Non-isolated Ventriculomegaly Research Articles

Isolated Fetal Ventriculomegaly: Diagnosis and Treatment in the Prenatal Period.

Fetal ventriculomegaly (VM) is a defect of the central nervous system, typically diagnosed during the second-trimester ultrasound in fetuses with an atrial diameter (AD) of >10 mm. Non-isolated ventriculomegaly (NIVM) is heterogeneous in nature, coexisting with additional intracranial and/or extracranial malformations and genetic syndromes, resulting in an unfavorable prognosis for the further development of the child. Both the pregnancy management and counseling are dependent on the findings of combined ultrasound/MRI, genetic testing, and gestational age at diagnosis. The purpose of this review is to propose a hypothesis that diagnostic advancements allow to define the process of identification of the isolated forms of VM (IVM). Based on the evidence presented in the literature, we consider whether prenatal decompression for severe isolated VM (ISVM) is supported by the experimental trials and whether it might be implemented in clinical practice. Also, we describe the evolution of the diagnostic methods and expert opinions about the previously used prenatal decompression techniques for ISVM. In conclusion, we introduce the idea that fetal surgery centers have either reached or nearly reached the necessary level of expertise to perform such procedures. Endoscopic cystoventriculostomy (ETV) appears to be the most promising, as it is associated with minimal perinatal complications and favorable neurological outcomes in the neonatal period. Randomized trials with long-term neurodevelopmental follow-up of children who underwent prenatal decompression due to ISVM are necessary.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly.

Genetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation. A total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM. The detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P < 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P > 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P < 0.001). The combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.

Perinatal and neurodevelopmental outcomes of fetal isolated ventriculomegaly: a systematic review and meta-analysis.

Isolated fetal ventriculomegaly can have a range of consequences, ranging from mild neurodevelopmental delay to perinatal death; the extent of these consequences often depend on the severity of ventriculomegaly. This systematic review and meta-analysis aims to investigate the impact of the degree of ventricular dilatation on the risk of neurodevelopmental delay and adverse perinatal outcomes in fetuses diagnosed with isolated fetal ventriculomegaly from gestational week 15 onwards. PubMed, Embase, Scopus and the Cochrane Library were searched electronically to identify studies investigating the prognosis of mild and/or severe isolated fetal ventriculomegaly. Articles were included if they reported neurodevelopmental or perinatal outcomes in fetuses prenatally diagnosed with isolated fetal ventriculomegaly from week 15 of gestation and onwards. Studies were excluded if they reported on non-isolated ventriculomegaly (IVM), failed to specify the degree of ventriculomegaly, were non-English papers, animal studies or published outside of the 21-year period of interest. Study quality was assessed by two independent reviewers using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Ventriculomegaly was defined as either mild or severe when ventricular diameter measured as 10-15 or >15 mm, respectively. Meta-analyses were conducted for adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality. Following the removal of duplicates, the search yielded 2,452 citations, of which 23 studies were included and 8 were eligible for meta-analysis. There were 767 and 347 cases of mild and severe isolated fetal ventriculomegaly, respectively. Adverse outcomes were consistently reported at a higher rate in severe cases than mild. The relative risks of adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality were 4.24 [95% confidence interval (CI): 2.46-7.30], 4.46 (95% CI: 1.64-12.11) and 6.02 (95% CI: 1.73-21.00), respectively, upon comparison of mild versus severe cases of isolated fetal ventriculomegaly. The likelihood of adverse neurodevelopmental and perinatal outcomes, including intrauterine and infant mortality, is increased in severe isolated fetal ventriculomegaly compared to mild isolated fetal ventriculomegaly.

Pregnancy outcomes and genetic analysis for fetal ventriculomegaly.

Introduction: Fetal ventriculomegaly (VM) is associated with neurodevelopmental disorders, partly caused by genetic factor. Methods: To systematically investigate the genetic etiology of fetal VM and related pregnancy outcomes in different subgroups: IVM (isolated VM) and NIVM (non-isolated VM); unilateral and bilateral VM; mild, moderate, and severe VM, a retrospective study including 131 fetuses with VM was carried out from April 2017 to August 2022. Results: 82 cases underwent amniocentesis or cordocentesis, of whom 8 cases (9.8%) were found chromosomal abnormalities by karyotyping. Meanwhile, additional 8 cases (15.7%) with copy number variations (CNVs) were detected by copy number variation sequencing (CNV-seq). The detection rate (DR) of chromosomal abnormalities was higher in NIVM, bilateral VM and severe VM groups. And CNVs frequently occurred in NIVM, bilateral VM and moderate VM groups. In the NIVM group, the incidence of chromosomal aberrations and CNVs in multiple system anomalies (19.0%, 35.7%) was higher than that in single system anomalies (10.0%, 21.1%). After dynamic ultrasound follow-up, 124 cases were available in our cohort. 12 cases were further found other structural abnormalities, and lateral ventricular width was found increased in 8 cases and decreased in 15 cases. Meanwhile, 82 cases underwent fetal brain MRI, 10 cases of brain lesions and 11 cases of progression were additionally identified. With the involvement of a multidisciplinary team, 45 cases opted for termination of pregnancy (TOP) and 79 cases were delivered with live births. One infant death and one with developmental retardation were finally found during postnatal follow-ups. Discussion: CNV-seq combined with karyotyping could effectively improve the diagnostic rate in fetuses with VM. Meanwhile, dynamic ultrasound screening and multidisciplinary evaluation are also essential for assessing the possible outcomes of fetuses with VM.

Concordance between US and MRI Two-Dimensional Measurement and Volumetric Segmentation in Fetal Ventriculomegaly.

We provide a study comparison between two-dimensional measurement and volumetric (3D) segmentation of the lateral ventricles and brain structures in fetuses with isolated and non-isolated ventriculomegaly with 3D virtual organ computer-aided analysis (VOCAL) ultrasonography vs. magnetic resonance imaging (MRI) analyzed with 3D-Slicer software. In this cross-sectional study, 40 fetuses between 20 and 38 gestational weeks with various degrees of ventriculomegaly were included. A total of 71 ventricles were measured with ultrasound (US) and with MRI. A total of 64 sonographic ventricular volumes, 80 ventricular and 40 fetal brain MR volumes were segmented and analyzed using both imaging modalities by three observers. Sizes and volumes of the ventricles and brain parenchyma were independently analyzed by two radiologists, and interobserver correlation of the results with 3D fetal ultrasound data was performed. The semiautomated rotational multiplanar 3D VOCAL technique was performed for ultrasound volumetric measurements. Results were compared to manually extracted ventricular and total brain volumes in 3D-Slicer. Segmentation of fetal brain structures (cerebral and cerebellar hemispheres, brainstem, ventricles) performed independently by two radiologists showed high interobserver agreement. An excellent agreement between VOCAL and MRI volumetric and two-dimensional measurements was established, taking into account the intraclass correlation coefficients (ICC), and a Bland-Altman plot was established. US and MRI are valuable tools for performing fetal brain and ventricular volumetry for clinical prognosis and patient counseling. Our datasets could provide the backbone for further construction of quantitative normative trajectories of fetal intracranial structures and support earlier detection of abnormal brain development and ventriculomegaly, its timing and progression during gestation.

Classification of Ventriculomegaly and its Associated Findings using Antenatal Ultrasound Scan at a Tertiary Care Hospital: Andhra Pradesh, India: A Retrospective Descriptive Study

Introduction: Foetal Ventriculomegaly (VM) is defined as the enlargement of the lateral ventricles in the developing foetal brain. The measurement of foetal cerebral lateral ventricles’ size is routinely recommended as part of the second-trimester foetal scan to screen for anomalies. VM can occur due to obstruction of the Cerebrospinal Fluid (CSF) tract, absorption disorders, inadequate brain development, or excessive CSF production. Aim: To classify VM based on severity to differentiate between isolated and non isolated VM. Materials and Methods: A retrospective descriptive study was conducted in the Department of Radiology at PESIMSR, Andhra Pradesh, India., a tertiary medical hospital, from April 2018 to April 2021. Cases were selected from computer records showing a diagnosis of hydrocephalus or foetal VM in patients who underwent the Ultrasound (US) anomaly scan. VM was defined as a lateral ventricle width of ≥10 mm. Foetal VM was classified, and associated CNS and extracranial abnormalities and their details were collected. Descriptive statistics were used, and results were expressed in terms of frequency and percentage. Results: The VM was observed in 91 foetuses, with mild VM in 59 foetuses (64%), moderate VM in 14 foetuses (15.2%), and severe VM in 18 foetuses (19.5%). The median age at diagnosis was 26.5 weeks. Isolated mild VM was seen in 26 cases (44%), and it was associated with other abnormalities in 33 cases (56%). Isolated moderate VM was observed in four cases (28.5%), while 10 cases (71.4%) were associated with other abnormalities. Isolated severe VM was seen in (33.3%) 6, and it was associated with abnormalities in 12 cases (66.6%). The most common associated abnormalities were foetal growth restriction (15 cases), absent cavum septum pellucidum (eight cases), and open spina bifida, Arnold-Chiari malformation (eight cases). Conclusion: Ultrasound is a sensitive tool for detecting VM. Once VM is diagnosed, a detailed examination of the fetus should be conducted to evaluate other CNS and non CNS anomalies, thereby differentiating isolated from non-isolated VM, as the prognosis may vary. This information will be valuable for counseling patients.

Chromosomal microarray analysis vs. karyotyping for fetal ventriculomegaly: a meta-analysis.

Background:Chromosomal abnormalities are important causes of ventriculomegaly (VM). In mild and isolated cases of fetal VM, obstetricians rarely give clear indications for pregnancy termination. We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis (CMA) in VM, providing more information on genetic counseling and prognostic evaluation for fetuses with VM.Methods:The Chinese language databases Wanfang Data, China National Knowledge Infrastructure, and China Biomedical Literature Database (from January 1, 1991 to April 29, 2020) and English language databases PubMed, Embase, and Cochrane Library (from January 1, 1945 to April 29, 2020) were systematically searched for articles on fetal VM. Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging (MRI) assessment of lateral ventricular atrium width: ≥10 to <15 mm for mild VM, and ≥15 mm for severe VM. Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI. R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM, and the combined rate and 95% confidence interval (CI) were calculated.Results:Twenty-three articles involving 1635 patients were included. The incidence of chromosomal abnormalities in VM was 9% (95% CI: 5%–12%) and incremental yield of CMA in VM was 11% (95% CI: 7%–16%). The incidences of chromosomal abnormalities in mild, severe, isolated, and non-isolated VM were 9% (95% CI: 4%–16%), 5% (95% CI: 1%–11%), 3% (95% CI: 1%–6%), and 13% (95% CI: 4%–25%), respectively.Conclusions:Applying CMA in VM improved the detection rate of abnormalities. When VM is confirmed by ultrasound or MRI, obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities. Moreover, CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis. CMA cannot completely replace chromosome karyotype analysis.

Correlation between mild fetal ventriculomegaly, chromosomal abnormalities, and copy number variations

Background Lateral ventriculomegaly is the most common abnormality of the fetal nervous system. This study investigated the incidence of chromosomal abnormalities and copy number variations (CNVs) in fetuses with mild ventriculomegaly (MV) based on various ultrasonic manifestations, identifying their corresponding features via ultrasound examination. Methods A retrospective analysis was performed on ultrasound and neurosonogram (NSG) manifestations and genetic profiles of 334 cases with MV and invasive prenatal diagnosis. Results Three hundred thirty-four cases with fetal MV were assessed via karyotyping. Further chromosomal microarray analysis (CMA) was performed in 182 cases with normal chromosome karyotypes; pathogenic chromosomal copy number variations (CNVs) were found in eight cases with a prevalence of 4.4% (8/182). In this study, the incidence rate of pathogenic abnormalities of chromosomes and CNVs was 5.7% (19/334). Based on whether lateral ventriculomegaly was complicated with other ultrasonic features, the 334 patients were divided into two groups: (1) 175 cases exhibited isolated ventriculomegaly (IVM; 52.4%, 175/334 group A) including two (1.1%, 2/175) with pathogenic chromosomal karyotype abnormalities—both trisomy 21; (2) 159 cases exhibited non-isolated ventriculomegaly (N-IVM; 47.6%, 159/334) with pathogenic chromosomal abnormalities and CNVs detected in17 cases (10.7%, 17/159). The N-IVM group was further divided into two groups: 105 cases exhibited MV with undetermined ultrasonic abnormalities (31.4%, 105/334, group B) with pathogenic chromosomal abnormalities and CNVs detected in eight cases (7.6%, 8/105); 54 cases exhibited MV with structural malformations (16.2%, 54/334, group C) of which nine cases (16.7%, 9/54) presented both pathogenic chromosomal abnormalities and CNVs, and five cases (55.6%, 5/9) were diagnosed with various cortical malformations. The pathogenicity rates of the IVM and N-IVM groups were statistically different (χ 2=14.159, p = 0.000). There were significant differences (χ2=7.992, p = 0.005) among groups A, B, and C. Conclusions Combinations of various ultrasonic abnormalities significantly affect the risk of pathogenic chromosomal abnormalities and CNVs in fetuses with MV. Cases involving cortical malformations require particular attention to the occurrence of pathogenic genetic abnormalities. When fetal MV is detected, a comprehensive ultrasound examination focusing on undetermined ultrasonic abnormalities is critical. Fetal NSG should be conducted to detect potential cerebral cortical malformation easily missed by routine ultrasound.

Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis in foetuses with ventriculomegaly

Ventriculomegaly is considered to be linked to abnormal neurodevelopment outcome. The aim of this retrospective study was to investigate the current applications of chromosomal microarray analysis (CMA) in foetuses with ventriculomegaly. A total of 548 foetuses with ventriculomegaly detected by prenatal ultrasound underwent single nucleotide polymorphism (SNP) array testing and were subjected to long-term follow-up. The overall prevalence of chromosomal aberrations was 7.30% (40/548), including 4.20% (23/548) with pathogenic/likely pathogenic copy number variants. The incidence of chromosomal aberrations was significantly higher in foetuses with bilateral ventriculomegaly than in those with unilateral ventriculomegaly (10.56% vs. 5.71%, P = 0.040), in foetuses with non-isolated ventriculomegaly than in those with isolated ventriculomegaly (12.99% vs. 2.38%, P < 0.0001), and in foetuses with severe ventriculomegaly than in those with mild-to-moderate ventriculomegaly (23.08% vs. 6.51%, P = 0.005). The outcome in foetuses with mild ventriculomegaly was significantly better than in those with moderate ventriculomegaly (95.60% vs. 84.00%, P = 0.003). Thus, CMA should be regarded as the first-tier test for prenatal diagnosis of foetal ventriculomegaly, especially in foetuses with bilateral or non-isolated ventriculomegaly. The outcome of foetuses with mild ventriculomegaly is favourable; however, there is an increased risk of neurodevelopmental disabilities in foetuses with moderate ventriculomegaly.

Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with ventriculomegaly.

To systematically investigate chromosomal abnormalities and copy number variants (CNVs) in fetuses with different types of ventriculomegaly (VM) by karyotyping and/or chromosomal microarray analysis (CMA). This retrospective study included 312 fetuses diagnosed with VM. Amniotic fluid and umbilical blood samples were collected by amniocentesis and cordocentesis, respectively, and subjected to karyotyping and/or CMA. Subgroup analysis by VM type, including mild VM (MVM) and severe VM (SVM), unilateral and bilateral VM, isolated VM (IVM), and non-isolated VM (NIVM), was performed. The detection rate of chromosomal abnormalities was 12.1% (34/281) by karyotyping and 20.6% when CMA was additionally performed (P<0.05). Abnormalities were identified by CMA in 17.4% (38/218) of fetuses and pathogenic CNVs in 5.0% (11/218). Notably, CMA detected CNVs in 10.6% (23/218) of fetuses with normal karyotypes. The incidence of chromosomal abnormalities by karyotyping was higher in bilateral than in unilateral VM (20.5% versus 6.5%), whereas the incidence detected by CMA was higher in NIVM than in IVM (21.4% versus 10.3%; both P<0.05). In NIVM, CMA provided an additional detection rate of 11.4% (16/140) and a detection rate of 10.0% for pathogenic CNVs and aneuploidies. Central nervous system (CNS) abnormalities were the most common other ultrasonic abnormalities. CMA is highly recommended for prenatal diagnosis of fetal VM together with karyotyping, especially in fetuses with bilateral VM and NIVM with abnormal CNS findings. Further study is necessary to explore the relationships between genotypes and phenotypes to facilitate prenatal diagnosis of fetal VM.

Prognosis of fetuses with ventriculomegaly: An observational retrospective study.

To investigate the prognosis of fetuses with ventriculomegaly (VM). Clinical data were collected from 234 cases of fetal VM diagnosed by ultrasound between March 2010 and July 2016. VM progression was monitored, and karyotyping and infection screening performed. Magnetic resonance imaging (MRI) was performed where increasing ventricular diameter was noted. Neonatal behavioral neurological assessment (NBNA) was carried out after birth, and Bayley Scales of Infant Development assessment at 6 months. The in utero outcomes of Group A were better than Group B in 173 pregnancies. Isolated VM (IVM) was associated with better prognosis than nonisolated VM (NIVM); the regression rates were 74.6% (59/79) and 52.1% (49/94), respectively (χ2 = 10.222, .006). The NBNA scores were significantly higher in Group A than Group B (χ2 = 4.231, .004), but not significantly different between IVM and NIVM. The composition ratios of both the psychomotor and mental developmental index (PDI and MDI) scores were not significantly different between Groups A and B (Z = 1.869, .062 and Z = 0.826, .409, respectively). Significant differences in in utero outcomes were observed between IVM and NIVM cases in Groups A and B. Fetal VM prognosis is affected by the width of ventricle, chromosome abnormalities, coexisted abnormalities, and in utero progression.

Is fetal magnetic resonance imaging indicated in patients with isolated ventriculomegaly?

ObjectiveVentriculomegaly is one of the most common anomalies encountered at obstetric ultrasound and it necessitates follow up. Fetal magnetic resonance imaging (MRI) can be used to confirm the ultrasound diagnose or to detect additional anomalies. Aim of this study is to assess follow up and management of fetal ventriculomegaly shown by ultrasound, and to evaluate additional diagnostic contribution of MRI. Study DesignThis study was conducted retrospectively including 89 patients who had fetal MRI subsequent to ultrasound diagnose of ventriculomegaly in between 2011-2017. Medical records of patients were investigated and accompanying anomalies, congenital infection, chromosomal examination, degree and progression of ventriculomegaly, neonatal imaging and diagnose, and neurodevelopmental findings on follow up were evaluated. Patients were classified in two groups as isolated and nonisolated ventriculomegaly, and subgroups mild, moderate, severe were formed according to their findings. SPSS 23.0 programme was used for statistical analysis. ResultsUltrasound and following MRI was performed in a range of 18-35th gestational weeks, diagnoses were isolated ventriculomegaly for 56 patients and nonisolated ventriculomegaly for 33 patients. Progression and neurodevelopmental delay was higher in severe nonisolated ventriculomegaly group. There was not significant contribution of MRI in the follow up of isolated ventriculomegaly (p < 0.001), and diagnostic imaging findings declined in neonatal period with proceeding normal neurodevelopment in 92.7% of patients followed with diagnosis of isolated ventriculomegaly. ConclusionWhen isolated ventriculomegaly is detected, ultrasound performed by an experienced team is mostly sufficient. MRI can be used in suspicious cases or when ventriculomegaly progresses.

Ventriculo-amniotic shunting for severe fetal ventriculomegaly.

Severe fetal cerebral ventriculomegaly, observed in about 1 in 1000 newborns, is associated with a high risk of perinatal death and neurodevelopmental delay in survivors. The objective of this study was to evaluate the efficiency of ventriculo-amniotic shunting for drainage of severe fetal cerebral ventriculomegaly and the neurodevelopment of survivors at the age of 2years. This was a retrospective study of 44 fetuses with severe bilateral ventriculomegaly treated with ventriculo-amniotic shunting in a tertiary fetal therapy center between 2010 and 2015. Shunt insertion was successfully carried out at a median gestational age of 25weeks (range 20-33weeks). There were three fetal deaths within 24hours of the procedure and 41 live births at a median gestational age of 37weeks (range 28-39weeks). Neurodevelopment at 2years of age was evaluated using the Bayley scale in the 38 survivors. In the 27 cases with isolated ventriculomegaly 19 (70.4%; 95% confidence interval [95% CI] 51.5%-84.2%) had normal or mild neurodevelopmental delay and 8 (29.6%; 95% CI 15.6%-48.5%) were moderately or severely delayed. In the 11 with non-isolated ventriculomegaly 2 (18.2%; 95% CI 5.1%-4.8%) had normal or mild neurodevelopmental delay and 9 (81.8%; 95% CI 52.3%-94.9%) babies were moderately or severely delayed. Ventriculo-amniotic shunting is an option for the management of severe ventriculomegaly and results in normalization of the ventricular diameter. However, a high proportion of survivors have neurodevelopmental delay and the possible beneficial effect of ventriculo-amniotic shunting needs to be assessed by randomized studies.

Long-term outcomes of prenatally diagnosed ventriculomegaly - 10 years of Polish tertiary centre experience.

To estimate the prevalence, associated anomalies, and postnatal outcomes in infants prenatally diagnosed with ventriculomegaly. All cases of ventriculomegaly that were examined and treated by the 1st Department of Obstet- rics and Gynecology, at the Medical University of Warsaw, from August 2007 until November 2017 were included in this study. Ultrasound data, and information on perinatal outcomes and long-term postnatal follow up were retrospectively collected by a standardised telephone survey. Ventriculomegaly was diagnosed when the atrial width of the lateral ventri- cles was ≥ 10 mm. The cases analyzed were divided into two subgroups: isolated ventriculomegaly (IVM) and non-isolated ventriculomegaly (NIVM). Neurodevelopmental complications were differentiated as either moderate or severe and were compared within each group and between groups. There were 118 cases of prenatally diagnosed ventriculomegaly. Complete follow up records were collected for 54 cases (45.8%). IVM was diagnosed in 29/54 (53.7%) cases, while NIVM was diagnosed in the remaining 25 (46.3%). The mean ventricular width for IVM was 16.93 mm (range 10.0 mm-73.0 mm) and 14.08 mm (range 9.0 mm-27.1 mm) for NIVM (p = 0.28). The mean gestational age at delivery for the IVM cases was 36 + 4 weeks and in the NIVM group 33 + 4 weeks (p = 0.022). Mild VM (10-12 mm) was diagnosed in 22/54 cases (40.7%), moderate VM (13-15 mm) in 12/54 (22.3%) and severe (≥ 15 mm) in 20/54 (37%). Among the infants with IVM the rate of severe medical complications was 29.6% (8/28) and for NIVM 667% (8/12) (p = 0.041). Less severe medical conditions affected 6/28 of the infants with IVM (21.4%) vs 9/12 NIVM cases (75%) (p = 0.012). In terms of prenatal diagnosis, treatment of ventriculomegaly remains challenging due to a lack of specific prognostic factors and the significant risk of neurodevelopmental disorders. Nevertheless, isolated ventriculomegaly has significantly better long-term outcomes compared with non-isolated ventriculomegaly. In our material, the rate of severe neurodevelopmental disorders in the non-isolated ventriculomegaly cases was associated with a 52% rate of adverse perinatal outcomes. On the other hand, less severe medical conditions occurred in 21.4% of the infants with IVM and in 75% of the NIVM cases. Furthermore, obstetrical data suggest that the risks of premature delivery and caesarean section are significantly higher in cases of non-isolated ventriculomegaly.

Meta analysis of fetal lateral ventriculomegaly and prognosis

Objective: To explore the neurological development of fetal with ventriculomegaly at 1 year after birth by systematically reviewing the domestic and international literature about prognosis of fetal ventriculomegaly. Methods: Wanfang database, CNKI, CBM, PubMed, EMBASE and the Cochrane Library were online searched to collect relevant literature published from January 1st, 1980 to November 22th, 2017. Literature were extracted based on the Newcastle-Ottawa Scale (NOS) , and analyzed by R software for meta-analysis. The corresponding model was selected according to the results of heterogeneity test to comprehensively analyze the prognosis of the fetus with ventriculomegaly. Results: Five studies were included in the meta analysis, all of them were of high quality (scores>5) . (1) The good prognosis rate of nervous system was 88% (95%CI:0.77-0.95) in fetus with mild ventriculomegaly, was 57% (95%CI:0.18-0.91) in those with moderate ventriculomegaly, and was 36% (95%CI:0.16-0.59) in those with severe ventriculomegaly. (2) The good prognosis rate of the nervous system was 86% (95%CI:0.75-0.94) in fetus with the isolated ventriculomegaly, while was 58% (95%CI:0.20-0.91) in those with non-isolated ventriculomegaly. The incidence of chromosomal abnormalities was 7% (95%CI:0.05-0.09) in ventriculomegaly. The improvement rate of lateral ventricle width in pregnancy was 41% (95%CI:0.27-0.57) . Conclusions: The prognosis of nervous system with mild ventriculomegaly is better than that of moderate and severe ventriculomegaly. The prognosis of nervous system with isolated ventriculomegaly is better than that of non-isolated ventriculomegaly. Fetal ventriculomegaly may be associated with fetal chromosomal abnormalities and intrauterine infection. The variation of fetal lateral ventricular width should be monitored regularly during pregnancy, the risk of poor prognosis should be informed, and pediatrician should be asked for evaluation.

Pregnancy outcomes and neurodevelopment in 173 cases of mild or moderate fetal ventriculomegaly

Objective To investigate pregnancy outcomes and neurodevelopment in fetuses with ventriculomegaly. Methods This was a cohort study of 173 gravidas with singleton pregnancy who were diagnosed with fetal ventriculomegaly by ultrasound in Prenatal Diagnostic Center of Nanfang Hospital Affiliated to Southern Medical University from March 2010 to July 2016. Thirty normal gravidas who received antenatal care in the same hospital and at the same period were selected as control. Clinical data were collected. Gravidas who had chosen to continue their pregnancy were followed up to monitor the variations of fetal ventricular. Fetal mild and moderate ventriculomegaly were respectively defined as a ventricular atrial width of 10-12 mm and >12 mm but <15 mm. Isolated ventriculomegaly (IVM) indicated those without any other ultrasound abnormalities, otherwise the case would be defined as non-isolated ventriculomegaly (NIVM). Among the 173 gravidas, 54 cases were mild IVM, 53 mild NIVM, 26 moderate IVM and 40 moderate NIVM. Fetuses with chromosome abnormalities were excluded from the study. Neonatal behavioral neurological assessment (NBNA) was used to analyze the neonatal neurodevelopment at the age of 7 days, and Bayley scales of infant development was used to evaluate the development of nervous system at the age of 6 months through analyzing their mental development index (MDI) and psychomotor development index (PDI). Statistical methods included t test, χ2 test (or Fisher's exact test), nonparametric test, Mann-Whitney test and multiple Kruskal-Wallis H test. Results (1) Among the 107 fetuses with mild ventriculomegaly, 72.9% (78), 23.4% (25) and 3.7% (4) of them regressed, stabilized and progressed,respectively; however, among the 66 moderate cases, the figures were 45.4% (30), 37.9% (25) and 16.7% (11) respectively (χ2=15.769, P 0.05). Conclusions Prognosis of fetal ventriculomegaly is affected by co-existed abnormalities and intrauterine progression. Fetus with mild ventriculomegaly can also have risk of abnormal neural development, suggesting that we should pay much attention to such cases and a regular follow-up is required. Key words: Ventriculomegaly; Pregnancy outcome; Central nervous system; Ultrasonography, prenatal; Follow-up studies

Application of chromosome microarray analysis for the delineation of pathogenesis for fetal ventriculomegaly

To assess the value of genome-wide high-resolution chromosomal microarray analysis (CMA) for the delineation of pathogenesis for fetal ventriculomegaly diagnosed by ultrasound or magnetic resonance imaging (MRI). Three hundred and forty-one cases of fetal ventriculomegaly were collected. The samples were grouped based on the extent of lateral ventricular dilatation, presence of additional features, site of occurrence, and the maternal age. All samples were subjected to karyotyping analysis. For those with a normal karyotype, DNA was extracted and hybridized with an Affymetrix CytoScan HD array. All cases were followed up. Among the 341 fetuses, 21 (6.2%) were detected with an abnormal karyotype. For the 320 cases with a normal karyotype, 179 (55.9%) have accepted CMA analysis. Potentially pathogenic CNVs were identified in 12 (6.7%) of the 179 cases, whose sizes ranged from 198 kb to 8.71 Mb. These included a 1q21.3q23.1 deletion, a 2q37.3 deletion, a 3p14.1p13 deletion, a 6q25.3 deletion, a 8q11.23 duplication, a 10q21.1 deletion, a 15q11.2 deletion and a 16p13.11p12.3 duplication, a 22q13.33 duplication, a 22q11.21 duplication and a Xp21.1 duplication (Duchenne muscular dystrophy). Pathogenic CNVs were detected respectively in 7.5% and 3.1% of those with mild and severe ventriculomegaly (P=0.615), in 6.1% and 7.4% of those with isolated and non-isolated ventriculomegaly (P=0.732), in 5.6% and 7.9% of those with unilateral and bilateral ventriculomegaly (P=0.511), and in 6.7% of both elderly and non-elderly groups (P=1.000). The detection rate for abnormal karyotypes among fetuses with ventriculomegaly was 6.2%. CMA can increase the detection rate by approximately 6.7%. There was no significant correlation between ventriculomegaly and presence of pathogenic CNVs. In clinical practice, fetuses with ventriculomegaly and a normal karyotype should be considered for CMA analysis.

Fetal ventriculomegaly: Pregnancy outcomes and follow-ups in ten years.

The aim of this study is to evaluate the pregnancy outcomes and prognoses for fetuses with ventriculomegaly. Two hundred and forty-one cases of fetuses with ventriculomegaly were included in this study. The subjects were divided into three groups according to their lateral ventricular width: "Mild Ventriculomegaly" (10 ‒ < 12 mm), "Moderate Ventriculomegaly" (12 ‒ < 15 mm) and "Severe Ventriculomegaly" (≥ 15 mm). Pediatric examination records and telephone interviews were conducted to track the outcomes of children until the age of 9 years. Eight-two cases were Isolated Ventriculomegaly (34.0%), while Non-Isolated Ventriculomegaly was found in 159 cases (66.0%). The pregnancy was terminated in 91 cases, and a higher abortion ratio was found in the NIVM (Non-Isolated Ventriculomegaly) group compared with the IVM (Isolated Ventriculomegaly) group. The fetuses were delivered in 150 cases, and four infants suffered deaths with NIVM. Of the surviving fetuses, 7 with IVM and 9 with NIVM showed significant abnormalities. The Mild and Moderate VM groups had more favorable prognoses compared with the Severe VM group. Regarding the outcomes and progression of lateral ventricular width, 1 out of 42 cases in the regressed group and 19 out of 108 cases in the stable group showed significant abnormalities. This study suggests that the degree and the progression of ventricular dilatation are main factors that affect pregnancy outcomes and prognoses.

Clinical significance and outcomes of fetal ventriculomegaly

Objective To evaluate the clinical significance and prognosis of tetus with lateral ventriculomegaly.Methods We retrospectively analyzed 92 singleton pregnant women who were antenatally diagnosed with fetal ventriculomegaly by ultrasound in genetic conselling clinics,Department of Gynaecology and Obstetrics,Nanfang Hospital,Southern Medical University between August 2007 and August 2010.All participants were divided into three groups according to the width of the lateral ventricles:group A (10.0-12.0 mm,n＝50),group B (12.1-14.9 mm,n=38) and severe ventriculomegaly group (≥15.0 mm,n=4).All fetuses were followed up.Chi-square test(or Fisher's exact test),Bonfferoni method,Mann Whitney or Kruskal-Wallis test were used for statistics.Results In group A,B and severe ventriculomegaly group,18％ (9/50),65.8％(25/38)and 3/4 of fetuses were complicated with structural malformation,respectively (x2 =22.934,P =0.000),and statistical significance were found only between group A and B (x2 =20.798,P=0.000).The incidences of fetal chromosomal aberration were 4.0％ (2/50),7.9％ (3/38)and 0/4 in the three groups,respectively (x2＝0.878,P ＝ 0.645).Eventually,all four cases with severe cerebral ventriculomegaly were terminated.Among cases of mild ventriculomegaly,63 women continued the pregnancy (48 in group A and 15 in group B).The intrauterine improvement of group B was poorerthan that of group A (Z=-3.317,P =0.001).Respectively,three,ten and two cases of ventriculomegaly deteriorated,stabilized and regressed in group B,and the corresponding figures were 3,15 and 30 in group A.In group A,the prognosis of fetus with non-isolated ventriculomegaly was poorer than that of fetus with isolated ventriculomegaly (Z=-2.631,P=0.009).For neonates 14 days after birth (n=62),the rates of normal neonatal behavioral neurological assessment (NBNA) scoring were respectively 93.8％ (45/48) and 71.4％ (10/14) for groups A and B with statistical difference (Fisher's exact test,P =0.040).Bayley scales of infant development (BSID) used to evaluate infants at 12-month-old revealed that the psychomotor developmental index (PDI) between group A and group B had statistical difference (8,26 and 1 case of good,moderate and poor development in group A; one,seven and three cases in group B; Z=-2.203,P=0.043).However,the mental developmental index (MDI) between group A and B had no statistical difference.Twenty babies among the survived ones received magnetic resonance imaging (MRI) examination.The results showed that lateral ventricle width regressed in nine babies (45.0％) and progressed in one baby (5.0％).Ten cases (50.0％) did not change.The change of ventriculomegaly after birth was related to BSID evaluation.Better prognosis of fetuses were found in those with regressed ventriculomegaly (P=0.033).Conclusions Fetuses with mild ventriculomegaly (10.0 12.0 mm) have a favorable outcome.Further investigations,such as fetal development,chromosomal examination,intrauterine infection screening and MRI if necessary,are suggested for fetus with ventriculomegaly.Moreover,intensive intrauterine and postnatal follow-up is recommended. Key words: Lateral ventricles ; Dilatation, pathologic ; Ultrasonography, prenatal; Prognosis

Epidemiology, Natural History, Progression, and Postnatal Outcome of Severe Fetal Ventriculomegaly

To estimate the prevalence, associated anomalies, progression, and clinical outcome in fetuses prenatally diagnosed with severe ventriculomegaly. This is a population-based study using prospectively collected data from the north of England. Data were obtained from the Northern Congenital Abnormality Survey for the period 1994-2008. Associated anomalies were categorized using the European Surveillance of Congenital Anomalies guidelines. Differences between isolated and nonisolated ventriculomegaly were examined using Fisher's exact test or Mann-Whitney U test. There were 157 cases of confirmed severe ventriculomegaly in singleton pregnancies among 441,247 eligible births, a prevalence of 3.6 per 10,000 births (95% confidence interval [CI] 3.0-4.2). Chromosomal anomalies were detected prenatally in five cases (3.2%, 95% CI 1.0-7.3) and associated structural anomalies in 67 (42.7%, 95% CI 34.8-50.8). One hundred one women (64.3%) elected to have a termination of pregnancy, more commonly in the presence of associated anomalies (76.9% compared with 51.9%, P=.001). Ultrasonographic follow-up data were available for 53 fetuses; in 13 cases (24.5%), atrium size decreased prenatally, whereas in the remainder, median atrium size increased by 4.1 mm over 3.5 weeks. Associated anomalies were detected postnatally in 22 of 79 cases suspected prenatally to be isolated (27.8%, 95% CI 18.3-39.1). Of 53 live births, there were 11 (20.8%) neonatal deaths, including six (16.2%) of the isolated group. Neonatal death was not predicted by atrial measurement progression. The prevalence of severe ventriculomegaly was 3.6 per 10,000 births. Although more than 50% opt to terminate, of those with live births, there were 21% neonatal deaths with nearly half in neonates with isolated ventriculomegaly.