Fetal Cerebral Ventricular Asymmetry Without Dilation: A Systematic Review

Abstract

The aim of this systematic review was to investigate the outcomes of pregnancies with fetal cerebral lateral ventricle asymmetry without dilation. We conducted a comprehensive literature search in the Embase, Medline, and Web of Science databases until April 29, 2024, of observational cohort studies that reported fetal ventricular asymmetry without dilation detected on ultrasound or magnetic resonance imaging. Of the 150 studies identified, 6 met the inclusion criteria. Among the cases of non-dilated ventricular asymmetry, 36.8–46.2% progressed to ventriculomegaly on follow-up by neurosonography or magnetic resonance imaging. Additional findings in the central nervous system were observed in 5.5–10.5% of cases, while 7.6% had additional fetal body findings. Abnormal genetic findings were present in 5.1% of cases. Postnatal follow-up indicated no abnormal developmental findings during the first year of life. By the age of 9–11 years, lower writing speed was observed, yet verbal fluency scores were higher than in the general population. In conclusion, non-dilated ventricular asymmetry in fetuses showed the potential for progression to ventriculomegaly, and linkage to genetic abnormalities. Larger prospective studies are essential to fully elucidate the condition’s natural history and refine clinical management strategies.

 

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Zusammenfassung

Das Ziel dieser systematischen Übersicht war es, den Ausgang von Schwangerschaften mit fetaler zerebraler Asymmetrie der Seitenventrikel ohne Erweiterung zu untersuchen. Wir führten eine umfassende Literaturrecherche in den Datenbanken Embase, Medline und Web of Science bis zum 29. April 2024 durch, in der Beobachtungskohorten-Studien gesucht wurden, die über Fälle mit fetaler Ventrikel-Asymmetrie ohne Erweiterung berichteten, die mittels Ultraschall oder Magnet-Resonanz-Tomografie festgestellt wurden. Von den 150 identifizierten Studien erfüllten 6 die Einschlusskriterien. Bei 36,8–46,2% der Fälle einer nicht dilatierten Ventrikel-Asymmetrie zeigte sich in der Folgeuntersuchung mittels Neurosonografie oder Magnet-Resonanz-Tomografie eine Ventrikulomegalie. In 5,5–10,5% der Fälle wurden zusätzliche ZNS-Auffälligkeiten beobachtet, während bei 7,6% weitere fetale anatomische Anomalien festgestellt wurden. In 5,1% der Fälle wurden genetische Erkrankungen diagnostiziert. Die postnatale Nachsorge ergab keine Hinweise auf Entwicklungsstörungen im ersten Lebensjahr. Im Alter von 9–11 Jahren wurde eine verlangsamte Geschwindigkeit beim Schreiben beobachtet, die Wortflüssigkeitswerte waren jedoch höher als in der Allgemeinbevölkerung. Zusammenfassend lässt sich sagen, dass eine fetale Ventrikel-Asymmetrie ohne Erweiterung ein potenzielles Risiko für eine spätere Ventrikulomegalie darstellt und im Zusammenhang mit genetischen Anomalien stehen kann. Umfangreichere prospektive Studien sind unerlässlich, um diese zerebrale Anomalie in vollem Umfang zu verstehen und die klinischen Behandlungsstrategien zu verfeinern.

 

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Keywords

fetal neurology - lateral ventricles - developmental outcome - asymmetry

Introduction

Human brain development results in distinct anatomical and volumetric variations across cerebral hemispheres and lateral ventricles, thereby shaping functional differences and behavioral nuances between genders. The asymmetry of the human brain is a remarkable natural feature observed from fetal development through adulthood and is influenced by genetic and endocrinological factors [1].

In routine fetal sonographic evaluations, the assessment of lateral ventricle size is pivotal, with particular attention being given to measuring the distal cerebral atria width. Typically, only one ventricle, the distal one, is visualized and measured during routine fetal anomaly scans. The lack of formal guidelines advocating for the systematic visualization or measurement of both ventricles may result in variability in identifying lateral ventricular asymmetry. This variability underscores the importance of exploring the outcomes of this condition. Ventriculomegaly, defined as a distal lateral ventricle measurement of 10mm or greater at any gestational age, requires further investigation – due to its potential indication of brain pathology [2]. Lateral ventricular asymmetry is generally defined as a difference of more than 2mm in width between the 2 ventricles, though some studies use alternative thresholds, such as 2.4mm or 2 standard deviations above the mean, thus highlighting the variability in the literature [1]. While postnatal ventricular asymmetry without dilatation is observed in 5–12% of healthy individuals [3], it is inconclusive whether it signifies a normal variant or potential brain pathology [4].

As ultrasound technology advances, prenatal evaluations increasingly detect subtle brain anomalies, which complicate prenatal counseling on infant outcomes. Unlike major fetal brain anomalies, subtle conditions pose challenges with respect to deciding which prenatal investigations should be performed. Additionally, in this context, the optimal approach regarding postnatal assessments, including neurocognitive status in childhood, is yet to be clarified. In this systematic review, we investigated the outcomes of pregnancies with cerebral lateral ventricle asymmetry without dilation. We searched for reported fetal and neonatal outcomes, and also later neurodevelopmental and neuropsychological outcomes. As this condition is occasionally encountered antenatally, our systematic review may provide insight into its clinical implications and management in prenatal care.

 

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Methods

For this systematic review, we followed the guidelines outlined in the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist [5] [6]. The study was preregistered with the International Prospective Register of Systematic Reviews (PROSPERO identifier CRD42024537299) prior to data extraction and analysis. We included observational cohort studies that reported on prenatal investigation results, neonatal outcomes, and neurodevelopmental and neuropsychological outcomes of pregnancies with fetal ventricular asymmetry without dilation, regardless of whether detected on ultrasound or magnetic resonance imaging (MRI). Studies that did not report on the specific outcomes of interest were excluded from those subsections of the review to maintain focus on the relevant data. Review articles, comments, guidelines, and case reports were excluded. Only studies published in English up to April 2024 were considered. A comprehensive literature search was conducted across Embase, Medline, and Web of Science databases from inception to April 29, 2024. Collaborating with information specialists from the Tel Aviv University Library, we developed a structured search strategy focused on pregnancies with cerebral lateral ventricle asymmetry without dilation. The detailed search strategies tailored to each database can be found in supplementary Table 1.

Two independent researchers (I.S. and M.O.) conducted the entire selection process. After removing duplicates, they reviewed the titles and abstracts of identified studies for relevance, and then thoroughly examined the full texts. References from selected papers were screened for additional relevant studies. Any disagreements in study selection were resolved through consultation with a senior researcher (L.L.). The methodological quality of included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale NOS) for observational studies [7].

We presented a descriptive synthesis and conducted a pooled analysis to summarize outcomes across studies. Notably, the substantial heterogeneity in study designs, imaging modalities, and reported outcomes precluded the use of advanced meta-analytic techniques.

 

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Results

Identification and characteristics of the included studies

The initial systematic search process generated 150 results through database querying. Upon reviewing the titles and abstracts, 137 references were identified as ineligible based on the inclusion criteria. The full texts of the 13 remaining references were reviewed. A detailed breakdown of the reasons for excluding full-text articles is provided in supplementary Table 2. Ultimately, 6 studies met the criteria for inclusion in this systematic review, as depicted in the flow diagram [8] [9] [10] [11] [12] [13] ([Fig. 1]). Notably, all of the included studies were deemed to be of high quality. They were all published during 1997 and 2023. One study defined non-dilated ventricular asymmetry as a difference exceeding 2.4mm between the fetal lateral cerebral ventricles [8], while the remaining studies defined it as a difference greater than 2mm [9] [10] [11] [12] [13]. Among the included studies, 3 reported fetal neurosonogram results [8] [12] [13], 2 compared fetal neurosonograms and MRI findings [12] [13], and 3 reported prenatal genetic test outcomes [8] [12] [13]. Five studies assessed neuropsychological and neurodevelopmental outcomes of children with in-utero isolated non-dilated ventricular asymmetry at various ages: 6 weeks [13], 6 months [8], 13–74 months [11], 24–42 months [9], and 9–11 years [10]. The mean gestational age at the time of the neurosonogram was 28.7 ± 3.8 weeks. Males comprised 66.7% of the cohort. [Table 1] provides a comprehensive overview of the characteristics and quality assessment of the included studies.

Fig. 1 PRISMA flowchart of the literature search.

Table 1 Characteristics and Quality Assessment of Studies Included in the Systematic Review.

Authors	Study location and period	Study design	Number of fetuses/children with non-dilated ventricular asymmetry included	Studies performed	Maternal age (years)	Gestational age/child age	Criteria for defining ventricular asymmetry	Mean right ventricular width	Mean left lateral ventricular width	Fetal/child gender	Quality assessment
‡ BSID-II – Bayley Scale of Infant Development II [15], # WISC-IVHEB – Wechsler Intelligence Scale for Children, 4th edition (Hebrew) [16], ^ CCTT-1 – Children’s Color Trails Test 1 [16], *CCTT-2 – Children’s Color Trails Test 2 [17], ƪ RAVLT – Rey’s Auditory Verbal Learning Test [18], ** BRIEF – Behavior Rating Inventory of Executive Function [19], *** CBCL/6–18 – Child Behavior Checklist for Ages 6–18 [20] [21], ^^VABS-II – Vineland-II Adaptive Behavior Scales [22] MRI: magnetic resonance imaging; IQR: interquartile range
Achiron et al. (1997) [8]	Israel (January 1994–Jauary 1996)	Retrospective cohort	21	Serial neurosonogram, prenatal karyotype, infant development at 6 months of age	Mean 28 (range 21–35)	Mean 20.8±1.6 weeks of gestation (GA at diagnosis and at the time of the examination)	>2.4mm difference in ventricular width, and both ventricles <10 mm	7.14±1.79	8.74±1.78	Male – 12 (57.1%) Female – 9 (42.9%)	9
Sadan et al. (2007) [9]	Israel (October 2001 to April 2003)	Case-control study	21 (compared to 20 with unilateral ventriculomegaly and 20 healthy controls)	Neuropsychological evaluation using the BSID-II‡	Not reported	Mean 32.4 ± 5.2 (range 24–42) months (study group) vs. 32.8 ± 5.9 months (control group) (child age at the time of the examination)	>2.0mm difference in ventricular width, and both ventricles < 10mm	Not reported	Not reported	Male – 13 (61.9%) Female – 8 (38.1%)	7
Atad-Rapaport et al. (2015) [10]	Israel (October 2001 to April 2003)	Case-control study	15 (compared to 18 with unilateral ventriculomegaly) Both groups were compared with age-related norms validated for the Israeli population	Parents’ reports on behavioral questionnaires and neuropsychological tests: WISC-IVHEB#, CCTT-1^ and CCTT-2*, RAVLTƪ, phonemic and semantic fluency tests [14]. The parents filled out the BRIEF 15** and the CBCL/6–18***	Not reported	9–11 years (child age at examination)	>2.0mm difference in ventricular width, and both ventricles <10mm	Not reported	Not reported	Not reported	7
Meyer et al. (2018) [11]	Israel (July 2011 and January 2015)	Case control	43 (compared to 94 controls)	VABS-II^^	Mean 30.8±4.4	Mean 36.35±13.3 months (range 13–74 months) (child age at the time of the examination)	>2.0mm difference in ventricular width, and both ventricles <10mm	Not reported	Not reported	Male – 33 (76.7%) Female – 10 (23.3%)	7
Meyer et al. (2021) [12]	Israel (January 2011 and September 2018.)	Retrospective cohort	145	Neurosonogram, fetal brain MRI, prenatal karyotype, chromosomal microarray	Median 32.0 (IQR 9.0–36.0)	Mean 29.9 ± 2.4 weeks of gestation at the time of the neurosonogram and 32.6 ± 1.6 weeks of gestation at the time of the fetal brain MRI	>2.0mm difference in ventricular width, and both ventricles <10mm	Not reported	Not reported	Male – 102 (70.3%) Female – 43 (29.7%)	8
Petpichetchian (2023) [13]	Canada (January 2012 and January 2020)	Retrospective cohort	17	Neurosonogram, fetal brain MRI	Mean 32.4±5.5	23.4 ± 2.9 at diagnosis, GA at the time of the MRI examination is not reported	>2.0mm difference in ventricular width, and both ventricles <10mm	Not reported	Not reported	Male – 9 (52.9%) Female – 8 (47.1%)	8

 

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Natural history of fetal non-dilated lateral ventricle asymmetry

In the study by Achiron et al. [8], isolated non-dilated ventricular asymmetry was identified during routine fetal anomaly scans conducted at 18–24 weeks of gestation. These women were monitored with ultrasound examinations every 3 weeks until delivery. Excluded were those with obstructive hydrocephalus, other associated central nervous system (CNS) anomalies, or ventriculomegaly. Among the 21 fetuses studied, 20% showed resolution of asymmetry, 5% progressed, and 75% remained stable. The sequential ultrasound examinations revealed one fetus with periventricular leukomalacia and one with a subacute cytomegalovirus infection, the latter was discovered due to an intraventricular adhesion.

Meyer et al. investigated 145 fetuses with asymmetric ventricles without dilation [12]. Initially, these were referred for neurosonography and subsequently underwent fetal MRI scans. Excluded were those with major CNS anomalies suspected on ultrasound. However, pregnancies with minor brain or other minor body ultrasound findings were included. MRI revealed a ventricular width of over 10mm in 46.2% of the fetuses and the resolution of ventricular asymmetry in 11.7%. Major CNS findings were not discovered on MRI. In 17.9% of the fetuses, additional minor findings in either the fetal brain or body were also reported. The MRI study did not contribute significantly to the neurosonogram findings, as rates of minor CNS findings did not differ significantly between neurosonogram and MRI results. Reported brain findings included mega cisterna magna, arachnoid cyst, choroid plexus cyst, narrow cavum septum pellucidum, periventricular pseudocyst, and a white matter hyperintense signal. Minor body findings included pyelectasis, single umbilical artery, a small ventricular septal defect, hypospadias, and undescended testis.

Petpichetchian et al. investigated 17 fetuses characterized by non-dilated ventricular asymmetry, all of which underwent fetal brain MRI at a later stage [13]. During a serial neurosonogram follow-up, 13 fetuses showed progression to mild ventriculomegaly (76%). However, 12 of these resolved before childbirth, as was evident in the subsequent ultrasound examinations. MRI scans revealed evidence of intraventricular hemorrhage (IVH) in 13 of 17 fetuses. Among these, 12 showed minor bleeding confined to the subependymal germinal matrix (grade I), while one exhibited grade II IVH with subtle fluid sediment in the ventricle. One woman was found to have autoantibodies targeting the platelet antigenic determinant glycoprotein IIb/IIIa, with no evidence of thrombocytopenia observed in either the mother or the newborn.

 

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Genetic findings in fetal non-dilated lateral ventricle asymmetry

Achiron et al. described 11 women who underwent karyotype analysis, with trisomy 21 being revealed in 1 case (1/11, 9.1%) [8]. Notably, this genetic study was prompted by the progression of asymmetry to ventriculomegaly.

Amniocentesis for karyotyping was conducted in 56 of the 145 women described by Meyer et al., while 30 of them underwent chromosomal micro-array (CMA) [12]. The rate of abnormal karyotype was 1.8% (1/56), while abnormal CMA was detected in 10% (3/30). In one woman, a chromosome 11 inversion was identified via karyotyping. However, CMA and whole exome sequencing yielded normal results, leading to the conclusion of a variant of unknown significance. The abnormal CMA findings included chromosomal 22q11.23 and 22q11 duplications and segmental X chromosome duplication. Two of these findings were interpreted as likely pathogenic. Petpichetchian et al. reported that 2 of 17 women underwent amniocentesis with normal results, but it is unclear whether they underwent CMA or karyotype testing [13].

 

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Neurodevelopmental outcomes of fetal non-dilated lateral ventricle asymmetry

The earliest postnatal neurological evaluation was reported by Petpichetchian et al. [13]. In this study, all newborns were evaluated by a neonatologist after birth, and none exhibited dysmorphic features or macrocephaly. Two infants showed evidence of germinal matrix hemorrhage on cranial ultrasound. Only one of them received a cranial ultrasound follow-up at 1 month, which showed normal results. At 6 weeks, the infant’s neurological evaluation was unremarkable. Achiron et al. followed 17 infants up to the age of 6 months; all of them exhibited normal development at this stage [8].

Meyer et al. compared 43 children with non-dilated ventricular asymmetry to a control group of 94 normal fetuses [11]. The children were assessed at ages 13–74 months using the Vineland-II Adaptive Behavior Scales (VABS-II) [22], which is a structured parent interview that assesses 4 scales of performance: communication, daily living skills, socialization, and motor skills. Social skill scores were lower for the children with ventricular asymmetry than for the control group. Nonetheless, the overall VABS-II scores remained within the normal range for both groups, and the composite scores did not differ significantly between the groups.

Sadan et al. studied the neuropsychological outcomes of 21 children diagnosed with isolated non-dilated ventricular asymmetry in utero, and 20 children with isolated unilateral ventriculomegaly [9]. They compared them to a control group of children with normal ultrasound during pregnancy. The mean infant age at the time of the examination was 32.1 months (range 24–42 months). For the asymmetrical ventricles group compared to the control group, the psychomotor and mental developmental indices were similar. However, behavior scale subtests (orientation, engagement, and emotional regulation) differed notably. Three children (15%) in the asymmetric ventricles group, 4 children (20%) in the unilateral ventriculomegaly group, and 1 child (5%) in the control group exhibited a Bayley developmental score below 85, indicating developmental delay [15]. However, in a subsequent follow-up study, one of the children with asymmetric ventricles was diagnosed with mucopolysaccharidosis type III and was consequently excluded from the study [10].

The neurodevelopmental outcomes of 17 infants, originally studied by Sadan et al. [8], were later reported by Atad-Rapaport et al. [9], when the children were aged 9–11 years. This study compared parameters of children with asymmetric ventricles or unilateral ventriculomegaly to age-related norms that were validated for the Israeli population. Most parameters showed no significant differences between the children diagnosed with either of the conditions and the controls. Mean full-scale IQ scores averaged 103.13 for the asymmetric ventricles group and 103.56 for the unilateral ventriculomegaly group. Minor differences were observed, including slower performance in writing speed tasks among the asymmetric ventricles group. In contrast, this group demonstrated unexpectedly higher scores in verbal fluency tests compared with the general population. The outcomes of the fetuses and the children with non-dilated ventricular asymmetry are presented in [Table 2].

Table 2 Outcomes of fetuses/children with in-utero non-dilated ventricular asymmetry.

US: ultrasound; MRI: magnetic resonance imaging; CNS: central nervous system
Antenatal follow-up
Characteristics	N (%)
Progression to ventriculomegaly (on follow-up ultrasound) (n=38)	14 (36.8)
Progression to ventriculomegaly (on follow-up MRI) (n=145)	67 (46.2)
Additional CNS findings during follow-up on US (n=183)	10 (5.5)
Additional CNS findings during follow-up on MRI (n=162)	17 (10.5)
Additional fetal body findings during follow-up on US or MRI (n=145)	11 (7.6)
Abnormal genetic findings (n=99)	5 (5.1)
Postnatal findings
Characteristics	Main findings
Abnormal developmental findings until 1 year of age (n=18)	No abnormal findings reported
Abnormal developmental findings at an age of 1–6 years (n=54)	Lower social score Lower behavioral score (including orientation, engagement and emotional regulation) Developmental delay in 2 of 20 children (10%), compared to 1 of 20 children (5%) in the control group
Abnormal developmental findings at 9–11 years of age (n=17)	Lower writing speed

 

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Discussion

The main finding of this systematic review is that 36.8–46.2% of fetuses with non-dilated ventricular asymmetry progressed to ventriculomegaly during antenatal follow-up, either on follow-up neurosonography or subsequent MRI. Abnormal genetic results were seen in 5.1% of the fetuses. Postnatally, no abnormal developmental findings were reported until 1 year of age. However, at an age of 1–6 years, lower social and behavioral scores were noted, and a minority exhibited developmental delays. At an age of 9–11 years, a lower writing speed was observed, while unexpectedly higher scores in verbal fluency tests were noted compared with the general population. Full-scale IQ scores were comparable to the general population.

Human brain asymmetry, observed in fetal cerebral hemispheres and ventricles, has been extensively documented in the medical literature [1] [23]. Notably, this asymmetry tends to be more prominent on the left side and is often observed to a greater extent in males [24]. In clinical practice, ventricular asymmetry within the normal width is generally considered a benign finding, as emphasized by guidelines that recommend against further investigations [4]. However, the studies included in this review reported rates of progression from ventricular asymmetry to ventriculomegaly ranging from 5% to 76.4% [8] [12] [13]. These rates varied considerably depending on the modality of assessment. For instance, one study found only a 5% progression rate when using neurosonography [8], while another study utilizing fetal brain MRI reported much higher rates, up to 76.4% [12]. This finding aligns with reports that ventricle measurements obtained via MRI are often larger than those obtained by ultrasound [25]. Additionally, the time gap between ultrasound and MRI examinations may have contributed to the higher proportion of ventricular dilation observed on MRI. This difference suggests that the higher rates reported in MRI-based studies may not directly correspond to the progression seen on neurosonography, making it important to interpret these findings in the context of the imaging technique used. Nonetheless, these findings suggest that as ventricular asymmetry has the potential to evolve into ventriculomegaly – careful monitoring could be important to better understand the natural course of this condition.

Notably, in fetuses in which ventriculomegaly developed, ventricular dilation never exceeded 15mm and resolved before birth [13]. This transient ventriculomegaly was attributed to a temporary obstruction at the foramina of Monro, likely induced by IVH [26]. However, Meyer et al. did not report a similarly high rate of IVH nor a considerable rate of additional brain findings despite observing ventriculomegaly on fetal brain MRI. This led them to conclude that MRI did not contribute substantially to the findings obtained through neurosonography [12]. These discrepancies may arise from differences in the interpretation of MRI studies. Nonetheless, the findings emphasize the importance of closely monitoring ventricular width in fetuses with asymmetric ventricles. Based on our results, we suggest measuring ventricular width during the standard second-trimester anomaly scan (18–24 weeks) and recommend bilateral measurements to improve the detection of asymmetry. While most cases resolve before birth and none progress to ventriculomegaly >15mm [13], the potential for progression in a subset of cases suggests that monitoring may still be advisable. When non-dilated ventricular asymmetry is detected during anomaly scans, a follow-up neurosonography examination within 3–4 weeks is generally sufficient. This interval balances the need for timely detection of significant changes with the avoidance of unnecessary interventions, considering the relatively low likelihood of severe progression. However, serial follow-ups should be considered when progression is evident or when additional findings raise concern. It is to be noted that bi-hemispheric visibility may decrease in advanced gestational weeks due to factors such as skull ossification, fetal positioning, and increased head size. These factors could complicate accurate assessment of ventricular asymmetry during later scans.

Our research suggests a notable rate of abnormal karyotype and CMA in fetuses displaying non-dilated ventricular asymmetry. However, it is important to note that only a subset of women underwent invasive genetic exams, so our findings may reflect a higher likelihood of abnormal results among those already suspected of having additional risk factors. The majority of fetuses who underwent genetic counseling were from the study by Meyer et al. [12], in which 86 out of 145 fetuses had either karyotype or CMA testing. In this study, progression to ventriculomegaly on MRI was noted in 46.2% of fetuses. Moreover, 3.4% had additional minor CNS findings, and 7.6% had additional body findings. However, it is not explicitly clear from the article whether the fetuses that experienced progression to ventriculomegaly or had additional findings were the same ones who underwent genetic studies. Meyer et al. [12] mentioned that minor CNS findings included arachnoid cysts, cavum verge, megacisterna magna, periventricular pseudocyst, and white matter hyperintense signals on MRI. In terms of body findings, pyelectasis, cardiac ventriculoseptal defect, a single umbilical artery, undescended testis, and hypospadias were reported. Given that only a subset of fetuses underwent genetic testing, and some of these had additional CNS or anatomical findings, the rate of abnormal genetic results observed in this review may not be representative of all cases of non-dilated ventricular asymmetry. Nonetheless, further research with larger sample sizes is needed to better understand the role of genetic testing in this context, particularly for cases that show progression or additional findings.

During earlier stages, children with asymmetric ventricles displayed lower social and behavioral scores, and a minority exhibited a developmental delay [9]. Yet, subsequent findings indicated notable improvement in their behavioral patterns over time [10]. Parents no longer reported persistent issues and noted enhanced executive functioning compared to typical norms. These observations suggest that children with fetal ventricular asymmetry might undergo a transient phase of developmental challenges that tend to resolve by school age. This implies that developmental abnormalities detected early may not have a lasting impact on mental development in individuals with non-dilated ventricular asymmetry. It is important to acknowledge that these results should be interpreted with caution. The studies included relatively small sample sizes, and some patients were lost to follow-up or declined participation. Therefore, it is difficult to determine whether these findings represent a true difference. Further larger prospective studies are needed to better understand the long-term outcomes of these fetuses and to determine whether these early findings have any lasting developmental implications.

Limitations of this study include the potential publication bias due to the identification of a limited number of studies, despite extensive search efforts. Additionally, all the included studies were retrospective and all but one were conducted in Israel, which could introduce a selection bias. The lack of formal guidelines advocating for the systematic visualization and measurement of both lateral ventricles during routine anomaly scans contributes to the variability in the detection and reporting of ventricular asymmetry. This variability may have influenced the inclusion criteria and reporting standards of the studies, thus reducing the comparability of their findings. The small sample size hinders the ability to draw conclusions regarding the utility of prenatal MRI imaging or long-term developmental outcomes. We suggest that MRI be reserved for situations in which neurosonography findings are inconclusive or when additional brain abnormalities are suspected. The strengths of the study include a thorough literature search and examination of outcomes related to non-dilated ventricular asymmetry, from prenatal to postnatal stages, covering data up to an age of 11 years. The presented evidence raises questions regarding the classification of non-dilated ventricular asymmetry as a normal variant. Larger prospective studies are warranted to elucidate the natural history of non-dilated ventricular asymmetry and its clinical implications. Moreover, the efficacy of serial neurosonogram follow-up and prenatal fetal brain MRI in this context should be examined. Additionally, given the relatively high rate of abnormal genetic results, further exploration of this aspect in larger cohorts is warranted.

 

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Conflict of Interest

The authors declare that they have no conflict of interest.

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Publication History

Received: 14 October 2024

Accepted after revision: 24 February 2025

Article published online:
23 April 2025