Shiri Shinar

Fetal intracranial hemorrhage (ICH) is a rare but serious prenatal diagnosis, and counseling affected families remains challenging. In this narrative review, we summarize current evidence on the classification, epidemiology, etiology, diagnosis and neurodevelopmental outcomes of fetal ICH, with a primary focus on intraventricular hemorrhage (IVH) as the most common presentation. The reported incidence of 0.5–1 per 10,000 pregnancies likely underestimates the true burden. Etiologies include fetal‐neonatal alloimmune thrombocytopenia, cerebral small vessel variants, congenital infection, fetal anemia, coagulopathy and twin‐related complications. Nonetheless, a cause is identified in fewer than half of cases even after complete workup, with a genetic etiology found in roughly 30% of fully investigated cases. Detailed neurosonography is the primary diagnostic tool, and fetal MRI is an important adjunct for defining hemorrhage extent, parenchymal injury and posterior fossa involvement. Outcomes vary with hemorrhage grade, location and laterality. Low‐grade IVH generally carries a favorable prognosis, whereas periventricular hemorrhagic infarction carries substantially higher rates of cerebral palsy, shunting and cognitive impairment, particularly when extensive and bilateral. However, prognostic data derive largely from small neonatal cohorts graded with a system not designed for the fetus, which limits individualized counseling. We propose a practical, fetal‐specific framework built on systematic evaluation, an interdisciplinary team approach and transparent communication about prognostic uncertainty. [Correction added on 26 October 2026, after first online publication: The abstract has been replaced with a revised version.]

Objectives: To describe, characterize and determine the frequency of interhemispheric fissure (IHF) distortion on ultrasound in fetuses with open spina bifida (OSB), evaluate its association with other intracranial findings and biometric parameters and assess its evolution after prenatal closure of the spinal defect. Methods: This retrospective cohort study included fetuses with suspected OSB referred to a single tertiary fetal center (Ontario Fetal Centre, Toronto, ON, Canada) between June 2017 and May 2025. Inclusion required prenatal diagnosis of OSB and at least one ultrasound examination with adequate axial transventricular and transthalamic planes of the fetal brain for evaluation of the IHF. IHF distortion was defined as deviation from the expected linear echogenic midline appearance. Biometric measurements were converted to gestational age‐adjusted Z ‐scores. Associations between IHF distortion and clinical and imaging variables were assessed using univariable and multivariable logistic regression. Postoperative imaging was reviewed in fetuses that underwent prenatal spinal defect closure to evaluate changes in IHF appearance. Results: Among 133 fetuses with confirmed OSB, IHF distortion was identified in 54 (40.6%). Interobserver agreement was excellent (Cohen's kappa coefficient = 0.83). Fetuses with IHF distortion had smaller transcerebellar diameter (TCD) Z ‐scores compared with those without distortion (−4.80 ± 2.11 vs −3.91 ± 2.54; P = 0.047). On multivariable logistic regression, later gestational age at OSB diagnosis (adjusted odds ratio (aOR), 1.43 (95% CI, 1.08–1.94); P = 0.01) and smaller TCD Z ‐score (aOR, 0.89 (95% CI, 0.76–0.99); P = 0.04) were independently associated with IHF distortion. Among fetuses that underwent prenatal closure and had postoperative imaging available, resolution of IHF distortion paralleled improvement in hindbrain herniation, whereas persistence of IHF distortion occurred only in cases with minimal or no improvement in hindbrain herniation. Conclusions: IHF distortion is a frequent and reproducible prenatal ultrasound finding in fetuses with OSB. Its association with a smaller TCD and its apparent resolution following prenatal closure of OSB in cases that demonstrated improvement in hindbrain herniation suggest that IHF distortion may represent a secondary mechanical manifestation within the Chiari II spectrum. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective: To document the natural history and complications of second‐ and third‐trimester non‐nuchal lymphatic malformations (LM) and identify predictors of these complications. Methods: We conducted a single‐centre retrospective review of fetuses diagnosed with LMs between January 2015 and January 2024. Lesion size was quantified using the lymphatic malformation volume ratio (LVR): LVR = 0.523 x width x length x height (cm ³ ) / head circumference (cm). Outcomes and LVR growth trends were analyzed using Student's t‐test and a linear mixed‐effects model. Results: Eighteen cases were included (10 cervical, 8 axillary). Uncomplicated cervical LMs grew at 0.3 cm ² /week ( p < 0.001). Intralesional bleeding ( n = 3) was associated with LVR > 11 cm ² and significantly higher growth rates (2.6 vs. 0.3 cm ² /week; p = 0.005). All cases with LVR > 5 cm ² required subsequent tracheostomy after birth. Axillary LMs grew at 0.21 cm ² /week. One case with bleeding had LVR 4.4 cm ² . Median LVR was significantly lower in vaginal deliveries compared with complicated births (2.0 vs. 7.3 cm ² ; p = 0.03). All LVR > 4 cm ² led to delivery complications. Conclusion: Higher LVR predicts haemorrhage and airway intervention in cervical LMs, and delivery complications in axillary LMs. These exploratory observations warrant confirmation in larger prospective cohorts.

Introduction: Severe brain injury has been reported following fetoscopic laser ablation (FLA) for twin‐to‐twin transfusion syndrome (TTTS), but imaging patterns and temporal evolution remain poorly defined. This study aimed to characterize the progression of severe brain injury after FLA. Methods: We conducted a retrospective case series of TTTS pregnancies with severe brain injury identified after FLA at the Ontario Fetal Center (June 2023–March 2025). FLA was performed for Quintero stage ≥ II and selected stage I cases. Severe abnormalities were defined as severe intraventricular haemorrhage or destructive lesions. Serial ultrasound and fetal MRI were reviewed and categorized as early (< 4 weeks) or late (≥ 4 weeks) post‐FLA. Results: Fifteen fetuses from 14 pregnancies were identified. Mean gestational age at FLA was 19.7 ± 3.2 weeks; 66.7% were stage III–IV and 60% were donor twins. Early imaging ( n = 8) most commonly showed periventricular haemorrhagic infarction (62.5%) and cerebellar haemorrhage (25.0%). Late imaging ( n = 13) predominantly demonstrated cerebral volume loss (76.9%), often involving the parietal lobes, with polymicrogyria (38.5%) and Wallerian degeneration (30.8%). Findings remained unchanged after 4 weeks. Conclusion: Brain injury after FLA evolves from acute haemorrhagic/ischaemic insults to irreversible destructive changes. These preliminary findings suggest a consistent pattern of injury that warrants further prospective study.

Objective: Characterize neuroimaging findings in foetuses with anaemia and identify associated risk factors. Methods: Retrospective cohort study of pregnancies with foetal anaemia (defined as haemoglobin > 2 standard deviations below the gestational age mean) confirmed by foetal blood sampling (FBS) and treated with intrauterine transfusion (IUT) at a tertiary centre between 2011 and 2024. Prenatal and/or early postnatal neuroimaging findings and perinatal outcomes were reviewed. Multivariable logistic regression was used to identify factors associated with brain injury on neuroimaging. Results: Of 100 foetuses with foetal anaemia that underwent neuroimaging, 93 met the eligibility criteria. Brain injuries were identified in 48 foetuses (52%). Injuries included intracranial haemorrhage (48%), ischaemia (21%), combined injury (6%), and non‐specific injuries (25%). Imaging was performed prenatally ( n = 36), postnatally ( n = 36), or both ( n = 21). Male sex was independently associated with brain injury (adjusted OR 5.04, 95% CI 1.64–15.52; p = 0.005). Anaemia severity, hydrops, cardiac dysfunction, and gestational age at diagnosis were not associated with brain injury. Immediate postnatal outcomes did not differ between the groups. Conclusion: In a clinically selected cohort of foetuses with anaemia who underwent neuroimaging after IUT, brain injuries were frequent and heterogeneous. These findings support the need for prospective studies with standardized imaging and longitudinal follow‐up to define true risk and identify subgroups most likely to benefit from surveillance.

Advances in genetics and imaging including antenatal US, fetal MRI, and postnatal imaging enable detailed morphological assessment of congenital posterior fossa malformations, pattern recognition, and genotype-phenotype correlation, thereby supporting accurate diagnosis and guiding targeted genetic testing and clinical management.

Objective: To characterise aetiologies and prenatal neuroimaging findings in fetuses with intracranial haemorrhage (ICH), and evaluate the ability of imaging to suggest underlying causes. Methods: We retrospectively reviewed fetuses with ICH diagnosed prenatally at a single tertiary fetal centre between 2015 and 2025. Cases with a known mechanism at presentation were excluded. Ultrasound (US) and MRI images were reassessed by fetal medicine and neuroradiology specialists blinded to aetiology. Clinical, laboratory, genetic, autopsy and placental findings were integrated to determine underlying causes and assess imaging patterns. Results: Sixty-seven fetuses were included; a definitive aetiology was identified in 38.8% (26/67). Genetic aetiologies were detected in 27.7% (13/47) of cases with advanced genetic testing, most commonly associated with cerebral small vessel disease (CSVD). Other causes included infection (5/67, 7.5%), fetal anaemia (6/67, 9%), and coagulopathy (3/67, 4.5%, of which one was genetic). Twenty-one cases (31.3%) remained unexplained despite comprehensive investigation, and 20 (29.9%) had incomplete investigations. Intraventricular haemorrhage (IVH) was present in 91% (61/67), with periventricular haemorrhagic infarction (PVHI) in 55.2% (37/67). CSVD was associated with multifocal PVHI, porencephaly, white matter injury and frequent brainstem involvement. In fetal anaemia, cerebellar haemorrhage was common, with brainstem and vermian involvement predominantly in non-parvovirus cases. Intraparenchymal haemorrhage without IVH occurred mainly with coagulopathy or infection. Although some phenotypic clustering was observed, there was substantial overlap among aetiologic groups. Conclusion: Genetic disorders, particularly CSVD, account for a significant proportion of prenatal ICH, supporting routine genomic testing. Imaging can suggest probable causes, but overlap limits its diagnostic specificity.

BORCS5 encodes a subunit of the BLOC-One-Related Complex (BORC), which is known to promote anterograde movement and fusion of lysosomes. We identified 16 individuals from 9 families with bi-allelic BORCS5 variants, revealing a spectrum of neurodevelopmental and neurodegenerative phenotypes. Carriers of homozygous protein-truncating variants (PTVs), resulting in complete loss of BORCS5, presented with prenatally lethal arthrogryposis multiplex congenita, brain malformations, and neuropathological evidence of neuroaxonal dystrophy. Individuals with missense or splice-site variants presented differently, with microcephaly, developmental epileptic encephalopathy, optic atrophy, spasticity, and progressive movement disorders. In this group, brain MRI showed diffuse hypomyelination, corpus callosum abnormalities, and progressive global cerebral atrophy, consistent with neurodegeneration. Borcs5 KO in zebrafish resulted in microcephaly, motor deficits, and increased seizure susceptibility, mirroring the patients’ clinical presentation. At the cellular level, only BORCS5 PTVs, but not missense variants, led to perinuclear lysosomal clustering and impaired lysosomal axonal trafficking in induced pluripotent stem cell–derived forebrain neurons. However, PTVs and missense variants were associated with reduced lysosomal proteolysis and activity of lysosomal hydrolases glucocerebrosidase and cathepsin B, indicating lysosomal dysfunction. Our study reveals a role for BORCS5 in modulation of lysosomal function, in addition to its known role in lysosome movement and fusion, possibly underlying the diverse clinical manifestations in individuals with BORCS5-related disorders.

Background The taenia-tela choroidea-choroid plexus complex has been proposed as an imaging marker to differentiate Dandy-Walker malformation from Blake’s pouch cyst on prenatal MRI. However, radiologic-pathologic correlation remains limited. Objective To characterize the taenia-tela choroidea-choroid plexus complex in normal and Dandy-Walker malformation fetuses and assess its visibility on routine prenatal MRI. Materials and methods Nine fetal autopsy specimens with Dandy-Walker malformation and eight gestational age-matched controls with normal posterior fossa were reviewed for taenia-tela choroidea-choroid plexus complex characteristics and correlated with available MRI. Separately, 100 fetal brain MRIs (gestational age 21–38 weeks) including normal cases and posterior fossa cystic malformations were retrospectively and independently reviewed by two pediatric neuroradiologists. Visibility of the tela choroidea and fourth ventricular choroid plexus was scored as confident, borderline, or not visible. Interobserver agreement was calculated using weighted kappa with 95% confidence intervals (CI). Results Pathologic examination demonstrates that in the normal fetal posterior fossa, the choroid plexus lies adjacent to the inferior medullary velum, whereas in Dandy-Walker malformation it is displaced inferolaterally. The tela choroidea in normal controls is thin and composed of a single-meningeal layer that delaminates into two membranes, while in Dandy-Walker malformation, the tela choroidea is thickened, formed by two layers of arachnoid membrane lined by attenuated choroid plexus epithelium. On fetal MRI, the tela choroidea visibility was rated as either confident or borderline confident in 53-72% (53-72/100), with moderate visibility in 28–33% (28-33/100) of cases, with moderate agreement (κ 0.49, 95% CI 0.34–0.62). The choroid plexus was confidently visible in 21–27% (21-27/100) of cases, with fair agreement (κ 0.27, 95% CI 0.10–0.44). Conclusion On histopathologic evaluation, the tela choroidea is outstretched and thickened with inferolateral displacement of the choroid plexus in Dandy-Walker malformation. However, taenia-tela choroidea complex visibility on prenatal MRI is variable, especially in normal cases, which may limit its reliability as a diagnostic marker for posterior fossa cystic malformations.

Objective: To document the natural progression of fetal cardiac rhabdomyomas and evaluate the impact of prenatal sirolimus (PNS) on tumor size, cardiac complications and brain‐tuber size. Methods: This was a single‐center retrospective cohort study of pregnancies with suspected fetal cardiac rhabdomyoma referred to our center from April 2013 to May 2024. Serial ultrasound and echocardiography reports were reviewed to obtain tumor characteristics, such as diameter and location, and cardiac complications, including inflow or outflow obstruction, arrhythmia and hydrops. The tumor‐to‐femur length (TFL) ratio was calculated to correct for fetal growth. Prenatal neurosonography reports were collected from clinical records. Pre‐ and postnatal brain magnetic resonance imaging (MRI) scans were reviewed by two observers who were blinded to PNS treatment. Brain‐lesion severity was assessed based on the presence of subependymal nodules, the EPISTOP score, the maximum diameter of the largest subcortical tuber, the maximum diameter of the largest subependymal giant cell astrocytoma (SEGA) and the diameter of the largest lateral ventricle. Prenatal or postnatal genetic testing results were documented when available. Results: Twenty‐seven pregnancies were included in the study, seven of which received PNS. Prior to initiation of treatment, the diameter of the largest cardiac tumor at diagnosis was similar between the non‐PNS and PNS groups (mean, 15.2 mm vs 14.3 mm; P = 0.72), with the left ventricle the most frequently affected location. Without treatment, rhabdomyomas grew rapidly from 20 + 0 to 27 + 6 weeks' gestation (mean, 2.58 mm/week) but growth slowed after 28 weeks (mean, 0.44 mm/week). Hydrops was reported in four cases and occurred at a mean tumor diameter of 31.7 ± 6.2 mm, mean TFL ratio of 0.68 ± 0.15 and at a mean growth rate of 4.3 ± 1.7 mm/week. In the seven women treated with PNS, treatment for > 7 days ( n = 3) resulted in tumor regression and/or resolution of outflow obstruction, and a reduction in TFL ratio; however, prenatal cessation of treatment resulted in rebound growth ( n = 2). Treatment for ≤ 7 days ( n = 4) did not impact tumor size or resolve existing cardiac complications. Among the 12 cases that underwent prenatal MRI, the median EPISTOP score was 7 (interquartile range (IQR), 1–15) and the median largest lateral ventricle diameter was 8.9 (IQR, 7.0–9.7) mm; subcortical tubers and subependymal nodules were each identified in 67% of cases, and SEGAs were identified in 58%. Among the 13 cases that underwent postnatal MRI, the median EPISTOP score was 14 (IQR, 3–16) and the median largest lateral ventricle diameter was 7 (IQR, 7–8) mm; brain tubers were identified in 92% of cases. In cases with both pre‐ and postnatal MRI findings who received PNS for > 7 days ( n = 3), on postnatal MRI compared with prenatal MRI, one patient showed no change in findings, one demonstrated a mild increase in the largest subcortical tuber diameter and one had no detectable brain tubers. Conclusions: Early and sustained PNS treatment was associated with reduced cardiac rhabdomyoma size and/or resolution of cardiac complications. Rebound tumor growth was observed after discontinuation of treatment. Brain tubers appeared unchanged with PNS treatment, although the sample size was too small to draw a definitive conclusion. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.