Fetal insular measurements in pregnancy with estimated fetal weight <10th centile and childhood neurodevelopmental outcomes.

BACKGROUND: A growing body of evidence suggests that fetal growth restriction is associated with changes in brain structures as a result of chronic hypoxia. However, less is known about the effects of growth restriction on the fetal insula, particularly in less severely affected late-onset growth-restricted fetuses. OBJECTIVE: This study aimed to (1) compare sonographic insular measurements between fetal-growth restricted, small-for-gestational-age, and appropriate-for-gestational-age control fetuses; and (2) evaluate the association of sonographic insular measurements with perinatal and neurodevelopmental outcomes in fetuses categorized as fetal-growth restricted or small-for-gestational-age. STUDY DESIGN: This was a cohort study of singleton nonanomalous pregnancies with an estimated fetal weight <10th centile. Using data from the last examination before delivery, fetal insular depth, Sylvian fissure depth, hypoechoic insular zone thickness, circumference, and area were measured. All measurements were adjusted for by head circumference. Neurodevelopmental outcomes were evaluated at 2 to 3 years of age using the Bayley-III scales. Kruskal-Wallis H tests were performed to compare insular measurements between groups. Paired t tests were used to compare insular measurements between appropriate-for-gestational-age fetuses and gestational age-matched growth-restricted fetuses. Insular measurements for patients with and without an adverse perinatal outcome were compared using independent-samples t-tests. Spearman correlations were performed to evaluate the relationship of insular measurements to the percentile scores for each of the 5 Bayley-III subscales and to a summative percentile of these subscales. RESULTS: A total of 89 pregnancies were included in the study; 68 of these pregnancies had an estimated fetal weight <10th percentile (fetal-growth restricted: n=39; small-for-gestational-age: n=29). The appropriate-for-gestational-age cohort consisted of 21 pregnancies. The gestational age at measurement was similar between fetal-growth restricted and small-for-gestational-age groups, but lower in the appropriate-for-gestational-age group. Differences between groups were noted in normalized insular depth, Sylvian fissure depth, and hypoechoic insular zone (P<.01). Normalized insular depth and hypoechoic insular zone circumference were larger in the growth-restricted cohort (P<.01). Normalized Sylvian fissure depth was smaller in the growth-restricted cohort (P<.01). There were no significant differences in insular measurements between pregnancies with and without an adverse perinatal outcome. Bayley-III results were available in 32 of the growth-restricted cases. Of all insular measurements, hypoechoic insular zone circumference was inversely correlated with the adaptive behavior Bayley-III score. CONCLUSION: In our cohort, fetuses with estimated fetal weight <10th percentile had smaller Sylvian fissure depths and larger insular depths and hypoechoic insular zone circumferences than normally grown controls. A larger hypoechoic insular zone circumference was substantially correlated with worse neurodevelopmental outcomes in early childhood. We speculate that enlargement of this region may be an indication of accelerated neuronal maturation in growth-restricted fetuses with mild hypoxia.

Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm premature rupture of membranes.

BACKGROUND: Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not by neurosonography along with amniotic fluid brain injury biomarkers. OBJECTIVE: This study aimed to evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm premature rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a risk mediator. STUDY DESIGN: In this prospective cohort study, fetal brain remodeling and injury were evaluated using neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm premature rupture of membranes between 24.0 and 34.0 weeks of gestation, with (n=41) and without (n=54) intra-amniotic inflammation. The controls for neurosonography were outpatient pregnant patients without preterm labor or preterm premature rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm premature rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin 6 concentrations of >13.4 ng/mL in preterm labor and >1.43 ng/mL in preterm premature rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. Neuron-specific enolase, protein S100B, and glial fibrillary acidic protein were selected as amniotic fluid brain injury biomarkers. Data were adjusted for cephalic biometrics, fetal growth percentile, fetal sex, noncephalic presentation, and preterm premature rupture of membranes at admission. RESULTS: Fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes showed signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in the intra-amniotic inflammation, non-intra-amniotic inflammation, and control groups, the transcerebellar diameter measurements were 32.7 mm (interquartile range, 29.8-37.6), 35.3 mm (interquartile range, 31.2-39.6), and 35.0 mm (interquartile range, 31.3-38.3), respectively (P=.019), and the vermian height measurements were 16.9 mm (interquartile range, 15.5-19.6), 17.2 mm (interquartile range, 16.0-18.9), and 17.1 mm (interquartile range, 15.7-19.0), respectively (P=.041). Second, they presented a lower corpus callosum area (0.72 mm2 [interquartile range, 0.59-0.81], 0.71 mm2 [interquartile range, 0.63-0.82], and 0.78 mm2 [interquartile range, 0.71-0.91], respectively; P=.006). Third, they showed delayed cortical maturation (the Sylvian fissure depth-to-biparietal diameter ratios were 0.14 [interquartile range, 0.12-0.16], 0.14 [interquartile range, 0.13-0.16], and 0.16 [interquartile range, 0.15-0.17], respectively [P<.001], and the right parieto-occipital sulci depth ratios were 0.09 [interquartile range, 0.07-0.12], 0.11 [interquartile range, 0.09-0.14], and 0.11 [interquartile range, 0.09-0.14], respectively [P=.012]). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes had higher concentrations of neuron-specific enolase (11,804.6 pg/mL [interquartile range, 6213.4-21,098.8], 8397.7 pg/mL [interquartile range, 3682.1-17,398.3], and 2393.7 pg/mL [interquartile range, 1717.1-3209.3], respectively; P<.001), protein S100B (2030.6 pg/mL [interquartile range, 993.0-4883.5], 1070.3 pg/mL [interquartile range, 365.1-1463.2], and 74.8 pg/mL [interquartile range, 44.7-93.7], respectively; P<.001), and glial fibrillary acidic protein (1.01 ng/mL [interquartile range, 0.54-3.88], 0.965 ng/mL [interquartile range, 0.59-2.07], and 0.24 mg/mL [interquartile range, 0.20-0.28], respectively; P=.002). CONCLUSION: Fetuses with preterm labor with intact membranes or preterm premature rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in fetuses with intra-amniotic inflammation.

Antenatal visualization of the caudo-thalamic groove at expert fetal neurosonography.

OBJECTIVE: to describe the normal features of the caudo-thalamic groove at antenatal brain ultrasound in a group of structurally normal fetuses at third trimester and to report a small series of cases with abnormal appearance of the caudothalamic groove at antenatal brain ultrasound. METHODS: This was an observational study conducted at two referral Fetal Medicine units. A non-consecutive cohort of pregnant women with a singleton non anomalous pregnancy were prospectively recruited and underwent 3D ultrasound of the fetal brain at 28-32 weeks. At offline analysis the ultrasound volumes were adjusted in the multiplanar mode according to a standardized methodology, until the caudothalamic groove was visible on the parasagittal plane. To evaluate the inter-observer agreement, two operators were independently asked to indicate if the caudothalamic groove was visible unilaterally or bilaterally on each volume. The digital archives of the two Centres were also retrospectively searched to retrieve cases with abnormal findings at the level of the caudothalamic groove at antenatal brain ultrasound which were postnatally confirmed. RESULTS: 180 non-consecutive cases fulfilling the inclusion criteria were prospectively included. At offline analysis of the 3D US volumes the caudo-thalamic groove was identified on the parasagittal plane by both operators at least unilaterally in 176 cases (97.8%) and bilaterally in 174 cases (96.6%). The K-coefficient for the agreement between the two independent operators in recognizing the caudo-thalamic groove was 0.89 and 0.83 on one and both hemispheres respectively. At the retrospective search of our archives 5 cases with abnormal appearance of the groove at antenatal brain ultrasound (2 haemorrhage and 3 cyst) were found. CONCLUSION: Our study has demonstrated that the caudo-thalamic groove is consistently seen among normal fetuses at third trimester submitted to multiplanar neurosonography and that abnormal findings at this level may be antenatally detected. This article is protected by copyright. All rights reserved.

Postnatal outcome of fetal cortical malformations: systematic review.

OBJECTIVE: Parental counseling for fetal malformations of cortical development (MCD) is based on data from studies in children and adults undergoing imaging investigation for abnormal neurodevelopment. However, such postnatal findings may not be applicable to prenatally diagnosed cases. The aim of this study was to review the existing data on postnatal neurodevelopmental outcome for fetuses diagnosed with MCD. METHODS: A literature search was conducted in PubMed, Web of Science and EMBASE for articles published between 2013 and 2023, using standardized keywords to describe fetal cortical malformations. Full-text articles were accessed for the retrieved citations and data on participant characteristics, imaging findings, and pregnancy and neonatal outcomes were extracted. Fetal MCD was defined as either complex or isolated, according to the presence or absence, respectively, of additional brain or extracranial defects. RESULTS: Overall, 30 articles including 371 cases of fetal MCD were reviewed. The cases were classified as complex (n = 324), isolated (n = 21) or unknown (n = 26). There were 144 terminations and four stillbirths, with pregnancy outcome unreported in 149 cases. A total of 108 cases had postnatal magnetic resonance imaging or postmortem examination data available. In nine of these cases, a diagnosis of complex fetal MCD was changed to isolated MCD after birth, and one case was found not to have MCD. There were 74 live births, for which postnatal neurodevelopment data were available in only 30 cases. Normal neurodevelopmental outcome was reported in seven (23.3% (95% CI, 9.9-42.2%)) infants, with the remaining 23 exhibiting various levels of neurodevelopmental delay (three mild, seven moderate and 13 severe) from 6 months to 7 years of age. CONCLUSIONS: Most reviewed cases of fetal MCD were complex in nature and underwent termination of pregnancy. There is a paucity of data on postnatal neurological development in fetuses diagnosed with MCD. The available data suggest antenatal overdiagnosis of case severity in about 5% of cases with known outcome, and either normal neurodevelopment or mild neurodevelopmental delay in approximately one-third of liveborn cases with neurological follow-up. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Midline structures and cortical development in late-onset fetal growth restriction according to Doppler status: prospective study.

OBJECTIVES: Fetuses with late-onset growth restriction (FGR) have a higher risk of suboptimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structure growth and cortical development in fetuses with late-onset FGR according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. METHODS: This was a prospective observational study that included fetuses with late-onset FGR (defined according to the Delphi FGR criteria) undergoing neurosonography between 32 and 34 weeks' gestation. Midline structure (corpus callosum (CC) and cerebellar vermis (CV)) length and cortical development, including the depth of the Sylvian (SF), parieto-occipital (POF) and calcarine (CF) fissures, were compared between late-onset FGR, small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) fetuses. Subgroup analysis according to the severity of FGR (normal vs abnormal fetal Doppler) was also performed. Univariate analysis was used to analyze the data. RESULTS: A total of 52 late-onset FGR fetuses with normal Doppler findings, 60 late-onset FGR fetuses with abnormal Doppler findings, 64 SGA fetuses and 100 AGA fetuses were included in the analysis. When comparing AGA controls with SGA fetuses, late-onset FGR fetuses with normal Doppler findings and late-onset FGR fetuses with abnormal Doppler findings, there was a progressive and significant reduction in the absolute values of the following parameters: CC length (median (interquartile range (IQR)), 43.5 (28.9-56.1) mm vs 41.9 (27.8-51.8) mm vs 38.5 (29.1-50.5) mm vs 31.7 (23.8-40.2) mm; K = 26.68; P < 0.0001), SF depth (median (IQR), 14.5 (10.7-16.8) mm vs 12.7 (9.8-15.1) mm vs 11.9 (9.1-13.4) mm vs 8.3 (6.7-10.3) mm; K = 75.82; P < 0.0001), POF depth (median (IQR), 8.6 (6.3-11.1) mm vs 8.1 (5.6-10.4) mm vs 7.8 (6.1-9.3) mm vs 6.6 (4.2-8.0) mm; K = 45.06; P < 0.0001) and CF depth (median (IQR), 9.3 (6.7-11.5) mm vs 8.2 (5.7-10.7) mm vs 7.7 (5.2-9.4) mm vs 6.3 (4.5-7.2) mm; K = 46.14; P < 0.0001). Absolute CV length was significantly higher in AGA fetuses compared with all other groups, although the same progressive pattern was not noted (median (IQR), 24.9 (17.6-29.2) mm vs 21.6 (15.2-26.1) mm vs 19.1 (13.8-25.9) mm vs 21.0 (13.5-25.8) mm; K = 16.72; P = 0.0008). When the neurosonographic variables were corrected for fetal head circumference, a significant difference in the CC length and SF, POF and CF depths, but not CV length, was observed only in late-onset FGR fetuses with abnormal Doppler findings when compared with AGA and SGA fetuses. CONCLUSIONS: Fetuses with late-onset FGR had shorter CC length and delayed cortical development when compared with AGA fetuses. After controlling for fetal head circumference, these differences remained significant only in late-onset FGR fetuses with abnormal Doppler. These findings support the existence of a link between brain development and impaired placental function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Disproportion of Corpus Callosum in Fetuses With Malformations of Cortical Development.

OBJECTIVE: To evaluate corpus callosum (CC) size in fetuses with malformations of cortical development (MCD) and to explore the diagnostic value of three CC length (CCL) ratios in identifying cortical abnormalities. METHODS: This is a single-center retrospective study in singleton fetuses at 20-37 weeks of gestation between April 2017 and August 2022. The midsagittal plane of the fetal brain was obtained and evaluated for the following variables: length, height, area of the corpus callosum, and relevant markers, including the ratios of corpus callosum length to internal cranial occipitofrontal dimension (CCL/ICOFD), corpus callosum length to femur length (CCL/FL), and corpus callosum length to cerebellar vermian diameter (CCL/VD). Intra-class correlation coefficient (ICC) was used to evaluate measurement consistency. The accuracy of biometric measurements in prediction of MCD was assessed using the area under the receiver-operating-characteristics curves (AUC). RESULTS: Fetuses with MCD had a significantly decreased CCL, height (genu and splenium), and area as compared with those of normal fetuses (P < .05), but there was no significant difference in body height (P = .326). The CCL/ICOFD, CCL/FL, and CCL/VD ratios were significantly decreased in fetuses with MCD when compared with controls (P < .05). The CCL/ICOFD ratio offered the highest predictive accuracy for MCD, yielding an AUC of 0.856 (95% CI: 0.774-0.938, P < .001), followed by CCL/FL ratio (AUC, 0.780 (95% CI: 0.657-0.904), P < .001), CCL/VD ratio (AUC, 0.677 (95% CI: 0.559-0.795), P < .01). CONCLUSION: The corpus callosum biometric parameters in fetuses with MCD are reduced. The CCL/ICOFD ratio derived from sonographic measurements is considered a promising tool for the prenatal detection of cortical malformations. External validation of these findings and prospective studies are warranted.

Use of greyscale and Doppler ultrasound in initial evaluation and follow-up of neurovascular malformations in children.

Pediatric intracranial arteriovenous shunts are rare vascular malformations that can be diagnosed prenatally or postnatally, as an incidental finding or due to complications. We propose a review of cerebral vascular malformations in newborns and infants with special emphasis on neurosonography and Doppler ultrasound as the first diagnostic method. Sonography can thus contribute in the planning of further studies that are always necessary, and in post-therapy follow-up.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVES: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Corpus Callosum Length and Cerebellar Vermian Height in Fetal Growth Restriction.

INTRODUCTION: Growth-restricted fetuses may have changes in their neuroanatomical structures that can be detected in prenatal imaging. We aim to compare corpus callosal length (CCL) and cerebellar vermian height (CVH) measurements between fetal growth restriction (FGR) and control fetuses and to correlate them with cerebral Doppler velocimetry in growth-restricted fetuses. METHODS: This was a prospective cohort of FGR after 20 weeks of gestation with ultrasound measurements of CCL and CVH. Control cohort was assembled from fetuses without FGR who had growth ultrasound after 20 weeks of gestation. We compared differences of CCL or CVH between FGR and controls. We also tested for the correlations of CCL and CVH with middle cerebral artery (MCA) pulsatility index (PI) and vertebral artery (VA) PI in the FGR group. CCL and CVH measurements were adjusted by head circumference (HC). RESULTS: CCL and CVH were obtained in 68 and 55 fetuses, respectively. CCL/HC was smaller in FGR fetuses when compared to control fetuses (difference = 0.03, 95% CI: [0.02, 0.04], p < 0.001). CVH/HC was larger in FGR fetuses compared to NG fetuses (difference = 0.1, 95% CI: [-0.01, 0.02], p = < 0.001). VA PI multiples of the median were inversely correlated with CVH/HC (rho = -0.53, p = 0.007), while CCL/HC was not correlated with VA PI. Neither CCL/HC nor CVH/HC was correlated with MCA PI. CONCLUSIONS: CCL/HC and CVH/HC measurements show differences in growth-restricted fetuses compared to a control cohort. We also found an inverse relationship between VA PI and CVH/HC. The potential use of neurosonography assessment in FGR assessment requires continued explorations.

Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction during Pregnancy on Fetal Brain Development Detected by Neurosonography: A Secondary Analysis of a Randomized Clinical Trial (IMPACT BCN).

INTRODUCTION: We investigated whether structured maternal lifestyle interventions based on Mediterranean diet or stress reduction influence fetal-infant neurodevelopment detected by detailed fetal neurosonography and Ages and Stages Questionnaires 3rd edition (ASQ) at 12 months old. METHODS: This was a secondary analysis of a randomized clinical trial (2017-2020), including 1,221 singleton pregnancies at high risk for small-for-gestational age. Participants were randomized into three groups at 19-23 weeks' gestation: Mediterranean diet intervention, stress reduction program, or usual care. A detailed neurosonography was performed on 881 participants at mean (SD) 33.4 (1.1) weeks' gestation. Neurosonographic measurements were done offline. ASQ was performed on 276 infants at 1 year of corrected age. RESULTS: Biparietal diameter was similar among study groups. Mediterranean diet group fetuses had deeper insula (26.80 [1.68] versus 26.63 [1.75], mm, p = 0.02) and longer corpus callosum (42.98 [2.44] versus 42.62 [2.27], mm, p = 0.04), with a lower rate of suboptimal score infants in ASQ problem-solving domain (6.2 vs. 16.3%, p = 0.03). Stress reduction group fetuses had deeper insula (26.90 [1.75] versus 26.63 [1.75], mm, p = 0.04) and lower rates of suboptimal score infants in ASQ fine motor domain (4.3 vs. 12.8%, p = 0.04), compared to usual care group fetuses. CONCLUSION: Maternal structured intervention during pregnancy of the trial has the potential to modify offspring's neurodevelopment.

Evaluation of Anterior and Middle Brain Structures With Cerebrovascular Flow in Fetuses With Fetal Growth Restriction: A Prospective Study.

OBJECTIVE: To investigate the adaptation of the anterior cerebral artery (ACA) in fetuses with fetal growth restriction (FGR) and assess if forebrain and midbrain structures are affected by vascular adaptations. METHODS: A prospective case-control study involving normally developed fetuses and those with late-onset FGR (estimated fetal weight < 3rd percentile and/or abdominal circumference < 3rd percentile). Doppler indices of the middle cerebral artery (MCA), ACA and umbilical artery (UA) were determined between 32 + 0 and 37 + 0 weeks. Neurosonography assessed the depth of the insula, the sylvian fissure, and the antero-posterior diameter of the frontal lobes (FAPD). RESULTS: The cerebral-placental ratio (CPR) and cerebro-placental-uterine ratio (CPUR) were lower in FGR cases. ACA PI percentile values were significantly lower in the FGR group (p = 0.020). Sylvian fissure depth was significantly lower in FGR fetuses. CONCLUSION: The ACA may be the first cranial vascular structure affected in fetuses with FGR. This may be related to the impact on postnatal cognitive functions in FGR patients. TRIAL REGISTRATION: NCT06215690.

The impact of gestational diabetes on the development of fetal frontal lobe: A case-control study from a tertiary center.

PURPOSE: To determine the effects of gestational diabetes mellitus (GDM) on fetal frontal lobe development. METHODS: This study was conducted prospectively between May 2023 and August 2023 in Ankara City Hospital perinatology clinic. Maternal age, maternal body mass index (BMI), gestational week (GW), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW), frontal antero-posterior diameter (FAPD), occipito-frontal diameter (OFD), FAPD/OFD ratio, and FAPD/HC ratio, were compared between GDM (n = 40) and low risk controls (n = 56). RESULTS: The mean maternal age was found higher in the GDM group compared to control group (p = 0.002). Maternal BMI was significantly higher in the GDM group than the control group (p = 0.01). Abdominal circumference (AC) was significantly higher in the GDM group compared to control group (p = 0.04). EFW was significantly higher in the GDM group compared to control group (p = 0.04). FAPD/OFD ratio was found to be higher in the GDM group than in the control group (p = 0.001). Among GDM patients, no statistically significant difference was found in the ultrasound measurements between the groups receiving insulin treatment and those without treatment. According to the correlation analysis results a moderate, positive, and statistically significant correlation was present between FAPD/OFD and GDM. In perinatal outcomes, the rate of neonatal intensive care unit admission was significantly higher in the GDM group. DISCUSSION: Fetal frontal lobe development seems to be affected by GDM.

First-trimester 3D fetal neurosonography: five standardised views.

BACKGROUND: There are several international guidelines for foetal anomalies scanning at 11-14 weeks' gestation. The aim of this study is to present our first-trimester specialist neurosonography protocol with examples of pathology in order to develop a systematic approach to evaluating the first-trimester foetal brain. METHODS: Women undergoing a first-trimester foetal medicine ultrasound scan between 2010 and 2020 for multiple indications underwent neurosonography according to a set protocol. 3D transvaginal brain examination was performed in all cases (2000 pregnancies scanned). We retrospectively reviewed all imaging to develop this protocol. RESULTS: We propose that the following five axial-plane parallel views should be obtained when performing neurosonography in the first trimester, moving from cranial to caudal: 1. Lateral ventricles; 2. Third ventricle; 3. Thalamus and mesencephalon; 4. Cerebellum; 5. Fourth ventricle. Examples of these images and abnormalities that can be seen in each plane are given. CONCLUSIONS: We have presented a specialist protocol for systematically assessing the foetal brain in the first trimester and given examples of pathology which may be seen in each plane. Further work is needed to prospectively assess detection rates of major abnormalities using this protocol and assess the reproducibility and learning curve of this technique.

This article suggests a way in which specialists scanning babies at 11­14 weeks of pregnancy can check the brain in a structured way. This involves looking at the brain at five levels or planes to view the developing structures. The suggested scan protocol is similar to images produced of the brain and heart at the second trimester (20 week) scan. We hope that specialists will find it useful to check the brain in this way if there are concerns raised at the dating (12 week) scan, and that this will lead to earlier detection of brain abnormalities or differences.

Role of fetal magnetic resonance imaging in fetuses with congenital cytomegalovirus infection: multicenter study.

OBJECTIVE: To investigate the role of fetal brain magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses with congenital cytomegalovirus (CMV) infection and normal neurosonography. METHODS: This was a multicenter, retrospective cohort study of patients examined between 2012 and 2021 in 11 referral fetal medicine centers in Italy. Inclusion criteria were fetuses with congenital CMV infection diagnosed by polymerase chain reaction analysis of amniotic fluid, pregnancies that underwent detailed multiplanar ultrasound assessment of the fetal brain as recommended by the International Society of Ultrasound in Obstetrics and Gynecology, maternal age ≥ 18 years, normal fetal karyotype and MRI performed within 3 weeks after the last ultrasound examination. The primary outcome was the rate of central nervous system (CNS) anomalies detected exclusively on MRI and confirmed after birth or autopsy in fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography at diagnosis. Additional CNS anomalies were classified into anomalies of the ventricular and the periventricular zone, intracranial calcifications in the basal ganglia or germinal matrix, destructive encephalopathy in the white matter, malformations of cortical development, midline anomalies, posterior fossa anomalies and complex brain anomalies. We evaluated the relationship between the incidence of structural CNS malformations diagnosed exclusively on fetal MRI and a number of maternal and gestational characteristics. Univariate and multivariate logistic regression analyses were used to identify and adjust for potential independent predictors of the MRI diagnosis of fetal anomalies. RESULTS: The analysis included 95 fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography referred for prenatal MRI. The rate of structural anomalies detected exclusively at fetal MRI was 10.5% (10/95). When considering the type of anomaly, malformations of cortical development were detected on MRI in 40.0% (4/10) of fetuses, destructive encephalopathy in 20.0% (2/10), intracranial calcifications in the germinal matrix in 10.0% (1/10) and complex CNS anomalies in 30.0% (3/10). On multivariate logistic regression analysis, only CMV viral load in the amniotic fluid, expressed as a continuous variable (odds ratio (OR), 1.16 (95% CI, 1.02-1.21); P = 0.02) or categorical variable (> 100 000 copies/mL) (OR, 12.0 (95% CI, 1.2-124.7); P = 0.04), was independently associated with the likelihood of detecting fetal anomalies on MRI. Associated anomalies were detected exclusively at birth and missed by both prenatal neurosonography and fetal MRI in 3.8% (3/80) of fetuses with congenital CMV infection. CONCLUSIONS: Fetal brain MRI can detect additional anomalies in a significant proportion of fetuses with congenital CMV infection and negative neurosonography. Viral load in the amniotic fluid was an independent predictor of the risk of associated anomalies in these fetuses. The findings of this study support a longitudinal evaluation using fetal MRI in congenital CMV infection, even in cases with negative neurosonography at diagnosis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal neurosonography as accurate tool for diagnosis of brain involvement in tuberous sclerosis.

OBJECTIVE: To demonstrate the potential utility of dedicated neurosonography for the diagnosis of fetal brain involvement in tuberous sclerosis complex. METHODS: This was a multicenter retrospective study of fetuses at high risk for tuberous sclerosis complex. Dedicated neurosonographic, fetal magnetic resonance imaging (MRI) and postnatal reports were reviewed. Data collected included reason for referral, gestational age at which cardiac rhabdomyoma was first suspected and final number of cardiac rhabdomyomas detected on dedicated imaging. We searched for tuberous sclerosis complex-related brain involvement, defined as the presence of one or more of the following findings: white-matter lesions; subependymal nodules; cortical/subcortical tubers; and subependymal giant-cell astrocytoma. RESULTS: We included 20 patients at high risk of tuberous sclerosis complex, of whom 19 were referred for the presence of cardiac rhabdomyomas and one for a deletion in chromosome 16 involving the tuberous sclerosis complex gene locus. Cardiac rhabdomyomas were diagnosed at a mean gestational age of 27 + 2 weeks (range, 16 + 0 to 36 + 3 weeks) and the mean number of cardiac rhabdomyomas per patient was 4 (range, 1-10). Brain involvement was present in 15 fetuses, in 13 of which the disease was confirmed in one or more of the following ways: chromosomal microarray analysis (n = 1), exome sequencing (n = 7), autopsy (n = 4), clinical tuberous sclerosis complex in the newborn (n = 4) and a sibling diagnosed with clinical tuberous sclerosis complex (n = 1). In two cases, the disease could not be confirmed: one was lost to follow-up and autopsy, following termination of pregnancy, was not performed in the other. Among the five cases without brain findings, tuberous sclerosis complex was confirmed in three by exome sequencing (n = 2) and/or autopsy findings (n = 2). The two remaining cases had normal exome sequencing; one case had five cardiac rhabdomyomas, which was a highly suggestive finding, while in the final case, the autopsy was considered normal, representing the only false-positive case in our cohort. CONCLUSIONS: Contrary to current literature, dedicated neurosonography appears to be effective in the diagnosis of brain involvement in fetuses at risk of tuberous sclerosis complex and should be used as the first-line approach. Although the number of cases in which MRI was performed was small, it seems that, in the presence of ultrasound findings, the added value of MRI is low. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Normal and abnormal appearance of fetal ganglionic eminence on second-trimester three-dimensional ultrasound.

OBJECTIVES: To describe the appearance and size of the ganglionic eminence (GE) in normal fetuses on midtrimester three-dimensional (3D) neurosonography and to report on the association between GE alterations (cavitation or enlargement) and malformation of cortical development (MCD). METHODS: This was a prospective multicenter cohort study of normal fetuses and a retrospective analysis of pathological cases with MCD. From January 2022 to June 2022, patients attending our tertiary centers for an expert fetal brain scan were recruited for the purpose of the study. A 3D volume of the fetal head, starting from the sagittal plane, was acquired in apparently normal fetuses using a transabdominal or transvaginal approach. Stored volume datasets were then evaluated independently by two expert operators. Two measurements (longitudinal diameter and transverse diameter) of the GE in the coronal view were obtained twice by each operator. Intra- and interobserver measurement variation was calculated. Reference ranges for GE measurements were calculated in the normal population. A previously stored volume dataset of 60 cases with MCD was also analyzed independently by the two operators using the same method in order to assess if GE abnormalities (cavitation or enlargement) were present. Postnatal follow-up was obtained in all cases. RESULTS: In the study period, 160 normal fetuses between 19 and 22 weeks of gestation were included in the study. The GE was visible in the coronal plane on 3D neurosonography in 144 (90%) cases and was not clearly visible in the remaining 16 (10%) cases. The intra- and interobserver agreement was almost perfect for the longitudinal diameter, with an intraclass correlation coefficient (ICC) of 0.90 (95% CI, 0.83-0.93) and 0.90 (95% CI, 0.86-0.92), respectively, and substantial for the transverse diameter, with an ICC of 0.80 (95% CI, 0.70-0.87) and 0.64 (95% CI, 0.53-0.72), respectively. A retrospective analysis of 50 cases with MCD in the second trimester showed that GE enlargement was present in 12 cases and GE cavitation was present in four cases. CONCLUSIONS: Systematic assessment of the GE in fetuses at 19-22 weeks of gestation is feasible on 3D neurosonography, with good reproducibility in normal cases. Cavitation or enlargement of the GE can be demonstrated in fetuses with MCD. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Tela-choroidea-to-anterior-cerebral-artery distance (TACAD): novel marker on color Doppler to identify fetuses with complete or partial agenesis of corpus callosum.

OBJECTIVES: To assess objectively the course of the anterior cerebral artery (ACA) by measuring its distance to the tela choroidea in the midsagittal view, and to compare this distance in normal fetuses with that in those with agenesis of the corpus callosum (ACC), a condition known to be associated with an abnormal course of the ACA. METHODS: The tela-choroidea-to-anterior-cerebral-artery distance (TACAD) was measured in the midsagittal view of the brain on color Doppler, between the anterior border of the tela choroidea and the ACA at the level of the callosal genu. Reference ranges in relation to gestational age were established in a prospective, cross-sectional study of 253 normal healthy fetuses between 19 and 36 weeks of gestation. The study group included fetuses with complete ACC (n = 28) or partial ACC (n = 18). RESULTS: TACAD of normal fetuses showed an increase during the second half of pregnancy, with a mean value of 10.1 mm and 14.2 mm at 22 and 30 weeks of gestation, respectively. All (28/28) fetuses with complete ACC and 83% (15/18) of those with partial ACC had significantly shorter TACAD, with mean values of 3.9 mm and 6.6 mm, respectively. CONCLUSIONS: TACAD is a measurement that is simple to obtain during fetal color Doppler neurosonography, which enables quantification of the course of the ACA and pericallosal artery. TACAD is shorter in fetuses with complete or partial ACC than in normal fetuses and provides an objective, quantifiable value, rather than merely descriptive information. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Corpus callosum-fastigium and tectal lengths in late-onset small fetuses.

OBJECTIVE: To investigate measurements on neurosonography of midbrain morphology, including corpus callosum-fastigium length and tectal length, in late-onset small fetuses subclassified as small-for-gestational-age (SGA) or growth-restricted (FGR). METHODS: This was a case-control study of consecutive singleton pregnancies delivered at term at a single center between January 2019 and July 2021, including those with late-onset smallness (estimated fetal weight (EFW) < 10th centile) and appropriate-for-gestational-age controls matched by age at neurosonography. Small fetuses were further subdivided into SGA (EFW between 3rd and 9th centile and normal fetoplacental Doppler) and FGR (EFW < 3rd centile or EFW < 10th centile with abnormal cerebroplacental ratio and/or uterine artery Doppler). Transvaginal neurosonography was performed at a mean ± SD gestational age of 33 ± 1 weeks in all fetuses to evaluate corpus callosum-fastigium length and tectal length in the midsagittal plane. Intra- and interobserver agreement was evaluated using the intraclass correlation coefficient and Bland-Altman plots. RESULTS: A total of 70 fetuses with late-onset smallness (29 with SGA and 41 with FGR) and 70 controls were included. Compared with controls, small fetuses showed significantly shorter corpus callosum-fastigium length (median (interquartile range), 44.7 (43.3-46.8) mm vs 43.7 (42.4-45.5) mm, P < 0.001) and tectal length (mean ± SD, 10.5 ± 0.9 vs 9.6 ± 1.0 mm, P < 0.001). These changes were more prominent in FGR fetuses, with a linear trend across groups according to severity of smallness. Corpus callosum-fastigium length and tectal length measurements showed excellent intra- and interobserver reliability. CONCLUSIONS: Small fetuses exhibited shorter corpus callosum-fastigium length and tectal length compared with controls, and these differences were more pronounced in fetuses with more severe smallness. These findings illustrate the potential value of midbrain measurements assessed on neurosonography as biomarkers for brain development in a high-risk population. However, further studies correlating these parameters with postnatal functional tests and follow-up are needed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance.

INTRODUCTION: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). MATERIAL AND METHODS: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. RESULTS: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. CONCLUSIONS: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected.

Reference ranges of fetal cisterna magna volume measurements by three-dimensional ultrasonography in the late second trimester considering sonographic experience.

BACKGROUND: Volume measurements of fetal cisterna magna (CM) by three-dimensional (3D) ultrasonography may have a role in the diagnosis of various posterior fossa abnormalities. PURPOSE: To evaluate reference intervals and reliability of fetal CM volume values by virtual organ computer-aided analysis (VOCAL) in structurally normal fetuses, considering experience of evaluators. MATERIAL AND METHODS: Three operators with different 3D sonography experience levels measured CM volumes of 100 structurally normal fetuses at 18-27 weeks of gestation. Reference intervals for CM volumes were generated. Intraclass correlation coefficients (ICC) were calculated. RESULTS: Mean fetal CM volume measurements by the three operators did not significantly (P = 0.49, P = 0.22, and P = 0.17, respectively) change through 20-23 weeks of gestation. Moderate degrees of inter-observer reliability were found with an ICC of 0.69 between novice and intermediate-level, ICC of 0.74 between experienced and intermediate-level, and ICC of 0.78 between experienced and novice observer, respectively. The novice sonographer generally overestimated CM measurements. Intra-observer reliability was good (ICC=0.85). CONCLUSION: A reference chart for fetal CM volume by VOCAL was formed, revealing uniform mean values of 20-23 weeks of gestation. The inter-observer reliability is moderate, and biases seem relatively common for all experience categories.