizes the current understanding of ZIKV biology and epidemiology, as well as possible interventions to prevent contagion and transmission.

Accuracy of neurosonography and MRI in clinical management of fetuses referred with central nervous system abnormalities

To assess the accuracy of expert neurosonography (two- and three-dimensional NSG) in the characterization of major fetal central nervous system (CNS) anomalies seen at a tertiary referral center and to report the differential clinical usefulness of magnetic resonance imaging (MRI) used as a second-line diagnostic procedure in the same cohort. This was a retrospective analysis of all 773 fetuses with confirmed CNS abnormalities referred to our center between 2005 and 2012. The following variables were analyzed: gestational age at NSG and MRI, NSG and MRI diagnoses, indication for MRI (confirmation of NSG findings; diagnostic doubt; search for possible additional brain anomalies), association with other malformations, diagnostic accuracy of NSG vs MRI (no additional clinical value for either MRI or NSG; additional information with clinical/prognostic significance on MRI relative to NSG; additional information with clinical/prognostic significance on NSG relative to MRI, NSG and MRI concordant but incorrect) and final diagnosis, which was made at autopsy or postnatal MRI/surgery. CNS malformations were associated with other anomalies in 372/773 (48.1%) cases and were isolated in the remaining 401 (51.9%) cases. NSG alone was able to establish the diagnosis in 647/773 (83.7%) cases. MRI was performed in 126 (16.3%) cases. The indication for MRI was: confirmation of NSG diagnosis in 59 (46.8%) cases; diagnostic query (in the case of inconclusive or uncertain finding on NSG) in 20 (15.9%) cases; search for possible additional brain anomalies in 47 (37.3%) cases. NSG and MRI were concordant and correct in 109/126 (86.5%) cases. Clinically relevant findings were evident on MRI alone in 10/126 (7.9%) cases (1.3% of the whole population) and on NSG alone in 6/126 (4.8%) cases; in all six of these cases, MRI had been performed at < 24 weeks of gestation. In one case, both NSG and MRI diagnoses were incorrect. The main type of malformation in w ich MRI played an important diagnostic role was space-occupying lesions, MRI identifying clinically relevant findings in 42.9% (3/7) of these cases. (1) In a tertiary referral center with good NSG expertise in the assessment of fetal CNS malformations, MRI is likely to be of help in a limited proportion of cases; (2) MRI is more useful after 24 weeks of gestation; (3) the lesions whose diagnosis is most likely to benefit from MRI are gross space-occupying lesions.

Avaliação do sistema nervoso central do feto e neonato

Central nervous system (CNS) malformations play a relevant role in the set of all fetal malformations, standing out for the following factors: • incidence: this is the second highest after cardiac malformations; • feasibility of prenatal diagnosis: currently, they are the most frequently diagnosed malformations, together with urinary tract malformations; • difficulty in evaluating the patient’s prognosis: many times, a multidisciplinary discussion is required to define the prognosis. Ultrasonography (US) is the best screening method to identify fetal CNS malformations(1). The echographic study of the cephalic pole at the 12th gestational week already constitutes a relevant biometric method for evaluating the gestational age. It also provides an early morphological appreciation of the development of the brain and of the fetus as a whole, together with other parameters, such as fetal dynamics (tonus, respiratory motion, heartbeats) and structural elements of the fetus (spine, skeleton, face, thorax and abdomen)(1). A good echographic study depends on several factors, such as positioning, fetal mobility and growth, volume of amniotic fluid, position of the placenta, maternal wall, quality of the apparatus, and the sonographer’s experience. Three-dimensional US (3DUS) has become an integral part in the assessment of a great number of fetal abnormalities. As conventional US and 3DUS are compared in the evaluation of medullary canal malformations, multiplanar 3DUS imaging provides more complete information on such alterations. Among others, the following benefits from this imaging modality are highlighted:

Fetopathological investigations after induced abortions performed in mid-term gemini pregnancies

Multiple pregnancies present a special obstetric condition whose importance has increased due to the spread of assisted reproductive techniques. We have processed the fetopathological data of 43 abortions induced in mid-term gemini pregnancies, owing to malformations affecting one or both fetuses. 67.4% of the gemini pregnancies were conceived naturally and 32.6% by assisted reproduction techniques. The most commonly occurring malformations affected the fetuses’ cardiovascular and central nervous systems. Positive histories could be detected in 23% of the cases. The male-to-female ratio was found to be 1.14. In the majority of the cases with central nervous system malformation, fetus “A” was affected (85.7%). In 29.4% of the cases, monochorionic placentation was established. Ultrasonography and fetopatological findings yielded perfectly matching results in 78.9% of the cases. The incidence of fetal malformations is probably not higher among fetuses conceived by assisted reproduction techniques compared to the ones conceived naturally. Fetal central nervous system malformations usually affect fetus “A”. Based on the results of the fetopathological examinations, ultrasonography is a reliable method in the diagnostics of malformations affecting twin fetuses. Fetal echocardiography is indicated simply because of the pregnancy being a multiple one.

Significance of a single umbilical artery in fetuses with central nervous system malformations.

To determine whether the presence of a single umbilical artery (SUA) is useful information for evaluating fetuses with known central nervous system (CNS) malformations, the present study reviewed 107 consecutive cases of fetal CNS malformations (hydrocephalus, meningomyelocele, Dandy-Walker malformation, and holoprosencephaly) identified by prenatal sonography. Of the 107 fetuses studied, 20 (18%) had a SUA noted at the time of delivery or autopsy and 87 (81.3%) had two umbilical arteries. Of the 20 fetuses with a SUA, six were prospectively recognized on sonography, six were identified retrospectively, and eight could not be evaluated due to oligohydramnios or technical factors. All 20 fetuses with a SUA had extra-CNS anomalies and 8 of 15 (53%) fetuses tested had chromosomal abnormalities. These rates were significantly higher (P less than .05) than observed in 87 fetuses with two umbilical arteries who had extra-CNS anomalies in 35 cases (39%) and chromosomal abnormalities in 11 of 45 (24%) cases tested. We conclude that identification of a SUA in combination with a CNS anomaly should suggest the presence of additional extra-CNS anomalies and is an indication for chromosomal analysis.