Evolution of Fetal Ventricular Dilatation inRelation to Severity at First Presentation

Sarah-Jane Lam, MRCOG,1 Sailesh Kumar, FRANZCOG, DPhil(Oxon)1,2

1 Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital, Du Cane Road, London, United Kingdom,W12 0HS2 Institute for Reproductive and Developmental Biology, Imperial College London, London, United Kingdom,W12 0HS

Received 12 January 2013; accepted 13 November 2013

ABSTRACT: Background. To assess the outcome of360 cases of fetal ventriculomegaly in a tertiary refer-ral center.

Methods. Cases of fetal ventriculomegaly betweenJune 1993 and December 2011 were identified fromthe departmental fetal database. The fetal medicinereports and obstetric notes were reviewed to ascer-tain the antenatal progression of the ventriculome-galy as well as the outcome of the pregnancy.Ventriculomegaly was defined by a lateral ventricularwall atrial measurement of greater than 10 mm. Caseswere subdivided into mild (>10 to <12 mm), moder-ate (�12 to <15 mm), and severe (�15 mm). Termina-tion of pregnancy was offered in cases where therewere associated anomalies, aneuploidy, or the ventri-culomegaly progressed.

Results. Of the 360 cases, 189 were mild, 79 weremoderate, and 92 were severe. Sixty-four percent ofcases had associated anomalies. Forty-six percent ofcases in the mild group and 26% in the moderategroup resolved. Only one case in the severe groupimproved. The mean rate of progression in the mildgroup was 1.07 (SD 1.03) mm/week, whereas in themoderate group progression was at a mean rate of1.41 (SD 0.77) mm/week. Progression of severe ventri-culomegaly was significantly higher at a mean rate of3.26 (SD 2.92) mm/week (p 5 0.007).

Conclusions. The majority of fetuses with mild ven-triculomegaly normalized, whereas the majority ofmoderate cases remained stable. The rate of progres-sion of ventriculomegaly increased with severity.Fetuses with ventriculomegaly should be offeredserial scans to allow the progression of ventriculome-

galy to be ascertained with the option of late termina-tion of pregnancy. VC 2014 Wiley Periodicals, Inc.J Clin Ultrasound 42:193–198, 2014; Published onlinein Wiley Online Library (wileyonlinelibrary.com). DOI:10.1002/jcu.22124

Keywords: ventriculomegaly; antenatal progression;MRI; obstetrics

Dilatation of the cerebral ventricles is one ofthe commonest brain anomalies identified in

the perinatal period. Ventriculomegaly that occursin the perinatal period has a reported incidence of0.48–0.81 per 1000 live births, is difficult to treat,and often results in the poorest neurological out-comes.1 The incidence of antenatally diagnosedfetal ventriculomegaly varies between 1.5 per10002 to 22 per 1000.3 The upper limit of the nor-mal range for the ventricular atrial measurementis 10 mm, this being 4 SD above the mean for therelevant gestation.4 Ventriculomegaly can be fur-ther classified into mild (>10 to <12 mm), moder-ate (�12 to <15 mm), and severe (�15 mm).5 Theetiology is diverse, and at least 40% of cases havean associated neural tube defect.

Severe ventriculomegaly and ventriculomegalyassociated with other malformations have apoorer prognosis and worse outcome.6,7 However,the prognosis for mild and moderate ventriculo-megaly is more uncertain, with a lack of consen-sus in the literature. Some studies havesuggested that isolated, non-progressive, mildventriculomegaly carries a better prognosis, fur-ther improved if it resolves.8,9 What is clear how-ever is that longstanding ventriculomegalyregardless of severity does cause aberrations inthe adjacent cerebral tissue, which in turn may be

Disclosure Statement: None of the authors of this manuscripthave conflicts of interests with this research.Correspondence to: S. Kumar

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responsible for adverse neurodevelopmental out-come.10 To counsel parents effectively and accu-rately, more information is needed on the naturalhistory of fetal ventriculomegaly and pregnancyoutcomes.

This retrospective study reviews the antena-tal progression and pregnancy outcome of 360cases of fetal ventriculomegaly. The purpose ofthis study was to ascertain the natural evolu-tion of ventriculomegaly when diagnosed ante-natally and to be able to use this information incounselling patients when this abnormality isidentified.

MATERIALS AND METHODS

This is a retrospective observational study of allcases with fetal ventriculomegaly referred tothe Centre for Fetal Care at Queen Charlotte’sand Chelsea Hospital. This is a major tertiaryreferral fetal medicine unit to which a widerange of fetal abnormalities are referred, in ajurisdiction in which late termination of preg-nancy is an option for severe abnormalities. Asthis study was part of a clinical audit, researchethics approval was not required.

All cases of fetal ventriculomegaly betweenJune 1993 and December 2011 were identifiedfrom the fetal medicine database (Viewpoint,GE Healthcare, United States and Astraia,Munich, Germany). The ventricles were meas-ured in the transverse plane at the level of thethird ventricle as defined by Cardoza et al.4 Amaximal atrial width of the lateral ventricle ofgreater than 10 mm was considered as abnor-mal and was therefore included in this study.Cases were subdivided into mild (>10 to <12mm), moderate (�12 to <15 mm), and severe(�15 mm). High-resolution ultrasound was per-formed to detect any associated abnormalities.Karyotyping and viral screening were offered inall cases. Fetal MRI was available only from2002 onwards. All patients were offered consul-tation with a pediatric neurologist to discussthe implications of the sonographic examinationfindings. The management options were clearlydiscussed with the parents by the fetal medicinespecialist and pediatric neurologist.

All patients were scanned at least once at theCentre for Fetal Care. In patients that electedto continue with the pregnancy, follow-up scanswere performed every 2–4 weeks to assess pro-gression of the ventriculomegaly.

Termination of pregnancy regardless of gesta-tion was offered in all cases of ventriculomegaly

that were either severe (ie, �15 mm), associatedwith other abnormalities or with aneuploidy, orprogressive. Cases were also discussed with apediatric neurologist who often not onlyreviewed the sonographic images in real-timebut also counselled these patients about thespectrum of disability likely to be expected.

Comparisons between multiple groups wereperformed using ANOVA. v2 test for trend wasused to assess differences in proportionsbetween groups. Significant differences wereconsidered when p�0.05.

RESULTS

During the study period 360 cases of fetal ventri-culomegaly were identified. Of the 360 cases, 189(52.5%) were classified as mild, 79 (21.9%) wereclassified as moderate, and 92 (25.6%) were classi-fied as severe at presentation (Table 1). Themedian maternal age was 30 years (range 17–46years). The median gestation at referral was 2115

weeks (range 181023011 weeks) in the mildgroup, 2212 weeks (range 161422915 weeks) inthe moderate group, and 2114 (range 151623215

weeks) in the severe group, respectively. Addi-tional anomalies were found in 232 of 360 (64%)cases of ventriuculomegaly. Only 128 cases (36%)were considered isolated ventriculomegaly. Ofthe 360 cases, 158 (43.9%) underwent karyotyp-ing. Of these, 22 fetuses were aneuploid, whichgives a total aneuploidy rate of 14% (22/158),with Trisomy 21 being the commonest abnormal-ity. One hundred and fifty-six fetuses (43%) wereterminated (25% in the mild group, 53% in themoderate group, and 72% in the severe category)(Table 2). The median gestation at terminationfor the mild group was 2210 weeks (range 16–31weeks), 2414 weeks (range 2313233 weeks) inthe moderate group, and 2216 weeks (range 19–36 weeks) in the severe category. Eight (2.2%)fetuses died in utero. There were 10 cases lost tofollow-up for which we do not know the preg-nancy outcome (ie, they did not return for subse-quent scans or elected to have a termination ofpregnancy elsewhere).

TABLE 1

General Characteristics of Study Cohorts

Mild Moderate Severe

Number of cases 189 79 92

Median gestation at

referral (weeks)

2115 2212 2114

Karyotyped (%) 74 (39%) 43 (54%) 41 (45%)

Abnormal karyotype 16 5 1

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Sonographic follow-up data were available in257 cases. Ventriculomegaly was more likely toresolve in milder cases (76/165 [46%] fetuses in themild group, 18/70 [26%] in the moderate group,and 1/22 [4.5%] in the severe group, p<0.05)(Table 3). As was described in previous studies8,12

and to include progression to a more severe cate-gory, progression of ventriculomegaly was definedas enlargement of the ventricles by greater than3 mm compared with the initial measurement atpresentation. Progression of ventriculomegaly wasmore likely with increasing severity (9/22 [44%] inthe severe group versus 18/165 [11%], and 8/70[11%] in the mild and moderate groups, respec-tively, p<0.05). The rate of progression was calcu-lated by the change in size of the ventriculomegalydivided by the number of weeks between the firstsonographic examination and the last antenatalsonographic examination. Eighteen cases in themild category progressed at a mean rate of 1.1 (SD1.0) mm/week. Eight cases in the moderate groupprogressed to severe at a mean rate of 1.4 (SD 0.8)mm/week. Progression of severe ventriculomegalywas significantly increased at a mean rate of 3.3(SD 2.9) mm/week (p 5 0.007).

Ventriculomegaly Associated with OtherAnomalies

The rate of other prenatally detected structuralanomalies increased with severity of ventriculome-galy. One hundred and four (55%) fetuses in the

mild group, 55 (70%) in the moderate group, and73 (79%) in the severe group had associated abnor-malities (p< 0.005) (Table 4). Central nervous sys-tem abnormalities (including neural tube defects)accounted for the majority of abnormalitiesdetected in all three categories. Of the 150 casesthat had MRI scans, 36 (24%) cases were found tohave other abnormalities not seen on ultrasound(eg, rhomboencephalosynapsis, hypoplastic corpuscallosum, pontocerebellar hypoplasia). Looking atcases of isolated ventriculomegaly where fetal MRIwas performed, 11% (7/64) had additional brainabnormalities detected. Furthermore, the meas-urements from MRI corresponded to the severityof ventriculomegly as indicated by the sonographicexamination measurements. There were onlythree positive results for fetal infection (two casesof cytomegalovirus, one case of parvovirus).

Isolated Ventriculomegaly

Table 5 shows the antenatal outcome for caseswith isolated ventriculomegaly. Overall, 58 of 128fetuses (45%) with isolated ventriculomegaly nor-malized, which decreased with severity (57% inthe mild group, 42% in the moderate group, andnone in the severe group, p< 0.005). There was apreponderance of male fetuses within the mild

TABLE 2

Fetal Outcome with Ventriculomegaly

Mild(n 5 189)

Moderate(n 5 79)

Severe(n 5 92)

Normalized 76 (40%) 18 (23%) 1 (1%)

TOP 48 (25%) 42 (53%) 66 (72%)

IUD 3 (2%) 2 (3%) 3 (3%)

Persistent

ventriculomegaly

58 (31%) 16 (20%) 17 (19%)

Unknown outcome 4 (2%) 1 (1%) 5 (5%)

Abbreviations: IUD, intrauterine death; TOP, termination of

pregnancy.

Data are presented as number (%).

TABLE 3

Progression of Ventriculomegaly

Mild(N 5 165)

Moderate(N 5 70)

Severe(N 5 22)

Regression 76 (46%) 18 (26%) 1 (4.5%) p< 0.005

Stable 71 (43%) 44 (63%) 12 (54.5%) p> 0.05

Progression 18 (11%) 8 (11%) 9 (41%) p< 0.05

Mean rate of

progression

mm/week (SD)

1. (1.0) 1.4 (0.8) 3.3 (2.9) p 5 0.007

TABLE 4

Ventriculomegaly with Associated Anomalies

Mild(n 5 189)

Moderate(n 5 79)

Severe(n 5 92)

Number of cases

with additional

anomaly (%)

104 (55%) 55 (70%) 73 (79%) p< 0.005

CNS 39 28 44

NTD 24 14 17

Face 2 4 1

Lungs 2 1 4

CVS 23 10 9

GIT 15 6 7

Kidneys 11 6 2

Extremities 22 4 15

Other 5 6 4

Abbreviations: CNS, central nervous system; CVS, cardiovascular

system; GIT, gastrointestinal tract; NTD, neural tube defect.

TABLE 5

Isolated Ventriculomegaly (n 5 128 cases)

Mild Moderate Severe

Number of cases 84 24 20

Male:female 51:18 (15

unknown)

14:4 (6

unknown)

5:9 (6

unknown)

Normalized (%) 48 (57%) 10 (42%) 0 (0%) p< 0.005

Aneuploidy/number

karyotyped

2/11 1/4 0/1

TOP (%) 4 (5%) 6 (25%) 15 (75%)

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and moderate groups. In contrast, the sex distri-bution in the severe group was less polarized.There were 16 cases in the isolated cohort thatreceived karyotyping, of which 3 cases of aneu-ploidy were detected (2 in the mild group, 1 in themoderate group). The rate of termination of preg-nancy increased with severity (5% for mild, 25%for moderate, and 75% for severe cases).

DISCUSSION

The prenatal progression of fetal ventriculomegalyis largely unclear from the published literature.Evidence obtained mostly from experimental stud-ies suggests that the gestation of onset stronglyinfluences the degree of impairment, with earlygestation a risk factor for poorer outcome. Althoughthe perinatal brain is more capable of plasticitythan the adult brain, there is no doubt that an inutero insult causing ventriculomegaly usually pre-dicts a worse neurologic outcome.10 There is a pau-city of information about the natural history andpostnatal neurodevelopmental outcome and prog-nosis in these patients, making counselling andparental decision-making difficult.

This large retrospective series attempts toaddress the first of these problems. In this series,58 of 128 cases (45%) of isolated ventriculomegalynormalized. This high-resolution rate is consistentwith previous studies.11,12 For mild and moderateventriculomegaly, the proportion that resolved ishigher for isolated cases compared with noniso-lated cases (57%, 42% versus 31%, 15%, respec-tively). When all the cases of ventriculomegalywere analyzed according to severity, 46% of casesin the mild group regressed, 43% were stable, and11% progressed. In the moderate group, 26%regressed, 63% were stable, and 11% progressed tothe severe group. Our data also confirm that whenthe ventricles measure in excess of 15 mm, they donot tend to normalize. Furthermore, the rate ofprogression of ventriculomegaly increases withseverity (1.1 mm/week versus 1.4 mm/week versus3.4 mm/week in the three groups, respectively),which has not previously been shown. However, itis important to note a potential bias in that follow-up in cases of severe ventriculomegaly was foundto be lower compared with mild and moderategroups (22/92 [24%] versus 165/189 [87%] and70/79 [89%], respectively), perhaps because ofincreased decisions for termination of pregnancy.

This review, in common with other stud-ies,7,13,14 confirms the association of ventriculo-megaly with other fetal abnormalities. Centralnervous system anomalies (including neural

tube defects) were the most commonly detectedin 48% of cases. Furthermore, associatedanomalies were more common with increasingseverity of fetal ventriculomegaly (53% in mildcases, 70% in moderate cases, and 79% insevere cases), consistent with other reports.14,15

A high percentage of cases, 43.9% (158/360),were karyotyped in this study to yield an over-all aneuploidy rate of 14% (22/158). Trisomy 21was the commonest aneuploidy overall. Surpris-ingly, the incidence of aneuploidy was highestin the mild group, which suggests that theseverity of ventriculomegaly is not predictive ofthe risk of aneuploidy, consistent with previ-ously reported data.16

This study confirms a predominance of malefetuses in isolated mild and moderate ventricu-lomegaly, which is consistent with earlier stud-ies.12,17,18 It has been postulated that malefetuses tend to have a greater atrial width thanfemale, and that borderline ventriculomegaly inmale fetuses may be a normal variant.19,20

Isolated ventriculomegaly, which if mild gen-erally has a better prognosis,8,9 is a diagnosis ofexclusion. There is growing evidence that fetalMRI provides a higher detection rate of fetalabnormalities than ultrasound and can be auseful adjunct in aiding management of fetalventriculomegaly.21,22 In this series, fetal MRIdetected further abnormalities in 24% casesoverall and in 11% of isolated ventriculomegalycases, supporting the premise that MRI shouldnow be done in all cases of brain anomalies.

In the majority of studies reviewed by Spareyand Robson23 the termination rates for fetalventriculomegaly, particularly if severe andassociated with other abnormalities, were high.This study also showed that rates of termina-tion increase with severity, and this increaseis more pronounced in cases of isolated ventri-culomegaly when compared with nonisolatedcases (5%, 25%, 75% versus 42%, 65%, 71%,respectively). Even in cases where the ventricu-lomegaly appears to be isolated, many parentselect to have the pregnancy terminated becauseof uncertainty about long-term neurodevelop-mental outcome.24 What appeared to be of sig-nificant reassurance to parents in our practicewas the availability of late termination of preg-nancy in the event that the ventriculomegalypersisted or progressed. This is an option avail-able to patients in the United Kingdom, France,and Israel. Anecdotally, many parents areunwilling to take the chance that their childmight be neurologically impaired, particularlyin the presence of a demonstrable sonographic

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abnormality. Counselling of these patients isalso difficult, because, when apprised of the pos-sible need for postnatal ventriculo-peritonealshunts and other complications, many of themagain opt for termination. The option of late ter-mination of pregnancy allows monitoring of theventriculomegaly with not just ultrasound butfurther detailed assessment of the fetal brainwith MRI before making a final decision.

In conclusion, this series confirms that themajority of fetuses with ventriculomegaly haveassociated structural anomalies. Most fetuseswith mild ventriculomegaly normalized,whereas the majority of moderate casesremained stable on follow-up. The limitation ofthis study is that postnatal neurodevelopmentaloutcome was not assessed, so we are not able toestablish a relationship between rate of progres-sion and long-term prognosis. The strength ofthis study is that 360 cases were reviewed,which makes this the largest study to look atthe antenatal evolution of ventriculomegaly.Our data may help to establish a clearer pictureof the natural course of antenatal ventriculome-galy, which may help clinicians in counselingparents antenatally. Patients with isolated mildventriculomegaly can therefore be reassuredthat it is very unlikely that progression tosevere ventriculomegaly will occur and that,even if progression occurs, it is at a low rate.These patients need not make a decisionregarding continuance of the pregnancy basedon just the initial finding. In contrast, resolu-tion in severe ventriculomegaly is unlikely withno cases seen in the series. The rate of progres-sion of ventriculomegaly increased with sever-ity. These parents can be counselled quiteclearly and definitely that improvement isunlikely to occur and that the prognosis islikely to be poor. The option of late termination(>24 weeks) is therefore an important factor inthe counselling of these patients. It allows themtime to come to terms with the severity of thediagnosis on serial scans before making theirrevocable decision to end the pregnancy.

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