Prenatal detection of mild fetal ventriculomegaly – a systematic review of the modern literature

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.

Zusammenfassung

Einleitung Während eine leichte fetale Ventrikulomegalie häufig als zufälliger und gutartiger Befund beobachtet wird, ist auch bekannt, dass sie mit strukturellen, genetischen und neurologischen Entwicklungsanomalien einhergeht. Ziel dieser Studie war es, eine systematische Übersicht der vorhandenen Literatur vorzunehmen, um den Zusammenhang zwischen scheinbar isolierter fetaler leichter Ventrikulomegalie und dem Vorliegen zusätzlicher struktureller Defekte, die durch fetale Hirn-MRT nachgewiesen wurden, sowie chromosomaler oder anderer genetischer Anomalien und neurologischer Entwicklungsverzögerungen zu bewerten.

Methoden Diese systematische Übersichtsarbeit wurde gemäß den Leitlinien der „Preferred Reporting Items for Systematic Reviews and Meta-Analyses“ erstellt. Die aktuelle Literatur vom 1. Januar 2011 bis zum 31. Juli 2023 wurde durchsucht.

Ergebnisse Es wurden 23 Studien mit insgesamt 2590 Patienten eingeschlossen. Neun Studien untersuchten den Zusammenhang zwischen einer leichten fetalen Ventrikulomegalie und einer beeinträchtigten neurologischen Entwicklung, darunter 536 Fälle, bei denen 64% bis 96,5% ein normales Outcome der neurologischen Entwicklung zeigten. Zehn Studien untersuchten den additiven Wert der fetalen MRT bei 1266 Feten, wobei die Detektionsrate hinsichtlich zusätzlicher Hirndefekte, die letztendlich das klinische Management veränderten, zwischen 0% und 19,5% lag. Sieben Studien mit 747 eingeschlossenen Fällen untersuchten die Korrelation zwischen leichter Ventrikulomegalie mit dem Vorliegen chromosomaler oder genetischer Ursachen, wobei die Rate zwischen 1,1% und 15,4% lag.

Schlussfolgerungen Die Prävalenz von Aneuploidie und genetischen Anomalien bei Ventrikulomegalie, insbesondere bei isolierten Fällen, ist Berichten zufolge relativ gering. Die Inzidenz neurologischer Entwicklungsverzögerungen scheint sowohl bei scheinbaren als auch wirklich isolierten Fällen derjenigen der Allgemeinbevölkerung zu entsprechen.

Keywords

mild ventriculomegaly - fetal ventriculomegaly - dilatation - fetal ventricular system - isolated

• References

• 1 Cardoza DJ, Goldstein RB, Filly RA. Exclusion of fetal ventriculomegaly with a single measurement: the width of lateral ventricular atrium. Radiology 1988; 169: 711-714
• 2 International Society of Ultrasound in Obstetrics and Gynecology Education Committee. Sonographic examination of the fetal central nervous system: guidelines for performing the ‘basic examination’ and the ‘fetal neurosonogram’. Ultrasound Obstet Gynecol 2007; 29: 109-116
• 3 Vergani P, Locatelli A, Strobelt N. et al. Clinical outcome of mild fetal ventriculomegaly. Am J Obstet Gynecol 1998; 178: 218-222
• 4 Hannon T, Tennant PW, Rankin J. et al. Epidemiology, natural history, progression, and postnatal outcome of severe fetal ventriculomegaly. Obstet Gynecol 2012; 120: 1345-1353
• 5 Melchiorre K, Bhide A, Gika AD. et al. Counseling in isolated mild fetal ventriculomegaly. Ultrasound Obstet Gynecol 2009; 34: 212-224
• 6 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71
• 7 Sun G, Jing B, Zhou F. et al. Neurodevelopmental outcomes in mild and moderate isolated ventriculomegaly originating in utero. J Matern Fetal Neonatal Med 2021; 1-8
• 8 Griffiths PD, Jarvis D, Connolly DJ. et al. Predicting neurodevelopmental outcomes in fetuses with isolated mild ventriculomegaly. Arch Dis Child Fetal Neonatal Ed 2022; 107 (04) 431-436
• 9 Scelsa B, Rustico M, Righini A. et al. Mild ventriculomegaly from fetal consultation to neurodevelopmental assessment: A single center experience and review of the literature. Eur J Paediatr Neurol 2018; 22 (06) 919-928
• 10 Thorup E, Jensen LN, Bak GS. et al. Neurodevelopmental disorder in children believed to have isolated mild ventriculomegaly prenatally. Ultrasound Obstet Gynecol 2019; 54 (02) 182-189
• 11 Gómez-Arriaga P, Herraiz I, Puente JM. et al. Mid-term neurodevelopmental outcome in isolated mild ventriculomegaly diagnosed in fetal life. Fetal Diagn Ther 2012; 31 (01) 12-18
• 12 Kutuk MS, Ozgun MT, Uludag S. et al. Postnatal outcome of isolated, nonprogressive, mild borderline fetal ventriculomegaly. Childs Nerv Syst 2013; 29 (05) 803-808
• 13 Tonni G, Vito I, Palmisano M. et al. Neurological Outcome in Fetuses with Mild and Moderate Ventriculomegaly. Rev Bras Ginecol Obstet 2016; 38 (09) 436-442
• 14 Pasquini L, Masini G, Gaini C. et al. The utility of infection screening in isolated mild ventriculomegaly: an observational retrospective study on 141 fetuses. Prenat Diagn 2014; 34 (13) 1295-1300
• 15 Lok WY, Kong CW, Hui SYA. et al. Chromosomal abnormalities and neurological outcomes in fetal cerebral ventriculomegaly: a retrospective cohort analysis. Hong Kong Med J 2021; 27 (06) 428-436
• 16 Ryan GA, Start AO, Cathcart B. et al. Prenatal findings and associated survival rates in fetal ventriculomegaly: A prospective observational study. Int J Gynaecol Obstet 2022; 159 (03) 891-897
• 17 Huang RN, Chen JY, Pan H. et al. Correlation between mild fetal ventriculomegaly, chromosomal abnormalities, and copy number variations. J Matern Fetal Neonatal Med 2022; 35 (24) 4788-4796
• 18 Duan HL, Zhu XY, Zhu YJ. et al. The application of chromosomal microarray analysis to the prenatal diagnosis of isolated mild ventriculomegaly. Taiwan J Obstet Gynecol 2019; 58 (02) 251-254
• 19 Gezer C, Ekin A, Ozeren M. et al. Chromosome abnormality incidence in fetuses with cerebral ventriculomegaly. J Obstet Gynaecol 2014; 34 (05) 387-391
• 20 Bijarnia-Mahay S, Puri RD, Kotecha U. et al. Outcome of Prenatally-Detected Fetal Ventriculomegaly. J Fetal Med 2015; 2: 39-44
• 21 Sethna F, Tennant PWG, Rankin J. et al. Prevalence, natural history, and clinical outcome of mild to moderate ventriculomegaly. Obstet Gynecol 2011; 117 (04) 867-876
• 22 Griffiths PD, Brackley K, Bradburn M. et al. Anatomical subgroup analysis of the MERIDIAN cohort: ventriculomegaly. Ultrasound Obstet Gynecol 2017; 50: 736-744
• 23 Lavongtheung A, Jedraszak G, Naepels P. et al. Should isolated fetal ventriculomegaly measured below 12 mm be viewed as a variant of the norm? Results of a 5-year experience in prenatal referral center. J Matern Fetal Neonatal Med 2017; 11: 1-7
• 24 MehlhornAJMorin CE, Wong-You-Cheong JJ. et al. Mild fetal cerebral ventriculomegaly: prevalence, characteristics, and utility of ancillary testing in cases presenting to a tertiary referral center. Prenat Diagn 2017; 37: 647-657
• 25 Baffero GM, Crovetto F, Fabietti I. et al. Prenatal ultrasound predictors of postnatal major cerebral abnormalities in fetuses with apparently isolated mild ventriculomegaly. Prenat Diagn 2015; 35: 783-788
• 26 Kandula T, Fahey M, Chalmers R. et al. Isolated ventriculomegaly on prenatal ultrasound: what does fetal MRI add?. J Med Imaging Radiat Oncol 2015; 59: 154-162
• 27 Parazzini C, Righini A, Doneda C. et al. Is fetal magnetic resonance imaging indicated when ultrasound isolated mild ventriculomegaly is present in pregnancies with no risk factors?. Prenat Diag 2012; 32: 752-757
• 28 Miguelote RF, Vides B, Santos RF. et al. Cortical maturation in fetuses referred for ‘isolated’ mild ventriculomegaly: a longitudinal ultrasound assessment. Prenat Diagn 2012; 32: 1273-1281
• 29 ENSO Working Group. Role of prenatal magnetic resonance imaging in fetuses with isolated mild or moderate ventriculomegaly in the era of neurosonography: international multicenter study. Ultrasound Obstet Gynecol 2020; 56 (03) 340-347
• 30 Leitner Y, Stolar O, Rotstein M. et al. The neurocognitive outcome of mild isolated fetal ventriculomegaly verified by prenatal magnetic resonance imaging. Am J Obstet Gynecol 2009; 201: 215.e1-215.e6
• 31 Atad-Rapoport M, Schweiger A, Lev D. et al. Neuropsychological follow-up at school age of children with asymmetric ventricles or unilateral ventriculomegaly identified in utero. BJOG 2015; 122: 932-938
• 32 Sadan G, Malinger G, Schweiger A. et al. Neuropsychological outcome of children with asymmetric ventricles or unilateral mild ventriculomegaly identified in utero. BJOG 2007; 114: 596-602
• 33 Pilu G, Falco P, Gabrielli S. et al. The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31 cases and review of the literature. Ultrasound Obstet Gynecol 1999; 14: 320-326
• 34 Devaseelan P, Cardwell C, Bell B. et al. Prognosis of isolated mild to moderate fetal cerebral ventriculomegaly: a systematic review. J Perinat Med 2010; 38: 401-409
• 35 Li Y, Estroff JA, Khwaja O. et al. Callosal dysgenesis in fetuses with ventriculomegaly: levels of agreement between imaging modalities and postnatal outcome. Ultrasound Obstet Gynecol 2012; 40: 522-529
• 36 Emerson E, Hatton C. Mental health of children and adolescents with intellectual disabilities in Britain. Br J Psychiatry 2007; 191: 493-499
• 37 Leonard H, Wen X. The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment Retard Dev Disabil Res Rev 2002; 8: 117-134
• 38 Jelliffe-Pawlowski LL, Hansen RL. Neurodevelopmental outcome at 8 months and 4 years among infants born full-term small for gestational age. J Perinatol 2004; 24: 505-514
• 39 Salomon LJ, Ouahba J, Delezoide AL. et al. Third-trimester fetal MRI in isolated 10- to 12-mm ventriculomegaly: is it worth it?. BJOG 2006; 113 (08) 942-947
• 40 Levine D, Feldman HA, Tannus JF. et al. Frequency and cause of disagreements in diagnoses for fetuses referred for ventriculomegaly. Radiology 2008; 247 (02) 516-527
• 41 Ouahba J, Luton D, Vuillard E. et al. Prenatal isolated mild ventriculomegaly: outcome in 167 cases. BJOG 2006; 113 (09) 1072-1079
• 42 Valsky DV, Ben-Sira L, Porat S. et al. The role of magnetic resonance imaging in the evaluation of isolated mild ventriculomegaly. J Ultrasound Med 2004; 23 (04) 519-523