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UOG Journal Club: November 2012

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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: the limited prenatal and/or postnatal assessment 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 Methods I 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: Isolated (no additional abnormalities) 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 Results I 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 (13%) prenatal diagnosis of callosal abnormalities Isolated Non-isolated 14 (24%) 44 (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 6

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 abnormalities (n = 14) Non-isolated callosal (n = 44) P-value ‡ Prenatal assessment Gestational age at imaging (weeks) 30.7 ± 4.8 (20–38) 26.2 ± 6.3 (19–38) 0.02 Abnormal karyotype 17 0.008 Ventricular diameter (mm) 15.8 ± 3.3 (11–21) 13.9 ± 5.6 (8–42) 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). 7

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 abnormalities (n = 14) Non-isolated callosal (n = 44) P-value * 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) 8

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 Strengths of the study Limitations
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?


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