Risk of 22q11.2 deletion in fetuses with right aortic arch and without intracardiac anomalies.

OBJECTIVE: To assess the risk of 22q11.2 deletion in fetuses with a prenatal diagnosis of right aortic arch without intracardiac anomalies (RAA-no ICA). METHODS: This was a retrospective study of all fetuses with RAA-no ICA diagnosed prenatally at three referral centers, between 2004 and 2014. A detailed sonographic examination was performed in each case, including visualization of the thymus and of the head and neck vessels to identify the presence of an aberrant left subclavian artery (ALSA). Karyotyping and fluorescence in situ hybridization analysis for diagnosis of 22q11.2 deletion were always offered either prenatally or postnatally. Clinical and echocardiographic examinations were performed in livebirths and a postmortem examination in cases of termination of pregnancy. RESULTS: During the study period, 85 fetuses were diagnosed prenatally with RAA-no ICA. Genetic or clinical data were not available for three cases and these were excluded from analysis. 22q11.2 deletion was found in 7/82 cases (8.5% (95% CI, 3.8-17.3%)). The thymus was small or non-visualized in all seven cases and additional abnormal sonographic findings were present in four. CONCLUSION: 22q11.2 deletion is present in a clinically significant proportion of fetuses with a prenatal diagnosis of RAA-no ICA. In such cases, a detailed sonographic examination, with assessment of the thymus in particular, may be useful to further define the level of risk for 22q11.2 deletion. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Bilateral cleft lip and palate without premaxillary protrusion is associated with lethal aneuploidies.

OBJECTIVE: To investigate the clinical implications of two categories of fetal bilateral cleft lip and palate (BCLP): with premaxillary protrusion and with a flattened profile. METHODS: This was a retrospective study of fetuses with a prenatal diagnosis of BCLP at the Department of Obstetrics and Gynecology of the University of Bologna in the period 1991-2005. RESULTS: BCLP was diagnosed prenatally in 14 cases (mean gestational age at diagnosis, 21 (range, 12-36) weeks). In nine of these, there was a premaxillary pseudomass; in the remaining five, the profile was flat. Associated structural and/or chromosomal anomalies were found in two of the nine with a premaxillary pseudomass and in all five of those with a flat profile (P = 0.02). All fetuses with a flat profile had aneuploidies (three trisomy 18, one trisomy 13, one trisomy 8 mosaic), as did one of the nine with a premaxillary pseudomass. Eight of the pregnancies were terminated, including three of those with a premaxillary pseudomass and all five of those without. All continuing pregnancies resulted in live births, although one neonate affected by Krabbe's disease died shortly after birth. CONCLUSIONS: Our findings suggest that a third of cases of BCLP diagnosed in utero have a flat profile and these are at high risk of lethal aneuploidies.

Diagnosis of midline anomalies of the fetal brain with the three-dimensional median view.

OBJECTIVE: To investigate the effectiveness of a simplified approach to the evaluation of the midline structures of the fetal brain using three-dimensional (3D) ultrasound. METHODS: Sonographic examinations were performed in normal fetuses and in cases with anomalies involving the midline cerebral structures. Two-dimensional (2D) median planes were obtained by aligning the transducer with the anterior fontanelle and midline sutures by either transabdominal or transvaginal scans. Median planes were also reconstructed using 3D ultrasonography from volumes acquired from transabdominal axial planes of the fetal head (3D median planes), by either multiplanar analysis of static volumes or volume contrast imaging in the coronal plane (VCI-C). 2D and 3D median planes were compared qualitatively and quantitatively by measuring the corpus callosum and cerebellar vermis. RESULTS: 2D median planes could be visualized in 54/56 normal fetuses. 3D median planes were obtained in all, usually more easily and rapidly. There was a good correlation between 2D and 3D images. Measurements of the corpus callosum and cerebellar vermis were highly correlated, with mean variations of 6% and 14%, respectively. The abnormal group included 13 fetuses (five with partial or complete agenesis of the corpus callosum, six with posterior fossa malformations, two with a combination of these two anomalies). In all cases the diagnosis could be made by both 2D and 3D views and was always confirmed by postnatal investigation. Although 2D median views were of better quality, 3D images were always adequate for diagnosis, both in normal and abnormal fetuses. CONCLUSIONS: 3D median planes are obtained more easily than 2D ones, and allow an accurate diagnosis of normal cerebral anatomy and anomalies. The 3D approach may be valuable particularly for rapid assessment of fetal cerebral anatomy in standard examinations.

Outcome of antenatally diagnosed intracranial hemorrhage: case series and review of the literature.

OBJECTIVES: Prenatal diagnosis of intracranial hemorrhage (ICH) has been widely reported. Hemorrhages may occur either within the cerebral ventricles, subdural space or infratentorial fossa. The aim of this study was to determine the sonographic criteria for the diagnosis of fetal ICH, the role of in utero magnetic resonance imaging (MRI) and the outcome of this condition. METHODS: The archives of our ultrasound laboratory and the literature were searched for all cases of antenatally diagnosed ICH. A grading system was used to classify the intraventricular lesions as suggested in postnatal sonographic studies. RESULTS: Adding our series of 16 fetuses to the 93 cases identified in the literature, a group of 109 fetal ICHs was obtained: 89 were intracerebral (79 intraventricular and 10 infratentorial) and 20 were subdural hemorrhages. Intraventricular lesions were mostly classified as severe (32 each for Grades III and IV). In 27 cases antenatal MRI was performed additionally to ultrasound and confirmed the sonographic findings. Of the entire group, 65 infants (59%) were reported to be alive 1 month after birth (51 intraventricular hemorrhages, three infratentorial hemorrhages, 11 subdural hematomas). At 12 months, of the 48 infants whose follow-up was available, 25 or 52% were judged neurologically normal (17/36 or 47% among the intraventricular hemorrhages, 6/9 or 66% among the hematomas, and 2/3 or 66% among the infratentorial hemorrhages). CONCLUSIONS: Fetal ICH may be accurately identified and categorized by antenatal sonography. The outcome is usually poor, especially for those fetuses affected by higher-grade intraventricular hemorrhages.

Two-dimensional ultrasound is accurate in the diagnosis of fetal craniofacial malformation.

OBJECTIVE: To assess the accuracy of antenatal ultrasound in the diagnosis of craniofacial malformations and to compare two-dimensional with three-dimensional ultrasound. METHODS: This was a retrospective study in which the archives of our ultrasound laboratory were searched for cases with an ultrasound diagnosis of craniofacial malformation in the period 1986-2001. No attempt was made to look for false-negative diagnoses. RESULTS: Sixty cases with an antenatal diagnosis of a craniofacial malformation were found: 37 with cleft lip/palate; 17 with heterogeneous dysmorphisms (including mostly micrognathia and craniosynostosis) and 6 with miscellaneous craniofacial malformations. Associated anomalies were present in 48/60 (80%) cases, and holoprosencephaly (25 cases) was the most frequent of these. In 43 (72%) cases the diagnosis was made before 24 weeks' gestation. Postnatal follow-up was available for 43 cases and there was always complete correlation between antenatal and postnatal diagnoses. Cleft lip/palate was always accurately differentiated from cleft lip. Three-dimensional ultrasound was performed in 12 cases and was successful in 11. However, it did not provide further diagnostic information with regard to the two-dimensional scan. DISCUSSION: Current two-dimensional ultrasound in expert hands allows an accurate diagnosis of craniofacial abnormalities from early gestation. In our hands, three-dimensional ultrasound did not add any valuable diagnostic information. Three-dimensional ultrasound may facilitate the understanding of the lesion by the parents and facilitate communication with the plastic surgeons. However, these potential benefits need to be carefully weighed against the costs of the ultrasound instrumentation, increased examination time and training of personnel.

Prenatal diagnosis of thrombosis of the dural sinuses with real-time and color Doppler ultrasound.

OBJECTIVE: To assess the sonographic findings and clinical implications of fetal thrombosis of dural sinuses. DESIGN: Retrospective study of cases with a prenatal diagnosis of thrombosis of the dural sinuses. RESULTS: The diagnosis of fetal thrombosis of the dural sinuses was established in three uncomplicated pregnancies at 21, 22 and 28 weeks' gestation by transabdominal and transvaginal sonography, demonstrating a blood clot within the dilated dural sinuses, always in the region of the torcular Herophilii. The diagnosis was further confirmed by the color Doppler demonstration of absence of blood flow within the dilated dural sinuses. Upon request of the couples two pregnancies were terminated. One infant was delivered at term by Cesarean section and died during neurosurgery. CONCLUSIONS: Thrombosis of the cerebral venous circulation can occur antenatally. Accurate diagnosis can be made using fetal real-time and color Doppler ultrasound.

Absence of the ductus venosus: report of 10 new cases and review of the literature.

OBJECTIVE: To assess the clinical significance of the absence of the ductus venosus. DESIGN: A retrospective study with a review of the literature. METHODS: The archives of our ultrasound laboratory and the English literature were searched for cases with a prenatal diagnosis of absence of the fetal ductus venosus. RESULTS: Between 1985 and 2000, 10 fetuses were diagnosed in our center as having absence of the ductus venosus. The review of the literature revealed 23 cases. Three main patterns of abnormal venous circulation were documented: (1) umbilical vein bypassing the liver and connecting directly to the right atrium (46%); (2) umbilical vein bypassing the liver and connecting to the inferior vena cava mostly through one of the iliac veins (25%); (3) umbilical vein connecting to the portal circulation without giving rise to the ductus venosus (21%). Major anomalies, including chromosomal aberrations, were found in 8/33 (24%) cases. Hydrops developed in 11/33 (33%) cases. Twenty fetuses with isolated absence of the ductus venosus were delivered, and 5 (20%) died. The portal vein was found to be absent in half of the infants examined after birth. CONCLUSIONS: Our results and the review of literature suggest that absence of the ductus venosus is associated with a high incidence of fetal anomalies and adverse outcomes, including associated malformations, chromosomal aberrations, in utero heart failure and absence of the portal vein. Heart failure and absence of the portal vein seem particularly frequent when absence of the ductus venosus is associated with a connection of the umbilical vein to either the inferior vena cava or the right atrium.

Diagnosis and management of fetal cardiac anomalies: 10 years of experience at a single institution.

OBJECTIVE: To assess the diagnostic accuracy of fetal echocardiography and the outcome of cardiac malformations diagnosed in utero. DESIGN: A retrospective study. METHODS: The archives of our ultrasound laboratory were searched for fetal cardiac abnormalities in the period 1991-2001. RESULTS: Diagnosis of a fetal cardiac anomaly was made in 339 pregnancies at a mean gestational age of 26.2 weeks. Pathology or a detailed postnatal follow-up was available in 260 cases, and the prenatal diagnosis was accurate in 236 cases (91%). Discrepancies included nine false positive diagnoses (six ventricular septal defects and three coarctation of the aorta) and 15 cases in which a cardiac anomaly different from the one suspected in utero was documented. Of the 142 fetuses with isolated cardiac malformations (no extracardiac anomalies, normal chromosomes) that were delivered in our center, 114 were alive (80.2%) at a mean follow-up of 38 months (range, 1-120 months). In this group of patients, conotruncal anomalies and univentricular lesions were the most frequent types of anomaly, and had a survival rate of 87% and 57%, respectively. Hypoplastic left heart was the most frequent isolated congenital heart defect in infants that were delivered (19 cases) and it was associated with a survival rate of 37%. CONCLUSION: In expert hands, fetal echocardiography is highly accurate. The long-term prognosis of cardiac lesions diagnosed in utero is similar to that reported in series of infants diagnosed after birth. The only exception is hypoplastic left heart in which the survival rate is much lower than expected from postnatal studies.

Ultrasound of the fetal central nervous system.

Current ultrasound equipment allows the antenatal identification of many central nervous system anomalies from early gestation. In selected cases, special techniques (transvaginal sonography, three-dimensional ultrasound, colour Doppler) may enhance the diagnostic potential. Diagnostic accuracy, however, remains heavily dependent upon the expertise of the sonologist. Fetal ultrasound is effective in identifying neural tube defects, although alpha-fetoprotein screening seems to yield a greater sensitivity. The sensitivity in the diagnosis of central nervous system malformations other than neural tube defects remains unclear because of the ascertainment biases of the few large prospective studies that have been carried out so far. Magnetic resonance imaging may play a major role in the evaluation of cases with suboptimal ultrasound visualization, or when specific anomalies are suspected, such as intracranial haemorrhage or migrational disorders.

Transabdominal sonography of the cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy.

OBJECTIVES: To assess the visualization rate and size of the cavum septum pellucidum (CSP) by transabdominal sonography in normal fetuses throughout pregnancy. METHODS: The CSP was prospectively researched and measured using an axial transventricular plane in 286 consecutive uncomplicated singleton pregnancies between 15 and 41 weeks of gestation. RESULTS: The CSP was seen in 40% of cases at 15 weeks, 82% at 16-17 weeks, 100% at 18-37 weeks and 79% at 38-41 weeks. Compared to biparietal diameter (BPD), the visualization rate was 33% between 31 and 32 mm, 45% between 33 and 34 mm, 84% between 35 and 43 mm, 100% between 44 and 88 mm and 86% between 89 and 99 mm. Mean CSP width was 5.3 +/- 1.7 mm (range 2-9 mm). The CSP width increased with gestational age and BPD but with a slight decrease around term. CONCLUSIONS: In normal fetuses the CSP should always be visualized between 18 and 37 weeks, or with a BPD of 44-88 mm. Failure to observe the CSP in this interval, or possibly the presence of a large CSP, may indicate abnormal cerebral development and warrant further investigation. Conversely, absence of the CSP prior to 18 weeks, or later than 37 weeks, is a normal finding.

Can transvaginal fetal biometry be considered a useful tool for early detection of skeletal dysplasias in high-risk patients?

OBJECTIVE: To evaluate the possibility of an early diagnosis of skeletal dysplasias in high-risk patients. METHODS: A total of 149 consecutive, uncomplicated singleton pregnancies at 9-13 weeks' amenorrhea, with certain menstrual history and regular cycles, were investigated with transvaginal ultrasound to establish the relationship between femur length and menstrual age, biparietal diameter and crown-rump length, using a polynomial regression model. A further eight patients with previous skeletal dysplasias in a total of 13 pregnancies were evaluated with serial examinations every 2 weeks from 10-11 weeks. RESULTS: A significant correlation between femur length and crown-rump length and biparietal diameter was found, whereas none was observed between femur length and menstrual age. Of the five cases with skeletal dysplasias, only two (one with recurrent osteogenesis imperfecta and one with recurrent achondrogenesis) were diagnosed in the first trimester. CONCLUSIONS: An early evaluation of fetal morphology in conjunction with the use of biometric charts of femur length against crown-rump length and femur length against biparietal diameter may be crucial for early diagnosis of severe skeletal dysplasias. By contrast, in less severe cases, biometric evaluation appears to be of no value for diagnosis.

The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31 cases and review of the literature.

OBJECTIVE: To assess the clinical significance of fetal isolated borderline cerebral lateral ventriculomegaly defined as a width of the atrium of the lateral cerebral ventricles of 10-15 mm in the absence of other sonographically demonstrable malformations. DESIGN: Retrospective study of the outcome of fetuses with a sonographic diagnosis of isolated borderline cerebral lateral ventriculomegaly and review of the English-language literature. RESULTS: Of 31 fetuses, two had chromosomal aberrations (trisomy 21 and trisomy 13) and three had neurological complications (one infant developed shunt-dependent hydrocephalus, one lissencephaly and one cerebral hemorrhage and periventricular leukomalacia). The literature search revealed eight independent studies. Including the present series, 234 cases were available for analysis. An abnormal outcome was documented in 22.8% of cases. Perinatal death occurred in 3.7%. Chromosomal aberrations, mostly trisomy 21, were present in 3.8%, malformations undetected at a second-trimester sonogram in 8.6% and neurological sequelae, mostly a mild to moderate delay in cognitive and/or motor development, were present in 11.5%. The risk of an abnormal neurological outcome was increased in females versus males (22.6% versus 4.6%, relative risk 4.892; 95% confidence interval 1.356-17.656), when the atrial width was 12 mm or more (13.9% versus 3.8%, relative risk 3.6, 95% confidence interval 1.035-12.846) and when the diagnosis was made in the second trimester versus later in gestation. CONCLUSIONS: In most cases, isolated borderline cerebral lateral ventriculomegaly has no consequence. However, this finding carries an increased risk of cerebral maldevelopment, delayed neurological development and, possibly, chromosomal aberrations. The optimal management of these cases remains uncertain.

Prenatal diagnosis of microcephaly assisted by vaginal sonography and power Doppler.

In two mid-trimester fetuses with microcephaly, transvaginal sonography revealed aberrant findings, including large subarachnoid spaces and a rudimentary shape of the lateral ventricles. In one of these fetuses, power Doppler ultrasound demonstrated a discrepancy in the size of the signals generated by the intracranial arteries branching from the internal carotids and those branching from the vertebral arteries, and this was interpreted as the consequence of a reduced blood supply to the undersized cerebral hemispheres. We suggest that evaluation of intracranial anatomy by transvaginal sonography and power Doppler examination of the cerebral vessels may be of value in the diagnosis of fetal microcephaly.

Differential diagnosis and outcome of fetal intracranial hypoechoic lesions: report of 21 cases.

Our objective was to evaluate the diagnostic and prognostic value of sonography hypoechoic lesions. A retrospective study revealed revealed a total of 21 cases diagnosed over a period of 10 years. Most of the diagnosis were made in the third trimester. The presence fluid-filled lesions within the brain matter always predicted porencephaly and a poor outcome. In most of these cases (nine out of ten), the lesions were seen to communicate with the cavity of the lateral ventricles. Among the 11 cases of hypoechoic lesions that were external to the brain matter, Doppler ultrasound was always able to distinguish between arachnoid cysts (seven cases) and vein of Galen aneurysms (four cases). Arachnoid cysts were associated with a good outcome in four out of the five pregnancies that delivered at term. Three of the four cases of vein of Galen aneurysm were associated with distortion of the cerebral architecture and/or hydrops: one pregnancy was terminated and two resulted in early postnatal death. One pregnancy with vein of Galen aneurysm and normal cerebral structures, without signs of hydrops, had a good outcome. It is concluded that current antenatal ultrasound has the capability of accurate differentiation between different clinical entities resulting in fetal intracranial hypoechoic lesions, and that the sonographic findings have practical clinical implications.

Ultrasound and molecular mid-trimester prenatal diagnosis of de novo achondroplasia.

In a low-risk pregnant patient at 21 weeks' gestation, ultrasound revealed shortening of fetal long bones compatible with achondroplasia. Funipuncture was performed and DNA analysis of fetal blood demonstrated the presence of the GR380R fibroblast growth factor receptor 3 (FGFR3), which is specifically associated with achondroplasia. After termination of the pregnancy, necropsy confirmed the prenatal diagnosis. A certain sonographic diagnosis of fetal de novo achondroplasia is rarely possible prior to viability. The specificity of the FGFR3 causative mutation has added a new diagnostic option which can be applied prenatally for diagnostic validation.