Congenital diaphragmatic hernia in Coffin Siris syndrome: Further evidence from two cases.

Coffin-Siris Syndrome (CSS) is a rare multi-system dominant condition with a variable clinical presentation mainly characterized by hypoplasia/aplasia of the nail and/or distal phalanx of the fifth digit, coarse facies, hirsutism/hypertrichosis, developmental delay and intellectual disability of variable degree and growth impairment. Congenital anomalies may include cardiac, genitourinary and central nervous system malformations whereas congenital diaphragmatic hernia (CDH) is rarely reported. The genes usually involved in CSS pathogenesis are ARID1B (most frequently), SMARCA4, SMARCB1, ARID1A, SMARCE1, DPF2, and PHF6. Here, we present two cases of CSS presenting with CDH, for whom Whole Exome Sequencing (WES) identified two distinct de novo heterozygous causative variants, one in ARID1B (case 1) and one in SMARCA4 (case 2). Due to the rarity of CDH in CSS, in both cases the occurrence of CDH did not represent a predictive sign of CSS but, on the other hand, prompted genetic testing before (case 1) or independently (case 2) from the clinical hypothesis of CSS. We provide further evidence of the association between CSS and CDH, reviewed previous cases from literature and discuss possible functional links to related conditions.

Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes.

Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11-13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay.

Family history is key to the interpretation of exome sequencing in the prenatal context: unexpected diagnosis of Basal Cell Nevus Syndrome.

OBJECTIVES: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies. METHODS: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus. RESULTS: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648_651dup in the PTCH1 gene was identified as causative of the fetal phenotype. CONCLUSIONS: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome.

Prenatal ultrasound findings associated with PIGW variants: One more piece in the FRYNS syndrome puzzle? PIGW-related prenatal findings.

OBJECTIVE: We describe the prenatal ultrasound findings and autopsy of three fetuses with multiple congenital anomalies (MCA) whose diagnostic workup suggested the same genetic etiology. We conducted a literature review to corroborate the molecular results and find evidence that the identified variants are responsible for the phenotype seen. METHODS: Trio-based Exome Sequencing (ES) analysis was performed on chorionic villus samples. We reviewed available reports dealing with prenatal manifestations of genes involved in the Glycosylphosphatidylinositols (GPI) biosynthesis defects (GPIBDs). RESULTS: Prenatal findings shared by all the three pregnancies included facial dysmorphisms, brain malformations of the posterior fossa, skeletal and genitourinary anomalies. ES analysis identified homozygous variants of uncertain significance in PIGW in the three fetuses. Prenatal findings of the three pregnancies overlapped with those previously described for PIGW variants and with those associated with PIGN, PIGV and PIGA variants. CONCLUSION: Based on the phenotypic overlap between the prenatal findings in our three cases and other cases with pathogenic variants in other genes involved in GPIBDs, we speculate that the variants identified in the three fetuses are likely causal of their phenotype and that the PIGWclinical spectrum might extend to MCA, mainly involving brain, skeletal and genitourinary systems. Moreover, we suggest that also PIGW could be involved in Fryns/Fryns-like phenotypes.

Cell-free DNA analysis of maternal blood in prenatal screening for chromosomal microdeletions and microduplications: a systematic review.

BACKGROUND AND AIM OF THE STUDY: Scientific Societies do not recommend the use of cell-free DNA (cfDNA) testing as a first-tier screening for microdeletion and microduplication syndromes (MMs). The aim of this study was to review the current available literature on the performance of cell-free DNA as a screening for MMs. METHODS: Medline, Embase and the Cochrane Library were searched electronically from 2000 to January 2020 and articles reporting the diagnostic performance of cfDNA screening for MMs in large (>5000 cases) series were included. Between-study heterogeneity and random effect model for screen positive rate (SPR), false positive rate (FPR) and positive predictive value (PPV) were calculated. RESULTS: We identified 42 papers, seven included, for a total of 474,189 pregnancies and 210 cases of MMs. Diagnostic verification of positive cases was available overall in 486 (71.68 %) of 678 cases. The weighted pooled SPR, FPR and PPV were 0.19% (95% CI = 0.09-0.33), 0.07 (95% CI = 0.02-0.15) and 44.1 (95% CI = 31.49-63.07). In conclusion, the pooled PPV of cfDNA testing in screening for MMs was about 40%, ranging from 29% to 91%, for an overall FPR <0.1%. CONCLUSIONS: No confirmatory analysis was available in cases that did not undergo invasive testing, which were the vast majority of cases with a negative test, and therefore, the DR and the negative predictive value cannot be determined.

Prenatal magnetic resonance imaging within the 26th week of gestation may predict the fate of isolated upward rotation of the cerebellar vermis: insights from a multicentre study.

OBJECTIVES: We investigated whether prenatal magnetic resonance imaging (MRI) within 26 weeks of gestation (GW) may predict the fate of isolated upward rotation of the cerebellar vermis (URCV). METHODS: This retrospective multicentre observational study included foetuses diagnosed with isolated URCV in prenatal MRI performed within 26 GW. Isolated URCV was defined by a brainstem-vermis angle (BVA) ≥ 12° in the MR midline sagittal view without abnormalities of the supratentorial structures, brainstem, or cerebellum hemispheres. The assessments included the BVA, clival-supraoccipital angle, transverse diameter of the posterior cranial fossa, tentorial angle, width of the cisterna magna (WCM), ventricular width, vermian diameters, hypointense stripes, and cerebellar tail sign. Late prenatal or postnatal MRI was used as a reference standard to assess the final vermian fate (rotated/de-rotated). RESULTS: Forty-five foetuses (mean GW at prenatal MRI = 21.5 ± 1.4 weeks) were included. In the reference standard, the vermis was de-rotated in 26 cases (57.7%). At least two of the following criteria were used to predict the persistence of URCV at imaging follow-up: BVA ≥ 23°, WCM ≥ 9 mm, and the cerebellar tail sign. The results were a sensitivity of 84.21% (95% CI, 60.4-96.6%), specificity of 80.8% (95% CI, 60.6-93.4%), positive predictive value of 76% (95% CI, 58.7-87.8%), and negative predictive value of 87.5% (95% CI, 70.9-95.2%). CONCLUSIONS: MRI within 26 GW on foetuses diagnosed with isolated URCV may predict delayed cerebellar vermis de-rotation, which is associated with good neurodevelopmental outcome in most cases. KEY POINTS: • Foetal MRI is a valuable tool in predicting the fate of isolated upward-rotated cerebellar vermis. • A wider angle between the brainstem and vermis is associated with higher risk of persistence of vermian rotation. • The presence of ≥ 2 factors among a brainstem-to-vermis angle ≥ 23°, width of the cisterna magna ≥ 9 mm, and the presence of the "cerebellar tail sign" has a sensitivity of 84.21% (95% CI, 60.4-96.6%) and specificity of 80.8% (95% CI, 60.6-93.4%) in predicting the persistence of the vermian rotation at imaging follow-up.

Micro-computed tomography of isolated fetal hearts following termination of pregnancy: A feasibility study at 8 to 12 weeks' gestation.

OBJECTIVES: To assess the feasibility of retrieval of intact human fetal hearts after first trimester surgical termination of pregnancy (TOP) and subsequent anatomical assessment by postmortem micro-computed tomography (micro-CT). METHODS: In a cohort of consenting women undergoing surgical TOP between 8 and 13 weeks' gestation, we attempted the retrieval of the fetal heart from the suction material. Specimens were immersion fixed in 10% formaldehyde, scanned by iodine-enhanced micro-CT and cardiac anatomy assessed by a multidisciplinary team using 3D-multiplanar analysis. RESULTS: The median gestational age at TOP was 10.7 weeks (range 8.3-12.9). In 57 (95.0%) out of 60 suction specimens, the heart could be retrieved. The median cardiac length was 5 mm (range 2-8 mm), in three (5.3%), the heart was too damaged to assess cardiac anatomy and in five (8.7%) only the four chambers could be examined. In the remaining 49 (86.0%) cases, a detailed assessment of cardiac anatomy was possible, showing a major defect in two (4.1%) and a minor defect in four (8.2%). CONCLUSIONS: Fetal hearts can be retrieved after first trimester TOP being intact in the vast majority of cases. Iodine-enhanced, postmortem micro-CT can be used to assess cardiac anatomy from as early as 8 weeks and to describe heart abnormalities.

Incidence of chromosomal abnormalities in fetuses with first trimester ultrasound anomalies and a low-risk cell-free DNA test for common trisomies.

OBJECTIVE: To examine the incidence and type of chromosomal abnormalities in fetuses with first trimester ultrasound anomalies and a low-risk cfDNA test for common trisomies. METHODS: In 486 singleton pregnancies undergoing invasive testing after combined screening, a detailed first trimester ultrasound assessment was carried out and a maternal blood sample was sent for cfDNA analysis. Ultrasound and cfDNA data were analyzed in relation to fetal karyotype. RESULTS: Invasive testing demonstrated a chromosomal abnormality in 157 (32.3%) of 486 fetuses. In 348 cases with a low-risk cfDNA test for common trisomies, NT ≥ 3.5 mm and/or a major structural defect were observed in 92 (26.4%) fetuses. A chromosomal abnormality was found in 17 (18.5%; 95%CI 10.55-26.41) of these pregnancies, including 1 (1.1%) case of trisomy 21 and 16 (17.4%) fetuses with abnormalities different from common trisomies. The respective incidence in the 256 cases with a low-risk cfDNA test result and no ultrasound anomalies was 2.3% (95% CI 0.49-4.20; n = 6). CONCLUSIONS: In fetuses with first trimester ultrasound anomalies and a low-risk cfDNA result for trisomy 21, 18 and 13, diagnostic testing should be offered with the main objective to detect chromosomal abnormalities beyond common trisomies.

Minimally invasive fetal surgery for myelomeningocele: preliminary report from a single center.

OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.

High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation: Normal foetal brain development.

PURPOSE: To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. METHODS: We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. RESULTS: Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. CONCLUSION: PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. KEY POINTS: • Post-mortem magnetic resonance imaging (PMMRI) of non-fixed head is feasible. • PMMRI of unfixed in situ foetal brains preserves the natural tissue contrast. • PMMRI provide a good depiction of the normal foetal brain development. • PMMRI of unfixed in situ foetal brains preserves the skull integrity. • PMMRI pattern of foetal brain development at early gestational age is described.

Fetal Doppler changes 1 week after endoscopic equatorial laser for twin-to-twin transfusion syndrome: A longitudinal study.

OBJECTIVE: To investigate sequential Doppler changes in donors and recipients before and 1 week after endoscopic laser for twin-to-twin transfusion syndrome (TTTS) and to examine factors that may be associated with such changes. METHODS: In TTTS pregnancies undergoing laser treatment, we examined fetal Doppler changes before and 1 week postintervention. Intrauterine death rates and preoperative factors were analyzed in relation to Doppler changes. RESULTS: Among 129 (85.4%) donors surviving at 1 week after laser, there was normalization of umbilical artery flow in 26 (72.2%) of 36 cases with preoperative abnormal Dopplers. In the remaining 10 (27.8%) fetuses, abnormal findings persisted. The rate of later intrauterine death was significantly higher in the latter group (6 of 10, 60.0%) compared with fetuses in which Doppler findings normalized (4 of 26, 15.4%; P < .05), with no difference in the rate of severe donor growth restriction between the 2 groups (80.0% vs 65.4%, respectively; P = .688). CONCLUSIONS: In about 70% of TTTS donors with preoperative abnormal umbilical artery Doppler, there was normalization 1 week after endoscopic laser. The incidence of fetal growth restriction was not significantly different in donors with persistence of Doppler abnormalities compared with those with normalized findings.

Fetoscopic Endoluminal Tracheal Occlusion in Fetuses with Severe Diaphragmatic Hernia: A Three-Year Single-Center Experience.

OBJECTIVE: To report on our experience in the prenatal treatment of severe congenital diaphragmatic hernia (CDH) by fetoscopic endoluminal tracheal occlusion (FETO). METHODS: Between 2012 and 2014, FETO was performed at our center in 21 cases of CDH considered to be severe based on sonographic measurement of observed/expected lung-to-head ratio (O/E LHR) and side of the defect. We reported pre- and postoperative ultrasound findings, procedure-related complications, pregnancy outcome and survival at 1-3 years of age. RESULTS: The median gestational age (GA) at balloon insertion was 28.1 weeks (range 26.0-31.1) and the median GA at delivery 34.7 weeks (range 31.6-39.0); delivery before 32 and 34 weeks occurred in 2 (9.5%) and 7 (33.3%) cases, respectively. Postnatal survival at 1-3 years of age in the 17 cases with isolated unilateral CDH was 47.1%. The percentage difference between pre-balloon removal O/E LHR and pre-FETO O/E LHR was significantly higher in survivors compared to neonates who died (40.8 vs. 21.2%, respectively; p < 0.05). CONCLUSIONS: In this study, FETO was associated with an infant survival of 47% in cases with isolated unilateral severe CDH. The post-FETO increase in O/E LHR was higher in fetuses that survived compared to those who died.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an overgrowth syndrome and it is usually diagnosed postnatally, on the basis of phenotype. Prenatal ultrasonography may show fetal alterations, but they are not pathognomonic and most of them are frequently detectable only from the 20th week of gestation. Nevertheless, early diagnosis is important to avoid neonatal complications and make timely and informed decisions about the pregnancy. We report on four fetuses from two unrelated families, in whom the application of whole exome sequencing and array-CGH allowed the identification of GPC3 alterations causing SGBS. The careful follow up of pregnancies and more sophisticated analysis of ultrasound findings led to the identification of early prenatal alterations, which will improve the antenatal diagnosis of SGBS. © 2016 Wiley Periodicals, Inc.

Postnatal survival after endoscopic equatorial laser for the treatment of twin-to-twin transfusion syndrome.

BACKGROUND: Endoscopic laser coagulation of placental anastomoses is the first-line treatment for severe twin-to-twin transfusion syndrome. A recent randomized controlled trial reported that laser coagulation along the entire vascular equator was associated with a similar dual survival and survival of at least 1 twin compared with the group that was treated with the selective technique. In addition, there was a significantly lower incidence of postoperative recurrence of twin-to-twin transfusion syndrome and the development of twin anemia-polycythemia sequence in the equatorial group. OBJECTIVE: The purpose of this study was to report on neonatal survival in twin-to-twin transfusion syndrome pregnancies that were treated with endoscopic laser therapy with the use of the equatorial technique and to examine the relationship between preoperative factors and twin loss. STUDY DESIGN: Endoscopic equatorial laser therapy was carried out as the primary treatment for twin-to-twin transfusion syndrome in all consecutive monochorionic diamniotic twin pregnancies that were referred at a single fetal surgery Center over a 4-year period. All visible placental anastomoses were coagulated; additional laser ablation of the placental tissue between the coagulated vessels was carried out. Pre-laser ultrasound data, periprocedural complications, pregnancy outcome, and postnatal survival at hospital discharge were recorded and analyzed. RESULTS: A total of 106 pregnancies were treated during the study period. Median gestational age at laser therapy was 19.7 weeks (range, 15.1-27.6 weeks). There was postoperative recurrence of twin-to-twin transfusion syndrome or the development of twin anemia-polycythemia sequence in 2 (1.9%) and 2 (1.9%) cases, respectively. The survival rates of both and at least 1 twin were 56.6% and 83.0%, respectively. Donor survival was significantly lower compared with the recipient co-twin (64.2% vs 75.5%, respectively; P < .05). The rate of fetal death, which was the most common cause of twin loss, was significantly higher in donors compared with recipient fetuses (23.6% vs 10.4%, respectively; P < .05). In cases with absent or reversed end-diastolic velocity in the donor umbilical artery, dual and donor survival rates were significantly lower compared with the remaining twin-to-twin transfusion syndrome pregnancies (40.0% vs 64.8% and 40.0% vs 76.1%, respectively; P < .05). There were no significant differences between the 2 groups in the survival of at least 1 twin and in the recipient survival. CONCLUSIONS: Endoscopic equatorial laser therapy was associated with a survival of both and at least 1 twin of approximately 55% and 83%, respectively, with a low rate of recurrent twin-to-twin transfusion syndrome and twin anemia-polycythemia sequence. In addition, the preoperative finding of abnormal donor umbilical artery Doppler on ultrasound identified a subgroup of twin-to-twin transfusion syndrome pregnancies with a lower dual survival rate caused by increased intrauterine deaths of donor twins.

Prenatal ultrasound factors and genetic disorders in pregnancies complicated by polyhydramnios.

OBJECTIVE: The objective of the study is to examine the incidence of chromosomal or genetic abnormalities in pregnancies complicated by polyhydramnios and to assess the value of prenatal ultrasound findings in the prediction of cases associated with such disorders. METHODS: We searched the prenatal records of all patients delivered in our hospital with a diagnosis of polyhydramnios during pregnancy. For each case, maternal characteristics, ultrasound findings, and genetic testing results were recorded. A postnatal follow-up program of at least 6 months, including a clinical assessment by a clinical geneticist, was carried out in all cases. RESULTS: On a total of 195 cases, genetic testing and clinical examination identified a chromosomal or genetic disease in 26 (13.3%) cases. Multivariate analysis demonstrated that significant predictors of a genetic disorder were a deepest vertical pocket of amniotic fluid of ≥13.0 cm (OR 4.306, 95%CI: 1.535-12.079) and reduced fetal movements (OR 25.084, 95%CI: 4.577-137.461), but not the presence of a structural defect. CONCLUSION: A postnatal clinical follow-up program can reveal chromosomal or genetic disorders in about 13% of neonates with a prenatal diagnosis of polyhydramnios. The severity of polyhydramnios and the reduction of fetal movements are independently associated with the presence of such diseases. © 2016 John Wiley & Sons, Ltd.

Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening.

OBJECTIVE: The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening. METHODS: In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphism-based methodology. RESULTS: The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. CONCLUSION: In high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies.

5D CNS+ Software for Automatically Imaging Axial, Sagittal, and Coronal Planes of Normal and Abnormal Second-Trimester Fetal Brains.

The purpose of this study was to test new 5D CNS+ software (Samsung Medison Co, Ltd, Seoul, Korea), which is designed to image axial, sagittal, and coronal planes of the fetal brain from volumes obtained by 3-dimensional sonography. The study consisted of 2 different steps. First in a prospective study, 3-dimensional fetal brain volumes were acquired in 183 normal consecutive singleton pregnancies undergoing routine sonographic examinations at 18 to 24 weeks' gestation. The 5D CNS+ software was applied, and the percentage of adequate visualization of brain diagnostic planes was evaluated by 2 independent observers. In the second step, the software was also tested in 22 fetuses with cerebral anomalies. In 180 of 183 fetuses (98.4%), 5D CNS+ successfully reconstructed all of the diagnostic planes. Using the software on healthy fetuses, the observers acknowledged the presence of diagnostic images with visualization rates ranging from 97.7% to 99.4% for axial planes, 94.4% to 97.7% for sagittal planes, and 92.2% to 97.2% for coronal planes. The Cohen κ coefficient was analyzed to evaluate the agreement rates between the observers and resulted in values of 0.96 or greater for axial planes, 0.90 or greater for sagittal planes, and 0.89 or greater for coronal planes. All 22 fetuses with brain anomalies were identified among a series that also included healthy fetuses, and in 21 of the 22 cases, a correct diagnosis was made. 5D CNS+ was efficient in successfully imaging standard axial, sagittal, and coronal planes of the fetal brain. This approach may simplify the examination of the fetal central nervous system and reduce operator dependency.

Prenatal ultrasound predictors of postnatal major cerebral abnormalities in fetuses with apparently isolated mild ventriculomegaly.

OBJECTIVE: We aim to examine the incidence of major cerebral abnormalities on postnatal imaging in cases with isolated mild ventriculomegaly on fetal sonography and to evaluate the relationship between the presence or absence of such defects and prenatal ultrasound factors. METHODS: We searched our databases to identify all cases with mild ventriculomegaly (10-15 mm) and no other major structural abnormalities on prenatal ultrasound, with normal karyotype and no evidence of maternal or fetal infection. For each case, we retrieved data on prenatal ultrasound follow-up, fetal magnetic resonance imaging (MRI), neonatal ultrasound and/or brain MRI, and pregnancy outcome. RESULTS: Postnatal imaging revealed a major cerebral abnormality in 9 (6.9%) of 130 live borns with isolated mild ventriculomegaly on prenatal ultrasound. In six (66.7%) of nine cases, the abnormality was known or suspected prenatally on fetal MRI. Multivariate analysis showed that the only significant contribution to the prediction of major cerebral abnormalities was provided by persistence or progression of ventricular enlargement on serial ultrasound examinations (p = 0.001, odds ratio 21.1 [95% confidence interval: 3.6-122.7]). CONCLUSION: Prenatal ultrasound follow-up identifies fetuses at higher risk for a major cerebral abnormality among cases with isolated mild ventriculomegaly. In cases with persistent or progressive enlargement, fetal MRI and postnatal imaging seem appropriate.