This Journal Club presentation provides a summary and discussion of the following free access article published in UOG: Callosal dysgenesis in fetuses with ventriculomegaly: levels of agreement between imaging modalities and postnatal outcome Y. Li, J.A. Estroff, O. Khwaja, T.S. Mehta, T.Y. Poussaint, C.D. Robson, H.A. Feldman, J. Ware, D. Levine Volume 40, Issue 5, Date: November 2012, pages 522–529 It can be accessed here: http://onlinelibrary.wiley.com/doi/10.1002/uog.11098/abstract

1. UOG Journal Club: November 2012
Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li Y, Estroff JA, Khwaja O, Mehta TS, Poussaint TY, Robson CD, Feldman HA,
Ware J, Levine D
Volume 40, Issue 5, Date: November 2012, pages 522–529
Journal Club slides prepared by Dr Aly Youssef
(UOG Editor for Trainees)

2. • Ventriculomegaly (lateral ventricles ≥ 10 mm) is often the first
ultrasonographic sign of corpus callosum (CC) abnormalities
• Corpus callosum abnormalities are often associated with central
nervous system (CNS), chromosomal, syndromic and other structural
abnormalities
• Main limitations of the existing studies on CC abnormalities are:
o the limited prenatal and/or postnatal assessment
o attrition is common due to termination of pregnancy or loss to
follow-up
• The actual data on the outcome of fetuses with callosal abnormalities
is limited and varies widely in the literature

3. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
The aim of the present study was to assess
neurodevelopmental outcome in fetuses diagnosed
with isolated and non-isolated callosal abnormalities
following referral for ventriculomegaly

4. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Methods I
Sub-analysis of a prospective study including 430 fetuses referred for ventriculomegaly.
Ultrasound (transabdominal and/or transvaginal) and MRI performed in all cases in the axial
(A), coronal (B) and sagittal planes (C). Sub-analysis included fetuses with a diagnosis of
corpus callosal abnormalities after recruitment into the main study.
A B C
Ultrasound
Complete agenesis of
the corpus callosum at
26 weeks’ gestation in a
fetus with lateral
ventricular
measurement of 10 mm
MRI

5. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Methods II
• Between 3–6 radiologists independently reviewed ultrasound and MR images
and final diagnoses decided by consensus
• All callosal abnormalities (hypoplasia, complete agenesis, partial agenesis) were
combined into a single group
• Patients with callosal abnormalities were further subdivided into two groups:
o Isolated (no additional abnormalities)
o Non-isolated (associated CNS, karyotypic, syndromic or other major
abnormalities)
• Pregnancy and postnatal outcomes in fetuses with callosal abnormalities
(including neurodevelopment at 6 months, 1, 2, and 3 years) were compared
between those with (non-isolated) and those without (isolated) other
abnormalities

6. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Results I
430 women referred for ventriculomegaly
58 prenatal diagnosis of callosal abnormalities
(13%)
Isolated Non-isolated
14 44
(24%) (76%)
• The kappa statistic for preconference agreement was 0.76 for ultrasound readers and 0.78
for MRI readers, indicating that both investigations had a similar level of operator dependence
• There were more true positives and false positives by MRI readers than by ultrasound
readers

7. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Results II
Prenatal consensus diagnosis
Characteristic Isolated callosal Non-isolated callosal P-value ‡
abnormalities abnormalities
(n = 14) (n = 44)
Prenatal assessment
Gestational age at imaging (weeks) 30.7 ± 4.8 (20–38) 26.2 ± 6.3 (19–38) 0.02
Abnormal karyotype 0 17 0.008
Ventricular diameter (mm) 15.8 ± 3.3 (11–21) 13.9 ± 5.6 (8–42) 0.02
Pregnancy outcome
Termination 2 12 0.48
Neonatal demise 0/12 1/31† > 0.99
Gestational age at birth (weeks) 39.6 ± 0.8 (39–41) 37.8 ± 1.6 (34–41) 0.003
Data shown as mean ± SD (range), n or n/total.
†One patient lost to birth outcome follow-up. ‡ Mann–Whitney test (continuous variables) or Fisher’s exact test (discrete variables).

8. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Results III
Prenatal consensus diagnosis
Characteristic Isolated callosal Non-isolated P-value *
abnormalities callosal
(n = 14) abnormalities
(n = 44)
Neurodevelopmental outcome 0.003
Number with neurodevelopmental follow-up 12 27
Normal or mild delays that resolved 67% (8/12)§ 7% (2/27)
Mild delays that persisted 8% (1/12)§ 22% (6/27)
Moderate to severe delays/abnormalities 25% (3/12)§ 70% (19/27)
Data shown as n or % (n/total).
§ Includes children with postnatal CNS abnormalities that were not detected prenatally
* Fisher’s exact test (discrete variables)

9. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Discussion
• Callosal abnormalities are present in a significant proportion of fetuses with
ventriculomegaly (13% in the present study)
• Normal neurodevelopment was observed in approximately two-thirds of fetuses
with isolated callosal abnormalities, and less than 10% of non-isolated cases
• Both ultrasound and MRI have substantial interrater agreement in the prenatal
diagnosis of CC anomalies, while MRI showed more true-positive and false-
positive diagnoses than did ultrasound
• Many associated anomalies in prenatally diagnosed isolated and non-isolated
callosal anomalies became apparent only later in gestation or postnatally.
This should be considered in counseling patients at the time of diagnosis of
callosal abnormalities.

10. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Strengths of the study
• Study population embedded within a prospectively enrolled cohort of
fetuses
• Large sample size of patients with callosal abnormalities
• Standardized and specialist evaluations by pediatric neurologists and/or
pediatric psychologists
• Long period of postnatal follow-up (up to 5 years of age)
Limitations
• Population included is a part of a cohort of fetuses referred for
ventriculomegaly. Therefore, no data can be provided on prenatally
diagnosed callosal abnormalities without ventriculomegaly.

11. Callosal dysgenesis in fetuses with ventriculomegaly: levels
of agreement between imaging modalities and postnatal outcome
Li et al., UOG 2012
Discussion points
• Should all women with prenatal diagnosis of callosal abnormalities be
referred for expert ultrasound assessment?
• Should fetal karyotype determination be routinely offered to these
women?
• Should MRI be routinely performed in all cases with prenatal diagnosis
of callosal abnormalities?
• How can the present data guide the clinician in the counseling of women
with prenatal diagnosis of isolated and non-isolated CC abnormalities?
• Should these women be offered specialist evaluation later in pregnancy?