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Jing XY, Yu QX, Zhen L, Xiao ZQ, Li DZ. Prenatal Diagnosis of KBG Syndrome: Phenotypic and Genotypic Features of 12 Fetal Cases With the Disorder. Prenat Diagn 2025; 45:551-558. [PMID: 40011197 DOI: 10.1002/pd.6768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/27/2025] [Accepted: 02/14/2025] [Indexed: 02/28/2025]
Abstract
OBJECTIVE To present prenatal sonographic features, genomic results, and pregnancy outcomes of fetuses with KBG syndrome (KBGS). METHOD This was a retrospective study of 12 cases with KBGS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected for these cases, including maternal demographics, prenatal sonographic findings, molecular test results, and pregnancy outcomes. RESULTS Twelve cases of KBGS were diagnosed prenatally with confirmatory genetic testing. Five had an abnormal first-trimester ultrasound with increased nuchal translucency (NT). Seven cases had a normal first-trimester ultrasound. Among these, four had mild ventriculomegaly in the second or third trimester, one had an arachnoid cyst found at 22 weeks, one had umbilical-systemic shunt, ventriculomegaly and polyhydramnios found at 24 weeks, and one presented with fetal growth restriction at 30 weeks. Four pregnancies continued to term, and infants presented with the classic phenotype of KBGS at a follow-up of 12 months. All ANKRD11 alterations in the 12 cases were de novo, and were characterized as either deletions encompassing ANKRD11 or loss-of-function variants. CONCLUSION Increased NT and mild ventriculomegaly are two common sonographic features of fetal KBGS. Prenatal diagnosis of KBGS can be achieved with ultrasound and comprehensive molecular testing.
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Affiliation(s)
- Xiang-Yi Jing
- Department of Prenatal Diagnosis, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Qiu-Xia Yu
- Department of Prenatal Diagnosis, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Li Zhen
- Department of Prenatal Diagnosis, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Zhi-Qing Xiao
- Department of Prenatal Diagnosis, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Dong-Zhi Li
- Department of Prenatal Diagnosis, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
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Sapantzoglou I, Asimakopoulos G, Fasoulakis Z, Tasias K, Daskalakis G, Antsaklis P. Prenatal detection of mild fetal ventriculomegaly - a systematic review of the modern literature. ULTRASCHALL IN DER MEDIZIN (STUTTGART, GERMANY : 1980) 2025; 46:73-85. [PMID: 39214136 PMCID: PMC11798645 DOI: 10.1055/a-2375-0118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 03/01/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION While mild fetal ventriculomegaly is frequently observed as an incidental and benign finding, it is also known to be linked with structural, genetic, and neurodevelopmental abnormalities. The objective of this study was to conduct a systematic review of the existing literature in order to evaluate the association between apparently isolated fetal mild ventriculomegaly with the presence of additional structural defects detected by fetal brain MRI, chromosomal or other genetic anomalies, and neurodevelopmental delay. METHODS This systematic review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Modern literature was searched from January 1, 2011, to July 31, 2023. RESULTS 23 studies were included, comprising a total of 2590 patients. Nine studies assessed the association between fetal mild ventriculomegaly and neurodevelopmental impairment, including 536 cases, with normal neurodevelopmental outcomes ranging from 64% to 96.5%. Ten studies evaluated the additive value of fetal MRI, including 1266 fetuses, with the detection rate of additional brain defects that eventually altered the clinical management ranging from 0% to 19.5%. Seven studies investigated the association of mild ventriculomegaly with the presence of underlying chromosomal or genetic conditions, including 747 cases, with the rate ranging from 1.1% to 15.4%. CONCLUSION The prevalence of aneuploidy and genetic abnormalities in ventriculomegaly, especially in isolated cases, is reported to be quite low and the incidence of neurodevelopmental delay appears to be similar to that of the general population in cases that are apparently and truly isolated.
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Affiliation(s)
- Ioakeim Sapantzoglou
- First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Asimakopoulos
- First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece
| | - Zacharias Fasoulakis
- First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Tasias
- First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Daskalakis
- First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece
| | - Panagiotis Antsaklis
- First Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, Athens, Greece
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Field NK, Venkatesan C, Gano D, Agarwal S, Young KA, Wheeler S, Russ JB, Lemmon ME. Communicating neurological prognosis in the prenatal period: a narrative review and practice guidelines. Pediatr Res 2025:10.1038/s41390-025-03805-8. [PMID: 39809859 DOI: 10.1038/s41390-025-03805-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/12/2024] [Accepted: 12/15/2024] [Indexed: 01/16/2025]
Abstract
Clinicians may face an array of challenges in conducting fetal neurological consultations including prognostic uncertainty, a lack of training in fetal counseling, and limited opportunity to build rapport with families. In this setting, it is critical to employ high-quality, family-centered care to allow expectant parents to make informed decisions. Despite the challenges and gravity of these consultations, there remains limited data outlining best conduct and communication practices. This narrative review aims to summarize relevant literature around counseling within fetal neurology, focusing on three key themes: (1) discussing neurological prognosis and uncertainty, (2) navigating evolving decision making, (3) recognizing bias and understanding patient context. We provide practical recommendations to clinicians conducting fetal neurological counseling and outline future research priorities. IMPACT: Fetal neurological conditions can have a significant impact on child short- and long-term health outcomes. Prenatal consultations are an important venue to discuss information regarding fetal prognosis and decision making with expectant parents. However, there is limited evidence supporting best communication practices within this setting. This review summarizes current literature around expectant parent prognostic communication preferences and outlines practical recommendations and priorities for future research.
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Affiliation(s)
| | - Charu Venkatesan
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Dawn Gano
- Departments of Neurology and Pediatrics, UCSF Benioff Children's Hospitals, University of California San Francisco, San Francisco, CA, USA
| | - Sonika Agarwal
- Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA
| | | | - Sarahn Wheeler
- Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
| | - Jeffrey B Russ
- Division of Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
| | - Monica E Lemmon
- Division of Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
- Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA.
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Yang C, Chi X, Wang Y, Zhang C, Zhou R, Jia X, Qiao F, Xu Z. Subgroup analysis of imaging scans, invasive examinations and prognosis in mild-to-moderate isolated foetal cerebral ventriculomegaly: a retrospective study in China. J Int Med Res 2024; 52:3000605241301879. [PMID: 39648848 PMCID: PMC11626665 DOI: 10.1177/03000605241301879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 11/05/2024] [Indexed: 12/10/2024] Open
Abstract
OBJECTIVE This study aimed to analyse the causes of foetal mild-to-moderate isolated ventriculomegaly (IVM) and to evaluate the prognosis of neurological development in surviving children in different subgroups. METHODS We retrospectively studied mild-to-moderate IVM diagnosed by prenatal ultrasound scans in different subgroups according to the laterality of IVM, the degree of IVM and foetal sex independently. The results of foetal chromosomal microarray analysis, virological tests of umbilical cord blood or amniotic fluid, foetal magnetic resonance imaging and ultrasound were collected. Long-term follow-up was performed to assess the neurodevelopment of children within 66 months through telephone interviews and/or the Ages and Stages Questionnaire-3. RESULTS The moderate group showed more chromosomal abnormalities (16.2% vs. 4.1%) and greater structural anomalies in the brain (31.8% vs. 7.5%) than the mild group. Female foetuses showed more structural anomalies than male foetuses (25.0% vs. 7.2%). However, an adverse prognosis of children was not different across the different subgroups. CONCLUSION Moderate IVM may be more strongly associated with chromosomal aberrations and structural malformations than mild IVM. However, the adverse prognosis of children was similar between the different subgroups analysed.
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Affiliation(s)
- Chun Yang
- Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
- Department of Obstetrics and Gynecology, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou, China
| | - Xia Chi
- Department of Children Healthcare, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
| | - Yan Wang
- Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
| | - Cuiping Zhang
- Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
| | - Ran Zhou
- Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
| | - Xuemei Jia
- Department of Gynecology, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
- Nanjing Medical Key Laboratory of Female Fertility Preservation and Restoration, Nanjing, China
| | - Fengchang Qiao
- Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
| | - Zhengfeng Xu
- Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), Nanjing, China
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于 蕾, 肖 雪, 战 军, 韩 刘. [Research Progress in Magnetic Resonance Imaging of Fetal Ventriculomegaly]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2024; 55:1133-1137. [PMID: 39507970 PMCID: PMC11536245 DOI: 10.12182/20240960107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Indexed: 11/08/2024]
Abstract
Fetal ventriculomegaly is a central nervous system disorder commonly seen in prenatal imaging, and the prognosis ranges from normal health to severe dysfunction. Currently, fetal predictive markers associated with postpartum individual neurodevelopmental function are still not available, which increases the difficulty of prenatal diagnosis and clinical management. Constant advancements in magnetic resonance imaging (MRI) technology have brought better accuracy and reliability of MRI applied in the diagnosis, prognosis assessment, and etiology investigation of ventriculomegaly. MRI plays a critical role in prognostic management and prenatal consultation. Nevertheless, due to the potential safety hazards and economic and technical constraints of MRI, it is not the first choice for prenatal imaging diagnosis. Moreover, there are different opinions regarding the measurement results and grading criteria of ultrasound and MRI. At present, it is accepted that three-dimensional volume may provide reliable information for prognosis. However, accurate segmentation and measurement of brain structure remain serious challenges, and no consensus on the MRI measurement of lateral ventricle volume has been reached. In this paper, based on the latest research reports from China and around the world, we reviewed the progress in applying MRI in the prenatal diagnosis and treatment of ventriculomegaly. This review offers a theoretical foundation for further exploration of the role of lateral ventricle volume measurement in disease diagnosis and management. We suggest that researchers combine two-dimensional width with three-dimensional volume in the future to identify the optimal cutoff value for prognostic prediction of fetal ventriculomegaly.
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Affiliation(s)
- 蕾 于
- 四川大学华西第二医院 妇产科 （成都 610041）Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- 出生缺陷与相关妇儿疾病教育部重点实验室（四川大学） （成都 610041）Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
| | - 雪 肖
- 四川大学华西第二医院 妇产科 （成都 610041）Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- 出生缺陷与相关妇儿疾病教育部重点实验室（四川大学） （成都 610041）Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
| | - 军 战
- 四川大学华西第二医院 妇产科 （成都 610041）Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- 出生缺陷与相关妇儿疾病教育部重点实验室（四川大学） （成都 610041）Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
| | - 刘杰 韩
- 四川大学华西第二医院 妇产科 （成都 610041）Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
- 出生缺陷与相关妇儿疾病教育部重点实验室（四川大学） （成都 610041）Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
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Agarwal S, Venkatesan C, Vollmer B, Scelsa B, Lemmon ME, Pardo AC, Mulkey SB, Tarui T, Dadhwal V, Scher M, Hart AR, Gano D. Fetal Cerebral Ventriculomegaly: A Narrative Review and Practical Recommendations for Pediatric Neurologists. Pediatr Neurol 2024; 156:119-127. [PMID: 38761643 DOI: 10.1016/j.pediatrneurol.2024.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 04/19/2024] [Indexed: 05/20/2024]
Abstract
Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists.
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Affiliation(s)
- Sonika Agarwal
- Division of Neurology & Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Division of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Charu Venkatesan
- Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Brigitte Vollmer
- Faculty of Medicine, Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK; Paediatric and Neonatal Neurology, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Barbara Scelsa
- Department of Pediatric Neurology, Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Monica E Lemmon
- Department of Pediatrics and Population Health Sciences, Duke University School of Medicine, Durham, North Carolina
| | - Andrea C Pardo
- Division of Neurology, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Sarah B Mulkey
- Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, District of Columbia; Departments of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; Division of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
| | - Tomo Tarui
- Division of Pediatric Neurology, Hasbro Children's Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Vatsla Dadhwal
- Professor, Maternal Fetal Medicine, Department of Obstetrics & Gynecology, All India Institute of Medical Sciences, New Delhi, India
| | - Mark Scher
- Emeritus Full Professor Pediatrics and Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Anthony R Hart
- Department of Paediatric Neurology, King's College Hospital NHS Foundation Trust, London, UK
| | - Dawn Gano
- Department of Neurology & Pediatrics, University of California San Francisco, San Francisco, California
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Yue F, Yang X, Liu N, Liu R, Zhang H. Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly. Front Med (Lausanne) 2024; 11:1349171. [PMID: 38784233 PMCID: PMC11111914 DOI: 10.3389/fmed.2024.1349171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 04/26/2024] [Indexed: 05/25/2024] Open
Abstract
Objective 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. Methods 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. Results 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). Conclusion 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.
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Affiliation(s)
- Fagui Yue
- Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China
- Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, China
| | - Xiao Yang
- Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China
- Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, China
| | - Ning Liu
- Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China
- Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, China
| | - Ruizhi Liu
- Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China
- Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, China
| | - Hongguo Zhang
- Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, China
- Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, China
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Navarro-Ballester A, Rovira-Ferrando RE, Ródenas-Hernández JM, Bandura A, Fernández-García P, Marco Doménech SF. New reference nomograms for the study of ventricular size in preterm infants. RADIOLOGIA 2024; 66:219-227. [PMID: 38908883 DOI: 10.1016/j.rxeng.2022.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 11/21/2022] [Indexed: 06/24/2024]
Abstract
INTRODUCTION Transfontanellar brain ultrasound is an essential tool for monitoring the size of the ventricles in preterm neonates and has many advantages over other alternative diagnostic techniques, including its accessibility and non-use of ionizing radiation. When considering the normal ventricular size, it is essential to have reference measurements based on age-matched populations. The objective of this article is to present our reference measures, based on a sample of preterm infants that we have studied. METHODS A retrospective observational study was conducted. Measurements of the Levene index, frontal horn thickness, and Evans index were obtained in preterm neonates from 25 to 45 weeks, over a period of 5 years, between January 2016 and December 2020. After applying the exclusion criteria, a sample of 199 patients and 350 ultrasound scans were obtained. The independent samples t-test and the Mann-Whitney test were used for the comparison of samples. RESULTS The distribution of the right and left Levene indices was normal (Shapiro-Wilk test with p = 0.16 and 0.05, respectively), unlike the thickness distribution of the frontal horns (p < 0.05 on both sides). No significant differences were detected between the sexes (p = 0.08). A linear correlation was found between the biparietal diameter and the Levene index. CONCLUSION From the results obtained in our study, we present reference tables for ventricular size, with the 3rd, 25th, 50th, 75th, and 97th, being the first ones made in our country.
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Affiliation(s)
- A Navarro-Ballester
- Departamento de Radiología, Hospital General Universitario de Castelló, Castellón de la Plana, Spain.
| | - R E Rovira-Ferrando
- Departamento de Radiología, Hospital General Universitario de Castelló, Castellón de la Plana, Spain
| | - J M Ródenas-Hernández
- Departamento de Radiología, Hospital General Universitario de Castelló, Castellón de la Plana, Spain
| | - A Bandura
- Departamento de Radiología, Hospital General Universitario de Castelló, Castellón de la Plana, Spain
| | - P Fernández-García
- Departamento de Radiología, Hospital General Universitario de Castelló, Castellón de la Plana, Spain
| | - S F Marco Doménech
- Departamento de Radiología, Hospital General Universitario de Castelló, Castellón de la Plana, Spain
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Wang X, Zhang S, Wang J, Zhang S, Feng L, Wu Q. Follow-up outcome analysis of 324 cases of early-onset and late-onset mild fetal ventriculomegaly: a retrospective cohort study. Eur J Med Res 2024; 29:128. [PMID: 38365795 PMCID: PMC10870476 DOI: 10.1186/s40001-024-01709-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/01/2024] [Indexed: 02/18/2024] Open
Abstract
BACKGROUND Mild fetal ventriculomegaly (VM) is a nonspecific finding common to several pathologies with varying prognosis and is, therefore, a challenge in fetal consultation. We aimed to perform a constant, detailed analysis of prenatal findings and postnatal outcomes in fetuses with early-onset and late-onset mild ventriculomegaly, and provide a new evidence basis and new perspective for prenatal counseling. METHODS This is a retrospective cohort study of women with a diagnosis of mild fetal VM between January 2018 and October 2020. The population was divided into two groups according to the gestational ages (GAs) at initial diagnosis: the early-onset group (diagnosed at/before 24+6 weeks) and the late-onset group (diagnosed after 24+6 weeks). Clinical data and pregnancy outcomes were obtained from hospital records. The children's neurodevelopment status was assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and telephone interviews. RESULTS Our study cohort comprised 324 fetuses, out of which 94 (29%) were classified as early-onset group and 230 (71%) late-onset group. Early-onset group was more likely to have concurrent additional abnormalities, whereas in the late-onset group, isolated enlargement was more common (P = 0.01). Unilateral enlargement was more common in the late-onset group (P = 0.05), and symmetrical enlargement in the early-onset group (P < 0.01). In addition, early-onset mild VM cases were more likely to have intrauterine progression (P = 0.03), and many had a higher proportion of complex multisystem abnormalities. Compared with the late-onset group, the early-onset group was more often associated with congenital brain structure malformations. Approximately 11% of fetuses with mild VM had postnatal neurodevelopmental delay/disorders, and the risk was higher in the early-onset group (19.4% vs. 7.4%). Regression analysis showed that the GA at first diagnosis, non-isolated, and intrauterine progression significantly correlated with neurodevelopmental abnormalities. CONCLUSIONS Early-onset and late-onset mild VM had significantly different ultrasound features and outcomes. Early-onset mild VM may have more complex potential abnormalities and are more likely to predict poor prognosis than the late-onset.
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Affiliation(s)
- Xuemei Wang
- Ultrasound Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's Republic of China
- Ultrasound Department, The Second Affiliated Hospital of Shandong First Medical University, 271000, Taian, Shandong, People's Republic of China
| | - Shanlong Zhang
- Ultrasound Department, The Second Affiliated Hospital of Shandong First Medical University, 271000, Taian, Shandong, People's Republic of China
| | - Jingjing Wang
- Ultrasound Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's Republic of China
| | - Simin Zhang
- Ultrasound Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's Republic of China
| | - Li Feng
- Ultrasound Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's Republic of China
| | - Qingqing Wu
- Ultrasound Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, No.251 Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's Republic of China.
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Di Mascio D, D'Antonio F, Rizzo G, Pilu G, Khalil A, Papageorghiou AT. Counseling in fetal medicine: update on mild and moderate fetal ventriculomegaly. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2024; 63:153-163. [PMID: 38301072 DOI: 10.1002/uog.26251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 03/31/2023] [Accepted: 05/07/2023] [Indexed: 02/03/2024]
Affiliation(s)
- D Di Mascio
- Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy
| | - F D'Antonio
- Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy
| | - G Rizzo
- Department of Obstetrics and Gynecology, Fondazione Policlinico Tor Vergata, University of Rome Tor Vergata, Rome, Italy
| | - G Pilu
- Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - A Khalil
- Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London, UK
- Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK
- Fetal Medicine Unit, Liverpool Women's Hospital, University of Liverpool, Liverpool, UK
| | - A T Papageorghiou
- Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK
- Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, UK
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Gómez-Arriaga PI, Núñez N, Zamora B, Villalaín C, Risco B, Liébana C, Herraiz I, Galindo A. Natural history and mid-term neurodevelopmental outcome of fetuses with isolated mild ventriculomegaly diagnosed in the second half of pregnancy. J Matern Fetal Neonatal Med 2023; 36:2214836. [PMID: 37217456 DOI: 10.1080/14767058.2023.2214836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 05/10/2023] [Accepted: 05/12/2023] [Indexed: 05/24/2023]
Abstract
INTRODUCTION Prenatal diagnosis and counseling of isolated ventriculomegaly (VM) represent a considerable challenge. We aimed to analyze the intrauterine evolution, associated anomalies, and neurodevelopmental outcome using the Battelle Development Inventory (BDI) of fetuses with an initial diagnosis of isolated mild VM. MATERIAL AND METHODS Retrospective cohort study of fetuses diagnosed with mild isolated VM (10 -12 mm) between 2012 and 2016 in a tertiary hospital. In 2018, parents were invited to complete the structured BDI test for the neurodevelopmental evaluation of their children in five domains (personal-social skills, adaptive behavior, psychomotor ability, communication, and cognition). Results exceeding two standard deviations were considered abnormal and referred to an expert neuropediatrician. RESULTS We identified 43 cases of mild isolated VM. In 5 (11%), structural abnormalities were detected during prenatal follow-up, being related to non-regressive forms (p = .01) and bilateral VM (p = .04). The BDI test was completed by 19/43 (44%). The global score was abnormal in 10/19 (53%). Of them, the neuropediatrician confirmed a neurodevelopmental delay solely in 3 cases that had already been diagnosed with neurological disorders. The most affected domains were gross motor skills (63%), personal-social (63%), and adaptive domains (47%). Communicative and cognitive areas were abnormal in 26% of cases. CONCLUSION In fetuses with isolated mild VM detected in the second half of pregnancy, 53% had an abnormal BDI test at 2-6 years, but a neurological disorder was only confirmed in the 30% of them.
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Affiliation(s)
- Paula I Gómez-Arriaga
- Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre. Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Noemí Núñez
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Pediatric Neurology Unit, Department of Neurology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Berta Zamora
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Pediatric Rare Diseases Unit, Department of Pediatrics, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Cecilia Villalaín
- Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre. Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Beatriz Risco
- Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre. Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Constanza Liébana
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Pediatric Radiology, Department of Radiology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Ignacio Herraiz
- Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre. Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Primary Care Interventions to Prevent Maternal and Child Diseases of Perinatal and Developmental Origin (RICORS network, Instituto de Salud Carlos III, Madrid, Spain
| | - Alberto Galindo
- Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre. Faculty of Medicine, Complutense University of Madrid, Madrid, Spain
- Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
- Primary Care Interventions to Prevent Maternal and Child Diseases of Perinatal and Developmental Origin (RICORS network, Instituto de Salud Carlos III, Madrid, Spain
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12
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Tao H, Zhang L, Tan F, Han Y, Wang X, Wu J, Zhai J. Pregnancy outcomes and genetic analysis for fetal ventriculomegaly. Front Genet 2023; 14:1186660. [PMID: 37795247 PMCID: PMC10545856 DOI: 10.3389/fgene.2023.1186660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/07/2023] [Indexed: 10/06/2023] Open
Abstract
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.
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Affiliation(s)
- Huimin Tao
- Xuzhou Central Hospital, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China
- Key Laboratory of Brain Diseases Bioinformation of Xuzhou Medical University, Xuzhou, China
- Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou, China
| | - Lin Zhang
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, Jiangsu, China
| | - Fangfang Tan
- Xuzhou Central Hospital, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China
- Key Laboratory of Brain Diseases Bioinformation of Xuzhou Medical University, Xuzhou, China
| | - Yu Han
- Xuzhou Central Hospital, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China
- Key Laboratory of Brain Diseases Bioinformation of Xuzhou Medical University, Xuzhou, China
- Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou, China
| | - Xuezhen Wang
- Xuzhou Central Hospital, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China
- Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou, China
| | - Jiebin Wu
- Xuzhou Central Hospital, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China
- Key Laboratory of Brain Diseases Bioinformation of Xuzhou Medical University, Xuzhou, China
| | - Jingfang Zhai
- Xuzhou Central Hospital, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China
- Key Laboratory of Brain Diseases Bioinformation of Xuzhou Medical University, Xuzhou, China
- Department of Prenatal Diagnosis Medical Center, Xuzhou Central Hospital, Xuzhou, China
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Zhang H, Linpeng S, Teng Y, Peng C, Liang D, Li Z, Wu L. A de novo heterozygous POU3F3 genotype for the p.(Q214*) variant in a fetus with transient isolated bilateral mild ventriculomegaly: a case report and review of the literature. Front Pediatr 2023; 11:1177137. [PMID: 37593446 PMCID: PMC10427865 DOI: 10.3389/fped.2023.1177137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 07/13/2023] [Indexed: 08/19/2023] Open
Abstract
The prenatal prevalence of isolated ventriculomegaly is 0.039%-0.087%. Most isolated mild ventriculomegaly (MV) fetuses (>90%) have a favorable prognosis. However, 5.6% to 7.9% of fetuses with isolated MV have adverse neurodevelopmental outcomes. In this study, we reported the first case of prenatal Snijders Blok-Fisher syndrome (OMIM: #618604) caused by a truncating variant of POU3F3 (OMIM: *602480) in a fetus with transient isolated bilateral MV. The results of karyotype analysis, chromosomal microarray analysis, and TORCH infection evaluation for the fetus were all negative. However, a de novo likely pathogenic nonsense variant of NM_006236.3 (POU3F3): c.640C > T [rs1254251078] p.(Q214*) was identified by whole-exome sequencing (WES). Despite sufficient genetic counseling, the mother refused to undertake further brain magnetic resonance imaging (MRI) and decided to keep the fetus. She gave birth to a male infant through a full-term vaginal delivery. With a long-term follow-up, the infant unfortunately gradually presented with delayed motor development. The postnatal brain MRI of the proband showed dysplasia of the corpus callosum and ventriculomegaly. Considering the high probability of misdiagnosis for such cases, we further summarized the prenatal phenotypes from 19 reported patients with variants in POU3F3. The results revealed that 14 patients displayed a normal prenatal ultrasonographic manifestation, while only approximately 26.32% of fetuses showed MV or cysts without structural deformity. Thus our findings expand the variant spectrum of POU3F3 and suggest the importance of undertaking WES and brain MRI when the fetus has isolated bilateral MV.
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Affiliation(s)
- Hongyun Zhang
- Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
| | - Siyuan Linpeng
- Department of Genetics and Eugenics, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University, Changsha, China
| | - Yanling Teng
- Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
| | - Can Peng
- Department of Genetics and Eugenics, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal University, Changsha, China
| | - Desheng Liang
- Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Laboratory of Molecular Genetics, Hunan Jiahui Genetics Hospital, Changsha, China
| | - Zhuo Li
- Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
| | - Lingqian Wu
- Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Laboratory of Molecular Genetics, Hunan Jiahui Genetics Hospital, Changsha, China
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14
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Whitehead MT, Limperopoulos C, Schlatterer SD, Mulkey SB, Fraser JL, du Plessis AJ. Hippocampal rotation is associated with ventricular atrial size. Pediatr Radiol 2023; 53:1941-1950. [PMID: 37183230 DOI: 10.1007/s00247-023-05687-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 04/13/2023] [Accepted: 04/27/2023] [Indexed: 05/16/2023]
Abstract
BACKGROUND Fetal ventriculomegaly is a source of apprehension for expectant parents and may present prognostic uncertainty for physicians. Accurate prenatal counseling requires knowledge of its cause and associated findings as the differential diagnosis is broad. We have observed an association between ventriculomegaly and incomplete hippocampal inversion. OBJECTIVE To determine whether ventricular size is related to incomplete hippocampal inversion. MATERIALS AND METHODS We retrospectively evaluated pre- and postnatal brain MRIs in normal subjects (mean GA, 31 weeks; mean postnatal age, 27 days) and patients with isolated ventriculomegaly (mean GA, 31 weeks; mean postnatal age, 68 days) at a single academic medical center. Lateral ventricular diameter, multiple qualitative and quantitative markers of hippocampal inversion, and evidence of intraventricular hemorrhage were documented. RESULTS Incomplete hippocampal inversion and ventricular size were associated in both normal subjects (n=51) and patients with ventriculomegaly (n=32) (P<0.05). Severe ventriculomegaly was significantly associated with adverse clinical outcome in postnatal (P=0.02) but not prenatal (P=0.43) groups. In all additional cases of isolated ventriculomegaly, clinical outcome was normal over the time of assessment (mean 1±1.9 years; range 0.01 to 10 years). CONCLUSION Lateral ventricular atrial diameter and incomplete hippocampal inversion are associated. Less hippocampal inversion correlates with larger atria. For every 1-mm increase in fetal ventricular size, the odds of incomplete hippocampal inversion occurring increases by a factor of 1.6 in normal controls and 1.4 in patients with ventriculomegaly.
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Affiliation(s)
- Matthew T Whitehead
- Department of Neuroradiology, Children's National Hospital, Washington, DC, USA.
- Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA.
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
- Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, DC, USA.
- Division of Neuroradiology, Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
- Department of Radiology Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Catherine Limperopoulos
- Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, DC, USA
| | - Sarah D Schlatterer
- Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, DC, USA
| | - Sarah B Mulkey
- Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, DC, USA
| | - Jamie L Fraser
- Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, DC, USA
| | - Adre J du Plessis
- Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA
- The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Division of Fetal and Transitional Medicine, Children's National Hospital, Washington, DC, USA
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15
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Nuevos normogramas de referencia para el estudio de la talla ventricular en neonatos pretérmino. RADIOLOGIA 2023. [DOI: 10.1016/j.rx.2022.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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16
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Geerts C, Sznajer Y, D'haenens E, Dumitriu D, Nassogne MC. Phenotypic spectrum of patients with Poretti-Boltshauser syndrome: Patient report of antenatal ventriculomegaly and esophageal atresia. Eur J Med Genet 2023; 66:104692. [PMID: 36592689 DOI: 10.1016/j.ejmg.2022.104692] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 11/12/2022] [Accepted: 12/29/2022] [Indexed: 01/01/2023]
Abstract
Poretti-Boltshauser syndrome (PTBHS) is an autosomal recessive disorder characterized by cerebellar dysplasia with cysts and an abnormal shape of the fourth ventricle on neuroimaging, due to pathogenic variants in the LAMA1 gene. The clinical spectrum mainly consists of neurological and ophthalmological manifestations, including non-progressive cerebellar ataxia, oculomotor apraxia, language impairment, intellectual disability, high myopia, abnormal eye movements and retinal dystrophy. We report a patient presenting with ventriculomegaly on antenatal neuroimaging and a neonatal diagnosis of Type III esophageal atresia. She subsequently developed severe myopia and strabismus with retinal dystrophy, mild developmental delay, and cerebellar dysplasia. Genetic investigations confirmed PTBHS. This report confirms previous reports of antenatal ventriculomegaly in PTBHS patients and documents a so far unreported occurrence of esophageal atresia in PTBHS. We additionally gathered phenotype and genotype descriptions of published cases in an effort to better define the spectrum of PTBHS.
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Affiliation(s)
- Chloé Geerts
- Paediatric Neurology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
| | - Yves Sznajer
- Center for Human Genetics, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Erika D'haenens
- Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium
| | - Dana Dumitriu
- Paediatric Radiology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium
| | - Marie-Cécile Nassogne
- Paediatric Neurology, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium
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Short-Term and Long-Term Outcomes of Fetal Ventriculomegaly beyond Gestational 37 Weeks: A Retrospective Cohort Study. J Clin Med 2023; 12:jcm12031065. [PMID: 36769715 PMCID: PMC9917544 DOI: 10.3390/jcm12031065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/17/2023] [Accepted: 01/28/2023] [Indexed: 01/31/2023] Open
Abstract
Birth defects have brought about major public health problems, and studying the clinical outcomes of the most common prenatal central nervous system abnormality, namely, fetal ventriculomegaly (VM), is helpful for improving reproductive health and fertility quality. This is a retrospective cohort study from 2011 to 2020 in the West China Second University Hospital, Sichuan University, aiming to evaluate the short-term and long-term outcomes of VM over 37 weeks' gestation to exclude the influence of preterm birth. The study analyzed data from 401 term pregnancies, with 179 VM and 222 controls. From the short-term outcomes, the rate of the neonatal intensive care unit (NICU) admission under the VM group (10.06%) was comparatively higher than the control (0.45%), but Apgar scores between both groups at 1 min, 5 min and 10 min were not significantly different. From the long-term outcomes, there were more infants with abnormal neurodevelopment under the VM group than control (14.53% vs. 2.25%, p < 0.001). In addition, NICU admission (p = 0.006), peak width of lateral ventricles (p = 0.030) and postnatal cranial ultrasound suggestive with VM (p = 0.002) were related to infants' long-term outcomes. NICU admission during the perinatal period was an independent risk factor for the adverse long-term outcomes (OR = 3.561, 95% CI 1.029-12.320, p = 0.045). In conclusion, VM impairs short-term and long-term outcomes of term infants. Short-term outcome, especially NICU admission, could predict their adverse long-term outcomes.
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Abstract
Ventriculomegaly (VM) is defined as an enlargement of the lateral ventricles of the developing fetal brain. The diagnosis is easily made by measuring the lateral ventricle width at the level of the atrium, which is normally <10 mm. VM is defined as mild when the atrial width is 10-12 mm, moderate 12-15 mm, severe >15 mm. VM is a non-specific sonographic sign which is common to different pathological entities and genetic conditions. When no associated anomaly can be found VM is defined as isolated. Since the prognosis of fetal VM mainly depends on the presence of associated anomalies, a careful diagnostic approach is necessary to rule out CNS and extra- CNS fetal anomalies. Magnetic Resonance Imaging can be a useful diagnostic tool complementary to ultrasound in order to recognize subtle brain anomalies, particularly cortical disorders. In this review the diagnostic approach to fetal VM will be discussed starting from ultrasound screening, moving to neurosonographic and MRI examination and genetic evaluation, in order to recognize the cause of VM and offer the appropriate counselling to the parents.
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Abstract
Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system diseases and disorders likely reflects shared vulnerability of their inflammatory and oxidative stress-based mechanisms and a corresponding ability to produce brain metal dyshomeo-stasis. Future research to define the responsible contaminants of air pollution underlying this neurotoxicity is critical to understanding mechanisms of these diseases and disorders and protecting public health.
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Affiliation(s)
- Deborah A Cory-Slechta
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA;
| | - Alyssa Merrill
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA;
| | - Marissa Sobolewski
- Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA;
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20
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Li Q, Ju XW, Xu J, Jiang J, Lu C, Ju XD. Maternal blood inflammatory marker levels increased in fetuses with ventriculomegaly. Front Hum Neurosci 2022; 16:998206. [PMID: 36545352 PMCID: PMC9760835 DOI: 10.3389/fnhum.2022.998206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/16/2022] [Indexed: 12/07/2022] Open
Abstract
Background Fetal ventriculomegaly (VM) is one of the most common abnormalities of the central nervous system (CNS), which can be significantly identified by brain anomalies prenatally by magnetic resonance imaging (MRI). Aberrant white blood cells (WBCs) levels indicate that the maternal is suffering from the infection. Previous studies have confirmed that prenatal infection can affect fetal brain structure, but there is no research revealed the association between maternal blood parameters with fetal VM until now. Methods We measured the width of the lateral ventricle of 142 fetuses, which were divided into the fetal VM group (n = 70) and the normal lateral ventricle group (n = 72). We compared maternal blood cell levels between the two groups and investigate potential biomarkers of fetal VM. Result High levels of maternal WBC and neutrophil (NE#) levels were observed in fetuses with VM (p < 0.001), while lymphocyte percentage, monocytes (MO#), neutrophil/lymphocyte ratio (NLR), and platelet were also increased in the fetal VM group (p = 0.033, 0.027, 0.034, and 0.025, respectively). receiver-operator curve (ROC) analysis suggested that WBC and NE# counts might be useful to distinguish fetuses with enlarged lateral ventricles (AUC = 0.688, 0.678, respectively). Conclusion The current study emphasizes the importance of maternal infection for fetal brain growth, which could provide important information for prenatal diagnosis of CNS anomalies. Future research needs longitudinal analysis and exploration of the influence of maternal blood inflammatory marker levels on fetal brain development.
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Affiliation(s)
- Qiang Li
- School of Psychology, Northeast Normal University, Changchun, China
| | - Xin-Wei Ju
- Department of Radiology, The First Hospital of Jilin University, Changchun, China
| | - Jing Xu
- School of Life Sciences, Northeast Normal University, Changchun, China
| | - Jiuhong Jiang
- School of Information Science and Technology, Northeast Normal University, Changchun, China
| | - Chang Lu
- School of Psychology, Northeast Normal University, Changchun, China,Jilin Provincial Key Laboratory of Cognitive Neuroscience and Brain Development, Changchun, China,*Correspondence: Chang Lu,
| | - Xing-Da Ju
- School of Psychology, Northeast Normal University, Changchun, China,Autism Centre of Excellence, Northeast Normal University, Changchun, China,Xing-Da Ju,
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Sohret NC, Tekin AN, Surmeli Onay O, Suman K, Aydemir O, Velipasaoglu M. Assessment of foetal ventriculomegaly from prenatal to early postnatal period: a single-centre retrospective cohort study. J OBSTET GYNAECOL 2022; 42:2999-3006. [PMID: 36149296 DOI: 10.1080/01443615.2022.2125295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The aim of this study was to evaluate the early neonatal outcomes of cases with foetal ventriculomegaly (VM) and to investigate the aetiological and prognostic factors according to the degree of VM in a single tertiary referring centre. The medical records of 87 foetuses diagnosed with VM (≥10 mm) within 6 years were evaluated. Postnatal evaluation and early neonatal prognosis were determined in 39 cases divided into two groups as mild (10-15 mm, 30 cases) and severe (>15 mm, 9 cases) according to the ventricular size. The mean gestational age at which foetal VM was detected was 22 + 3 weeks. In terms of severity, severe cases of VM were more frequent in terminated pregnancies. There was no difference in gestational age, birth weight, fifth minute Apgar scores, or cord blood gases between mild and severe cases at delivery. Isolated VM was detected in 63% of mild and 22% of severe cases. In severe cases, the need for intensive care and surgery was higher than in mild cases. Antenatal VM regressed in 50% of mild cases and 22% of severe cases. Increasing knowledge about neonatal prognosis, the factors involved in aetiology, and the degree of VM will guide the management of foetal VM.IMPACT STATEMENTWhat is already known in this subject? Some cases of foetal VM resolve spontaneously, and postnatal ultrasonography can detect normal ventricle sizes. While 74.6% of isolated VM cases show spontaneous regression, this rate is 52.1% in nonisolated cases. The gestational week at the time of diagnosis, the degree and cause of VM, intrauterine progression and the presence of any genetic, infectious, cerebral, or extracerebral disorders all influence the prognosis.What do the results of this study add? Antenatal VM regressed in 50% of mild cases and 22% of severe cases. In severe cases, the need for intensive care and surgery was higher than in mild cases. The higher frequency of accompanying cerebral findings in severe cases was striking.What are the implications of these findings for clinical practice and/or further research? The current study revealed that isolated VM with ventricular diameter less than 15 mm, after excluding out chromosomal abnormalities and prenatal infections, and no prior history of VM, has a favourable neonatal prognosis in terms of mortality and morbidity. In cases of foetal VM, increased knowledge of neonatal prognosis will guide pregnancy care and postnatal follow-up planning. Prospective multicentre studies on the neonatal period are required to bridge the gap between foetal VM and long-term consequences.
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Affiliation(s)
- Nurullah Cihan Sohret
- Department of Pediatrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.,Division of Neonatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey
| | - Ayse Neslihan Tekin
- Department of Pediatrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.,Division of Neonatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey
| | - Ozge Surmeli Onay
- Department of Pediatrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.,Division of Neonatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey
| | - Kamuran Suman
- Department of Gynecology and Obstetrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.,Division of Perinatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey
| | - Ozge Aydemir
- Department of Pediatrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.,Division of Neonatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey
| | - Melih Velipasaoglu
- Department of Gynecology and Obstetrics, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.,Division of Perinatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey
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22
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Griffiths PD, Jarvis D, Connolly DJ, Mooney C, Embleton N, Hart AR. Predicting neurodevelopmental outcomes in fetuses with isolated mild ventriculomegaly. Arch Dis Child Fetal Neonatal Ed 2022; 107:431-436. [PMID: 34844985 DOI: 10.1136/archdischild-2021-321984] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 10/16/2021] [Indexed: 11/04/2022]
Abstract
BACKGROUND Fetal ventriculomegaly is the the most common intracranial abnormality detected antenatally. When ventriculomegaly is mild and the only, isolated, abnormality detected (isolated mild ventriculomegaly (IMVM)) the prognosis is generally considered to be good. We aim to determine if there are features on in utero MRI (iuMRI) that can identify fetuses with IMVM who have lower risks of abnormal neurodevelopment outcome. METHODS We studied cases recruited into the MRI to enhance the diagnosis of fetal developmental brain abnormalities in utero (MERIDIAN) study, specifically those with: confirmed IMVM, 3D volume imaging of the fetal brain and neurodevelopmental outcomes at 3 years. We explored the influence of sex of the fetus, laterality of the ventriculomegaly and intracranial compartmental volumes in relation to neurodevelopmental outcome. FINDINGS Forty-two fetuses met the criteria (33 male and 9 female). There was no obvious correlation between fetal sex and the risk of poor neurodevelopmental outcome. Unilateral IMVM was present in 23 fetuses and bilateral IMVM in 19 fetuses. All fetuses with unilateral IMVM had normal neurodevelopmental outcomes, while only 12/19 with bilateral IMVM had normal neurodevelopmental outcomes. There was no obvious correlation between measure of intracranial volumes and risk of abnormal developmental outcomes. INTERPRETATION The most important finding is the very high chance of a good neurodevelopmental outcome observed in fetuses with unilateral IMVM, which is a potentially important finding for antenatal counselling. There does not appear to be a link between the volume of the ventricular system or brain volume and the risk of poor neurodevelopmental outcome.
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Affiliation(s)
| | - Deborah Jarvis
- Academic Unit of Radiology, The University of Sheffield, Sheffield, UK
| | - Daniel J Connolly
- Neuroradiology, Sheffield Childrens Hospital NHS Foundation Trust, Sheffield, UK
| | - Cara Mooney
- Clinical Trials Research Unit, School of Health and Related Research, The University of Sheffield, Sheffield, UK
| | - Nicholas Embleton
- Newcastle Neonatal Service, Ward 35 Neonatal Unit, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Anthony Richard Hart
- Department of Paediatric and Perinatal Neurology, Sheffield Children's NHS Foundation Trust, Sheffield, UK
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23
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Dai Y, Liu Y, Zhang L, Ren T, Wang H, Yu J, Liu X, Chen Z, Deng L, Tao M, Tan H, Huang CC, Zhang J, Luo Q, Feng J, Cao M, Li F. Shanghai Autism Early Development: An Integrative Chinese ASD Cohort. Neurosci Bull 2022; 38:1603-1607. [PMID: 35739378 PMCID: PMC9723093 DOI: 10.1007/s12264-022-00904-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/14/2022] [Indexed: 02/07/2023] Open
Affiliation(s)
- Yuan Dai
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Yuqi Liu
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Lingli Zhang
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Tai Ren
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Hui Wang
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Juehua Yu
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China ,grid.414902.a0000 0004 1771 3912Center for Experimental Studies and Research, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032 China
| | - Xin Liu
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Zilin Chen
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Lin Deng
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Minyi Tao
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Hangyu Tan
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
| | - Chu-Chung Huang
- grid.22069.3f0000 0004 0369 6365Key Laboratory of Brain Functional Genomics (Ministry of Education), Affiliated Mental Health Center, School of Psychology and Cognitive Science, East China Normal University, Shanghai, 200062 China ,grid.410642.5Shanghai Changning Mental Health Center, Shanghai, 200335 China
| | - Jiaying Zhang
- grid.20513.350000 0004 1789 9964State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875 China ,grid.20513.350000 0004 1789 9964Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, 100875 China ,grid.20513.350000 0004 1789 9964IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875 China
| | - Qiang Luo
- grid.8547.e0000 0001 0125 2443National Clinical Research Center for Aging and Medicine at Huashan Hospital, Fudan University, Shanghai, 200433 China ,grid.8547.e0000 0001 0125 2443Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 200433 China ,grid.8547.e0000 0001 0125 2443State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai, 200032 China ,grid.8547.e0000 0001 0125 2443Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, Fudan University, Shanghai, 200433 China
| | - Jianfeng Feng
- grid.8547.e0000 0001 0125 2443Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 200433 China ,grid.8547.e0000 0001 0125 2443Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, Fudan University, Shanghai, 200433 China
| | - Miao Cao
- grid.8547.e0000 0001 0125 2443Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 200433 China ,grid.8547.e0000 0001 0125 2443Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, Fudan University, Shanghai, 200433 China
| | - Fei Li
- grid.16821.3c0000 0004 0368 8293Department of Developmental and Behavioral Pediatric and Child Primary Care, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China
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24
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Yang Y, Zhao S, Sun G, Chen F, Zhang T, Song J, Yang W, Wang L, Zhan N, Yang X, Zhu X, Rao B, Yin Z, Zhou J, Yan H, Huang Y, Ye J, Huang H, Cheng C, Zhu S, Guo J, Xu X, Chen X. Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing. NPJ Genom Med 2022; 7:31. [PMID: 35562572 PMCID: PMC9106651 DOI: 10.1038/s41525-022-00301-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 04/06/2022] [Indexed: 11/09/2022] Open
Abstract
Structural anomalies of the central nervous system (CNS) are one of the most common fetal anomalies found during prenatal imaging. However, the genomic architecture of prenatal imaging phenotypes has not yet been systematically studied in a large cohort. Patients diagnosed with fetal CNS anomalies were identified from medical records and images. Fetal samples were subjected to low-pass and deep whole-genome sequencing (WGS) for aneuploid, copy number variation (CNV), single-nucleotide variant (SNV, including insertions/deletions (indels)), and small CNV identification. The clinical significance of variants was interpreted based on a candidate gene list constructed from ultrasound phenotypes. In total, 162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only. Hypoplasia of the cerebellum (including the cerebellar vermis) and holoprosencephaly had the highest primary diagnosis yields (>70%), while only four (11.8%) out of 34 neural tube defects achieved genetic diagnosis. Compared with the control group, rare singleton loss-of-function variants (SLoFVs) were significantly accumulated in the patient cohort.
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Affiliation(s)
- Ying Yang
- BGI-Shenzhen, Shenzhen, 518083, China
| | - Sheng Zhao
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Guoqiang Sun
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Fang Chen
- BGI-Shenzhen, Shenzhen, 518083, China
| | | | - Jieping Song
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Wenzhong Yang
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Lin Wang
- BGI-Shenzhen, Shenzhen, 518083, China
| | | | - Xiaohong Yang
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Xia Zhu
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Bin Rao
- BGI-Shenzhen, Shenzhen, 518083, China
| | | | - Jing Zhou
- BGI-Shenzhen, Shenzhen, 518083, China
| | | | | | - Jingyu Ye
- BGI-Shenzhen, Shenzhen, 518083, China
| | - Hui Huang
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Chen Cheng
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China
| | - Shida Zhu
- BGI-Shenzhen, Shenzhen, 518083, China
| | - Jian Guo
- BGI-Shenzhen, Shenzhen, 518083, China.
| | - Xun Xu
- BGI-Shenzhen, Shenzhen, 518083, China.
| | - Xinlin Chen
- Maternal and Child Health Hospital of Hubei Province, Hubei, 430070, China.
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25
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Hart AR, Vasudevan C, Griffiths PD, Foulds N, Piercy H, de Lacy P, Boxall S, Howe D, Vollmer B. Antenatal counselling for prospective parents whose fetus has a neurological anomaly: part 2, risks of adverse outcome in common anomalies. Dev Med Child Neurol 2022; 64:23-39. [PMID: 34482539 DOI: 10.1111/dmcn.15043] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 07/31/2021] [Accepted: 08/02/2021] [Indexed: 12/14/2022]
Abstract
After diagnosis of a fetal neurological anomaly, prospective parents want to know the best and worst-case scenarios and an estimation of the risk to their infant of having an atypical developmental outcome. The literature on developmental outcomes for fetal neurological anomalies is poor: studies are characterized by retrospective design, small sample size, often no standardized assessment of development, and differing definitions of anomalies. This review provides an aide-memoir on the risks of adverse neurodevelopmental outcome for ventriculomegaly, cortical anomalies, microcephaly, macrocephaly, agenesis of the corpus callosum, posterior fossa anomalies, and myelomeningocele, to assist healthcare professionals in counselling. The data in this review should be used alongside recommendations on counselling and service design described in part 1 to provide antenatal counselling.
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Affiliation(s)
- Anthony R Hart
- Department of Perinatal and Paediatric Neurology, Sheffield Children's NHS Foundation Trust, Ryegate Children's Centre, Sheffield, UK
| | - Chakra Vasudevan
- Department of Neonatology, Bradford Royal Infirmary, Bradford, UK
| | - Paul D Griffiths
- Academic Unit of Radiology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
| | - Nicola Foulds
- Department of Clinical Genetics, Princess Anne Hospital, University Southampton NHS Foundation Trust, Southampton, UK
| | - Hilary Piercy
- The Centre for Health and Social Care, Sheffield Hallam University, Sheffield, UK
| | - Patricia de Lacy
- Department of Paediatric Neuosurgery, Sheffield Children's NHS Foundation Trust, Sheffield, UK
| | - Sally Boxall
- Wessex Fetal Medicine Unit, Princess Anne Hospital, Southampton, UK
| | - David Howe
- Wessex Fetal Medicine Unit, Princess Anne Hospital, Southampton, UK
| | - Brigitte Vollmer
- Clinical and Experimental Sciences, Faculty of Medicine, Paediatric and Neonatal Neurology, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, UK
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26
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Ding FJ, Lyu GZ, Zhang VW, Jin H. Missense mutation in DYNC1H1 gene caused psychomotor developmental delay and muscle weakness: A case report. World J Clin Cases 2021; 9:9302-9309. [PMID: 34786417 PMCID: PMC8567516 DOI: 10.12998/wjcc.v9.i30.9302] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/09/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The DYNC1H1 gene encodes a part of the dynamic protein, and the protein mutations may further affect the growth and development of neurons, resulting in degeneration of anterior horn cells of the spinal cord, and a variety of clinical phenotypes finally resulting in axonal Charcot-Marie-Tooth disease type 20 (CMT20), mental retardation 13 (MRD13) and spinal muscular atrophy with lower extremity predominant 1 (SMA-LED). The incidence of the disease is low, and it is difficult to diagnose, especially in children. Here, we report a case of DYNC1H1 gene mutation and review the related literature to improve the pediatrician’s understanding of DYNC1H1 gene-related disease to make an early correct diagnosis and provide better services for children.
CASE SUMMARY A 4-mo-old Chinese female child with adducted thumbs, high arch feet, and epileptic seizure presented slow response, delayed development, and low limb muscle strength. Electroencephalogram showed abnormal waves, a large number of multifocal sharp waves, sharp slow waves, and multiple spasms with a series of attacks. High-throughput sequencing and Sanger sequencing identified a heterozygous mutation, c.5885G>A (p.R1962H), in the DYNC1H1 gene (NM_001376) of the proband, which was not identified in her parents. Combined with the clinical manifestations and pedigree of this family, this mutation is likely pathogenic based on the American Academy of Medical Genetics and Genomics guidelines. The child was followed when she was 1 year and 2 mo old. The magnetic resonance imaging result was consistent with the findings of white matter myelinated dysplasia and congenital giant gyrus. The extensive neurogenic damage to the extremities was considered, as the results of electromyography showed that the motor conduction velocity and sensory conduction of the nerves of the extremities were not abnormal, and the degree of fit of the children with severe contraction was poor. At present, the child is 80 cm in length and 9 kg in weight, with slender limbs and low muscle strength, and still does not raise her head. She cannot sit or speak. Speech, motor, and mental development was significantly delayed. There is still no effective treatment for this disease.
CONCLUSION We herein report a de novo variant of DYNC1H1 gene, c.5885G>A (p.R1962H), leading to overlapping phenotypes (seizure, general growth retardation, and muscle weakness) of CMT20, MRD13, and SMA-LED, but there is no effective treatment for such condition. Our case enriches the DYNC1H1 gene mutation spectrum and provides an important basis for clinical diagnosis and treatment and genetic counseling.
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Affiliation(s)
- Feng-Juan Ding
- Prenatal Diagnosis Center, Jinan Maternal and Child Health Hospital, Jinan 250001, Shandong Province, China
| | - Gui-Zhen Lyu
- AmCare Genomics lab (Guangzhou), Guangzhou 510300, Guangdong Province, China
| | - Victor Wei Zhang
- AmCare Genomics lab (Guangzhou), Guangzhou 510300, Guangdong Province, China
- Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77001, United States
| | - Hua Jin
- Prenatal Diagnosis Center, Jinan Maternal and Child Health Hospital, Jinan 250001, Shandong Province, China
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27
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The Term Newborn: Postnatal Screening and Testing. Clin Perinatol 2021; 48:555-572. [PMID: 34353580 DOI: 10.1016/j.clp.2021.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Prenatal genetic screening, including evaluation for inherited genetic disorders, aneuploidy risk assessment, and sonographic assessment, combined with a thorough newborn examination and standard newborn screening, including blood, hearing, and congenital heart disease screening, can reveal conditions requiring further evaluation after delivery. Abnormal prenatal or newborn screening results should prompt additional diagnostic testing guided by maternal fetal medicine, perinatal genetics, or pediatric specialists.
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28
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Sun G, Jing B, Zhou F, Liu H, Liu L, Chen J, Hou X. Neurodevelopmental outcomes in mild and moderate isolated ventriculomegaly originating in utero. J Matern Fetal Neonatal Med 2021; 35:6691-6698. [PMID: 33944669 DOI: 10.1080/14767058.2021.1919869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To determine the differences in outcomes between mild and moderate isolated ventriculomegaly (IVM). METHODS We conducted a prospective cohort study on 94 fetuses with IVM and evaluated the neurodevelopmental outcomes at 12 months of age using the ASQ-3 and BSID-I neurodevelopmental assessment tools. Progression of VM was defined as an increase in the width of the ventricular by at least 3 mm during sequential ultrasound monitoring. The population was divided into two groups according to ventricular width: mild (10-12 mm) and moderate (12.1-15 mm), which were further evaluated for VM progression in utero separately. RESULTS Neurodevelopmental assessments at 12 months were the main form of evaluations. Neurodevelopmental impairment (NDI) was defined as a mental development index (MDI) or psychomotor development index (PDI) < 85. There were no significant differences in NDI values between the mild and moderate groups (p = .155). Compared with the non-in utero progression group (7.6%), the rate of NDI was significantly higher (p = .004) in the group with progression (33.3%). Using linear regression and correlation, no negative correlation was found between the maximum value of atrial diameter (AD) in utero and the PDI (r = -0.021, p = .914) or MDI (r = -0.073, p = .703) score. However, the maximum change in the AD in utero was negatively correlated with both PDI (r = -0.460, p = .011) and MDI (r=-0.422, p = .020) scores. CONCLUSION There were likely no differences in neurodevelopmental outcomes between mild and moderate IVM. In fetuses with mild to moderate VM, intrauterine progression may be a poor prognostic factor for neurodevelopmental outcomes.
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Affiliation(s)
- Guoyu Sun
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Baihua Jing
- Department of Obstetrics & Gynecology, Peking University First Hospital, Beijing, China
| | - Faliang Zhou
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Hongyan Liu
- Department of Obstetrics & Gynecology, Peking University First Hospital, Beijing, China
| | - Lili Liu
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Junya Chen
- Department of Obstetrics & Gynecology, Peking University First Hospital, Beijing, China
| | - Xinlin Hou
- Department of Pediatrics, Peking University First Hospital, Beijing, China
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29
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Zhu R, Chen JY, Hou XL, Liu LL, Sun GY. Asymmetric cortical development and prognosis in fetuses with isolated mild fetal ventriculomegaly: an observational prospective study. BMC Pregnancy Childbirth 2021; 21:199. [PMID: 33691645 PMCID: PMC7945606 DOI: 10.1186/s12884-021-03692-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 03/01/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Assessments of cortical development and identifying factors that may result in a poor prognosis for fetuses with isolated mild ventriculomegaly (IMVM) is a hot research topic. We aimed to perform a constant, detailed assessment of cortical development in IMVM fetuses using ultrasound and determine whether asymmetric cortical development occurred. Moreover, we aimed to estimate the prognosis of IMVM fetuses and compare the difference in the prognosis of IMVM fetuses presenting symmetric and asymmetric cortical maturation. METHODS IMVM was diagnosed by regular ultrasound, neurosonography and fetal MRI. Genetic and TORCH examinations were conducted to exclude common genetic abnormalities and TORCH infection of fetuses. Ultrasound examinations were conducted at an interval of 2-3 weeks to record sulcus development in IMVM fetuses using a scoring system. The neonatal behavioral neurological assessment (NBNA), the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Bayley Scales of Infant Development, First Edition (BSID-I) were performed after birth. RESULTS Forty fetuses with IMVM were included: twenty showed asymmetric cortical maturation and twenty showed symmetric cortical maturation. For IMVM fetuses presenting asymmetric cortical maturation, the mean gestational age (GA) at the first diagnosis of relatively delayed development was 24.23 weeks for the parieto-occipital sulcus, 24.71 weeks for the calcarine sulcus, and 26.43 weeks for the cingulate sulcus. All the sulci with delayed development underwent 'catch-up growth' and developed to the same grade as the sulci of the other hemisphere. The mean GA at which the two sides developed to the same grade was 29.40 weeks for the parieto-occipital sulcus, 29.30 weeks for the calcarine sulcus and 31.27 weeks for the cingulate sulcus. The NBNA, ASQ-3 and BSID-I scores of all patients were in the normal range. CONCLUSIONS IMVM fetuses may show mild asymmetric cortical maturation in the second trimester, but the relatively delayed sulci undergo 'catch-up growth'. The neurodevelopment of IMVM fetuses presenting asymmetric cortical maturation and 'catch-up growth' is not statistically significantly different from IMVM fetuses presenting symmetric cortical maturation.
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Affiliation(s)
- Rong Zhu
- Department of Obstetrics & Gynecology, Peking University First Hospital, No. 1 Xi-An-Men Street, Xi-Cheng District, Beijing, 100034, China
| | - Jun Ya Chen
- Department of Obstetrics & Gynecology, Peking University First Hospital, No. 1 Xi-An-Men Street, Xi-Cheng District, Beijing, 100034, China.
| | - Xin Lin Hou
- Department of Pediatrics, Peking University First Hospital, No. 1 Xi-An-Men Street, Xi-Cheng District, Beijing, 100034, China.
| | - Li Li Liu
- Department of Pediatrics, Peking University First Hospital, No. 1 Xi-An-Men Street, Xi-Cheng District, Beijing, 100034, China
| | - Guo Yu Sun
- Department of Pediatrics, Peking University First Hospital, No. 1 Xi-An-Men Street, Xi-Cheng District, Beijing, 100034, China
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30
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Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays. Sci Rep 2021; 11:5291. [PMID: 33674646 PMCID: PMC7935846 DOI: 10.1038/s41598-021-83147-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 01/28/2021] [Indexed: 11/08/2022] Open
Abstract
Etiopathogenesis of fetal ventriculomegaly is poorly understood. Associations between fetal isolated ventriculomegaly and copy number variations (CNVs) have been previously described. We investigated the correlations between fetal ventriculomegaly-with or without other ultrasound anomalies-and chromosome abnormalities. 222 fetuses were divided into four groups: (I) 103 (46.4%) cases with isolated ventriculomegaly, (II) 41 (18.5%) cases accompanied by soft markers, (III) 33 (14.9%) cases complicated with central nervous system (CNS) anomalies, and (IV) 45 (20.3%) cases with accompanying anomalies. Karyotyping and single nucleotide polymorphism (SNP) array were used in parallel. Karyotype abnormalities were identified in 15/222 (6.8%) cases. Karyotype abnormalities in group I, II, III, and IV were 4/103 (3.9%), 2/41 (4.9%), 4/33 (12.1%), and 5/45 (11.1%), respectively. Concerning the SNP array analysis results, 31/222 (14.0%) were CNVs, CNVs in groups I, II, III, and IV were 11/103 (10.7%), 6/41 (14.6%), 9/33 (27.3%), and 5/45 fetuses (11.1%), respectively. Detections of clinical significant CNVs were higher in non-isolated ventriculomegaly than in isolated ventriculomegaly (16.81% vs 10.7%, P = 0.19). SNP arrays can effectively identify CNVs in fetuses with ventriculomegaly and increase the abnormal chromosomal detection rate by approximately 7.2%, especially ventriculomegaly accompanied by CNS anomalies.
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Ma'ayeh M, Ward CL, Chitwood A, Gee SE, Schneider P, Rood KM. Outcomes of Isolated Fetal Ventriculomegaly That Resolve In Utero. Am J Perinatol 2021; 38:111-114. [PMID: 32772358 DOI: 10.1055/s-0040-1715086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
OBJECTIVE Isolated fetal ventriculomegaly is often an incidental finding on antenatal ultrasound. It is benign in up to 90% of cases, although it can be associated with genetic, structural, and neurocognitive disorders. The literature suggests that over 40% of isolated mild ventriculomegaly will resolve in utero, but it is unclear if resolution decreases the associated risks.The aim of this study is to compare the fetal and neonatal genetic outcomes of ventriculomegaly that persists or resolves on subsequent ultrasound. STUDY DESIGN This is a retrospective cohort study of women diagnosed with isolated ventriculomegaly via fetal ultrasound at a tertiary referral center between 2011 and 2019. Patients were excluded if other structural anomalies were identified on ultrasound. RESULTS A total of 49 patients were included in the study, 19 in the resolved ventriculomegaly group and 30 in the persistent ventriculomegaly group. Women in the resolved ventriculomegaly group were more likely to be diagnosed earlier (24 vs. 28 weeks, p = 0.007). Additionally, they were more likely to have mild ventriculomegaly (63 vs. 84%, p = 0.15), and less likely to have structural neurological abnormalities diagnosed on postnatal imaging (5 vs. 17%, p = 0.384), although these were not statistically significant. Aneuploidy risk for resolved compared with persistent ventriculomegaly was similar (5 vs. 7%, p = 0.999). CONCLUSION This study suggests that resolution of isolated ventriculomegaly in utero may not eliminate the risk of genetic or chromosomal abnormalities in this population and may warrant inclusion as part of the counselling of these at-risk patients. Larger prospective studies are needed to confirm these findings. KEY POINTS · Ventriculomegaly is known to be associated with genetic and chromosomal abnormalities.. · Resolution of the ventriculomegaly in utero may not eliminate those risks.. · Patients with resolved ventriculomegaly should be offered aneuploidy screening or testing..
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Affiliation(s)
- Marwan Ma'ayeh
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Calvin L Ward
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Abigail Chitwood
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Stephen E Gee
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Patrick Schneider
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
| | - Kara M Rood
- Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio
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Drukker L, Cavallaro A, Salim I, Ioannou C, Impey L, Papageorghiou AT. How often do we incidentally find a fetal abnormality at the routine third-trimester growth scan? A population-based study. Am J Obstet Gynecol 2020; 223:919.e1-919.e13. [PMID: 32504567 DOI: 10.1016/j.ajog.2020.05.052] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 05/08/2020] [Accepted: 05/28/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND Third-trimester scans are increasingly used to try to prevent adverse outcomes associated with abnormalities of fetal growth. Unexpected fetal malformations detected at third-trimester growth scans are rarely reported. OBJECTIVE To determine the incidence and type of fetal malformations detected in women attending a routine third-trimester growth scan. STUDY DESIGN This was a population-based study of all women with singleton pregnancy attending antenatal care over a 2-year period in Oxfordshire, UK. Women who had a viable singleton pregnancy at dating scan were included. Women had standard obstetrical care including the offer of a routine dating scan and combined screening for trisomies; a routine anomaly scan at 18 to 22 weeks; and a routine third-trimester growth scan at 36 weeks. The third-trimester scan comprises assessment of fetal presentation, amniotic fluid, biometry, umbilical and middle cerebral artery Dopplers, but no formal anatomic assessment is undertaken. Scans are performed by certified sonographers or clinical fellows (n=54), and any suspected abnormalities are evaluated by a team of fetal medicine specialists. We assessed the frequency and type of incidental congenital malformations identified for the first time at this third-trimester scan. All babies were followed-up after birth for a minimum of 6 months. RESULTS There were 15,244 women attending routine antenatal care. Anomalies were detected in 474 (3.1%) fetuses as follows: 103 (21.7%) were detected before the anomaly scan, 174 (36.7%) at the anomaly scan, 11 (2.3%) after the anomaly scan and before the third-trimester scan, 43 (9.1%) at the third-trimester scan and 143 (30.2%) after birth. The 43 abnormalities were found in a total of 13,023 women who had a 36 weeks scan, suggesting that in 1 out of 303 (95% confidence interval, 233-432) women attending such a scan, a new malformation was detected. Anomalies detected at the routine third-trimester scan were of the urinary tract (n=30), central nervous system (5), simple ovarian cysts (4), chromosomal (1), splenic cyst (1), skeletal dysplasia (1), and cutaneous lymphangioma (1). Most urinary tract anomalies were renal pelvic dilatation, which showed spontaneous resolution in 57% of the cases. CONCLUSION When undertaking a program of routine third-trimester growth scans in women who have had previous screening scans, an unexpected congenital malformation is detected in approximately 1 in 300 women.
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Role of prenatal magnetic resonance imaging in fetuses with isolated mild or moderate ventriculomegaly in the era of neurosonography: international multicenter study. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2020; 56:340-347. [PMID: 31917496 DOI: 10.1002/uog.21974] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Revised: 11/25/2019] [Accepted: 12/20/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To assess the role of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses presenting with mild or moderate isolated ventriculomegaly (VM) undergoing multiplanar ultrasound evaluation of the fetal brain. METHODS This was a multicenter, retrospective, cohort study involving 15 referral fetal medicine centers in Italy, the UK and Spain. Inclusion criteria were fetuses affected by isolated mild (ventricular atrial diameter, 10.0-11.9 mm) or moderate (ventricular atrial diameter, 12.0-14.9 mm) VM on ultrasound, defined as VM with normal karyotype and no other additional central nervous system (CNS) or extra-CNS anomalies on ultrasound, undergoing detailed assessment of the fetal brain using a multiplanar approach as suggested by the International Society of Ultrasound in Obstetrics and Gynecology guidelines for the fetal neurosonogram, followed by fetal MRI. The primary outcome of the study was to report the incidence of additional CNS anomalies detected exclusively on prenatal MRI and missed on ultrasound, while the secondary aim was to estimate the incidence of additional anomalies detected exclusively after birth and missed on prenatal imaging (ultrasound and MRI). Subgroup analysis according to gestational age at MRI (< 24 vs ≥ 24 weeks), laterality of VM (unilateral vs bilateral) and severity of dilatation (mild vs moderate VM) were also performed. RESULTS Five hundred and fifty-six fetuses with a prenatal diagnosis of isolated mild or moderate VM on ultrasound were included in the analysis. Additional structural anomalies were detected on prenatal MRI and missed on ultrasound in 5.4% (95% CI, 3.8-7.6%) of cases. When considering the type of anomaly, supratentorial intracranial hemorrhage was detected on MRI in 26.7% of fetuses, while polymicrogyria and lissencephaly were detected in 20.0% and 13.3% of cases, respectively. Hypoplasia of the corpus callosum was detected on MRI in 6.7% of cases, while dysgenesis was detected in 3.3%. Fetuses with an associated anomaly detected only on MRI were more likely to have moderate than mild VM (60.0% vs 17.7%; P < 0.001), while there was no significant difference in the proportion of cases with bilateral VM between the two groups (P = 0.2). Logistic regression analysis showed that lower maternal body mass index (adjusted odds ratio (aOR), 0.85 (95% CI, 0.7-0.99); P = 0.030), the presence of moderate VM (aOR, 5.8 (95% CI, 2.6-13.4); P < 0.001) and gestational age at MRI ≥ 24 weeks (aOR, 4.1 (95% CI, 1.1-15.3); P = 0.038) were associated independently with the probability of detecting an associated anomaly on MRI. Associated anomalies were detected exclusively at birth and missed on prenatal imaging in 3.8% of cases. CONCLUSIONS The incidence of an associated fetal anomaly missed on ultrasound and detected only on fetal MRI in fetuses with isolated mild or moderate VM undergoing neurosonography is lower than that reported previously. The large majority of these anomalies are difficult to detect on ultrasound. The findings from this study support the practice of MRI assessment in every fetus with a prenatal diagnosis of VM, although parents can be reassured of the low risk of an associated anomaly when VM is isolated on neurosonography. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
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Chang Q, Yang Y, Peng Y, Liu S, Li L, Deng X, Yang M, Lan Y. Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with ventriculomegaly. Eur J Paediatr Neurol 2020; 25:106-112. [PMID: 32014392 DOI: 10.1016/j.ejpn.2020.01.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 01/03/2020] [Accepted: 01/20/2020] [Indexed: 12/24/2022]
Abstract
OBJECTIVES 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). METHODS 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. RESULTS 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. CONCLUSIONS 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.
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Affiliation(s)
- Qingxian Chang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Yanping Yang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yixian Peng
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Siping Liu
- Technology Center of Prenatal Diagnosis and Genetic Diseases Diagnosis, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Liyan Li
- Technology Center of Prenatal Diagnosis and Genetic Diseases Diagnosis, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xujie Deng
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Ming Yang
- Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yu Lan
- Department of Obstetrics and Gynecology, Guangzhou Red Cross Hospital Affiliated to Jinan University, Guangzhou, Guangdong, China
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Hart AR, Embleton ND, Bradburn M, Connolly DJA, Mandefield L, Mooney C, Griffiths PD. Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome: postnatal follow-up of the MERIDIAN cohort. THE LANCET CHILD & ADOLESCENT HEALTH 2019; 4:131-140. [PMID: 31786091 PMCID: PMC6988445 DOI: 10.1016/s2352-4642(19)30349-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 10/15/2019] [Accepted: 10/17/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND In utero MRI (iuMRI) detects fetal brain abnormalities more accurately than ultrasonography and provides additional clinical information in around half of pregnancies. We aimed to study whether postnatal neuroimaging after age 6 months changes the diagnostic accuracy of iuMRI and its ability to predict developmental outcome. METHODS Families enrolled in the MERIDIAN study whose child survived to age 3 years were invited to have a case note review and assessment of developmental outcome with the Bayley Scales of Infant and Toddler Development, the Ages and Stages Questionnaire, or both. A paediatric neuroradiologist, masked to the iuMRI results, reviewed the postnatal neuroimaging if the clinical report differed from iuMRI findings. Diagnostic accuracy was recalculated. A paediatric neurologist and neonatologist categorised participants' development as normal, at risk, or abnormal, and the ability of iuMRI and ultrasonography to predict developmental outcome were assessed. FINDINGS 210 participants had case note review, of whom 81 (39%) had additional investigations after age 6 months. The diagnostic accuracy of iuMRI remained higher than ultrasonography (proportion of correct cases was 529 [92%] of 574 vs 387 [67%] of 574; absolute difference 25%, 95% CI 21 to 29; p<0·0001). Developmental outcome data were analysed in 156 participants, and 111 (71%) were categorised as normal or at risk. Of these 111 participants, prognosis was normal or favourable for 56 (51%) using ultrasonography and for 76 (69%) using iuMRI (difference in specificity 18%, 95% CI 7 to 29; p=0·0008). No statistically significant difference was seen in infants with abnormal outcome (difference in sensitivity 4%, 95% CI -10 to 19; p=0·73). INTERPRETATION iuMRI remains the optimal tool to identify fetal brain abnormalities. It is less accurate when used to predict developmental outcome, although better than ultrasonography for identifying children with normal outcome. Further work is needed to determine how the prognostic abilities of iuMRI can be improved. FUNDING National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Anthony R Hart
- Department of Paediatric and Perinatal Neurology, Sheffield Children's Hospital NHS Foundation Trust, Ryegate Children's Centre, Sheffield, UK
| | - Nicholas D Embleton
- Newcastle Neonatal Service, Ward 35 Neonatal Unit, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Michael Bradburn
- Clinical Trials Research Unit, School Health and Related Research, University of Sheffield, Sheffield, UK
| | - Daniel J A Connolly
- Department of Paediatric Neuroradiology, Sheffield Children's Hospital NHS Foundation Trust, Western Bank, Sheffield, UK
| | - Laura Mandefield
- Clinical Trials Research Unit, School Health and Related Research, University of Sheffield, Sheffield, UK
| | - Cara Mooney
- Clinical Trials Research Unit, School Health and Related Research, University of Sheffield, Sheffield, UK.
| | - Paul D Griffiths
- Academic Unit of Radiology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK
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