Etiology and Prognosis of Severe Ventriculomegaly Diagnosed at Late Gestation

Abstract

Objectives We sought to assess the causes and outcomes of severe VM diagnosed de novo after 24 weeks of gestation where a mid-trimester anomaly scan was described as normal.

Methods Multicenter retrospective study of five European fetal medicine centers. The inclusion criteria were normal anatomy at the mid-trimester scan, uni/bilateral finding of posterior ventricle measuring ≥ 15 mm after 24 weeks with neonatal and postnatal pediatric and/or neurological assessment data.

Results Of 74 potentially eligible cases, 10 underwent termination, the outcome was missing in 19 cases and there was 1 neonatal death. Therefore, 44 formed the study cohort with a median gestation at diagnosis of 32 + 0 weeks (25 + 6 – 40 + 5). VM was unilateral in five cases. Agenesis of the corpus callosum (ACC) and grade III/IV intraventricular hemorrhage (IVH) accounted for 14 cases each. ACC was isolated in 9 fetuses. Obstructive abnormalities included 5 arachnoid and 1 cavum velum interpositum cyst. Four fetuses had an associated suspected or confirmed genetic condition, 2 congenital infections, 1 abnormal cortical development and the etiology was unknown in 3/44. Postnatal assessment at median 20 months (3 – 96) showed 22/44 (50 %) normal, 7 (16 %) mildly abnormal and 15 (34 %) severely abnormal neurodevelopmental outcomes.

Conclusion One half of babies with severe VM diagnosed after 24 weeks have normal infant outcome with ACC and IVH representing the most common causes. Etiology is the most important factor affecting the prognosis of fetuses with severe VM diagnosed at late gestation.

Zusammenfassung

Ziel Bestimmung der Ursachen und Folgen einer schweren Ventrikulomegalie (VM) mit de-novo Diagnose nach 24 Schwangerschaftswochen (SSW) bei unauffälligem Basisultraschall im 2. Trimenon.

Methoden Multizentrische retrospektive Studie in 5 europäischen Pränatalzentren. Die Einschlusskriterien waren eine normale Fetoanatomie beim Screening im 2. Trimenon, ein nach der 24. SSW auftretender uni-/bilateraler Befund im Hinterhorn von > 15 mm sowie neonatale und postnatale pädiatrische und / oder neurologische Befunde.

Ergebnisse Von 74 potentiell geeigneten Fällen wurde bei 10 die Schwangerschaft beendet, in 19 Fällen fehlte der Ausgang und in einem Fall verstarb das Neugeborene. Folglich bildeten 44 Fälle die Studienkohorte, die bei Diagnosestellung eine mediane SSW von 32 + 0 (25 + 6 bis 40 + 5) aufwies. In 5 Fällen war die VM einseitig. Eine Agenesie des Corpus Callosum (ACC) sowie eine intraventrikuläre Hämorrhagie (IVH) Grad III / IV bestand bei jeweils 14 Fällen. Eine isolierte ACC wurde bei 9 Feten festgestellt. Zu den obstruktiven Anomalien gehörten 5 arachnoidale Zysten und 1 Zyste des Cavum velum interpositum. Bei vier Feten war dies mit einer vermuteten oder bestätigten Erbkrankheit assoziiert, zwei hatten kongenitale Infektionen, bei einem lag eine abnormale Entwicklung des Cortex vor und in 3/44 Fällen war die Ätiologie nicht bekannt. Die postnatale Bewertung nach median 20 Monaten (3 – 96) ergab bei 22/44 (50 %) eine normale, in 7 (16 %) eine leicht auffällige und in 15 (34 %) schwer auffällige neurologische Entwicklung.

Schlussfolgerung Die Hälfte der Babys mit einer nach 24 SSW diagnostizierten schweren VM hatte ein normales pädiatrisches Outcome, wobei ACC und IVH die häufigsten Ursachen waren. Die Ätiologie ist der wichtigste Einflussfaktor auf die Prognose von Feten mit Diagnose einer schweren VM in der Spätschwangerschaft.

Key words

fetal neurosonography - central nervous system - antenatal ultrasound - third-trimester scan

• References

• 1 European Surveillance of Congenital Anomalies EUROCAT. Prevelance Tables for Nervous system anomalies (per 10000 births). EUROCAT. Available via 2012 http://www.eurocat-network.eu/accessprevalencedata/prevalencetables . [29 November 2016]
• 2 Guibaud L, Lacalm A. Etiological diagnostic tools to elucidate “isolated” ventriculomegaly. Ultrasound Obstet Gynecol 2015; 46: 1-11
• 3 Lam SJ, Kumar S. Evolution of fetal ventricular dilatation in relation to severity at first presentation. J Clin Ultrasound 2014; 42: 193-198
• 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 Gaglioti P, Danelon D, Bontempo S. et al. Fetal cerebral ventriculomegaly: outcome in 176 cases. Ultrasound Obstet Gynecol 2005; 25: 372-377
• 6 Breeze AC, Alexander PM, Murdoch EM. et al. Obstetric and neonatal outcomes in severe fetal ventriculomegaly. Prenat Diagn 2007; 27: 124-129
• 7 Graham E, Duhl A, Ural S. et al. The degree of antenatal ventriculomegaly is related to pediatric neurological morbidity. J Matern Fetal Med 2001; 10: 258-263
• 8 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
• 9 International Society of Ultrasound in Obstetrics & 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
• 10 Italian Society of Ultrasound in Obstetrics and Gynecology (Società Italiana di Ecografia Ostetrico Ginecologica, SIEOG). SIEOG guidelines. 2015 http://www.sigo.it/wp-content/uploads/2015/12/LineeGuidaSieog_2015.pdf
• 11 Fetal anomaly screening programme: programme handbook June 2015. https://www.gov.uk/government/publications/fetal-anomaly-screening-programme-handbook
• 12 Spanish Society of Obstetrics and Gynecology (SEGO). Guidelines for antenatal ultrasound screening. http://www.gapsego.com/categoria-guia-asistencia/ecografia/
• 13 Dutch Society of Obstetrics and Gynecology (Nederlandse Vereniging voor Obstetrie en Gynaecologie, NVOG). Structureel echoscopisch onderzoek (SEO) Versie 2.0. http://www.rivm.nl/dsresource?objectid=c05e9286-9198-47a4-88fc-99abfec96553&type=org&disposition=inline
• 14 Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ventriculomegaly with a single measurement: the width of the lateral ventricular atrium. Radiology 1988; 169: 711-714
• 15 Volpe JJ. Intracranial Hemorrhage: Germinal Matrix Intraventricular Hemorrhage of the Preterm Infant (Neuropathology and Pathogenesis). In: Volpe JJ. editor Neurology of the Newborn. Philadelphia: W.B. Saunders; 2001: 428-447
• 16 von Elm E, Altman DG, Egger M. et al. The strengthening the reporting of the observational studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453-1457
• 17 D’Antonio F, Pagani G, Familiari A. et al. Outcomes Associated With Isolated Agenesis of the Corpus Callosum: A Meta-analysis. Pediatrics 2016; 138 DOI: 10.1542/peds.2016-0445.
• 18 Santo S, D’Antonio F, Homfray T. et al. Counseling in fetal medicine: agenesis of the corpus callosum. Ultrasound Obstet Gynecol 2012; 40: 513-521
• 19 Sotiriadis A, Makrydimas G. Neurodevelopment after prenatal diagnosis of isolated agenesis of the corpus callosum: an integrative review. Am J Obstet Gynecol 2012; 206: 337.e1-337.e5
• 20 Barkovich AJ, Norman D. Absence of the septum pellucidum: a useful sign in the diagnosis of congenital brain malformations. Am J Roentgenol 1989; 152: 353-360
• 21 Malinger G, Lev D, Kidron D. et al. Differential diagnosis in fetuses with absent septum pellucidum. Ultrasound Obstet Gynecol 2005; 25: 42-49
• 22 Ghi T, Carletti A, Contro E. et al. Prenatal diagnosis and outcome of partial agenesis and hypoplasia of the corpus callosum. Ultrasound Obstet Gynecol 2010; 35: 35-41
• 23 Malinger G, Lev D, Lerman-Sagie T. Abnormal sulcation as an early sign for migration disorders. Ultrasound Obstet Gynecol 2004; 24: 704-705
• 24 Malinger G, Kidron D, Schreiber L. et al. Prenatal diagnosis of malformations of cortical development by dedicated neurosonography. Ultrasound Obstet Gynecol 2007; 29: 178-191
• 25 Guibaud L, Selleret L, Larroche JC. et al. Abnormal Sylvian fissure development on prenatal cerebral imaging. Significance and correlation with neuropathological and postnatal data. Ultrasound Obstet Gynecol 2008; 32: 50-60
• 26 Ghi T, Simonazzi G, Perolo A. et al. Outcome of antenatally diagnosed intracranial hemorrhage: case series and review of the literature. Ultrasound Obstet Gynecol 2003; 22: 121-130
• 27 Kutuk MS, Balta B, Kodera H. et al. Is there relation between COL4A1 / A2 mutations and antenatally detected fetal intraventricular hemorrhage?. Childs Nerv Syst 2014; 30: 419-424
• 28 Malinger G, Lev D, Zahalka N. et al. Fetal cytomegalovirus infection of the brain: the spectrum of sonographic findings. Am J Neuroradiol 2003; 24: 28-32
• 29 Malinger G, Werner H, Rodriguez Leonel JC. et al. Prenatal brain imaging in congenital toxoplasmosis. Prenat Diagn 2011; 31: 881-886
• 30 Youssef A, D’Antonio F, Khalil A. et al. Outcome of fetuses with supratentorial extra-axial intracranial cysts: a systematic review. Fetal Diagn Ther 2016; 40: 1-12