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Prenatal evaluation and postnatal early outcomes of fetal
1. Prenatal evaluation and
postnatal early outcomes of
fetal ventriculomegaly
Official Journal of the European Paediatric
Neurology Society
2. a b s t r a c t
• Objective: This study aims to determine the
incidence, etiology, diagnostic criteria and
early outcomes of prenatally diagnosed fetal
ventriculomegaly (VM).
• Methods: Diagnostic criteria for the fetal VM
was atrial diameter of lateral ventricle
measuring 10 mm, independent from
gestational age.
3. • Results of our patients from ultrasonography (USG), karyotyping,
congenital infections, and associated abnormalities were noted.
• Progress during pregnancy, postnatal USG results and
neurobehavioral outcomes were recorded.
• Results: In our study, 40 subjects of fetal VM were recorded. 16 and
24 of those were bilateral (40%) and unilateral (60%) respectively.
Female to male fetus ratio was 19/21 (0.9). Median gestational age
at the diagnosis was 22 weeks (ranging between 16 and 34 weeks).
While 21 VM subjects were isolated (52.5%) only 19 of the total
were shown associated structural abnormalities in (47.5%) in
addition to VM.
• Toxoplasmosis were diagnosed only in one subject (2.5%). Nineteen
subjects had amniocentesis (47.5%) and 2 of them were showed
abnormalities (10.5%) as follows; “inversion and duplication 8
(p11.2p23)” and “deletion 3”. VM got back in to normal size during
pregnancy in 24 subjects (24/40, 60%). Eight pregnancies were
terminated (8/40) (20%). Five babies passed away during neonatal
and post- neonatal period. Some other structural abnormalities
were diagnosed after the birth at six babies who classified as mild
“isolated” VM.
4. Conclusions:
• Our study revealed that amongst mild VM
subjects, incidence of associated
abnormalities and termination rates were
higher. Although most of mild VM subjects are
thought to be benign, associated
abnormalities should be carefully evaluated
and determined pre- and postnatally.
5. Introduction
• Fetal ventriculomegaly is an USG diagnosis that
refers to dilatation of lateral ventricles of the
brain. When atrial diameter of lateral ventricle is
greater than 10 mm, it is considered as VM.
• American College of Obstetricians and
Gynecologists (ACOG) recommends routine
prenatal USG screening which includes the
evaluation of fetus intracranial anatomy as well
as fetal ventricular size.
6. Contd..
• Previously, some authors used the definition of mild (10-
12 mm), moderate (13-15 mm), and severe (>16 mm) to
distinguish the severities of vetriculomegaly.
• There is no argument about the definition of the severe
VM that, if the size of lateral ventricle diameter is over
15, it is assumed as severe VM.
• But many researchers and clinicians recently started to
use the term “mild VM” to define lateral venticle
diameter between 10 and 15 mm.
• Melchiorre et al. showed with their meta-analysis that
isolated mild VM of 12 mm do not have significant better
neurologic prognosis compared with those of 12-15
mm.
• The incidence of VM is between 0.3 and 2 per 1000
pregnancies.
7. • There are many causes of fetal VM among which are
obstruction (leading to hydrocephalus), focal or
generalized loss of brain volume, and CNS
malformations.
• At the same time, some of the subjects have no known
cause of VM in prenatal and postnatal period.
• Ventriculomegaly is generally bilateral. Unilateral VM
incidence and its clinical significance is still unclear.
• Some reports show that if there are not any associated
malformations and chromosomal abnormalities, mild
VMs have favorable neurologic outcomes.
8. Contd..
• Severe VM is associated with an increased risk of
prenatal and neonatal neurodevelopmental
problems and death.
• The prognosis and management of severe forms
primarily depends on whether the severity is
complicated by additional intracranial or extracranial
abnormalities.
• Detailed imaging, which consists of fetal
neurosonography and fetal magnetic resonance
imaging (MRI), gives physicians highly accurate
information to redefine extra and intracranial
abnormalities of fetus.
• If there are not any intracranial or extracranial
abnormalities, it is termed as “isolated”severe VM.
9. • The aim of this retrospective study is to review
the information regarding the background and
progress of the VM subjects, whose mothers had
received well prenatal care, were born in Baskent
University, Ankara Hospital.
• We tried to figure out and attract attention to the
role of prenatal diagnosis, at the same time, to
understand different etiologic factors and early
outcomes of isolated and associated VM.
10. Material and method
• Forty subjects of fetal VM were identified from the
records of Department of Perinatology, Baskent
University Ankara Hospital, between January 2006 and
June 2013.
• Cross validation with genetics and pediatric cardiology
databases allowed us maximal subject ascertainment.
• Standardization guidelines of Department of
Perinatology, Baskent University Ankara Hospital for
the management of fetal VM subjects (atrium
measurement of 10 mm or greater) were agreed
and VM records were carefully noted.
• The subjects were examined according to their
ventricle size (mild and severe) and if they had
associate abnormalities (isolated and associated).
11. • To determine possible etiologies, karyological
records, whether performed by amniocentesis or
chorionic villus sampling (CVS), were noted.
• Any related structural (intracranial or
extracranial) abnormalities and syndromes were
examined and noted.
• Serological evaluation of Toxoplasma, Rubella,
Cytomegalovirus and Herpes Simplex Virus
(TORCH) infections in maternal blood was also
routinely investigated.
12. • Gestational age of VM subjects were noted after birth.
Multiple USG examinations were performed every 2-4 weeks
until the end of progress. The progress and outcomes of each
pregnancy was followed up closely. Cranial USG and MRI
results were collected.
• We also examined the postnatal USG or MRI results, and their
postnatal progresses were noted via telephone interview if
the babies did not come to follow-up appointment at our
outpatient clinic.
• We asked whether any mortality or morbidity occurred due to
his/her VM and related structural abnormalities in his/her 6
month.
• Mild and severe categories were not used in the analysis due
to discrepancy of the numbers of the subjects in to each
groups.
• Descriptive statistics were used in reporting ultrasonography
and follow-up characteristics for all VM subjects.
14. Results
• Forty subjects of mild-to-severe form of VM were
identified from perinatology records between January
2006 and June 2013 among 4152 pregnancies. Of
those, median age of mothers was 29 (mean: 28.58 ±
5.349), median gestational age was 22 weeks (ranging
between 16 and 34 weeks). Sixty-five % of the total
was diagnosed before 24th gestational age.
• Nineteen of subjects were female (47.5%) and female
to male ratio was (19/21) 90%. Twenty-three subjects
were nulliparous while only 1 VM subject was the 4th
gravidity of mother (2.5%). Three subjects got pregnant
via in vitro fertil- ization (3/40, 7.5%). Multiple
pregnancy rate was 2.5% (1/40). Only one of twins was
affected. At the time of VM was detected, median of
nuchal translucency of the fetuses was 1.4 mm (mean:
1.908 ± 1.396).
15. • Median atrium width of lateral ventricles was 10.5 mm
ranging between 10 and 27 mm (mean: 11.58 ± 3.727).
Twenty- four of the 40 VM subjects were unilateral (60%),
while 16 of them were bilateral (40%).
• Twenty-one VM subjects were isolated (21/40, 52.5%)
while there were associated structural abnormalities in 19
subjects (47.5%). Thirty-seven of the 40 VM subjects were
identified as mild VM (92.5%) and 3 of them were classified
as severe VM form (7.5%).
• Sixteen of 37 mild VM subjects had at least one associated
abnormalities (43.3%) and 21 of 37 mild VM subjects were
classified as “isolated” form (56.7%). All of the three severe
VM subjects had associated abnormalities (100%).
16. • All subjects were screened for “TORCH” infections, and only one
was resulted positive for toxoplasmosis in mild VM group (2.5%).
• Nineteen subjects had amniocentesis (40%) and 2 of them showed
abnormalities (10.5%). First one was “inversion and duplication
chromosome 8 (p11.2p23)”, who had mild, associated VM and was
terminated at 26 weeks of pregnancy. The second one was
“deletion chromosome 3” who had mild VM and after birth, MRI
revealed “galen vein aneurysm” and “cystic hygroma”. She passed
away on her 2nd postnatal day.
• All of the isolated mild VM subjects (n ¼ 21) and 3 of the 16 non-
isolated mild VM subjects were improved and their ventricle sizes
returned to normal during pregnancy (<10 mm) (Total n ¼ 24). Four
of 16 associated VM subjects had stable ventricle sizes (25%) while
ventricle size of 1 of the 16 mild associated VM subjects increased
during pregnancy (6.2%). The ventricle sizes of all severe VM
subjects increased during pregnancy (3/3, 100%).
17. • One of the severe VM subject was born on 39th
gestational weeks. MRI showed “Cerebellar Vermis
Agenesis” and he underwent neurosurgical intervention
in postneonatal period. The other severe VM subject
was born on 41st gestational age. MRI showed
“Colpocephaly þ Corpus Callosum Agenesis”.
• She was reported dead when she was 8th months old.
The last severe VM subject was born on 32nd gestational
age and MRI confirmed “Galen vein aneurysm”.
• She passed away on her2nd postnatal day. None of the
severe VM subjects were found to be isolated. None of
the severe VM subjects went under termination. The
ventricle sizes of all severe VM subjects were increased
during pregnancy (3/3, 100%).
18. • Eight subjects were terminated due to fetal abnormalities
(20%) and 32 babies born alive (80%). Terminations were
performed between 16 and 28 weeks of gestation (median:
22 weeks). All of the terminated fetus' were in associated
and mild VM group. Six of the 8 terminated fetuses
underwent postnatal autopsy (75%).
• Pathology reports demonstrated that one of the fetus had
features of Goldenhar Syndrome with lemon head shape.
• In one subject, severe skeletal dysplasia with
meningomyelocele was identified. In other subjects,
autopsy findings were consistent with the prenatal imaging
and provided no additional information.
19. • Three of the autopsy results were not identified because they were
performed in different health care centres.
• There were 2 neonatal and 3 postneonatal deaths among all VM subjects
(12.5%) (5/40) . Three of the deaths among a total of 5 neonatal and
postneonatal deaths were classified in the mild associated group, while 2
were classified in the severe associated group (Table 4). The mortality rate
of our associated VM subjects was found out to be 68.4% .
(13 (5 postnatal and 8 terminated)/19).
• Six of 21 live born babies (28.5%), who had previously detected to have
mild isolated VM were consulted to pediatric neurology (n:3, Two had
choroid plexus cysts and 1 had arachnoid cyst, all which were determined
on 5th day with cranial USG), pediatric cardiology (n:2; one had atrial
septal defect and the other one had ventricular septal defect, referred due
to murmur), and with pediatric nephrology (n:1; one had Grade1-2
unilateral hydroureteronephrosis, referred due to oliguria after birth), in
their postnatal period.
20. Discussion
• In literature incidence of fetal VM is 0.3 to 2 per 1000
preg-nancies.
• However our study showed incidence of VM in our
clinic is 9.6 per 1000 pregnancies. It's probably because
our clinic is a tertiary referral centre. The European
Surveillance of Congenital Abnormalities reported a
incidence of severe fetal hyrdrocephalus and VM as
4.25 per 10,000 births.
• We confirmed 3 severe fetal VM among 4385 births,
incidence of severe VM is 6.6 per 10,000 births in our
clinic.
• In our series, the main gestational age at diagnosis was
found 22 weeks (range: 16-31 weeks).
21. • Breeze et al. reported that median gestation at detection of severe
VM was 28 weeks (range 16-36 weeks), while Kennelly et al.
informed median gestation at referral was 26.9 weeks (range 19-
40).
• The incidence of associated structural malformation was found
47.5% in our report. However Madazlı et al. reported a higher
incidence of associated abnormalities with VM that 77.4% of their
VM subjects had at least one associated structural abnormality.
• Same study reported a mortality rate of 86% among their
associated VM subjects. The mortality rate of our VM subjects
having associated malformations was 68.4% (13/19). This deaths
were assumed to be due to the associated anomalies seen with
ventriculomegaly, rather than the ventriculomegaly “group” itself.
22. • In our study, all severe VM were associated with
at least one severe CNS malformation (100%) in
accordance with the report by Gaglioti et al.
• Hannon T et al. reported that 49.7% of all severe
fetal VM forms were associated with an
abnormal-ity.
• Graham E et al. reported a high association
between severity of VM and mortality.
• We found a mortality rate of 66.6% (2/3) among
severe VM subjects, which was higher than the
study of Levitsky et al. among severe VM subjects
with a mortality rate of 26.6%.
• Vergani P. revealed that most of the mild isolated
VM forms improve and have good outcomes.
23. • Lipitz et al. reported that almost all of their mild (both
isolated or non-isolated) VM forms diagnosed at mid-
gestation resolved or stable in the neonatal period.
• In concordant with these studies, ventricle sizes of all of
“isolated mild” VM (21 subjects) were resolved during
progress of pregnancy. But after birth, 28.5% of our
“isolated mild” VM subjects were detected to have some
ab-normalities when examined carefully (6/21).
• In our study; 19 of 40 VM subjects had karyotype analysis
(47.5%) and chromosomal abnormality was detected in 2 of
19 subjects (2/19) (10.5%). Both of these subjects were
mild VM forms which match well with previous reports
confirming that chromosomal abnormalities are highly
encountered in the mild form VMs.
24. • Congenital infections are considered as one of the
etiologic causes of VM. In our report, only one VM
subject was attrib-uted to congenital infection which
was diagnosed positive for toxoplasmosis and
terminated on 29th gestational age (1/40, 2.5%). In
subjects of mild VM, the rate of congenital infections
varies between 1 and 5%.
• The termination rate of VM determined pregnancies
was 8/ 40 (20%). All of the terminated subjects were in
the mild VM class and found to have at least one
associated intracranial abnormality together with VM.
Breeze et al. reported 50% of their fetal VM subjects
underwent termination.
• Gaglioti et al. also reported a high termination rate
when VM diagnosis was made before 24 weeks.
25. • The main limitation of this study is lack of imaging of VM
subjects with intrauterine MR (iu MR). iuMR imaging is
started to be used widely because of its high value in
diagnostic pathway. Griffiths PD et al. showed that 17% of
147 singleton fetuses referred from sonography with a
confident diagnosis of isolated VM, has shown to have
brain abnormalities other than VM, when examined
carefully with iuMR imaging.
• In conclusion; our report revealed that there were a high
associated abnormality incidence and termination rate in
mild VM subjects. Although most of mild VM subjects are
thought to be benign, associated abnormalities must be
carefully evaluated and determined pre and postnataly.