Bibliography in fetal ultrasound
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With this bibliographical review, we aim to offer obstetric ultrasound practitioners an original tool to aid in scientific monitoring, positioned between the conventional abstract and the often lengthy and time-consuming full reading of the original article.
This hybrid format ensures substantial time savings by enabling the rapid and targeted identification of publications that, based on their content, warrant an in-depth reading.
Transposition of the Great Arteries
Overview
Prenatal diagnosis of Transposition of the Great Arteries (TGA), a significant congenital heart defect (CHD) characterized by ventriculoarterial discordance and atrioventricular concordance with a parallel relationship of the great arteries, is crucial for improving postnatal outcomes. TGA accounts for 5% to 8% of fetuses or infants with CHD and is a common cyanotic heart defect. Despite advancements in prenatal ultrasound screening, TGA is commonly underdiagnosed in utero, with prenatal detection rates often remaining below 50%. This low detection rate has been attributed to technical difficulties in consistently imaging the outflow tracts using standard obstetric ultrasonography.
Accurate prenatal diagnosis offers several benefits, including facilitating effective prenatal counseling, enabling early postnatal intervention and treatment, enhancing perinatal decision-making and delivery planning, and providing for optimal management of the unique transitional physiology of affected newborns. Delays in diagnosis and treatment can lead to rapid hemodynamic compromise, significant morbidity, and even death. Studies suggest that prenatal diagnosis of TGA can reduce neonatal morbidity and mortality. Furthermore, it may lead to earlier balloon atrial septostomy (BAS) and less need for mechanical ventilation pre-operatively. While mortality rates between pre- and postnatally diagnosed patients may not always show statistical significance due to overall low mortality in modern cardiac centers, prenatal diagnosis may confer long-term benefits, potentially minimizing pre-operative morbidity and positively impacting neurodevelopmental outcomes.
Several ultrasound techniques and markers are employed for the prenatal diagnosis of TGA:
The detection rate of TGA by standard obstetric ultrasonographic evaluation is historically low. However, the prenatal diagnosis rate has shown improvement over time, although it still often remains below 50%. Factors influencing detection include the experience of the examiner, the gestational age at examination, and the incorporation of specific views like the outflow tract view (OTV) and the three vessels and trachea view into routine screening protocols. Recommendations from international ultrasound societies now emphasize the importance of the OTV as an integral part of fetal cardiac screening.
TGA can occur as an isolated anomaly or in association with other cardiac and extracardiac malformations. When associated with other cardiac anomalies visible on the four-chamber view (e.g., ventricular septal defect, abnormal cardiac axis, chamber size discrepancy), prenatal detection may be easier compared to simple TGA with a normal four-chamber view. Chromosomal and extracardiac anomalies are relatively rare in isolated TGA, but their presence warrants consideration. TGA has been linked to maternal pre-gestational diabetes, exposure to pesticides, and first-trimester retinoic acid use.
Studies on prenatal diagnosis of TGA often have limitations such as being retrospective, single-center studies with relatively small sample sizes. Further prospective studies are needed to validate novel markers like the I-shaped sign and the rightward convexity of the aorta. Ongoing research continues to explore the long-term benefits of prenatal diagnosis on functional and neurodevelopmental outcomes. The focus should be on improving education and consistent performance and interpretation of key ultrasound views to increase prenatal detection rates of this critical CHD. A multidisciplinary approach to diagnosis and management, along with improved secondary and tertiary prevention systems for birth defects, is essential for optimizing outcomes for fetuses with TGA.
Bibliographie
This report describes the ultrasonographic findings of Transposition of the Great Arteries (TGA) based on a systematic approach using 4-dimensional echocardiography with Spatiotemporal Image Correlation (STIC). STIC is presented as a recent technological advance in ultrasonographic imaging that allows for dynamic multiplanar slicing and surface rendering of the fetal heart. A previously developed technique for systematically visualizing the outflow tracts from volume data sets acquired with STIC is highlighted. The addition of color and power Doppler imaging to STIC technology enables the dynamic display of rendered views of the outflow tracts with minimal manipulation of the volume data set.
The prenatal diagnosis of TGA is associated with a significant reduction in both preoperative and postoperative mortality, a decrease in the rate of metabolic acidosis and multiorgan failure during the neonatal period, reduced need for ventilatory support, and shorter hospitalization time. Despite these benefits, prenatal detection rates for TGA have historically been low. Reasons for this low detection include the absence of risk factors to identify a target population for screening and the need to systematically examine the outflow tracts to establish the diagnosis. Although scientific societies recommend extending the basic fetal cardiac examination to include visualization of the outflow tracts, this remains a technical challenge for many sonographers.
The authors propose that a 4-dimensional volume data set acquisition followed by a systematic approach to image the outflow tracts may reduce the operator dependency of prenatal ultrasonography. While volume acquisition remains operator-dependent, once a good-quality volume data set is acquired, the outflow tracts can be systematically imaged using developed algorithms for gray scale, color, or power Doppler imaging. It is anticipated that these algorithms may eventually become automated by computer software (automated multiplanar imaging).
The objective of this report was to describe the ultrasonographic findings of TGA using this systematic 4-dimensional echocardiography with STIC approach. A case report is presented involving a 43-year-old patient at 20 3/7 weeks’ gestation with a suspected heart anomaly on 2-dimensional ultrasonography. The examination aimed to verify whether the authors’ previously described techniques for systematic visualization of the outflow tracts using 4-dimensional volume data sets acquired by STIC could be used to examine the heart [6, 3–5].
Two-dimensional ultrasonography in the case revealed a normal 4-chamber view. However, visualization of the outflow tracts showed the great arteries exiting the ventricular chambers in parallel.
Volume data sets were acquired using STIC with a Voluson 730 Expert ultrasound system. Both gray scale ultrasonography and gray scale plus power Doppler imaging were used during acquisition, which lasted between 7.5 and 15 seconds with an acquisition angle of 25° to 35°.
A 4-step approach to evaluate the fetal heart using multiplanar display images was applied to the 4-dimensional volume data set. TGA was demonstrated in steps 3 and 4. Rotation of the volume data set around the y-axis (step 3) allowed visualization of two vessels leaving the ventricular chambers in parallel. Positioning the reference dot at the center of the vessel leaving the left ventricle (step 4) and examining the sagittal orthogonal view confirmed that this vessel was actually the pulmonary artery.
Volume-rendered power Doppler images of the outflow tracts in a normal case showed crisscrossing of the great arteries, whereas in the case with TGA, the great vessels were visualized leaving the ventricular chambers in parallel. The technique used to obtain these rendered images is illustrated in Figure 5.
The findings were independently confirmed by fetal and neonatal echocardiography.
The discussion section highlights that TGA is a common cyanotic congenital heart defect, occurring in approximately 0.2 to 0.4 per 1000 live births and representing 2.5% to 5% of all congenital heart defects. In TGA, the pulmonary artery arises from the left ventricle, and the aorta arises from the right ventricle. Associated anomalies can include ventricular septal defects, pulmonary stenosis, and coarctation of the aorta. Postnatal oxygenation depends on mixing of blood through a patent foramen ovale, ductus arteriosus, or a ventricular septal defect due to the parallel functioning of the ventricles.
Prenatal diagnosis of TGA is linked to a reduction in perinatal morbidity and mortality. Studies have shown that prenatal diagnosis is associated with a reduced need for mechanical ventilation, a decreased frequency of metabolic acidosis and multiorgan failure, shorter hospitalization stays, and decreased preoperative and postoperative mortality. The definitive treatment for TGA is the “arterial switch” operation, with surgical mortality potentially as low as 2%. Preoperative mortality is therefore a significant concern.
This report demonstrates that 4-dimensional gray scale and power Doppler STIC can be used to systematically visualize the abnormal relationship of the outflow tracts in fetuses with TGA. Volume acquisition requires only clear visualization of the apical 4-chamber view during 2-dimensional ultrasonography for a short period. The low detection rate of TGA by standard obstetric ultrasonography is attributed to technical difficulties in consistently imaging the outflow tracts.
Four-dimensional ultrasonography may overcome technical limitations related to the skills required to obtain appropriate planes. STIC allows for automatic volume acquisition of the fetal heart, storing complete volume data sets and reducing dependency on the examiner’s experience [16, 1–5]. The user can digitally store, optimize, and slice images iteratively and even transmit them to experts. Additional benefits of STIC include improved temporal resolution, an increased number of stored 2-dimensional images, and complete rotation of the heart for 3-dimensional multiplanar anatomy examination. Furthermore, the clear contrast between normal and TGA hearts obtained by 4-dimensional rendering techniques may improve parental understanding and enhance prenatal counseling.
The authors conclude that 4-dimensional STIC is a valuable tool for the prenatal diagnosis of TGA by providing a systematic approach to visualize the abnormal relationship of the outflow tracts.
This study investigates the ‘I-shaped’ sign as a novel echocardiographic marker for the antenatal diagnosis of d-transposition of the great arteries (dTGA) during routine cardiac examinations. The primary objectives were to determine the prevalence of this sign in fetuses with dTGA, those with other congenital heart diseases (CHDs), and those with normal structural hearts. This was a retrospective evaluation involving 1134 fetuses who underwent echocardiography to screen for CHD over a 4-year period.
Methods:
The researchers defined the I-shaped sign as the characteristic appearance of the aortic arch, resembling the letter ‘I’, from the most anterior to the most posterior point of the descending aorta visible in the three vessels and trachea view. A single experienced cardiologist reviewed DVD clips of the fetal echocardiograms, specifically assessing the three-vessel view and the three vessels and trachea view, from the outflow tracts to the descending aorta. The frequency of this sign was then evaluated in cases with dTGA, other CHDs, and normal hearts. The reliability of CHD diagnosis at the center was confirmed by postnatal echocardiographic examination. Statistical analysis using Pearson’s χ2 test was performed to compare the prenatal detection rates of the I-shaped sign across the different groups.
Results:
CHD was diagnosed in 671 (59.1%) of the 1134 cases, and 31 (4.6%) of these had dTGA. The I-shaped sign was observed in 30 out of 31 (96.8%) cases of dTGA. In contrast, it was seen in only 31 out of 640 (4.8%) cases with other cardiac anomalies. These other CHDs included single ventricle with pulmonary atresia or severe pulmonary stenosis, hypoplastic left heart syndrome with aortic atresia, corrected transposition of the great arteries, and double outlet right ventricle with malposition of the great arteries. Importantly, the I-shaped sign was never observed in fetuses with structurally normal hearts.
The frequency of the I-shaped sign was significantly higher in the dTGA group compared to both the normal group and the other CHDs group (both P < 0.001). The I-shaped sign demonstrated a sensitivity of 96.8% and a specificity of 97.1% for the diagnosis of dTGA. The positive predictive value for diagnosing dTGA was 49.2%, while the negative predictive value was 99.9%.
Under normal circumstances, in the three vessels and trachea view, the aortic and ductal arches are seen in a tangential cross-section, forming a V-shape pointing to the posterior thorax on the left side of the spine. However, dTGA is characterized by the I-shaped aortic arch in the same view, typically showing only one great artery. The main pulmonary artery in dTGA appears shorter than normal, and its bifurcation is visible in the three-vessel view. Computed tomography (CT) images of neonates with dTGA in the axial upper mediastinal view also showed an elongated aortic arch running across the chest in an anteroposterior direction.
Discussion:
The study highlights that the detection rate of dTGA in a non-selected population remains low because isolated dTGA often presents with a normal four-chamber view, which is the standard screening view. Prenatal diagnosis of dTGA is crucial for improving early neonatal management and reducing associated mortality and morbidity. The I-shaped sign, characterized by a long aortic arch running across the chest in an anteroposterior direction in the three vessels and trachea view, can serve as a marker to improve the sensitivity and specificity of antenatal dTGA detection, even with a normal four-chamber view.
The fact that the I-shaped sign was never observed in structurally normal hearts and its high sensitivity and specificity make it a valuable marker. While the I-shaped sign was also observed in a small percentage of other CHDs, these conditions (like single ventricle and hypoplastic left heart syndrome) are often detectable in the four-chamber view during routine screening. The I-shaped sign in these other CHDs can be attributed to the abnormal origin or course of the great vessels.
The study acknowledges that the low positive predictive value of the I-shaped sign for dTGA is due to the low prevalence of the disease. However, the high negative predictive value suggests that the absence of the I-shaped sign strongly suggests the absence of dTGA.
The authors conclude that the I-shaped sign is a sensitive, specific, and simple method for detecting dTGA during fetal echocardiography. Its detection should raise suspicion of CHD, and the combination of a normal four-chamber view with an I-shaped sign is particularly suggestive of dTGA. They believe this novel marker has the potential to improve the prenatal diagnosis of dTGA in the general low-risk population.
The study notes a limitation in its exclusive use of previously diagnosed cases, although the reviewer was blinded to the diagnosis. A prospective trial is recommended to further confirm the diagnostic effectiveness of the I-shaped sign.
This comprehensive synthesis integrates the findings and discussions from two distinct studies focusing on the prenatal diagnosis of transposition of the great arteries (TGA): a retrospective evaluation of temporal trends and outcomes over a 20-year period, and an investigation into a novel echocardiographic marker, the ‘I-shaped’ sign, for antenatal dTGA diagnosis [conversation history].
Study 1: Temporal Trends in Prenatal Diagnosis of TGA/IVS and its Impact
This retrospective study, conducted at Boston Children’s Hospital, evaluated the temporal trends in the prenatal diagnosis rate of transposition of the great arteries with intact ventricular septum (TGA/IVS) over a 20-year period (1992-2011) and its impact on neonatal morbidity and mortality. The study included 340 newborns with TGA/IVS referred for surgical management. The study period was divided into five 4-year periods, and the primary outcome was the rate of prenatal diagnosis. Secondary outcomes included neonatal pre-operative status and perioperative survival.
Key Findings:
Discussion of Study 1:
The study highlights the improvement in prenatal detection rates of TGA/IVS, likely due to increased utilization and quality of ultrasound imaging, particularly the outflow tract view (OTV). The historical reliance on the four-chamber view (4CV) alone precluded the diagnosis of TGA/IVS due to its normal appearance. The formal recommendation for incorporating the OTV by prenatal ultrasound societies in 2013 followed the trend observed in this study.
While mortality rates were not significantly different, the study emphasizes the pre-operative benefits of prenatal diagnosis, such as earlier BAS and reduced need for mechanical ventilation, potentially leading to improved hemodynamics and less hypoxemia. The lack of significant difference in pre-operative acidosis might be due to limitations in data availability from outside hospitals or the chosen pH threshold.
The authors acknowledge that the single-center, retrospective nature of the study and the exclusion of patients who died before reaching their center are limitations. The study suggests that while neonatal mortality may not show a significant difference, prenatal diagnosis might confer long-term benefits, particularly on neurodevelopmental outcomes, as suggested by other research.
Study 2: The ‘I-shaped’ Sign as a Novel Marker [conversation history]
This retrospective study investigated the ‘I-shaped’ sign in the three vessels and trachea view as a novel echocardiographic marker for the antenatal diagnosis of d-transposition of the great arteries (dTGA) [conversation history]. The study involved 1134 fetuses undergoing echocardiography [conversation history].
Key Findings:
Discussion of Study 2:
This study suggests that the ‘I-shaped’ sign is a sensitive and specific marker for antenatal detection of dTGA, potentially improving diagnostic rates even when the four-chamber view appears normal [conversation history]. The normal four-chamber view in isolated dTGA contributes to low detection rates with standard screening [conversation history].
The ‘I-shaped’ sign’s absence in normal hearts and high sensitivity make it a valuable tool [conversation history]. While observed in a small percentage of other CHDs, those conditions are often detectable via the four-chamber view [conversation history]. The low positive predictive value is attributed to the low prevalence of dTGA, but the high negative predictive value indicates that the absence of the sign strongly suggests the absence of dTGA [conversation history].
The authors conclude that the ‘I-shaped’ sign is a simple and effective method for detecting dTGA during fetal echocardiography and its detection should prompt further investigation, especially when combined with a normal four-chamber view [conversation history].
Integration and Conclusion:
Both studies underscore the importance of improving prenatal diagnosis of TGA. The first study demonstrates a temporal improvement in detection rates, likely influenced by the increasing use of the outflow tract view. However, it also highlights that detection rates remain suboptimal. The second study introduces a novel marker, the ‘I-shaped’ sign in the three vessels and trachea view, which exhibits high sensitivity and specificity for dTGA [conversation history].
Integrating these findings suggests that incorporating the three vessels and trachea view, specifically looking for the ‘I-shaped’ sign, into routine prenatal ultrasound screening protocols could significantly enhance the detection rate of TGA, even in cases with a normal four-chamber view [8, conversation history]. Improved prenatal diagnosis, as shown in the first study, can lead to earlier interventions like BAS and reduced pre-operative morbidity, potentially contributing to better long-term neurodevelopmental outcomes, although mortality benefits may be less apparent in contemporary settings due to advancements in postnatal care. Further prospective studies are warranted to validate the clinical utility of the ‘I-shaped’ sign in broader populations [conversation history]. The ongoing efforts to educate sonographers and physicians on the performance and interpretation of views beyond the four-chamber view, as emphasized in the first study, are crucial for achieving higher prenatal detection rates of critical CHDs like TGA.
This updated review focuses on the ultrasound markers that can be used in the antenatal diagnosis of transposition of the great arteries (TGA), emphasizing the tools utilized by ultrasonographers, the obstetric and fetal medicine team, and perinatal cardiologists to improve the diagnosis of this condition.
Introduction and Significance of Prenatal Diagnosis:
Simple TGA is a cyanotic heart disease that accounts for 5% to 7% of all congenital heart diseases (CHDs). It is commonly underdiagnosed in utero, with prenatal detection rates of less than 50%. Simple TGA is characterized by ventriculoarterial (VA) discordance, atrioventricular (AV) concordance, and a parallel relationship of the great arteries. The prenatal diagnosis of TGA influences postnatal outcomes and therefore necessitates planned delivery and perinatal management. Consequently, the identification of key ultrasound markers of TGA is crucial to enhance prenatal diagnosis and subsequently provide appropriate perinatal assistance. The diagnosis of several CHDs has improved through the evaluation of outflow tracts in the four-chamber view during cardiac screening and the use of advanced ultrasound technologies like 3D and 4D ultrasonography/echocardiography. However, simple TGA remains one of the most commonly underdiagnosed CHDs in utero.
Terminology and Morphology of TGA:
In TGA, the aortic artery arises from the anterior ventricle (morphological right ventricle – RV), while the pulmonary artery originates from the posterior ventricle (morphological left ventricle – LV). Earlier definitions of TGA sometimes included other cardiac malformations, leading to the use of the term “complete TGA” to avoid ambiguity. Complete transposition is defined by AV concordance and VA discordance and can occur with a normal (solitus) or mirror-imaged (inversus) arrangement of the atria, excluding hearts with atrial isomerism. It is important to differentiate TGA from congenitally corrected transposition of TGA, which involves ventricular inversion along with a transposed relationship of the great arteries (discordant VA and AV connections).
The primary morphological characteristics of TGA include:
Types of TGA include d-TGA, levo-TGA, simple TGA (without associated cardiac anomalies), and complex TGA (with other cardiac malformations). Simple TGA is more prevalent than the complex form. Common associated cardiac anomalies are ventricular septal defects (VSDs), often with malalignment of the outlet septum, and LV or RV outflow tract obstructions. Sub-pulmonary stenosis is suspected if the outlet septum deviates posteriorly and leftward, while sub-aortic stenosis may occur with anterior and rightward deviation and fibrous continuity between the pulmonary and mitral valves. LV outflow tract obstruction is more common in TGA patients with VSD. Other congenital cardiac anomalies associated with TGA include coronary anomalies, right aortic arch, and anomalous venous connections, more frequent in TGA patients with VSDs. Chromosomal and extracardiac anomalies are rare in patients with TGA. TGA is more frequent in fetuses of pregnant women with pre-gestational diabetes mellitus, a history of exposure to pesticides, or retinoic acid use in the first trimester.
Prenatal Diagnosis of TGA by Ultrasonography and Echocardiography:
Guidelines for fetal cardiac screening and training programs can maximize CHD detection rates, especially in low-risk fetuses. Since 2013, the International Society of Ultrasound in Obstetrics and Gynecology and the American Institute of Ultrasound in Medicine have included the evaluation of outflow tracts in the four-chamber view for cardiac ultrasound screening. This has improved the sensitivity of ultrasound screening for CHD from approximately 30% to 69%-83%. The three-vessel view and three-vessel tracheal view were also incorporated into the cardiac ultrasound screening protocol, involving the assessment of the aorta, pulmonary artery, and superior vena cava. Despite these advancements, the antenatal diagnosis rate of TGA has not significantly improved.
The key markers for diagnosing TGA include:
In addition to these classical signs, other two-dimensional ultrasound markers include:
Advanced ultrasound technologies can also aid in diagnosis:
Studies have shown that detailed analysis of the outflow tract views is crucial for prenatal detection. The increase in antenatal diagnosis rates of TGA in some studies has been attributed to improvements in outflow tract screening aided by the four-chamber view on routine obstetric ultrasound.
Conclusion:
TGA is a critical CHD that remains underdiagnosed prenatally. Antenatal diagnosis, especially of simple d-TGA, is essential for reducing morbidity and mortality. Reliable clues for diagnosis through obstetric cardiac screening and fetal echocardiography are therefore vital. While the “misnomer three vessels” provides a strong suspicion, it is not pathognomonic. An I-shaped appearance of the arterial vessel increases suspicion. Detailed analyses of the outflow tracts serve as a clue to improve in utero diagnosis. Traditionally, diagnosis relied on identifying the pulmonary artery bifurcation from the LVOT, which is difficult. However, the LVOT should be assessed if a long vessel with a rightward reverse curvature (aorta) arises. The “boomerang sign” appears to be an easier and earlier marker.
This original research article, published on March 6, 2024, in Frontiers in Cardiovascular Medicine, presents a retrospective analysis of 121 prenatally diagnosed patients with transposition of the great arteries (TGA) at a single Chinese hospital (Fujian Maternity and Child Health Hospital) between January 2012 and September 2022. The study aimed to assess the diagnostic value of prenatal echocardiography for identifying TGA during pregnancy and evaluating the associated outcomes. The analysis included prenatal ultrasound, prenatal screening, clinical management, and follow-up procedures.
Objective and Methods: The primary objective was to evaluate the diagnostic capabilities of prenatal echocardiography for TGA and its impact on pregnancy outcomes. The study retrospectively analyzed data from 103 fetuses that met the inclusion criteria out of the initial 121 pregnant women diagnosed with TGA. The inclusion criteria involved undergoing routine prenatal screening with complete measurements, having pathological examinations (if pregnancy was terminated), and undergoing fetal echocardiography and neonatal congenital heart disease screening at their hospital. Pregnant women and their families provided consent for the study, which was approved by the hospital’s Ethics Committee. Prenatal assessments were conducted using GE Voluson E8 and E10 ultrasonic diagnostic devices with convex array probes (2.0–9.0 MHz) for transabdominal examinations and intracavitary probes (5.0–8.0 MHz) for suspected TGA in early pregnancy. Neonatal examinations utilized a Phillips IPEIQ 7C device with a phased array probe (3.0–8.0 MHz). Data on perinatal management and follow-up outcomes were collected from medical records. Fetal heart exams, including four-section, nine-section, and two-section examinations across trimesters, were performed with sequential segmental analysis focusing on the connections of the atria, ventricles, and great arteries. Key aspects assessed during ultrasound included atrioventricular and ventriculoarterial connections, great artery characteristics and crossing relationship, and the presence of ventricular septal defect (VSD) and outflow tract stenosis. The size and blood flow of the foramen ovale and ductus arteriosus were evaluated in fetuses without VSD, and extracardiac malformations were also noted. Prenatal diagnosis was strongly recommended, including noninvasive prenatal genetic testing (NIPT) for chromosomal aneuploidy and mid-trimester serological screening. Amniocentesis and umbilical vein puncture were performed for further evaluation with G-banded karyotype analysis and single nucleotide polymorphism microarray (SNP array) analysis. A multidisciplinary approach involving obstetrics, ultrasound, and paediatrics departments facilitated personalized pregnancy plans and neonatal care, with referral to paediatric cardiac surgeons when needed. Live-born infants underwent postnatal echocardiography, with follow-up via telephone communication. Statistical analysis was performed using SPSS Statistics 26 software, with a significance level of P < 0.05.
Results: Out of the 103 fetuses, 90 (87.4%) were diagnosed with complete transposition of the great arteries (D-TGA), and 13 (12.6%) exhibited corrected transposition of the great arteries (CC-TGA). Diagnoses occurred across all trimesters: 8 D-TGA and 2 CC-TGA in the first trimester, 68 D-TGA and 9 CC-TGA in the second trimester, and 14 D-TGA and 2 CC-TGA referred in the third trimester. Characteristic echocardiographic features of D-TGA in early pregnancy included rightward-bent great vessels in the three-vessel-tracheal view, juxtaposed great vessels in the outflow tract oblique view, and consistent atrioventricular connections in the four-chamber view. In the second trimester, D-TGA showed the aorta connected to the right ventricle and the pulmonary artery to the left ventricle, with parallel great arteries (aorta anterior to the pulmonary artery). CC-TGA presented with discordant atrioventricular connections in early pregnancy. In the second trimester, CC-TGA displayed reversed ventricular positions, parallel outflow tracts, pulmonary arteries from the left ventricle, and the aorta from the right ventricle positioned anterior to the pulmonary artery. The earliest diagnosis was at 12 weeks and 3 days of gestation. Combined intracardiac malformations were observed in 80 (77.7%) TGA patients, while 31 (30.0%) had extracardiac abnormalities. Among D-TGA patients, common intracardiac malformations were ventricular septal defects (VSDs) in 56 (62.2%), pulmonary artery stenosis in 19 (21.1%), and tricuspid valve abnormalities in 9 (10.0%). Common extracardiac abnormalities in D-TGA included fetal growth restriction (12.2%), NT/NF thickening (5.5%), and single umbilical artery (3.3%). In CC-TGA, VSD was the most prevalent intracardiac abnormality in 8 (61.5%) patients. Prenatal screening for Down syndrome was performed in 46 fetuses, with 7 high-risk cases (6 D-TGA, 1 CC-TGA). NIPT was low risk in all 16 cases where it was performed. Prenatal diagnosis was conducted in 40 fetuses, revealing chromosomal abnormalities in 3 cases: standard trisomy 18, partial trisomy 5, and 21pstk + polymorphism, leading to pregnancy termination in all three cases. Induction of labour was pursued for 76 D-TGA patients (84.4%) and 11 CC-TGA patients (84.6%), while 14 D-TGA patients (15.6%) and 2 CC-TGA patients (15.4%) continued pregnancy until delivery. Among the D-TGA patients who continued pregnancy, 9 (10.0%) underwent surgery, with 7 positive outcomes and 2 inadvertent fatalities. Seven D-TGA patients received palliative care, leading to 4 fatalities (5.2%), while 1 survived. Among CC-TGA patients who continued pregnancy, surgery was not recommended, and telephone follow-up indicated a good prognosis for the survivors.
Discussion: The study highlights the feasibility of accurate prenatal TGA diagnosis, even in early pregnancy, emphasizing the role of comprehensive ultrasound scanning techniques. The detection rate of TGA has increased significantly in recent years due to improved screening protocols. Prenatal diagnosis is crucial for informed parental decisions and timely postnatal intervention, potentially reducing severe complications and mortality. While TGA is typically not strongly linked to chromosomal abnormalities or extracardiac malformations, this study found a higher rate of chromosomal abnormalities in D-TGA fetuses (7.5%) compared to the general population. The study acknowledges that some TGA cases were missed during early pregnancy, possibly due to the near-normal appearance of the four-chamber view and misinterpretation of outflow tract views. The short axis view of the great arteries and basal outflow tract view are important for accurate diagnosis and for assessing associated VSDs. The high rate of induced labour in this study (74.8% of pregnancies diagnosed in the second trimester were terminated) might be attributed to China’s previous fertility policy, where families often chose termination if fetal heart abnormalities were detected. However, with the implementation of the three-child policy, this trend is expected to decrease as societal views on fetuses with congenital heart disease evolve and treatment options improve. The study underscores the importance of detailed prenatal ultrasound assessment, including the interventricular septum, valve morphology, and the presence of stenosis in the pulmonary arteries. Postoperative ultrasound monitoring should focus on aortic and pulmonary artery conditions, VSD, aortic coarctation, and potential arrhythmias. The direction of prenatal diagnosis should align with integrated management, involving multidisciplinary consultation and individualized treatment plans.
Limitations and Conclusion: The study acknowledges limitations such as the small sample size from a single center, its retrospective design, a limited number of genetic examinations, and a relatively short follow-up duration. The study did not report on fetal brain and nervous system lesions, which would be clinically significant. Further research is needed to investigate the long-term mobility, mortality, and quality of life of TGA patients. The conclusion of the study reiterates that precise TGA diagnosis is achievable in early pregnancy through echocardiography. For pregnancies that continue, comprehensive prenatal ultrasound monitoring, personalized perinatal management, and multidisciplinary intervention during delivery are vital for optimizing outcomes in the TGA population.
This original paper, published in Ultrasound in Obstetrics and Gynecology in 2013, presents a study investigating a novel fetal marker for transposition of the great arteries (TGA): the rightward convexity of the great vessel arising from the anterior ventricle. The authors aimed to determine if this finding could aid in the prenatal diagnosis of TGA, as traditional methods relying on the bifurcation of the great vessel from the posterior ventricle and the parallel course of the great arteries can be difficult to demonstrate, sometimes requiring additional echocardiographic features.
Background and Objectives: The authors begin by highlighting that the diagnosis of conotruncal abnormalities, including TGA, remains challenging despite advancements in technology and training, with antenatal detection rates for simple TGA being notably low compared to other congenital heart diseases. Traditionally, the fetal diagnosis of TGA has depended on observing the bifurcation of the great vessel originating from the posterior (left) ventricle and the parallel path of the great arteries leaving the heart, indicating a lack of crossover. However, these signs can be challenging to visualize, particularly in simple TGA cases where the four-chamber view might appear normal. The study also mentions the importance of the three vessels and trachea (3VT) view, also known as the transverse arches view, in diagnosing conotruncal abnormalities, including TGA. Emphasizing the importance of prenatal TGA detection for anticipatory management of the newborn, the researchers undertook a review of their experience to explore the prevalence of the rightward convexity of the great vessel from the anterior ventricle in confirmed TGA cases as a potentially easier diagnostic finding.
Methods: The researchers retrospectively reviewed fetal ultrasound studies conducted between 2006 and 2010 where an antenatal diagnosis of TGA was confirmed postnatally. They specifically analyzed images of the great vessel originating from the anterior ventricle, scanned cranially towards the superior mediastinum at the level of the three vessels and trachea view. These images were then compared with similar views obtained from normal fetal hearts with normally related great arteries. The study included 21 confirmed cases of TGA. The researchers meticulously followed the course of the great vessel from the anterior ventricle up to the 3VT view in all these cases.
Results: The study found that in all 21 confirmed cases of TGA, the great vessel arising from the anterior ventricle (which is the aorta in TGA) demonstrated an abnormal convexity to the right as it coursed cranially. This was consistently different from normal hearts, where the great vessel arising from the anterior ventricle (the pulmonary artery) showed either a convexity to the left or a lack of convexity in similar views. Notably, in two cases, the rightward vessel convexity from the anterior ventricle served as the initial clue that suggested TGA during the initial scan, which was subsequently confirmed. Furthermore, the study observed that in fetuses with TGA, the so-called 3VT view often appeared as a two-vessel view, showing only the superior vena cava and the aorta, because the pulmonary artery and ductus arteriosus were positioned below (caudal to) the transverse arch. In contrast, normal fetal hearts in the 3VT view show three vessels: the superior vena cava, the pulmonary artery, and the transverse aortic arch, with the pulmonary artery exhibiting a leftward convexity. The authors were unable to definitively determine if any TGA cases were missed during the study period due to limitations in follow-up data from fetuses delivered at other hospitals. However, they considered it likely they would have been informed of any missed TGA diagnoses given the centralized pediatric cardiac care in Melbourne.
Discussion and Conclusions: The authors discussed the feasibility and importance of the 3VT view as a routine part of fetal cardiac screening, aligning with guidelines from the International Society of Ultrasound in Obstetrics and Gynecology that recommend visualizing the ventricular outflow tracts. They noted that sequential segmental imaging of the fetal heart could aid in diagnosing TGA, especially when traditional signs are unclear. The study highlights the contrast between the normal fetus, where the pulmonary artery exhibits leftward convexity or a straight course in the superior mediastinum, and the fetus with TGA, where the aorta from the anterior ventricle shows a distinct rightward convexity. The finding of a two-vessel 3VT view in TGA, due to the altered spatial relationship between the aorta and pulmonary artery, is also emphasized as a potential screening tool, although not definitively diagnostic. The authors propose that the rightward convexity of the great vessel from the anterior ventricle is a relatively simple sonographic sign that could aid even less experienced sonographers in the prenatal diagnosis of TGA. While the two-vessel 3VT view can also be suggestive, the rightward convexity was the initial clue in two of their prospectively identified cases. The authors caution that other cardiac anomalies, such as double outlet right ventricle or tetralogy of Fallot (especially with pulmonary atresia), might also present with an aorta taking a convex course from the right ventricle, meaning this sign is not entirely pathognomonic for TGA. Nevertheless, they suggest that this finding should prompt further investigation and referral to a specialist center. The authors conclude by suggesting that these easily obtainable sonographic signs could enhance routine screening for TGA and might become preferred views for antenatal detection. They recommend a prospective study to further evaluate if following the course of the great vessel from the anterior ventricle can improve TGA detection rates, particularly in uncertain cases where traditional views are not easily obtained.
This case report, available online through ScienceDirect on the journal homepage of Elsevier, presents the experience of the authors in the sonographic diagnosis of D-Transposition of Great Arteries (d-TGA) during the mid-trimester of pregnancy. The authors, from various military hospitals in India, report four cases of d-TGA that were diagnosed antenatally by demonstrating parallel outflow tracts. The paper emphasizes that although d-TGA is a common critical cardiac lesion in newborns, it is frequently missed on antenatal sonography, with recent studies indicating only 23% detection of isolated cardiac anomalies antenatally. The authors aim to highlight their experience using a systematic approach to differentiate d-TGA from L-Transposition of Great Arteries (l-TGA).
Case Reports:
The paper details four case reports where d-TGA was diagnosed during routine anomaly scans:
Discussion:
The authors note that d-TGA is the second most common cyanotic congenital heart disease diagnosed in the first year of life, with a reported incidence of 315 per million live births. It is more prevalent in males, with a male to female ratio of 2:1 to 3:1. Embryologically, d-TGA is hypothesized to result from a failure of conoventricular rotation and the persistence of the subaortic conus with complete resorption of the subpulmonic conus, leading to this conotruncal anomaly.
The authors highlight that unlike other conotruncal anomalies, d-TGA is rarely associated with chromosomal anomalies or extracardiac malformations, which was consistent with their cases. While maternal diabetes has been linked to an almost three-fold increased risk of TGA, none of the patients in this series were diabetic. Animal studies have also suggested a link between maternal use of phenobarbitone and cardiovascular anomalies, including TGA.
The antenatal diagnosis of d-TGA essentially relies on demonstrating parallel outflow tracts or the absence of criss-crossing of the great arteries. The authors propose that the reliable differentiation from physiologically corrected TGA (l-TGA) can be achieved by incorporating the following steps into routine fetal heart evaluation:
The authors emphasize that antenatal diagnosis is crucial as it allows for planned delivery at a tertiary care hospital, which reduces mortality among survivors.
Conclusion:
The authors conclude that d-TGA remains a significant cause of critical heart anomaly in newborns associated with substantial mortality and morbidity. However, by implementing a step-wise scientific approach, this conotruncal anomaly, which is uncommonly detected antenatally, can be more easily diagnosed during anomaly scans. They suggest that the inclusion of these systematic and reproducible steps can improve antenatal detection rates.
This original paper, published in Ultrasound in Obstetrics and Gynecology in 2008, presents a prospective observational study aimed at assessing the utility of four-dimensional (4D) echocardiography with color Doppler imaging in determining the spatial relationships of the great arterial trunks in fetuses diagnosed with Transposition of the Great Arteries (TGA). The main objective of the study was to evaluate whether the reconstructed en-face view of the four cardiac valves could demonstrate different types of spatial arrangements of the great arteries, thereby helping to predict the risk of coronary arterial abnormalities. A secondary objective was to evaluate the type of coronary arterial branching pattern in relation to the spatial arrangement of the great arteries. The authors emphasize that coronary arterial abnormalities are a significant negative prognostic indicator in TGA.
Methods:
The study included 23 consecutive fetuses with a confirmed diagnosis of isolated TGA (no major associated cardiac defect) referred to two institutions (University Federico II of Naples and Di Venere Hospital, Bari) between January 2004 and December 2006. The gestational age at the time of 4D echocardiography ranged from 19 to 33 weeks. During the same period, a total of 496 fetuses with congenital heart disease (CHD) were seen at these centers.
All fetuses underwent 2D and 4D echocardiography using a Voluson 730 Expert ultrasound machine. Color Doppler volume datasets were acquired in each case, with a total of 28 volumes available for assessment. Specific criteria were followed during volume acquisition: 1) the apical four-chamber view was used as a reference plane, and 2) a high persistence setting was used for color Doppler to simultaneously display atrioventricular and ventriculoarterial flow. The acquisition angle ranged from 25° to 30°, and the acquisition time from 10 to 15 seconds.
The 4D volume datasets were processed offline using dedicated software (4D-viewer 5.0, General Electric). Post-processing involved standardization of the image appearance and the activation of the rendering function. The region of interest (ROI) box was placed across the atrioventricular plane, with the green reference line initially on the atrial side; if the arterial orifices were not clearly separated, the green line was moved to the ventricular side. The transparent mode was used for the grayscale component, and the surface mode for the color Doppler component. The cineloop sequence of the rendered glass-body image was reviewed frame by frame to identify the best frame showing the relationship between the atrioventricular and ventriculoarterial valves, identified by color flow mapping.
The classification system used to define the spatial relationships of the great arteries was based on a postmortem study by Massoudy et al., which includes five variants in decreasing order of frequency:
Confirmation of the vessels’ arrangement and coronary arterial distribution was obtained at neonatal echocardiography and/or surgery in all cases. The spatial relationships and coronary arterial distribution were gathered from catheterization and/or surgical files.
Results:
The spatial relationships of the great arteries could be demonstrated in all 10 normal fetuses in the preliminary series and were correctly identified in 20 out of 23 (87%) cases with TGA.
Neonatally, the following spatial relationships of the great arteries were found in the 23 TGA cases:
The two rarer variants (aorta anterior and to the left of the pulmonary artery; aorta posterior and to the right of the pulmonary artery) were not observed in this fetal series.
In the three misdiagnosed cases, prenatal assessment suggested the aorta was anterior and to the right of the pulmonary artery, while it was actually directly anterior. Notably, all three of these cases had an associated ventricular septal defect (VSD), and two also had aortic coarctation (AoCo).
Five of the 23 TGA fetuses (21.7%) had abnormal coronary arterial distribution. The distribution of these abnormalities based on the spatial relationship of the great arteries was as follows:
Table 1 provides a detailed breakdown of the spatial arrangement of the great arteries, coronary arterial distribution, gestational age, and additional anomalies in each of the 23 cases.
Discussion:
The authors highlight that abnormalities of the coronary arteries can complicate the surgical approach to TGA. These abnormalities, such as intramural origin, tangential course, and dual or single sinus origin, are generally too subtle to be directly visualized on fetal echocardiography. Therefore, prenatal counseling for TGA fetuses has historically lacked this crucial prognostic information.
However, the study demonstrates that 4D echocardiography, specifically the en-face view of the four cardiac valves, allows for the definition of the spatial relationships of the great arteries in fetuses with TGA with a high degree of accuracy (87%). This information is significant because the incidence of abnormal coronary arterial distribution is related to the spatial relationships of the arterial trunks.
The study’s findings on the relative incidence of the different spatial arrangements of the great arteries were reasonably similar to those reported in postmortem and neonatal echocardiographic studies, despite the smaller sample size of this fetal series (Table 2). The most common arrangement, aorta anterior and to the right of the pulmonary artery, was consistent across all three series.
The authors address two key technical aspects: the identification of the four cardiac valves and the use of color Doppler. They emphasize that valve identification should be done on multiplanar imaging before switching to the en-face view, using the ROI window markers. Regarding color Doppler, while a high persistence setting was used to visualize both atrioventricular and ventriculoarterial flow simultaneously in a single frame, the spatial relationships can also be assessed by evaluating the whole cineloop sequence even with lower persistence, provided the four-chamber view was appropriately oriented during volume acquisition.
The analysis of the incidence of coronary arterial branching abnormalities based on the spatial arrangement showed some differences compared to the postmortem and neonatal series, potentially due to the different sample populations and the small size of the fetal cohort. The rarer spatial arrangements associated with the highest risk of coronary anomalies in other studies were not encountered in this series, likely due to the limited number of cases.
Conclusion:
The study concludes that 4D echocardiography can reliably assess the spatial relationships of the great arteries in fetuses with TGA. This capability allows for the derivation of the risk of coronary arterial distribution abnormalities, providing valuable information for prenatal counseling. It enables healthcare professionals to reassure couples whose fetus has a TGA with an anatomy associated with a low risk of coronary anomalies and to highlight potential increased surgical risks in cases with spatial arrangements where abnormal coronary patterns are more likely. The authors suggest that this advancement can contribute to more informed and customized prenatal counseling for fetuses diagnosed with TGA.
Fetal thoracic ultrasound pathologies
Overview
This body of work gathers a collection of scientific articles addressing various fetal malformations of the thorax and upper abdomen diagnosed through prenatal ultrasound, along with their management and prognosis. The main topics explored include congenital chylothorax, congenital diaphragmatic hernia (CDH), congenital pulmonary malformations (CPM), Pallister-Killian syndrome (PKS) when it presents with thoracic involvement, and fetal mediastinal teratoma.
Regarding congenital chylothorax, these articles delve into diagnostic aspects, such as the biological characteristics of pleural fluid, and the diverse strategies for prenatal management, spanning from observation to pleural aspiration and pleuro-amniotic shunting. The prognosis is evaluated considering factors like the extent of the fluid collection and the presence of anasarca.
A significant portion of this literature focuses on congenital diaphragmatic hernia (CDH). Numerous articles emphasize the importance of antenatal ultrasound diagnosis, including the identification of associated anomalies and prognostic assessment using measurements such as the Lung-to-head ratio (LHR) and the observed-to-expected LHR (O/E-LHR). Management protocols in specialized centers, comprehensive fetal evaluation to exclude concurrent abnormalities, and therapeutic options, including fetal interventions like tracheal occlusion (FETO) and sildenafil administration, are also extensively discussed. One study specifically investigates the role of fetal stomach position as a predictor of gastrointestinal morbidity at 2 years in children with left-sided CDH. The association of CDH with genetic conditions, notably Pallister-Killian syndrome (PKS), is also highlighted, underscoring the need for specific testing for trisomy 12p in certain cases.
Congenital pulmonary malformations (CPM) constitute another key area of investigation. These articles examine prenatal detection via ultrasound, the classification of lesions (cystic, hyperechoic, mixed), and the natural progression of the volume of these malformations during gestation, particularly using the Congenital Pulmonary Malformation Volume Ratio (CVR). The primary aim is to identify predictors of neonatal respiratory distress and related complications, thereby optimizing perinatal care and guiding delivery to specialized facilities. The consistency between prenatal ultrasound findings and postnatal diagnoses is also a subject of analysis.
Pallister-Killian syndrome (PKS) is specifically examined through a retrospective multicenter study comparing prenatal (ultrasound) and fetopathological data. This work aims to define prenatal indicators suggestive of PKS beyond the classic diaphragmatic hernia, highlighting the broad spectrum of malformations associated with this rare condition.
Finally, a case study of fetal mediastinal teratoma is presented, illustrating the potential for misdiagnosis with cystic lung lesions on prenatal ultrasound and emphasizing the associated fetoplacental complications.
Overall, this body of work provides insights into the challenges and advancements in the prenatal diagnosis of fetal malformations affecting the thorax and upper abdomen. It underscores the critical role of ultrasound as a central tool for screening, diagnosis, and prognostic evaluation, while acknowledging the complexity of these conditions and the necessity of a multidisciplinary approach to optimize management and improve outcomes for affected fetuses and newborns. The detailed examination of these various aspects contributes to a deeper understanding of the clinical issues and future research directions in this field.
Bibliographie
The article “Prise en charge prénatale des chylothorax” by R. Favre discusses the prenatal management of congenital chylothorax, also initially referred to as primary hydrothorax.
Definition and Incidence:
Etiology and Pathophysiology:
Diagnostic Approach:
Natural History and Prognosis:
Prenatal Management:
The article discusses several approaches to prenatal management:
Conclusion:
The article by Romain Favre provides a comprehensive overview of the prenatal management of chylothorax, emphasizing the importance of accurate diagnosis, assessment of prognostic factors like anasarca, and the different therapeutic options available with their respective outcomes. It highlights the ongoing debates and the lack of randomized controlled trials to definitively guide management strategies.
The article “Prenatal diagnosis, imaging, and prognosis in Congenital Diaphragmatic Hernia” by Anne-Gael Cordier et al. discusses the advancements in the prenatal assessment of fetuses with Congenital Diaphragmatic Hernia (CDH), emphasizing prenatal diagnosis through ultrasound screening, the role of imaging in predicting outcome, and prognostic factors.
Introduction:
Prenatal Diagnosis:
Prenatal Imaging and Prognosis:
The article emphasizes the role of various imaging modalities and parameters in predicting the outcome of CDH:
Prenatal Interventions:
Associated Anomalies and Genetics:
Right-Sided CDH (RCDH):
Postnatal Management and Follow-up:
Conclusion:
The article provides a comprehensive overview of the prenatal aspects of CDH, highlighting the importance of early diagnosis, thorough imaging, and the consideration of various prognostic factors to optimize management and outcomes.
The article by Desseauve et al. focuses on the prenatal diagnosis of Pallister-Killian syndrome (PKS), a rare genetic disorder, through a retrospective multicenter study of 10 cases (6 with detailed prenatal ultrasound data) and a review of the literature. The authors aim to define prenatal clues that can suggest PKS beyond the classically associated diaphragmatic hernia.
Introduction:
Methods:
Results:
Discussion:
Conclusion:
The article by Basurto et al. in Best Practice & Research Clinical Obstetrics and Gynaecology provides a comprehensive overview of the prenatal diagnosis and management of congenital diaphragmatic hernia (CDH). CDH is characterized by the failed closure of the diaphragm, allowing abdominal viscera to herniate into the thoracic cavity, thereby interfering with normal lung development. This leads to pulmonary hypoplasia and persistent pulmonary hypertension (PHT) at birth, which can be lethal in up to 32% of patients.
The authors highlight that in isolated cases, the outcome may be predicted prenatally by medical imaging and advanced genetic testing. Prenatal ultrasound screening identifies more than 60% of CDH cases, typically by the second trimester. This early diagnosis is crucial as it provides the opportunity for in utero referral to a tertiary care center for expert assessment and perinatal management. The goal of prenatal assessment is to rule out associated anomalies (up to 40%) and individualize prognosis through genetic testing and advanced imaging. This information allows parents to make informed decisions regarding expectant management with prenatal referral for elective delivery, termination of pregnancy, or fetal intervention in selected cases. The defect is most commonly posterolateral (Bochdalek, ~70%) and usually left-sided (LCDH, 85%), with right-sided (RCDH, 13%) and bilateral (2%) hernias being rarer. Rarer forms include anterior (Morgagni, ~27%) and central (~2%) hernias.
Prenatal diagnosis often involves ultrasound which can reveal the herniation of abdominal organs into the thorax, potentially showing the stomach in the thorax in left-sided CDH, or the liver in right-sided CDH, as well as a mediastinal shift and compression of the heart. The lung-to-head ratio (LHR), calculated using ultrasound, is a key prognostic factor. Advances in prenatal imaging, including magnetic resonance imaging (MRI), allow for a more accurate assessment of fetal lung volume and the degree of liver herniation. The observed-to-expected total fetal lung volume (O/E TLV), often determined by MRI, has become an important predictor of survival. The position of the stomach and liver, assessed by ultrasound, can also provide prognostic information. The presence of a hernia sac has been associated with better fetal lung growth and outcomes. Doppler studies of the fetal pulmonary vasculature are also used to assess the risk of postnatal pulmonary hypertension.
For fetuses with a predicted poor outcome, fetoscopic endoluminal tracheal occlusion (FETO) may be offered. This procedure aims to improve lung development by temporarily obstructing the trachea, leading to fluid accumulation in the lungs. The TOTAL trial is a global randomized clinical trial evaluating FETO. The article also mentions the investigation of alternative strategies, including transplacental sildenafil administration, to reduce the occurrence of persistent PHT.
At birth, infants with CDH require management in specialized high-volume tertiary centers with standardized protocols. Despite optimal neonatal care, mortality remains around 30%. Survivors may suffer from chronic lung disease, persistent PHT, gastroesophageal reflux, feeding and growth problems, neurocognitive delay, hearing loss, thoracic deformations, and hernia recurrence. Therefore, multidisciplinary follow-up is essential for survivors.
The authors emphasize the importance of continuous efforts to improve the quality and consistency of prenatal diagnosis and evaluation for both right and left CDH. Research linking antenatal markers for CDH-PH with long-term morbidity is still needed. Standardized prenatal ultrasound assessment protocols have been proposed by the European reference network on rare inherited and congenital anomalies (ERNICA).
In conclusion, the article underscores the advancements in prenatal diagnosis and management of CDH, highlighting the critical role of early detection, comprehensive prenatal assessment for prognosis and associated anomalies, and the potential for fetal interventions like FETO in selected severe cases. Optimal postnatal care in specialized centers and long-term multidisciplinary follow-up are crucial for improving outcomes for infants with CDH.
The article, written by H. Bouchghoul et al., provides a methodological guide on performing an ultrasound scan on a fetus with a congenital diaphragmatic hernia (CDH). The authors emphasize that while prenatal diagnosis of CDH is feasible from the first trimester, the key challenges lie in confirming the diagnosis, identifying associated anomalies, and evaluating the prognosis to optimize prenatal counseling. The goal of prognostic evaluation is also to select fetuses eligible for in utero fetal therapy. Delivery should be planned in a type 3 maternity unit equipped for specialized care of CDH.
Diagnostic Ultrasound Examination:
The article outlines a structured approach to the ultrasound examination of a fetus suspected of having CDH.
The authors conclude that a thorough prenatal ultrasound evaluation of CDH is necessary to refine the prognosis and provide appropriate prenatal counseling. While several prenatal prognostic tools exist, including ultrasound, no single factor is 100% reliable for predicting postnatal outcome. However, a combination of prenatal factors allows for establishing a likely prognosis. Fetal thoracic MRI can also be used for prognostic evaluation by assessing the observed/expected lung volume and the volume of liver herniation. Despite the advancements, ultrasound remains an essential examination for guiding parents and referring them to specialized centers for consideration of in utero fetal therapy. The role of fetal therapy remains controversial due to limitations in study power and control groups.
The article by Darouich and Bellamine presents a case report of a fetal mediastinal teratoma that was initially misinterpreted as congenital cystic lesions of the lung on prenatal ultrasound. The authors highlight that while teratomas are among the most common congenital tumors, thoracic teratomas can be challenging to diagnose prenatally and may be confused with other conditions such as congenital adenomatoid malformation of the lung, bronchogenic cysts, diaphragmatic hernia, or bronchopulmonary sequestration. The case underscores the importance of careful Doppler ultrasound assessment for accurate prenatal diagnosis and fetal outcome evaluation.
Case Report:
The case involved a 31-year-old patient, gravida 2, para 2, who was referred at 23 weeks gestation for investigation of fetal hydrops. The patient had no history of gestational diabetes or abnormal glucose tolerance, and her blood group was A positive. A first morphology ultrasound at 17 weeks gestation was unremarkable.
At 23 weeks, ultrasound revealed severe fetoplacental hydrops, moderate posthemorrhagic hydrocephalus, and multiple pulmonary cysts suggesting cystic adenomatoid malformation. The heart was also noted to be displaced to the left side. Due to these findings, a congenital cystic adenomatoid malformation was suspected in a male fetus with a normal karyotype.
However, autopsy of the hydropic 24-week male fetus revealed a large cystic-solid mediastinal mass consistent with a nonmetastatic immature teratoma. The autopsy also demonstrated thymic, cardiac, and pulmonary hypoplasia, and confirmed the germinal matrix-intraventricular hemorrhage. Additionally, placental diffuse multifocal chorangiomatosis was observed.
Discussion:
The authors emphasize that mediastinal teratoma is a life-threatening tumor due to associated fetoplacental complications. In this case, a large cystic and solid immature mediastinal teratoma was prenatally interpreted as a congenital cystic adenomatoid malformation.
The article notes that prenatal diagnosis of mediastinal teratoma can usually be made using two-dimensional ultrasonography as the mass often exhibits both cystic and solid components, along with calcification spots and acoustic shadows. However, as seen in this case, large masses occupying the entire thoracic cavity can be misinterpreted as bronchogenic cysts, congenital cystic adenomatoid malformation of the lung, diaphragmatic hernia, or bronchopulmonary sequestration. Retrospective reevaluation of the ultrasound imaging in this case also revealed a hyperechoic linear plaque of calcification with acoustic shadowing within the mass, which are characteristic features of teratomas.
The presence of periventricular echogenic areas with moderate dilatation of the lateral ventricle on ultrasound suggested posthemorrhagic hydrocephalus, which was confirmed by autopsy as germinal matrix intraventricular hemorrhage. The authors suggest that decreased cardiac output, likely due to compression by the mediastinal mass, can lead to rupture of the sensitive capillaries in the germinal matrix, causing hemorrhage. Ultrasound also clearly demonstrated a large placenta, and increased umbilical artery systolic/diastolic ratio detected by Doppler velocimetry can indicate substantial compression of the cardiovascular system.
The authors conclude that accurate prenatal diagnosis of mediastinal teratoma may be achieved through careful Doppler ultrasound assessment, which also allows for evaluating the fetal outcome. This case highlights the challenges in differentiating mediastinal teratoma from other congenital thoracic lesions on prenatal ultrasound and emphasizes the importance of considering teratoma in the differential diagnosis of fetal cystic lung lesions, especially when associated with hydrops and mediastinal shift.
The article also refers to literature indicating that ultrasonography has high sensitivity and low false-positive rates in identifying fetal teratoma. However, the potential for misinterpretation, as demonstrated in this case, necessitates a thorough evaluation including the search for characteristic features like calcifications and a comprehensive assessment of the surrounding structures and potential signs of compression.
The article by Ruchonnet-Metrailler et al. investigates the neonatal respiratory outcomes of congenital pulmonary malformations (CPM) that were primarily identified prenatally. The authors note that while CPM are frequently detected during routine second-trimester ultrasound examinations, the factors predicting which newborns will develop respiratory distress at birth are not well-defined. Understanding these predictive factors is crucial for determining the appropriate level of care and delivery location for these pregnancies, ideally in a tertiary care center.
Background and Objectives:
The authors highlight that CPM encompass various histologic entities, with congenital cystic adenomatoid malformations being the most frequent. While many children with CPM are asymptomatic at birth, some experience respiratory distress severe enough to necessitate mechanical ventilation and immediate surgery. The study aims to identify potential prenatal parameters predictive of respiratory distress in neonates with CPM. This knowledge is essential for optimizing the care pathway following prenatal diagnosis.
Methods:
The study utilized data from RespiRare, the French prospective multicenter registry for liveborn children with rare respiratory diseases, collected between 2008 and 2013. The researchers selected cases with a prenatal diagnosis of hyperechoic and/or cystic lung lesions. They then correlated prenatal parameters with the neonatal respiratory outcome.
The prenatal data collected included: gestational age at diagnosis, appearance of the lesion (size, location, type), associated abnormalities (mediastinal shift, polyhydramnios defined as an amniotic fluid index greater than the 90th percentile, or hydrops). Neonatal data included: gestational age at delivery, birth weight, and respiratory status (tachypnea defined as a respiratory rate >60 inspirations per minute, chest wall retraction, need for oxygen supplementation or ventilation). Lesions were classified as cystic (diameter >5 mm), hyperechoic, or mixed.
Maximum prenatal malformation area (calculated from the two largest dimensions) and maximum congenital pulmonary malformation volume ratio (CVR) were analyzed for a subgroup of patients (n=50) from the center with the largest number of cases, where this data was reliably available. CVR was estimated using the formula for an ellipsoid: length × height × width × π/6, divided by the head circumference.
Results:
Data from 89 children were analyzed, of whom 22 (25%) had abnormal breathing at birth, and 12 (13%) experienced severe respiratory distress requiring oxygen supplementation or ventilatory support.
The study found that respiratory distress at birth was significantly associated with the following prenatal parameters:
Limiting the analysis to the subgroup with severe respiratory distress requiring oxygen supplementation (n=12) yielded similar significant associations with the prenatal signs of compression, mediastinal shift, polyhydramnios, ascites, maximum malformation area, maximum malformation volume, and maximum CVR.
Receiver operating characteristic (ROC) curve analysis showed that a CVR cutoff of 0.84 yielded the highest significance for predicting the need for oxygen at birth, with a sensitivity of 0.87 and a specificity of 0.81 (P = .0006). The area under the ROC curve was 0.804.
Interestingly, apparent regression of the CPM during the third trimester did not affect oxygen requirement at birth. Furthermore, polyhydramnios, ascites, and a maximum CVR >0.84 were more reliable predictors of oxygen requirement at birth than mediastinal shift. For predicting the need for oxygen, specificity was highest for the prenatal detection of polyhydramnios and/or ascites, while sensitivity was highest for a maximum CVR >0.84.
Conversely, a low CVR was significantly associated with the absence of oxygen requirement at birth (odds ratio: 0.02 [95% confidence interval: 0.001–0.58]; P < .03).
Conclusions:
The authors conclude that maximum CVR and prenatal signs of intrathoracic compression are significant risk factors for respiratory complications at birth in fetuses with CPM. Specifically, a CVR >0.84, polyhydramnios, and ascites were significantly associated with more severe respiratory distress requiring at least oxygen supplementation. In such situations, the authors recommend that delivery should be planned at a tertiary care center.
The study highlights the importance of these prenatal ultrasound parameters in predicting neonatal respiratory outcomes in CPM and emphasizes the need for delivery in specialized centers for cases with high CVR or signs of fetal compression.
The article by Wong et al. explores the concordance between prenatal ultrasound findings of hyperechoic lung lesions and postnatal diagnoses based on CT scans, highlighting the challenge of accurately diagnosing the underlying etiology of such lesions prenatally. The study emphasizes that while hyperechoic lung lesions are frequently detected, their non-specific appearance makes definitive prenatal diagnosis difficult, impacting prenatal counseling and perinatal management.
Background and Objectives:
The authors note that prenatal ultrasound commonly detects hyperechoic lung lesions, which can represent a spectrum of congenital lung malformations, including bronchopulmonary sequestrations (BPS), pulmonary cystic malformations (PCM), congenital lobar emphysemas (CLE), bronchogenic cysts (BC), and hybrid malformations. Given that postnatal CT scans have demonstrated higher diagnostic accuracy than ultrasound and MRI, they are considered the gold standard for final diagnosis. The aim of this retrospective study was to determine the concordance between prenatal ultrasound diagnoses of hyperechoic lung lesions and the corresponding postnatal diagnoses established by CT scan or histological examination. The ultimate goal was to provide parents with more reliable, evidence-based information during prenatal counseling and to optimize perinatal management by ensuring delivery in appropriate birthing centers.
Methods:
This was a retrospective study conducted at a single institution, including all patients diagnosed prenatally with hyperechoic lung images between January 2009 and December 2018. Prenatal ultrasound evaluations were performed by fetal medicine specialists. Postnatal diagnoses were primarily based on CT scans, with histological examination used in some cases. Information on pre- and postnatal periods, as well as imaging findings, were retrieved from medical charts.
The study analyzed various prenatal ultrasound features, including the presence of cystic components and mediastinal shift. The prenatal detection of a systemic arterial supply was also noted. Neonatal symptoms, such as respiratory distress requiring oxygen assistance, were recorded. Postnatal diagnoses were categorized as BC, PCM, CLE, BPS, or hybrid malformations. The researchers then assessed the concordance between these prenatal findings and postnatal diagnoses.
Results:
A total of 75 patients with prenatal hyperechoic lung lesions were included in the study. The main prenatal ultrasound diagnoses were BPS (24%-32%), PCM (19%-25%), and CLE (15%-20%). Mediastinal shift was observed in 18 cases (24%).
The study found that:
Conclusions:
The authors concluded that prenatal ultrasound detection of hyperechoic lung malformations reflects a heterogeneous group of lesions with good concordance for bronchopulmonary sequestration when a systemic arterial supply is identified. However, the ability to accurately predict cystic components postnatally based on prenatal hyperechoic images is limited.
The study also suggests that isolated prenatal mediastinal shift in the context of hyperechoic lung lesions may not be a reliable predictor of neonatal respiratory distress. The authors emphasize that the absence of compression signs on prenatal ultrasound does not guarantee the absence of neonatal respiratory distress.
Overall, this study highlights the challenges in achieving definitive prenatal diagnoses of hyperechoic lung lesions and underscores the importance of postnatal CT imaging for accurate classification and appropriate long-term management. The findings contribute to better informed prenatal counseling by providing data on the concordance between prenatal ultrasound findings and postnatal diagnoses of these complex fetal anomalies.
The article by Delacourt et al. presents the findings of the MALFPULM study, a national, multicenter, prospective cohort study conducted in France to assess the prenatal natural history of congenital pulmonary malformations (CPM). The study specifically aimed to evaluate changes in CPM volume over gestation and to determine if these changes differ between lesions appearing cystic versus hyperechoic on ultrasound. Furthermore, it investigated the relationship between CPM volume, quantified by the congenital pulmonary malformation volume ratio (CVR), and the risk of fetal compression.
Background and Objectives:
The authors emphasize that while ultrasound is the primary modality for prenatal diagnosis of CPM, the histological diagnosis often remains uncertain based solely on ultrasound findings. CPM encompass various entities like congenital cystic adenomatoid malformations (CCAM), sequestrations, bronchial atresia, congenital lobar emphysema, and bronchogenic cysts.
A key concern with CPM is the risk of fetal compression due to the lesion’s volume, which can lead to mediastinal shift, diaphragm eversion, polyhydramnios, ascites, and even hydrops. The CVR has been developed as an indicator of mass size to predict prenatal complications and neonatal respiratory distress, as discussed in the Ruchonnet-Metrailler et al. article we previously summarized. The current study addresses the lack of prospective, population-based data on the intrauterine growth patterns of CPM and their determinants, which complicates clinical decision-making for optimal fetal follow-up and treatment.
Methods:
The MALFPULM study is a nationally representative cohort recruiting pregnant women with a prenatal diagnosis of fetal CPM from 37 Multidisciplinary Centers for Prenatal Diagnosis (MCPD) in France between March 2015 and November 2016. The study included 579 ultrasound examinations in 176 women. Several ultrasound examinations were performed between diagnosis and delivery, including measurement of CPM volume.
CPM volume was estimated using the formula for an ellipsoid (length × width × height × π/6), and the CVR was calculated by dividing the CPM volume by the estimated fetal head circumference. Changes in CVR were modeled as a function of gestational age, both overall and separately for cystic/mixed versus hyperechoic malformations. The association between CVR and signs of compression (mediastinal shift, polyhydramnios, ascites, hydrops) during pregnancy was also examined. Standardized definitions for CPM types based on ultrasound characteristics were used.
Results:
The study included 176 women with a mean of 4.4 ultrasound examinations per woman. The cohort comprised 90 (51%) hyperechoic CPMs and 86 (49%) cystic/mixed CPMs. Systemic vascularization was noted in 56 (32%) CPMs at some point during pregnancy. At least one sign of compression was observed in 80 (45%) fetuses.
Key findings regarding the natural history of CPM volume:
Regarding the association between CVR and fetal compression:
Conclusions:
The authors conclude that CPM volume, as measured by CVR, tends to decrease over gestational age, with hyperechoic lesions showing a more pronounced decrease than cystic/mixed lesions. This provides valuable information on the expected prenatal evolution of these malformations.
Crucially, the study confirms a strong association between a higher initial CVR and an increased risk of fetal compression, even in cases without initial compressive signs. This highlights the prognostic significance of CVR in predicting potential complications during pregnancy. The findings underscore the importance of serial ultrasound monitoring of CPM volume to assess the risk of fetal compression and inform clinical management. The use of standardized ultrasound definitions for CPM types strengthens the reliability of the study’s conclusions.
This population-based, prospective study provides more precise and reliable data on the prenatal natural history of CPM than previous smaller, retrospective studies, aiding in better prenatal counseling and management of pregnancies complicated by these fetal anomalies.
The article by A. G. Cordier et al. investigates the long-term gastrointestinal morbidity (GIM) in children with isolated left-sided congenital diaphragmatic hernia (CDH) and evaluates the predictive value of prenatal stomach position on this morbidity at 2 years of age. This study acknowledges that while survival rates for CDH have improved, long-term morbidity, particularly related to gastrointestinal issues, remains a significant concern.
Background and Objectives:
The authors highlight that gastroesophageal reflux and oral aversion affect a large proportion of children with left-sided CDH and can persist as major problems at 2 years of age. Despite the well-described long-term morbidity, the prenatal factors that predict these specific outcomes are not fully understood. Previous research has focused on prenatal predictors of survival, such as the observed-to-expected lung-area-to-head-circumference ratio (O/E-LHR) and liver position. This study specifically aims to evaluate the effect of fetal stomach position on the risk of GIM at 2 years in children with isolated left-sided CDH, both with and without prior fetal endoscopic tracheal occlusion (FETO).
Methods:
This was a retrospective, observational multi-center cohort study conducted between January 2010 and January 2014. The study included 47 patients whose fetuses had isolated left-sided CDH and for whom prenatal ultrasound images at the level of the four-chamber view of the heart and O/E-LHR measurements were available. Patients with associated malformations, chromosomal abnormalities, right-sided or bilateral CDH, medical termination of pregnancy, or death before 2 years of age were excluded.
Fetal stomach position was evaluated a posteriori by two observers using the same ultrasound images used for LHR measurement. The stomach position was graded into four categories:
The primary outcome was GIM at 2 years of age, assessed in a composite manner including the occurrence of gastroesophageal reflux disease (GERD), need for gastrostomy, duration of parenteral and enteral nutrition, and persistence of oral aversion. Regression analysis was performed to investigate the effect of O/E-LHR, stomach position, and FETO on various GIM outcome variables. Postnatal management followed national recommendations.
Results:
At 2 years of age, 13 out of 47 infants (27.7%) did not meet the criterion of exclusive oral feeding. The study found a significant and independent association between fetal stomach position grade and the duration of parenteral nutrition (higher grade associated with longer duration) and the persistence of oral aversion at 2 years (higher grade associated with increased risk).
Specifically:
The median O/E-LHR decreased with increasing fetal stomach position grade. O/E-LHR was predictive of the need for prosthetic patch repair but not for GIM. FETO did not appear to affect the risk of GIM at 2 years. Fetal stomach position was an independent predictor of the length of stay in the neonatal intensive care unit and the total duration of hospitalization. Approximately one-quarter of children had GERD, and nearly half had oral aversion at 2 years. The risk of oral aversion increased with higher fetal stomach position grades.
Conclusions:
The authors concluded that in isolated left-sided CDH, fetal stomach position is the only factor that is predictive of GIM at 2 years of age. Specifically, a more superiorly positioned fetal stomach (higher grade) was associated with a higher risk of prolonged parenteral nutrition and persistent oral aversion. This finding suggests that prenatal ultrasound assessment of fetal stomach position can provide valuable information for predicting long-term gastrointestinal outcomes in these children. The study emphasizes that this simple, reliable, and reproducible marker can be used to standardize information given to parents regarding postnatal prognosis and to improve the follow-up care for children with left-sided CDH. While O/E-LHR remains important for predicting pulmonary outcomes and the need for surgical repair, fetal stomach position appears to be a key prenatal indicator for long-term gastrointestinal morbidity. The authors acknowledge the study’s limitations, including its retrospective nature and small sample size, and suggest the need for larger prospective studies to confirm these findings.
Prenatal Diagnosis of Corpus Callosum Anomalies
Overview
The corpus callosum (CC), the largest commissural tract in the human brain, plays a vital role in interhemispheric communication and integration of motor, sensory, and cognitive information. Anomalies of the corpus callosum—ranging from complete or partial agenesis to dysplasia, hypoplasia, or hyperplasia—are among the most frequently diagnosed brain malformations in fetal medicine.
The prenatal diagnosis of CC anomalies remains a clinical and diagnostic challenge due to:
This synthesis integrates findings from ten recent articles, including original cohort studies, meta-analyses, systematic reviews, and narrative reviews, to provide a multidimensional overview of current evidence surrounding prenatal CC anomalies.
The CC begins developing around the 10th week of gestation and continues until term, with anterior-to-posterior formation (genu → body → splenium). By 18–20 weeks, its four anatomical segments—rostrum, genu, body, and splenium—are typically identifiable on imaging.
Anomalies are classified into five major categories:
Terminological inconsistency remains problematic, as highlighted by Mahallati et al., with the same findings variably labeled as hypoplasia, dysgenesis, or partial agenesis across studies. Standardization is needed to ensure consistent communication and data aggregation.
III. Prenatal Imaging Modalities and Their Diagnostic Performance
Ultrasound is the primary imaging modality for evaluating fetal CNS anatomy. Key indirect markers of ACC include:
Neurosonography, a multiplanar approach with targeted CNS evaluation, improves diagnostic sensitivity.
Key metrics from Zhang (2023):
Conclusion: Neurosonography significantly increases diagnostic yield. However, first-trimester scans (Ungureanu et al.) are limited in detecting CC anomalies due to incomplete anatomical development before 20 weeks.
MRI offers superior soft tissue contrast and is especially valuable when US findings are equivocal. According to D’Antonio et al. (2021), MRI revealed additional CNS anomalies in 11.2% of fetuses with “isolated” CC anomalies diagnosed by ultrasound, mainly malformations of cortical development. Even so, 3.9% of anomalies were missed by both modalities and diagnosed postnatally.
MRI is thus a critical adjunct in prenatal CC assessment, particularly in cases of suspected pACC, cortical abnormalities, or abnormal neurodevelopmental prognosis.
Measuring the length and thickness of the CC provides quantitative assessment but remains controversial. As discussed by D’Antonio et al. (2024):
Tutschek et al. (2020) documented short CC in fetuses with Down syndrome and normal brain morphology, suggesting it may serve as an early soft marker for genetic syndromes.
Currently, there is no consensus on routine measurement or the threshold for clinical concern in isolated short CC findings.
The genetic basis of CC anomalies is increasingly recognized. According to Mustafa et al. (2024):
Variants were distributed across 83 genes, with recurrent mutations in TUBA1A, L1CAM, FGFR2, ARID1B, and ZEB2, among others.
These findings support the routine integration of ES into the diagnostic pathway for fetal ACC, particularly in cases where standard karyotyping and CMA are normal.
Numerous studies, including Huang et al. (2024) and Di Pasquo et al. (2022), emphasize the prognostic importance of distinguishing isolated CC anomalies from non-isolated cases (those with other CNS or extracranial findings):
In Huang’s study, 86% of children with isolated dysplastic CC had normal development, compared to 17% in the non-isolated group.
Huang et al. also compared outcomes by CC morphology:
This suggests that “thin but complete” CC may be a benign variant, while short or thick CC may be associated with more severe developmental consequences.
Di Pasquo et al. showed that 19% of fetuses with isolated absence of the septum pellucidum were diagnosed postnatally with SOD, including 9% of those with apparently normal optic pathways on imaging. This underscores the need for cautious counseling even in “isolated” midline defects.
VII. Counseling, Follow-Up, and Management
Effective counseling must address the uncertainty of neurodevelopmental outcomes, even in isolated cases. Wu & Chen (2024) emphasize:
Where available, postnatal follow-up with neurodevelopmental assessments (e.g., ASQ-3) should be recommended.
In addition, serial prenatal imaging is advised, as shown by Ungureanu et al., since some anomalies may not be detectable until the second or third trimester.
VIII. Conclusion and Future Directions
The prenatal diagnosis of corpus callosum anomalies is a rapidly evolving field. Key conclusions include:
As imaging resolution, genetic diagnostics, and outcome databases continue to improve, future approaches will likely shift toward precision prognostication and individualized counseling based on combined imaging-genetic-risk models.
Bibliographie
Introduction and General Context
This article is a correspondence piece in Ultrasound in Obstetrics & Gynecology, which addresses the topic of corpus callosum (CC) biometry in the fetus and its implications for prenatal counseling. The authors begin by recalling the increasing role of corpus callosum assessment in fetal neurosonography. They note that while complete agenesis of the CC can often be identified using indirect sonographic signs, subtler forms of CC anomalies—such as partial agenesis or hypoplasia—require more precise morphometric evaluation.
The central theme of the article is the variability in corpus callosum length and the uncertainty surrounding its clinical interpretation when measurements are “too short” or “too long” relative to gestational age or head size. The authors emphasize the need for accurate biometric reference charts for CC length and highlight the challenges in distinguishing physiological variants from early manifestations of abnormal neurodevelopment.
Anatomical and Clinical Importance of the Corpus Callosum
The corpus callosum is described as a major commissural structure in the fetal brain, crucial for interhemispheric communication. The article underscores its clinical importance in several fetal conditions, such as:
In these contexts, deviations in CC length may be linked to increased risk of neurodevelopmental impairment, though the exact prognostic significance remains variable.
The authors explain that the CC’s dimensions vary significantly between individuals, across ethnic groups, and with gestational age. A short CC may reflect a normal physiological variant or may be an early indicator of a more significant developmental abnormality.
Overview of the Current Literature and Reference Charts
The article references a recent systematic review (Corroenne et al., 2023), which analyzed methodologies for constructing fetal CC biometric charts. The authors summarize that many existing studies:
They also mention other systematic reviews that assessed the methodological quality of brain charts based on ultrasound and MRI. These reviews similarly highlighted limitations in existing references for fetal brain biometry, including the corpus callosum.
Presentation of the Authors’ Own Study
The authors describe a cross-sectional study conducted on 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. All pregnancies were accurately dated in the first trimester.
Corpus Callosum Measurement:
This approach allowed for the generation of percentile charts that reflect the natural distribution of CC measurements in the study population.
Advantages of Quantile Regression in CC Charting
The article explains the rationale for using quantile regression to model fetal CC length:
The authors also highlight the decision to normalize CC length by head circumference rather than gestational age alone. This adjustment is considered particularly important in scenarios where the fetal head may be under- or overgrown (e.g., in FGR or macrosomia), allowing for more appropriate assessment of CC development in these contexts.
They provide two visual plots:
Role of the International Guidelines
The article notes that current ISUOG guidelines on fetal neurosonography do not specify whether CC length should be measured routinely. They also do not indicate how to interpret the finding of a short but morphologically normal CC.
As a result, when a short CC is identified in isolation, clinicians face uncertainty in prognostication and in deciding whether further testing or follow-up is warranted. This ambiguity can complicate counseling and management planning for expectant parents.
Complementary Role of Fetal MRI
The authors discuss the role of fetal MRI as an adjunct to ultrasound in cases of suspected CC anomalies. They explain, however, that fetal MRI also suffers from:
Therefore, while MRI may help visualize subtle structures more clearly, it does not eliminate the diagnostic uncertainty when CC measurements are borderline.
Summary of the Authors’ Findings and Tools
In summary, the authors:
They include several supplementary tables in the online version:
Conclusion and Clinical Implications
The authors conclude that:
They emphasize that further longitudinal studies with outcome data are needed to validate the predictive value of CC length centiles. In the interim, specialists should remain prudent when interpreting isolated findings of short CC length and should integrate these findings with the broader clinical picture.
Introduction and General Context
This article reports on a clinical observation linking a shortened fetal corpus callosum (CC) with trisomy 21 (Down syndrome). The authors note that while neurodevelopmental delay and intellectual disability are hallmark features of Down syndrome, overt structural anomalies of the brain—particularly in the prenatal period—are generally rare. The study seeks to explore whether a short CC might constitute a subtle, yet detectable, brain feature associated with trisomy 21 in fetuses that otherwise appear structurally normal.
The motivation for this investigation arises from postnatal neuroimaging and autopsy studies that have described CC anomalies and reduced CC volume in individuals with Down syndrome. Despite this, fetal imaging studies had not previously characterized CC length in fetuses diagnosed with trisomy 21. The authors thus aimed to describe CC length in a small sample of fetuses with trisomy 21, observed through routine prenatal neurosonographic assessment.
Background on Corpus Callosum in Down Syndrome
The article references earlier studies in postnatal populations that showed:
These findings raise the question of whether the CC may already be affected during fetal development, even in the absence of overt malformations or additional CNS anomalies.
Study Design and Protocol
The article reports on the first four fetuses with confirmed trisomy 21 in whom the corpus callosum length (CCL) was measured in a routine clinical setting following the introduction of a new institutional neurosonographic protocol. All four fetuses:
The CC measurements in the study were compared against a reference chart developed by Cignini et al. (2014), which includes CC length data for 2950 normal fetuses. The authors selected this reference because:
Results
Sonographic Technique and Reproducibility
The authors emphasize that:
Discussion of Soft Markers and Diagnostic Implications
The article situates its findings within the broader context of soft markers for Down syndrome. Over the last decades, numerous sonographic markers have been described, such as:
However, brain anomalies are not usually considered a hallmark of trisomy 21. The findings of this study suggest that a short but morphologically normal corpus callosum may be a previously under-recognized feature in some cases.
All four fetuses in the study had abnormal first-trimester nuchal translucency measurements, and most had undergone non-invasive prenatal testing (NIPT) or invasive karyotyping prior to the sonographic assessment.
The authors propose that CC length may become an additional parameter worth observing in fetuses with confirmed or suspected trisomy 21, especially when the brain appears structurally normal in other respects.
Future Directions
Although the current study includes only four cases, the authors note that:
They emphasize that the clinical implications of a short CCL in fetuses with trisomy 21 remain to be determined. However, the consistent finding of shortened CC in this small sample suggests a possible link with underlying developmental patterns that merit further investigation.
Conclusion
The article concludes that:
Introduction and Context
This article presents a systematic review focused on the definitions, terminology, and classification of fetal corpus callosum (CC) anomalies in the prenatal imaging literature. The authors observe that, while agenesis of the corpus callosum (ACC) has been well described in both prenatal and postnatal literature, there is significant inconsistency in the way partial or atypical anomalies of the CC are defined and labeled in fetal imaging studies.
The aim of the review is to examine and document the heterogeneity of nomenclature and definitions used in studies of fetal CC abnormalities diagnosed via ultrasound or MRI, with the ultimate goal of promoting a more standardized classification system that aligns prenatal terminology with postnatal diagnostic standards.
Objective
The study’s main objectives are:
Methods
The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
Inclusion criteria:
Exclusion criteria:
Results
The review identified a total of ten different terms used across the studies to describe CC anomalies other than complete agenesis:
Many of these terms were used inconsistently, and several (e.g., PACC, hypoplasia, dysgenesis, short CC) had multiple definitions depending on the study.
Examples of variability:
The added diagnostic yield of MRI was generally modest when expert neurosonography had already been performed.
Classification and Definitions
The review highlights that:
This lack of standardization hinders:
Key Tables and Figures
Summary and Recommendations
The authors conclude that:
Such a system would:
Introduction and Clinical Context
This article presents a large multicenter retrospective cohort study designed to evaluate the role of prenatal magnetic resonance imaging (MRI) in fetuses diagnosed with an apparently isolated anomaly of the corpus callosum (CC) based on neurosonographic assessment. The CC is one of the most commonly affected structures in fetal central nervous system (CNS) malformations, and its anomalies—particularly agenesis—can occur in isolation or in association with other cerebral or extracerebral defects.
The authors note that, although prenatal ultrasound is the primary tool for detecting CC anomalies, MRI is often employed as a second-line modality to detect subtle or additional abnormalities that may influence prognosis. However, the added diagnostic value of MRI when expert neurosonography has already been performed remains uncertain. This study aims to quantify that added value.
Study Design and Methodology
Results
Imaging Protocols
MRI was used to identify abnormalities such as:
Discussion of Outcomes
Summary Tables and Figures
Conclusion
The authors conclude that:
The study affirms that MRI should be offered in cases of isolated CC anomalies to increase diagnostic precision, although even combined imaging strategies are not infallible.
Introduction and Background
This article presents the results of a retrospective cohort study combined with a systematic review and meta-analysis, focusing on the prenatal diagnosis of isolated agenesis of the septum pellucidum (ASP) and the associated postnatal outcomes, including the risk of septo-optic dysplasia (SOD).
The septum pellucidum (SP) is a thin midline brain structure located between the lateral ventricles. Isolated absence of the SP may be benign, but it can also be a sign of serious conditions like SOD, which is associated with optic nerve hypoplasia and pituitary dysfunction. Diagnosing ASP accurately during pregnancy is challenging, especially in distinguishing isolated ASP from more complex cerebral anomalies.
The aim of this work is to evaluate:
Study Design and Methods
The article is composed of:
Inclusion criteria:
Exclusion criteria:
Number of studies included: 6
Total cases analyzed (cohort + literature): 78 fetuses
Results
Postnatal outcomes:
Imaging and Diagnostic Protocols
Definitions and Classifications Used
Figures and Tables
Conclusion
The authors conclude that:
Introduction and Background
This article presents a systematic review and meta-analysis assessing the diagnostic yield of exome sequencing (ES) following negative chromosomal microarray analysis (CMA) in pregnancies with a prenatal diagnosis of agenesis of the corpus callosum (ACC). ACC is a common congenital anomaly of the central nervous system that can be complete or partial and may occur in isolation or in association with other anomalies.
Given the genetic heterogeneity of ACC, standard karyotyping and CMA may fail to detect many underlying monogenic disorders. Exome sequencing has emerged as a powerful tool for uncovering pathogenic variants in such cases, but its use in the prenatal setting, particularly for ACC, is not yet standardized. This study aims to provide a quantitative synthesis of the diagnostic yield of ES in this specific context.
Methods
Results
Additional Findings
Tables and Figures
Study Quality Assessment
Conclusions
The authors conclude that:
The study supports the integration of prenatal ES into clinical practice for structural brain anomalies, particularly when standard cytogenetics and microarrays are unrevealing.
Introduction and Background
This article presents a retrospective cohort study conducted in China, aimed at analyzing the long-term outcomes and genetic characteristics of fetuses diagnosed prenatally with dysplasia of the corpus callosum (DCC) or partial agenesis of the corpus callosum (PACC).
The corpus callosum (CC), the largest commissural structure in the fetal brain, plays a critical role in interhemispheric communication. CC anomalies are common findings in fetal neurosonography and may range from isolated anomalies with good outcomes to complex malformations associated with neurodevelopmental delays. The study categorizes CC abnormalities into distinct morphotypes—short, thin, and thick CCs—and compares outcomes based on whether the malformation was isolated or associated with other anomalies.
Methods
Results
Statistical significance:
No significant difference in P/LP rate between groups (χ² = 3.566, P = 0.05897), but clear trend toward more variants in non-isolated group.
Key Tables and Figures
Discussion Points (Descriptively Reported)
Conclusion
The authors conclude that:
Introduction and Background
This article presents a meta-analysis evaluating the diagnostic accuracy of prenatal ultrasound in detecting agenesis of the corpus callosum (ACC), using postnatal imaging or postmortem diagnosis as the reference standard.
ACC is a relatively frequent fetal anomaly of the central nervous system (CNS). Its prenatal detection is important for perinatal counseling and prognostication, yet it is often challenging because the diagnosis relies on indirect signs rather than direct visualization of the corpus callosum (CC), especially in routine second-trimester ultrasound screening.
The objective of this meta-analysis is to comprehensively quantify the sensitivity, specificity, and overall diagnostic performance of prenatal ultrasound in identifying ACC.
Methods
Results
These results indicate high overall diagnostic accuracy, especially in terms of specificity.
Subgroup Analysis
This comparison shows that dedicated neurosonography significantly outperforms routine second-trimester screening in detecting ACC.
Figures and Tables
Sonographic Techniques
Quality Assessment
Discussion (Descriptive Summary)
Conclusion
The author concludes that:
The study reinforces the need for systematic assessment of the fetal midline and CC, ideally through standardized neurosonographic protocols, to improve prenatal diagnosis and counseling for ACC.
Introduction and Objectives
This article is a narrative review summarizing current knowledge and recommendations on the prenatal diagnosis of anomalies of the corpus callosum (CC) using two-dimensional ultrasound, with a focus on diagnostic criteria, ultrasound markers, and implications for counseling. The CC is a critical structure for interhemispheric brain communication, and its absence or abnormal development may be associated with a broad spectrum of neurological outcomes.
The review aims to:
Development and Anatomy of the Corpus Callosum
The corpus callosum is described as a white matter interhemispheric tract responsible for integrating motor, sensory, and cognitive functions. It develops in a stepwise fashion:
The CC is composed of four primary anatomical segments:
Postnatally, additional subregions such as the isthmus are identified.
Etiology of CC Anomalies
The authors describe the development of the CC as a complex neurodevelopmental process involving multiple signaling pathways and molecular cues, such as:
Abnormal CC development can result from:
Epidemiologically:
Categories of Corpus Callosum Anomalies
The article identifies and explains five major categories:
Sonographic Features and Diagnostic Approach
Genetic Testing and Associations
Prognostic Outcomes
Counseling and Management Implications
Conclusion
This narrative review provides a structured summary of:
The authors underscore that careful imaging, follow-up, and genetic testing are essential in managing pregnancies affected by CC anomalies. While some isolated forms of ACC are associated with favorable outcomes, others—especially those associated with dysgenesis, hypoplasia, or syndromic features—carry a risk of neurodevelopmental impairment. Accurate classification and counseling are therefore fundamental.
Introduction and Objectives
This article presents the results of a prospective, single-center, three-year study aiming to evaluate the performance of first-trimester ultrasound (FTUS) in detecting major central nervous system (CNS) anomalies, including early signs of corpus callosum anomalies. The study emphasizes the importance of CNS assessment during 11–13+6 weeks of gestation, a period traditionally focused on aneuploidy screening.
Objectives:
Methods
A detailed FT anomaly scan (FTAS) was performed with focus on CNS structures:
Transabdominal ultrasound (TAUS) was used primarily; transvaginal ultrasound (TVUS) was performed when needed.
Results
These findings indicate that some CNS anomalies—particularly corpus callosum anomalies and posterior fossa malformations—may escape early detection and only manifest later in pregnancy.
Diagnostic Accuracy
These values reflect high diagnostic accuracy when a detailed CNS evaluation protocol is applied in the first trimester.
Sonographic Features of CC-Related and Midline Anomalies
While the first trimester scan was able to detect gross malformations (anencephaly, open spina bifida), midline anomalies such as agenesis of the corpus callosum (ACC) were not identified until the second trimester.
Indirect signs such as:
The authors highlight that complete evaluation of the corpus callosum is not feasible before 20 weeks due to its ongoing development.
Tables and Figures
Limitations and Technical Factors
Counseling and Clinical Implications
Conclusion
The authors conclude that:
