Fetal ventriculomegaly is the most common abnormal manifestation of the central nervous system on ultrasound examination. During pregnancy, an atrial width of ≥10.0 mm can be diagnosed as ventriculomegaly, which is further classified into mild ventriculomegaly when the atrial width is between 10.0 mm and 12.0 mm, moderate ventriculomegaly when the atrial width is between 12.1 and 15.0 mm, and severe ventriculomegaly when the atrial width is >15.0 mm. Ventriculomegaly is defined as isolated when it is not associated with additional structural abnormalities. The degree of lateral ventriculomegaly is an important factor in the prognosis of the fetus.1 Severe ventriculomegaly can lead to neonatal cerebral palsy and death. Therefore, cost-effective prenatal testing is necessary, and ultrasound is the preferred option for fetal lateral ventricle examination. In addition, the more advanced magnetic resonance imaging (MRI) can be used as a supplementary test for ultrasound imaging. The combination of these two tests can significantly increase the efficiency of prenatal examination. In this study, we aimed to assess the value of ultrasound combined with MRI in the diagnosis of fetal lateral ventriculomegaly and to evaluate the fetal prognosis, to provide further guidance for clinical practice.
Materials and methods
We recruited 136 pregnant women whose fetus had ventriculomegaly or ventriculomegaly with other neurological diseases by prenatal ultrasound at the Tianjin Central Hospital of Obstetrics and Gynecology from January 2016 to December 2017. One hundred and thirty-six cases underwent MRI (completed within 7 days of ultrasound examination), among them 39 cases were lost to follow-up. A total of 97 singleton pregnancies were entered into the study. The mean maternal age was 29 years (range 18–42 years), and the mean fetal gestational age at diagnosis was 31 weeks (range 19+4 to 37+3 weeks). Among the 97 subjects, 37 were delivered via induced labor because of central nervous system malformations, other organ malformations, or severe ventriculomegaly. Eventually, 61 infants were delivered and followed up. Follow-up included pregnancy outcomes and infant intelligence, language, and motor development. The study protocol was approved by the Ethics Committee of the Tianjin Central Hospital of Gynecology Obstetrics (2016KY039).
Instruments and inspection methods
Ultrasound examinations were performed using the Voluson E-8 (GE Medical Systems, Kretz sonography, Zipf, Austria) ultrasound platforms, Low-frequency convex array probes with a frequency range of 2–5 MHz were employed. In fetuses with a lateral ventricle width of ≥10.0 mm, measured at the level of the glomus of the choroid plexus, perpendicular to the ventricular cavity and with the calipers positioned inside the echoes generated by the lateral walls, detailed fetal neurological malformation screening, and systematic ultrasonography were performed. All fetuses with widened ventricles and MRI examinations were included in the study. For fetuses with isolated lateral ventriculomegaly during the second trimester, the ultrasound scans were reviewed once every 2–4 weeks (at least three times, except for induction), and the changes of lateral ventricle width were measured. The prognosis after birth was followed up through telephone interviews for 1–3 years.
The subjects were assessed according to the degree of ventriculomegaly combined with other central nervous system abnormalities. Ventriculomegaly was defined as a unilateral or bilateral lateral ventricle width of >10.0 mm measured with ultrasound. MRI of the fetal head was conducted in all cases. Subjects with central nervous system abnormalities diagnosed with ultrasound were considered the ultrasound group, and those whose central nervous system abnormalities were diagnosed with ultrasound + MRI were categorized as the ultrasound + MRI group. Central nervous system abnormalities included partial or total absence of the corpus callosum, dysplasia or deficiency of the cerebellar vermis, malignant tumor, cerebral leukomalacia, intraventricular hemorrhage, cerebellar hemispheric dysplasia, cerebral midline dysplasia, and other abnormalities. Choroid plexus cysts, ependymal cysts, and arachnoid cysts were not considered central nervous system abnormalities.
According to the lateral ventricle width, fetuses with isolated lateral ventriculomegaly were divided into the mild group (10.0–12.0 mm), moderate group (12.1–15.0 mm), and severe group (>15.0 mm).2 Some fetuses with severe lateral ventricular dilatation and those with lateral ventricle dilatation with nervous system or other malformations were excluded from follow-up because of pregnancy termination. According to the degree of isolated lateral ventricle dilatation before birth, the growth and development of the subjects after birth were observed, mainly including intelligence, language, and physical functioning. Because the subjects were followed up only within 3 years after birth, social skills, and integration, hyperactivity, and emotional problems were not followed up. Language impairment was defined as the inability of a child to call out to his or her parents at around the age of 1 year, and the inability to fully express his or her wishes after the age of 2.5 years. Mild dyskinesia refers to hobbling and poor coordination, and severe dyskinesia is defined as cerebral palsy or progressive myopathy.3
Normally distributed continuous variables were presented as mean ± SD. Categorical variables were presented as frequencies, and were analyzed using the χ2 test or Fisher test. Data were analyzed using SPSS 20.0 (IBM, Armonk, NY, USA). Two-sided P <0.05 was considered statistically significant.
The diagnosis of fetal central nervous system abnormality was compared between ultrasound and ultrasound + MRI. In 97 pregnancy cases, ultrasound or ultrasound + MRI showed fetal lateral ventricle widening and suspected central nervous system abnormalities in 36 cases. Among them, ultrasound and MRI were fully consistent in 15 cases, MRI added new diagnostic information or supplemented the ultrasound diagnosis in eight cases, and MRI corrected the ultrasound diagnosis in two cases. There were 11 cases with an ultrasound diagnosis but with no MRI diagnosis (Table 1). Among the 36 cases, ultrasound diagnosed central nervous system abnormalities in 15 cases (15/36, 41.7%). Ultrasound + MRI diagnosed central nervous system abnormalities in 25 cases, including 15 cases that were considered suspicious on ultrasound (25/36, 69.4%). All pregnant women whose fetus was confirmed to have central nervous system dysplasia, except for four women who continued their pregnancy, had induced labor. Among the four cases of continued pregnancy, one infant died after birth, one infant had cerebral palsy and mental retardation, one infant had delayed myelination, and one infant was normal. The detection rate of central nervous system dysplasia by ultrasound + MRI was significantly higher than that of ultrasound alone. Pearson χ2 test was used to compare the detection rates between groups, and the difference was statistically significant (Table 2).
The degree of lateral ventriculomegaly and the neonatal prognosis were evaluated. A total of 61 infants with isolated lateral ventriculomegaly were followed up for 1–3 years after birth. According to the degree of isolated lateral ventricle dilatation, we observed the growth and development after birth (Table 3). The rate of normal growth and development in the mild group was 90.9% (30/33), that in the moderate group was 69.6% (16/23), and that in the severe group was 40.0% (2/5). The analysis was performed using RxC χ2 (RxC Chi-square test), and the difference between the groups was statistically significant (P < 0.01) (Table 4).
Value of MRI in the diagnosis of fetal lateral ventricle widening
Ultrasound examination of the fetal lateral ventricle is the most commonly performed prenatal test; however, prenatal MRI can make a more accurate judgment of the degree of fetal lateral ventricle dilatation and the development around the ventricle.4 In this study, 97 cases of lateral ventriculomegaly were detected by ultrasound. All cases were subjected to fetal head MRI. Among them, ultrasound showed suspicious findings of central nervous system abnormalities in 26 cases. Fifteen cases were diagnosed abnormal by MRI, and 11 cases were diagnosed without abnormalities. Whereas MRI added new diagnostic information or supplemented the ultrasound diagnosis in eight cases. The most common abnormality was corpus callosum dysplasia or lack of corpus callosum. In two cases, MRI corrected the ultrasound diagnosis to pineal cyst and cerebral hemisphere dysplasia. In 11 cases with an ultrasound diagnosis, there was no MRI diagnosis. The most common diagnosis was ventricular hemorrhage, followed by corpus callosum dysplasia, which is a common cause of fetal lateral ventriculomegaly. In seven subjects with suspected corpus callosum dysplasia on ultrasound, an absence of corpus callosum was diagnosed on MRI. Moreover, MRI newly diagnosed three cases of absence of corpus callosum that were not found by ultrasound. The sagittal section of the corpus callosum is the best aspect of the corpus callosum. Ultrasound is not easy to obtain the sagittal section due to the position of the fetal head and the skull. In the diagnosis of corpus callosum dysplasia, it mainly through indirect signs such as axial ventricle morphological abnormalities. However, the prenatal MRI sagittal position can clearly show the whole body of the corpus callosum, provide direct signs of the absence of the corpus callosum, and can be comprehensively analyzed in combination with the axial and coronal positions. For the dysplasia of the corpus callosum, the diagnostic accuracy of MRI is significantly better than ultrasound.5,6 Dandy-Walker malformation can also cause fetal lateral ventriculomegaly. Because ultrasound cannot show the size and shape of the cerebellar vermis and the location of the cerebellum curtain, it has some limitations in diagnosing mutation-related Dandy-Walker malformation, leading to missing the diagnosis or a misdiagnosis. As MRI is a multidirectional imaging modality that can clearly show the development of the cerebellar vermis, it has certain advantages for the diagnosis of variant Dandy-Walker malformation. In this study, MRI diagnosed lateral ventriculomegaly with Dandy-Walker malformation in one case. For the diagnosis of brain dysplasia, MRI is superior to ultrasound because it can clearly show the sulci and gyri of the fetal brain, as well as distinguish gray matter and white matter.7 At the same time, MRI has a high sensitivity in diagnosing fetal intracranial hemorrhagic lesions. Multidirectional imaging can accurately reveal the bleeding site and can determine the bleeding time according to the signal characteristics of the lesion. However, MRI is not suitable for diagnosing early fetal malformations and cannot detect fetal development in real-time; thus, it is not suitable for prenatal review. Therefore, the effective combination of ultrasound and MRI can improve the accuracy of diagnosis and allow providing counseling and prognostic guidance in the clinic.
Fetal ventriculomegaly is the most common intracranial structural abnormality diagnosed with ultrasound and other imaging modalities. It is a heterogeneous disease with various causes and neurodevelopmental outcomes. The diagnosis of ventriculomegaly is usually based on the reference range established by Cardoza et al.,8 in which a lateral ventricle width of <10.0 mm is considered normal. Tonni et al.9 made the criteria more refined by defining a lateral ventricle width of 10.1–12.0 mm as mild ventricular widening and 12.1–15.0 mm as moderate ventriculomegaly. It is currently believed that lateral ventriculomegaly is associated with brain structure abnormalities, chromosomal abnormalities, intrauterine viral infections, heredity, and irrational use of drugs during pregnancy. In this study, there were 61 cases of fetus with isolated lateral ventricle widening, including 33 cases of mild, 23 cases of moderate, and 5 cases of severe lateral ventricle widening. Clinically, the fetal prognosis depends on the extent of lateral ventriculomegaly, in which severe ventriculomegaly leads to neonatal cerebral palsy and death. The fetal prognosis is good in the case of isolated mild ventricle widening. Some mild unilateral isolated ventriculomegaly may be normal anatomical variations of the fetus, which have a certain probability of causing neurological deficits including attention deficit hyperactivity disorder, epilepsy, gait abnormalities, and hearing loss.10
Fetal prognosis in isolated mild ventriculomegaly
The prognosis of isolated mild ventriculomegaly remains the focus of prenatal care and is one of the important concerns of parents. Scala et al.3 found that the incidence of neurodevelopmental disorders in fetuses with unilateral isolated ventriculomegaly with a lateral ventricle width of <15.0 mm was 5.9%, and the incidence of combined brain malformations was 5.0% in prenatal and postpartum MRI. Baffero et al.11 reported that the incidence of neurologic abnormalities in fetuses with isolated ventriculomegaly with a lateral ventricle width of 10.0–15.0 mm during postpartum ultrasound follow-up was 6.9%. In this study, no neonatal malformation was found postpartum, which may be related to the use of MRI and ultrasonography during pregnancy, 61 children with long-term follow-up outcomes in this study. They were evaluated by the Bayley scales of infant development. The intelligence scale is used to assess cognitive, linguistic and social interaction abilities, and the results are expressed by mental developmental index. The exercise scale is used to evaluate coarse motion and fine motion, and the result is expressed by pychomotor developmental index. Mental developmental index and pychomotor developmental index development index ≥120 is excellent, 80–119 is moderate, and ≤79 is low development. As a result, of the 61 children, 48 had normal mental and motor development. Thirteen cases of mental retardation or mental and sports depression. Of the 33 subjects with mild lateral ventriculomegaly, 90.9% had normal growth and development, none had a poor prognosis. Three cases of dyskinesia or mental retardation of the 23 subjects with moderate lateral ventriculomegaly, 69.6% had normal growth and development. Four cases of dyskinesia or mental retardation; of the 5 subjects with severe lateral ventriculomegaly 40.0% had normal growth and development, one cases of dyskinesia and mental retardation; and two cases of mortality after birth (in which the causes of death were unknown). Isolated lateral ventricle dilatation accounts for 20% of the diagnosis of lateral ventricular dilatation by ultrasound.12 It has been reported that the neonatal survival rate of isolated mild ventriculomegaly is high (about 93%–98%). The probability of normal neurodevelopmental outcome is >90% and may not differ from that of the general population. Newborns with isolated moderate ventriculomegaly are more likely to have adverse outcomes than those with mild ventriculomegaly. Similar to the data in this study, it was also reported that the survival rate of neonates with isolated moderate ventriculomegaly was 80%–97%, and the probability of normal neurodevelopmental outcome was 75%–93%.1 However, there is an increased risk of neurodevelopmental disability. In fetuses with isolated ventriculomegaly, if the lateral ventricle width is <12.0 mm, the prognosis after birth is mostly good. If the width is ≥12.0 mm, the asymmetry of the lateral ventricles is widened, and the child shows abnormal neurological manifestations after birth, head MRI examination should be performed to determine the existence of neurological diseases and long-term follow-up should be emphasized. In summary, when the lateral ventricle of the fetus is observed to be widened on ultrasound and other intracranial diseases are suspected, it is recommended to conduct a prenatal MRI examination to determine the degree of widening and its influence on the surrounding brain tissue, as well as to find the cause and accompanying malformations13 to reduce the neonatal defects. MRI examination not only can improve the prenatal detection of abnormalities, but can also be the main method for the evaluation of prognosis after birth.
Early pregnancy screening combined with high-throughput sequencing technology in the diagnosis of birth defects (17YFZCSY00830).
Study on the interference factors of non-invasive detection accuracy of fetal aneuploid (18ZXDBSY00230).
Xiao-Min Zhao had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Xiao-Min Zhao. Ying Chang, Xing Li. Acquisition of data: Xiao-Min Zhao, Ying Chang, Xing Li, Wen Li. Analysis and interpretation of data: Xiao-Min Zhao, Ying Chang, Xing Li, Wen Li, Shan-Shan Li. Drafting of the manuscript: Xiao-Min Zhao, Ying Chang, Xing Li.
Conflicts of Interest
. Fox NS, Monteagudo A, Kuller JA, et al. Society for maternal-fetal medicine (SMFM) consult series 45: mild fetal ventriculomegaly
: diagnosis, evaluation, and management. Am J Obstet Gynecol 2018;219(1):B2–B9. doi: 10.1016/j.ajog.2018.04.039.
. Melchiorre K, Bhide A, Gika AD, et al. Counseling in isolated mild fetal ventriculomegaly
Obstet Gynecol 2010;34(2):212–224. doi:10.1002/uog.7307.
. Scala C, Familiari A, Pinas A, et al. Perinatal and long-term outcomes in fetuses diagnosed with isolated unilateral ventriculomegaly
: systematic review and meta-analysis. Ultrasound
Obstet Gynecol 2017;49(4):450–459. doi: 10.1002/uog.15943.
. Malinger G, Lerman-Sagie T. Re: additional value of fetal magnetic resonance imaging
in the prenatal diagnosis of central nervous system anomalies: a systematic review of the literature. Ultrasound
Obstet Gynecol 2015;45(2):236–237. doi:10.1002/uog.14740.
. Manfredi R, Tognolini A, Bruno C, et al. Agenesis of the corpus callosum in fetuses with mild ventriculomegaly
: role of MR imaging. Radiol Med 2010;115(2):301–312. doi:10.1007/s11547-009-0474-7.
. Cignini P, D’Emidio L, Padula F, et al. The role of ultrasonography in the diagnosis of fetal isolated complete agenesis of the corpus callosum: a long-term prospective study. J Matern Fetal Neonatal Med 2010;23(12):1504–1509. doi:10.3109/14767051003678101.
. Monika Bekiesińska-Figatowska, Herman-Sucharska I, Romaniuk-Doroszewska A, et al. Brain development of the human fetus
in magnetic resonance imaging
. Medycyna wieku rozwojowego 2010;14(1):5–14.
. Cardoza JD, Goldstein RB, Filly RA. Exclusion of fetal ventriculomegaly
with a single measurement: the width of the lateral ventricular atrium. Radiology 1988;169(3):711–714. doi:10.1148/radiology.169.3.3055034.
. Tonnig G, Vito I, Palmisano M, et al. Neurological outcome in fetuses with mild and moderate ventriculomegaly
. Rev Bras Ginecol Obstet 2016;38(9):436–442. doi:10.1055/s-0036-1592315.
. Chiu TH, Haliza G, Lin YH, et al. A retrospective study on the course and outcome of fetal ventriculomegaly
. Taiwan J Obstet Gynecol 2014;53(2):170–177. doi:10.1016/j.tjog.2014.04.008.
. Baffero GM, Crovetto F, Fabietti I, et al. Prenatal ultrasound
predictors of postnatal major cerebral abnormalities in fetuses with apparently isolated mild ventriculomegaly
. Prenat Diagn 2015;35(8):783–788. doi:10.1002/pd.4607.
. Griffiths PD, Reeves MJ, Morris JE, et al. A prospective study of fetuses with isolated ventriculomegaly
investigated by antenatal sonography and in utero MR imaging. AJNR Am J Neuroradiol 2010;31(1):106–111. doi:10.3174/ajnr.A1767.
. We JS, Young L, Park IY, et al. Usefulness of additional fetal magnetic resonance imaging
in the prenatal diagnosis of congenital abnormalities. Arch Gynecol Obstet 2012;286(6):1443–1452. doi:10.1007/s00404-012-2474-4.