Outcome of fetuses with isolated borderlineunilateral ventriculomegaly diagnosed atmid-gestation

S. Lipitz, S. Yagel*, G. Malinger†, I. Meizner‡, Y. Zalel and R. Achiron

Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer; *Hadassah MedicalCenter, Mount Scopus, The Hebrew University, Jerusalem; †Wolfson Medical Center, Holon; ‡Rabin Medical Center(Beilinson Campus), Petah Tikva, Israel

Key words: FETUS, PRENATAL DIAGNOSIS, UNILATERAL VENTRICULOMEGALY

ABSTRACT

Objective To evaluate the outcome of fetuses with iso-lated borderline, unilateral ventriculomegaly.

Design A retrospective survey was conducted at four peri-natal centers in Israel.

Subjects and methods Only fetuses with one ventricularwidth of ≥ 11 mm and the other < 10 mm were included inthe study. In all cases, the difference of the ventricularwidth between the two ventricles was > 2.4 mm (twostandard deviations). Fetuses with other malformations,chromosomal abnormalities, or those with evidence of inutero infection, were not included in the study.

Results Unilateral ventriculomegaly was found in 27 sub-jects (after excluding one case with unilateral ventriculo-megaly and Down’s syndrome). The mean width of theenlarged ventricle was 11.7 ± 0.9 mm, while the othernormal ventricle was 7.2 ± 0.9 mm. The mean gestationalage at diagnosis of the unilateral ventriculomegaly was23.6 ± 2.7 weeks. In one case, pregnancy was terminated,and pathological examination of the fetal brain failed todetect any structural abnormality. Twenty-five patientsdelivered at term and only one at 34 weeks’ gestation. Theneurological development in all 25 fetuses was normal, andone fetus had petit mal seizures.

Conclusion Fetuses with isolated, borderline unilateralventriculomegaly, but without other abnormalities, have agood neurological outcome.

INTRODUCTION

Ventriculomegaly diagnosed prenatally is almost alwaysbilateral and symmetrical. In general, the prognosis is poor,with high rates of mortality and neurological disabilities.

The poor prognosis is often related to associated structuraland chromosomal abnormalities1,2.

It is assumed that unilateral ventriculomegaly isuncommon. Only a few cases that were diagnosedprenatally have been reported (mainly case reports). How-ever, most of these dealt with overt unilateral ventri-culomegaly (i.e. unilateral hydrocephalus)3–10. Theprognosis of fetuses with unilateral ventriculomegaly isunclear, but it is reputed to be far better than that of fetuseswith bilateral ventriculomegaly.

Improvements in ultrasound technology, combinedwith its widespread use, have facilitated an increasinglythorough evaluation of the fetal brain. We recentlyreported11 that cerebral lateral ventricular asymmetry alone(when the two asymmetric ventricles are < 10 mm) is prob-ably not clinically significant and may be considered as anormal variant, rather than a pathological finding.

The purpose of the present study was to report ourexperience with borderline unilateral ventriculomegalydiagnosed in utero, using high-resolution ultrasonography,and to present the results of prenatal investigation andneonatal outcome in such cases.

MATERIALS AND METHODS

In Israel, routine ultrasonographic examination of everywoman at mid-gestation is an integral part of antenatalcare. The study population included only low-risk, preg-nant women examined during the years 1993–96 in theobstetric ultrasonographic units of four major districtmedical centers in Israel: The Chaim Sheba, Wolfson,Rabin (Beilinson Campus) and Hadassah Medical Centers,all affiliated to the Sackler Faculty of Medicine, Tel AvivUniversity.

Correspondence: Dr S. Lipitz, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel

Ultrasound Obstet Gynecol 1998;12:23–26

ORIGINAL PAPER Received 15–12–97Revised 10–3–98

Accepted 27–4–98

23

97/219 AMA: First Proof

A detailed, biometric and structural evaluation of allfetuses was performed using various ultrasound machines(Elscint ESI 3000, Synergy, Haifa, Israel; Acuson 128Xp10, Mountain View, CA, USA; ATL HDI 9, AdvancedTechnology Laboratory, Bothell, WA, USA). A detailedfetal brain evaluation is an integral part of the ultra-sonographic screening of the fetus. The evaluation of thefetal cranium was performed according to recommenda-tions for obstetric sonography12. The lateral ventricularatrium was assessed by measuring the true transverse axialplane through the thalamic nuclei, as originally describedby Cardoza and colleagues13. To avoid the effect of mea-surement error on sonographic evaluation, measurementswere obtained in an axis perpendicular to the long axis ofthe ventricle, and not to the cerebral midline14. In eachexamination, an attempt was made to inspect and measureboth lateral ventricles.

Borderline unilateral ventriculomegaly of the lateralventricle was defined when only one of the lateral ventri-cular widths was between 11 and 15 mm, while the otherventricular width was < 10 mm. The difference of theventricular width between the two ventricles was, in allcases, > 2.4 mm (2 standard deviations (SD) of the meandiameter of the ventricular atrium)15. Once unilateralventriculomegaly was detected, a thorough ultrasono-graphic examination was performed. Chromosomal evalu-ation by amniocentesis or fetal blood sampling wasperformed, as well as Toxoplasma, rubella, cytomegalo-virus, herpes (TORCH) antibody examination in maternalblood. Serial ultrasonographic examinations (mean of3-week intervals; range 2–4 weeks) were undertaken untilthe end of the pregnancy. In cases with vertex position,transvaginal sonography was performed to increase resolu-tion of the fetal lateral ventricular measurements.

Only cases with unilateral ventriculomegaly as the onlysonographic finding, without chromosomal aberration orevidence of in utero infection, were included in the study.Cases with other associated central nervous system anoma-lies were excluded. The data for each woman found to haveunilateral ventriculomegaly were recorded in a computer-ized medical file. The progress and outcome of each preg-nancy were followed up.

Neonatal brain computed tomography (CT) and mag-netic resonance imaging (MRI) scans were performed onindex cases, while neonatal neurodevelopmental assess-ment was carried out in all subjects (mean 13 months;range 6–32 months). Head ultrasound scans were per-formed on all neonates after delivery. In cases in whichventricular enlargement was found, the newborn wasfollowed up by the Institute of Child Development, in therespective hospital. Statistical evaluation was performed bythe Student’s t test.

RESULTS

Twenty-eight fetuses were diagnosed as having unilateralventriculomegaly. In one case, Down’s syndrome was diag-nosed by amniocentesis, and this case was therefore

excluded. The study group comprised 27 cases withadequate, prenatal sonographic documentation and post-natal follow-up (Table 1).

The mean maternal age at diagnosis was 28 years (range21–36 years). The mean gestational age at diagnosis was23.6 ± 2.7 weeks (range 20–29 weeks; median 23 weeks).There was a significant statistical difference between thesize of the lateral ventricles. The mean widths of theenlarged and the normal ventricles were 11.7 mm ± 0.9 SDand 7.2 mm ± 0.9 SD (p < 0.001), respectively. The ultra-sonographic appearance of unilateral ventriculomegaly isshown in Figures 1 and 2.

In one patient, termination of pregnancy was performedat the parents’ request; however, macroscopic and micro-scopic examination of the fetal brain failed to reveal anypathology. Serial prenatal sonographic examination andneonatal cranial scans performed on the 26 fetuses showedthat, in four (15.4%), unilateral ventriculomegaly resolved;in one (3.8%), it progressed; and in the remaining 21(80.8%), it persisted.

Twenty-five patients delivered at term, and only one at34 weeks’ gestation. In this last patient (Case 24), theventriculomegaly progressed from 12 mm (at 21 weeks’gestation) to 17 mm (at 31 weeks). At 10 months of age,this infant is developing normally.

Only in one instance (Case 7) was there evidence of aneurological sequela: after delivery the neonate developednormally, but at the age of 8 months the infant had petitmal-like convulsions. All remaining infants are developingnormally.

DISCUSSION

Measurement of the atrial region of the lateral ventricle isparticularly important for determination of the normalityof ventricular size, and is a sensitive ultrasonographic indi-cator for normal brain development. Fetuses with mild-to-moderate ventriculomegaly are at increased risk forneurological maldevelopment. It is frequently the presenceof other abnormalities that exacerbates the prognosis for

Figure 1 Transabdominal axial scan through the fetal head at 23weeks’ gestation, showing normal proximal ventricle (arrow) andenlarged distal ventricle

97/219

Mid-gestational unilateral ventriculomegaly Lipitz et al.

AMA: First Proof

24 Ultrasound in Obstetrics and Gynecology

the fetus, rather than the degree of ventricular enlargement.However, it is assumed that mild bilateral ventriculo-megaly, when isolated, is typically associated with a goodprognosis.

Unilateral ventriculomegaly, although considered a rarepathology, can be diagnosed prenatally, as shown by thepresent and previous studies3–10. However, the ultrasono-grapher must be aware of the reverberation from the near-calvarial wall that often obscures the lateral ventricle lyingclosest to the transducer. Thus, the ventricles often appearto be asymmetrical when enlarged. Scanning the fetalcranium in both axial and coronal planes with properlyfocused, high-resolution sonographic transducers, andgiving careful attention to scanning techniques, are there-fore important for the prevention of diagnostic errors.

When borderline unilateral ventriculomegaly is diag-nosed prenatally, a thorough investigation should be per-formed. This should include serial sonograms to excludeother possible abnormalities and to seek other subtle signsof cerebral injury (such as viral infection, or insidioushemorrhagic event), determination of fetal karyotype,α-fetoprotein analysis, and viral cultures and titers inmaternal blood. However, a TORCH screen seems prudentin these cases, but at present there is no evidence of an

Gestational age (weeks)

Case SexMaternal

age (years)At

diagnosisAt

deliveryDiameter of

ventricles (mm)Follow-upsonograms

Mode ofdelivery

Birthweight (g) Outcome

123456789

1011121314

15161718192021222324

252627

FMMFMFFMFMFMFF

FMMFMMMMMF

FMM

2731262724253525252829273228

36283027212730292630

292734

2223262821282821252223262322

29232229232423212021

232221

37404237404039403739404140

TOP (25)

42384037403841394034

403838

14/811/812/812/811/611/613/911/612/912/812/712/811/712/8

14/711/611/814/611/711/711/712/811/712/8

11/611/611/7

stableresolvedstablestable

resolvedstablestable

resolvedstablestablestablestablestable

—

stablestablestablestablestablestablestablestablestable

increased

resolvedstablestable

SVDSVDSVDSVDSVDSVDSVDSVDSVDSVDSVDSVDSVDTOP

SVDSVDSVDSVDSVDSVDLSCSSVDSVDSVD

SVDLSCSSVD

3250420037203470335034503800260036503150308037003075

3080374037752540398027203165387034002140

343027353100

normalnormalnormalnormalnormalnormal

petit malnormalnormalnormalnormalnormalnormal

pathological examination:normal brain

normalnormalnormalnormalnormalnormalnormalnormalnormal

normal at 7 months:progressed from

12 mm (at 21 weeks) to17 mm (at 31 weeks)

normalnormalnormal

SVD, spontaneous vaginal delivery; TOP, termination of pregnancy; LSCS, low segment Cesarean section; F, female; M, male

Table 1 Clinical data of cases with unilateral ventriculomegaly

Figure 2 Transvaginal posterior coronal view of a fetus at 22weeks’ gestation, showing unilateral ventriculomegaly

97/219

Mid-gestational unilateral ventriculomegaly Lipitz et al.

AMA: First Proof

Ultrasound in Obstetrics and Gynecology 25

increased risk of these infections. If the aforementioned arenegative, the parents should be encouraged to continue thepregnancy. Our study shows that, when mild ventriculo-megaly (11–14 mm) was diagnosed at mid-gestation, in allcases except one it was stable or resolved in utero, or in theneonatal period. Furthermore, in the only fetus with pro-gression of the ventricular enlargement, the outcome ofthe newborn (at least at 7 months of age), was uneventful.In our study, in only one newborn (Case 7) were theresome neurological abnormalities in the form of petit malconvulsions, but apart from this the newborn is developingnormally.

Asymmetry of cerebral ventricles has been previouslyreported in human fetuses11 and human neonates16,17

without brain pathology. However, in these studies theventricles were asymmetrical, but both were in the normalrange (< 10 mm).

Most reported cases of unilateral ventriculomegaly thatare seen later in life are a result of obstruction of theforamen of Monro, from inflammatory adhesions, ventri-culitis, subependymal gliosis, membranous occlusions andpedunculated tumors3. Complete agenesis of the foramenof Monro can also occur. In the present study, the etiologyof the unilateral ventriculomegaly remains unclear. Even inthe patient who underwent termination of pregnancy, thepathological examination of the fetal brain failed to revealany abnormality. It is possible that, at least in some fetuseswith mild unilateral ventriculomegaly, when underlyingpathology is excluded, this represents a normal anatomicalvariation in the fetal brain. However, our study group wasrelatively small and it is possible that some neurologicalimpairment could appear in a longer follow-up period.

In summary, it is possible to diagnose unilateral ventri-culomegaly in utero, but the incidence is unclear, as is theetiology. However, in fetuses with isolated borderline uni-lateral ventriculomegaly and no other abnormalities, theneurological outcome is good.

ACKNOWLEDGEMENT

This study was undertaken with the support of the GabrielPinkas Chair for the prevention and diagnosis of congenitalanomalies, Sackler School of Medicine, Tel Aviv University,Israel.

REFERENCES1. Nyberg DA, Mack LA, Hirsch J, Pagon RO, Shepard TH.

Fetal hydrocephalus: sonographic detection and clinicalsignificance of associated anomalies. Radiology 1987;163:187–91

2. Chervenak FA, Duncan C, Ment LR, Hobbins JC, McClureM, Scott D, Berkowitz RL. Outcome of fetal ventriculo-megaly. Lancet 1984;2:179–81

3. Patten RM, Mack LA, Finberg HJ. Unilateral hydrocephalus:prenatal sonographic diagnosis. Am J Roentgenol 1991;156:359–63

4. Gaston BM, Jones BE. Perinatal unilateral hydrocephalus:atresia of the foramen of Monro. Pediatr Radiol 1989;19:328–9

5. Hartung RW, Yiu-Chiu V. Demonstration of unilateral hydro-cephalus in utero. J Ultrasound Med 1983;2:369–71

6. Anderson N, Malpas T, Davison M. Prenatal diagnosis ofunilateral hydrocephalus. Pediatr Radiol 1993;23:69–70

7. Nakamura S, Makiyama H, Miyagi A, Tsubokawa T,Ushinohama H. Congenital unilateral hydrocephalus. Child’sNerv Syst 1989;5:367–72

8. Weiner Z, Bronshtein M. Transient unilateral ventriculo-megaly: sonographic diagnosis during the second trimester ofpregnancy. J Clin Ultrasound 1994;22:59–61

9. Chari R, Bhargava R, Hammond DI, Ventureyra EC, LalondeAB. Antenatal unilateral hydrocephalus. Can Assoc Radiol J1993;44:57–9

10. Tsao PN, Teng RJ, Wu TJ, Yau KI, Wang PJ. Nonprogressivecongenital unilateral ventriculomegaly. Pediatr Neurol 1996;14:66–8

11. Achiron R, Yagel S, Rotstein Z, Inbar O, Mashiach S, Lipitz S.Cerebral lateral asymmetry: is this a normal ultrasonographicfinding in the fetal brain? Obstet Gynecol 1997;89: 233–7

12. Nyberg DA. Recommendations for obstetric sonography inthe evaluation of fetal cranium. Radiology 1989;172:309–11

13. Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ventri-culomegaly with a single measurement: the width of the lateralventricular atrium. Radiology 1988;169:711–14

14. Heiserman J, Filly RA, Goldstein RB. Effect of measurementerrors on sonographic evaluation of ventriculomegaly. J Ultra-sound Med 1991;10:121–4

15. Achiron R, Schimmel M, Achiron A, Mashiach S. Fetal mildidiopathic lateral ventriculomegaly: is there a correlation withfetal trisomy? Ultrasound Obstet Gynecol 1993;3:89–92

16. Horbar JD, Leahy KA, Lucey JF. Ultrasound identification oflateral ventricular asymmetry in the human neonate. J ClinUltrasound 1983;11:67–9

17. Cohen MD, Slabaugh RD, Smith JA, Jansen R, Greeman GF,MacDonald N. Neurosonographic identification of ventri-cular asymmetry in premature infants. Clin Radiol 1984;35:29–31

97/219

Mid-gestational unilateral ventriculomegaly Lipitz et al.

AMA: First Proof

26 Ultrasound in Obstetrics and Gynecology