Abnormal sonographic appearance of posterior brain at 11-14 weeks and fetal outcome.

OBJECTIVE: The aim of this retrospective study was to describe the sonographic appearance of the posterior brain anatomy in normal fetuses at 11 to 14 weeks of pregnancy and to determine the fetal outcome when one of the posterior brain anatomical space is not recognized. METHODS: Two groups of patients were included in the study: a control group of consecutive 311 healthy fetuses with a normal sonogram and a study group of 21 fetuses with absence of one of the three posterior brain spaces. In each fetus, images of the mid-sagittal view of the fetal face and brain at 11 to 14 weeks of gestation were obtained. RESULTS: In all fetuses with absence of one of the three posterior brain spaces, a severe anomaly, including open spina bifida, cephalocele, Dandy-Walker complex, and chromosomal aberrations, was associated. CONCLUSION: Our study indicates that the sonographic finding characterized by the absence of one of the three posterior brain spaces seems to facilitate not only the detection of open spina bifida, as previously reported, but also of other neural tube defects, such as cephalocele, and is an important risk factor for cystic posterior brain anomalies, and/or chromosomal abnormalities. Thus it seems a poor prognostic finding for major fetal abnormalities.

Aberrant right subclavian artery (ARSA) in unselected population at first and second trimester ultrasonography.

OBJECTIVES: To evaluate the feasibility of examining aberrant right subclavian artery (ARSA) at first and second trimester gestation, its prevalence and associations in an unselected population. METHODS: Right subclavian artery (RSA) was prospectively evaluated in 6617 routine patients. When ARSA was detected, fetal echocardiography was offered and fetal karyotyping was discussed. If invasive testing was performed with normal karyotype, fluorescence in situ hybridization for 22q11.2 microdeletion and additionally, in case of nuchal translucency (NT) measurement above the 99(th) centile, oligo array-based comparative genomic hybridization, were offered. In all aneuploidies, NT and first trimester additional ultrasonographic (US) markers assessment (nasal bone, tricuspid valve, ductus venosus) were recorded. RESULTS: RSA assessment was feasible in 85.3% and 98% of first and second trimester examinations, respectively (overall feasibility 94%). There were detected 89 ARSA (1.42% of the feasible cases), of which 66 in the first trimester. More than 20% were associated to other abnormalities: 10 aneuploidies; 2 microdeletions (15q11.2 and 22q11.2); in the euploid fetuses, 8 associated abnormalities were observed, 4 of which were cardiac defects. In the case of 22q11.2 microdeletion, ARSA was associated only with increased NT. CONCLUSION: Prenatal routine US assessment of the RSA is feasible by highly experienced operators in first trimester screening. There is an important association of ARSA detected in unselected population with fetal abnormalities, including aneuploidies, cardiac defects and genetic anomalies. In trisomy 21 fetuses, ARSA can be the only first trimester US marker or, when associated to increased NT, it can represent the only 'additional' marker.

Prenatal diagnosis and outcome of fetal posterior fossa fluid collections.

OBJECTIVE: To evaluate the accuracy of fetal imaging in differentiating between diagnoses involving posterior fossa fluid collections and to investigate the postnatal outcome of affected infants. METHODS: This was a retrospective study of fetuses with posterior fossa fluid collections, carried out between 2001 and 2010 in two referral centers for prenatal diagnosis. All fetuses underwent multiplanar neurosonography. Parents were also offered fetal magnetic resonance imaging (MRI) and karyotyping. Prenatal diagnosis was compared with autopsy or postnatal MRI findings and detailed follow-up was attempted by consultation of medical records and interview with parents and pediatricians. RESULTS: During the study period, 105 fetuses were examined, at a mean gestational age of 24 (range, 17-28) weeks. Sonographic diagnoses (Blake's pouch cyst, n = 32; megacisterna magna, n = 27; Dandy-Walker malformation, n = 26; vermian hypoplasia, n = 17; cerebellar hypoplasia, n = 2; arachnoid cyst, n = 1) were accurate in 88% of the 65 cases in which confirmation was possible. MRI proved more informative than ultrasound in only 1/51 cases. Anatomic anomalies and/or chromosomal aberrations were found in 43% of cases. Blake's pouch cysts and megacisterna magna underwent spontaneous resolution in utero in one third of cases and over 90% of survivors without associated anomalies had normal developmental outcome at 1-5 years. Isolated Dandy-Walker malformation and vermian hypoplasia were associated with normal developmental outcome in only 50% of cases. CONCLUSION: Prenatal neurosonography and MRI are similarly accurate in the categorization of posterior fossa fluid collections from mid gestation. Blake's pouch cyst and megacisterna magna are risk factors for associated anomalies but when isolated have an excellent prognosis, with a high probability of intrauterine resolution and normal intellectual development in almost all cases. Conversely, Dandy-Walker malformation and vermian hypoplasia, even when they appear isolated antenatally, are associated with an abnormal outcome in half of cases.

Fetal interrupted aortic arch: 2D-4D echocardiography, associations and outcome.

OBJECTIVES: To analyze fetal two-dimensional (2D) echocardiographic characteristics of interrupted aortic arch (IAA) and its different types, to explore whether the use of 4D ultrasound with B-flow imaging and spatiotemporal image correlation (STIC) can improve prenatal diagnostic accuracy, and to describe associations and outcome. METHODS: The study comprised IAA fetuses examined exclusively by 2D conventional echocardiography during the period from 1994 to 2003, and those identified by conventional echocardiography and examined further by 4D ultrasound with B-flow imaging and STIC during the period January 2004 to July 2008, identified among fetuses examined at two referral centers for congenital heart defects (CHD). Postnatal follow-up was available in all cases. Karyotyping and fluorescent in-situ hybridization (FISH) analysis for the DiGeorge critical region (22q11.2) were performed in all cases. RESULTS: Twenty-two cases of isolated IAA (15 Type B and seven Type A, seven and three of which, respectively, underwent B-flow imaging and STIC) were detected among 2520 cases of fetal CHD. In seven of the 15 Type B cases, a right subclavian artery arose anomalously (ARSA). 2D echocardiography failed to distinguish the type of IAA in only two cases and the ARSA in five of the seven cases. B-flow imaging and STIC successfully identified IAA types in all 10 cases examined and clearly visualized the origin and course of the ARSA, including cervical ones. FISH detected 22q11.2 microdeletion in 10 of the 15 Type B cases and an unusual association with Type A in one of the seven cases. Fetal/neonatal outcome included: eight terminations of pregnancy, one intrauterine death and four postoperative deaths in the neonatal period, and nine neonates were alive after surgery at a mean follow-up time of 58 months (range, 4 months-13 years). CONCLUSION: Our results confirm the feasibility of prenatal characterization of IAA and its different types based on 2D echocardiographic examination, albeit with some limitations in the thorough assessment. 4D ultrasound with B-flow imaging and STIC can apparently facilitate visualization and detailed examination of the anatomical features of the IAA types, including visualization of the neck vessels, thus supplying additional information with respect to 2D sonography. As for the known association with microdeletion 22q11.2, our data indicate that Types A and B are distinct, there being a close association only with IAA Type B.

Disorders of prosencephalic development.

Abnormal ventral induction may result in disorders of formation, cleavage, and midline development of prosencephalic structures. Holoprosencephaly is a developmental field defect of impaired cleavage of prosencephalon. The most widely accepted classification of holoprosencephaly recognizes three major varieties: the alobar, semilobar and lobar types, according to the severity of the malformation. The brain malformations, characterized by the fusion of the cerebral hemisphere along the midline are commonly associated with facial anomalies. Corpus callosum agenesis and septo-optic dysplasia are disorders of prosencephalic midline development, and usually have less severe presentations but still, affected subjects may suffer from neurodevelopmental retardation, and/or endocrinologic and visual disorders. In this article we report an up-to-date of pathogenesis, prenatal sonographic findings, differential diagnosis and prognosis of the aforementioned anomalies.

Maxillary length at 11-14 weeks of gestation in fetuses with trisomy 21.

OBJECTIVE: To determine the value of measuring maxillary length at 11-14 weeks of gestation in screening for trisomy 21. METHODS: In 970 fetuses ultrasound examination was carried out for measurement of crown-rump length (CRL), nuchal translucency and maxillary length, and to determine if the nasal bone was present or absent, immediately before chorionic villus sampling for karyotyping at 11-14 weeks of gestation. In 60 cases the maxillary length was measured twice by the same operator to calculate the intraobserver variation in measurements. RESULTS: The median gestation was 12 (range, 11-14) weeks. The maxilla was successfully examined in all cases. The mean difference between paired measurements of maxillary length was -0.012 mm and the 95% limits of agreement were -0.42 (95% CI, -0.47 to -0.37) to 0.40 (95% CI, 0.35 to 0.44) mm. The fetal karyotype was normal in 839 pregnancies and abnormal in 131, including 88 cases of trisomy 21. In the chromosomally normal group the maxillary length increased significantly with CRL from a mean of 4.8 mm at a CRL of 45 mm to 8.3 mm at a CRL of 84 mm. In the trisomy 21 fetuses the maxillary length was significantly shorter than normal by 0.7 mm and in the trisomy 21 fetuses with absent nasal bone the maxilla was shorter than in those with present nasal bone by 0.5 mm. In fetuses with other chromosomal defects there were no significant differences from normal in the maxillary length. CONCLUSION: At 11-14 weeks of gestation, maxillary length in trisomy 21 fetuses is significantly shorter than in normal fetuses.

Likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan.

OBJECTIVE: To update the likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan. METHODS: Ultrasound examination of the fetal profile was carried out and the presence or absence of the nasal bone was noted immediately before karyotyping in 5918 fetuses at 11 to 13+6 weeks. Logistic regression analysis was used to examine the effect of maternal ethnic origin and fetal crown-rump length (CRL) and nuchal translucency (NT) on the incidence of absent nasal bone in the chromosomally normal and trisomy 21 fetuses. RESULTS: The fetal profile was successfully examined in 5851 (98.9%) cases. In 5223/5851 cases the fetal karyotype was normal and in 628 cases it was abnormal. In the chromosomally normal group the incidence of absent nasal bone was related first to the ethnic origin of the mother, being 2.2% for Caucasians, 9.0% for Afro-Caribbeans and 5.0% for Asians; second to fetal CRL, being 4.7% for CRL of 45-54 mm, 3.4% for CRL of 55-64 mm, 1.4% for CRL of 65-74 mm and 1% for CRL of 75-84 mm; and third to NT, being 1.6% for NT < or = 95th centile, 2.7% for NT > 95th centile-3.4 mm, 5.4% for NT 3.5-4.4 mm, 6% for NT 4.5-5.4 mm and 15% for NT > or = 5.5 mm. In the chromosomally abnormal group there was absent nasal bone in 229/333 (68.8%) cases with trisomy 21 and in 95/295 (32.2%) cases with other chromosomal defects. Logistic regression analysis demonstrated that in the chromosomally normal fetuses significant independent prediction of the likelihood of absent nasal bone was provided by CRL, NT and Afro-Caribbean ethnic group, and in the trisomy 21 fetuses by CRL and NT. The likelihood ratio for trisomy 21 for absent nasal bone was derived by dividing the likelihood in trisomy 21 by that in normal fetuses. CONCLUSION: At the 11-14-week scan the incidence of absent nasal bone is related to the presence or absence of chromosomal defects, CRL, NT and ethnic origin.

Assessment of the fetal nasal bone at 11-14 weeks of gestation by three-dimensional ultrasound.

OBJECTIVE: To evaluate the benefit of three-dimensional (3D) ultrasound in the examination of the fetal nasal bone at 11-14 weeks of gestation. METHOD: We examined the fetal nasal bone in 120 stored volumes acquired transabdominally with a 3D scanner from singleton pregnancies at 11-14 weeks of gestation. The volume acquisition had been performed following conventional ultrasound examination that had demonstrated presence of the fetal nasal bone. The volumes were obtained with two-dimensional (2D) start images in transverse, coronal mid-sagittal, parasagittal and oblique longitudinal sections of the fetal head. RESULTS: In the transverse and coronal sections, a satisfactory image demonstrating presence of the nasal bone was achieved in only three and one, respectively, of the 20 volumes that we obtained. In mid-sagittal sections, the nasal bone was always visible when the angle was within a range of 30-60 degrees, without the need for sectional image analysis. None of the images with an angle >60 degrees or <30 degrees was satisfactory. In the parasagittal sections with the fetal profile at 45 degrees, a good-quality image of the nasal bone was possible in all cases that were examined, irrespective of the distance from the mid-sagittal plane. In the oblique longitudinal sections with the fetal profile at 45 degrees, there were 10 volumes where the 2D start section was at 0-25 degrees from the midline and in all these cases the nasal bone was successfully visualized. In contrast, only 5/20 cases where the 2D start section was at 25-90 degrees from the midline provided a satisfactory image demonstrating the nasal bone. In 5/10 volumes obtained with the fetus facing downwards the nasal bone was visible in both the 2D and 3D images. CONCLUSION: In a 3D volume the extent to which the nasal bone can be demonstrated to be present in a given reconstructed section is entirely dependent on obtaining a good initial 2D view.

Umbilical cord diameter at 11-14 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring umbilical cord diameter (UCD) at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: The UCD was measured in 1323 fetuses immediately before chorionic villus sampling for karyotyping at 11-14 weeks of gestation. In the group of chromosomally normal fetuses, regression analysis was used to determine the association between UCD and crown-rump length (CRL). UCD was compared in normal fetuses and those with chromosomal abnormalities. RESULTS: The median gestation was 12 (range, 11-14) weeks. The UCD was successfully measured in all cases. The fetal karyotype was normal in 1150 pregnancies and abnormal in 173, including 97 cases of trisomy 21. In the chromosomally normal group the UCD increased significantly with CRL from a mean of 2.9 mm at a CRL of 45 mm to 4.4 mm at a CRL of 84 mm. The UCD in the group of fetuses with trisomy 21 was significantly smaller than normal. Conversely, there were no significant differences from normal in the UCD of fetuses with other chromosomal abnormalities. CONCLUSION: At 11-14 weeks of gestation the UCD of fetuses with trisomy 21 is significantly smaller than normal but the magnitude of the difference is too small for useful inclusion of this measurement in screening.

Single umbilical artery at 11-14 weeks' gestation: relation to chromosomal defects.

OBJECTIVE: To determine the possible association between single umbilical artery (SUA) at 11-14 weeks of gestation and the incidence of chromosomal abnormalities. METHODS: Color flow imaging of the fetal pelvis was used to determine the number of umbilical arteries in 717 fetuses immediately before chorionic villus sampling for karyotyping at 11-14 weeks' gestation. RESULTS: Single umbilical artery (SUA) was diagnosed in 21/634 (3.3%) chromosomally normal fetuses, in 5/44 (11.4%) with trisomy 21, 14/18 (77.8%) with trisomy 18 and 2/21 (9.5%) with other chromosomal defects. In the chromosomally normal group there was no significant difference in median fetal crown-rump length or nuchal translucency (NT) between those with a single and those with two umbilical arteries. In the 42 fetuses with SUA the expected number of cases of trisomy 21, estimated on the basis of maternal age, gestational age and fetal NT, was 4.7, which was not significantly different from the observed 5. The corresponding numbers for trisomy 18 were 2.0 for expected and 14 for observed (Fisher's exact test P = 0.0016). CONCLUSION: A SUA at 11-14 weeks' gestation has a high association with trisomy 18 and other chromosomal defects.

Ear length in trisomy 21 fetuses at 11-14 weeks of gestation.

OBJECTIVE: To determine the value of measuring fetal ear length at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: The fetal ear length was measured in 450 fetuses immediately before chorionic villus sampling for karyotyping at 11-14 weeks of gestation. RESULTS: The median gestational age was 12 (range, 11-14) weeks. The fetal ear was successfully examined in all cases. The fetal karyotype was normal in 409 cases and abnormal in 41, including 32 cases of trisomy 21. In the chromosomally normal group the fetal ear length increased significantly with crown-rump length from a mean of 3.7 mm at 45 mm to 6.9 mm at 84 mm. In the trisomy 21 fetuses the median ear length was significantly below the normal mean for crown-rump length by 0.45 mm (P = 0.013) but it was below the 5(th) centile of the normal range in only two (6.3%) of the cases. There was no significant association between the delta score of ear length and delta nuchal translucency in either the chromosomally normal (r = - 0.015, P = 0.753) or the trisomy 21 fetuses (r = - 0.014, P = 0.94). CONCLUSIONS: At 11-14 weeks of gestation the ear length in trisomy 21 fetuses is significantly reduced but the degree of deviation from normal is too small for this measurement to be useful in screening for trisomy 21.

Sonographic markers of fetal aneuploidy--a review.

The most effective sonographic marker of trisomy 21 and other chromosomal defects is increased nuchal translucency (NT) thickness at 11-14 weeks. Extensive studies over the last decade have examined the methodology of measuring NT, the development of the necessary algorithms for calculating the individual patient risk for trisomy 21 by NT in combination with maternal age and with various maternal serum biochemical markers, and the performance of this test. Another promising marker for trisomy 21, both in the first and second trimesters, is absence of the fetal nasal bone. There is also an extensive literature on the association between chromosomal abnormalities and a wide range of second trimester ultrasound findings. However, there are very few reports that have prospectively examined the screening performance of second trimester markers. This article reviews the association between sonographically detectable fetal abnormalities and chromosomal defects, and examines the value of incorporating these defects in screening policies.

Absent nasal bone at 11-14 weeks of gestation and chromosomal defects.

OBJECTIVE: To examine the association between absence of the nasal bone at the 11-14-week ultrasound scan and chromosomal defects. METHODS: Ultrasound examination was carried out in 3829 fetuses at 11-14 weeks' gestation immediately before fetal karyotyping. At the scan the fetal crown-rump length (CRL) and nuchal translucency (NT) thickness were measured and the fetal profile was examined for the presence or absence of the nasal bone. Maternal characteristics including ethnic origin were also recorded. RESULTS: The fetal profile was successfully examined in 3788 (98.9%) cases. In 3358/3788 cases the fetal karyotype was normal and in 430 it was abnormal. In the chromosomally normal group the incidence of absent nasal bone was related firstly to the ethnic origin of the mother (2.8% for Caucasians, 10.4% for Afro-Caribbeans and 6.8% for Asians), secondly to fetal CRL (4.6% for CRL of 45-54 mm, 3.9% for CRL of 55-64 mm, 1.5% for CRL of 65-74 mm and 1.0% for CRL of 75-84 mm) and thirdly, to NT thickness, (1.8% for NT < 2.5 mm, 3.4% for NT 2.5-3.4 mm, 5.0% for NT 3.5-4.4 mm and 11.8% for NT > or = 4.5 mm. In the chromosomally abnormal group the nasal bone was absent in 161/242 (66.9%) with trisomy 21, in 48/84 (57.1%) with trisomy 18, in 7/22 (31.8%) with trisomy 13, in 3/34 (8.8%) with Turner syndrome and in 4/48 (8.3%) with other defects. CONCLUSION: At the 11-14-week scan the incidence of absent nasal bone is related to the presence or absence of chromosomal defects, CRL, NT thickness and ethnic origin.

Fetal nasal bone length in chromosomally normal and abnormal fetuses at 11-14 weeks of gestation.

OBJECTIVE: To determine the value of measuring fetal nasal bone length at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: The fetal profile was examined and the nasal bone length was measured in 1092 fetuses immediately before chorionic villous sampling for karyotyping at 11-14 weeks of gestation. RESULTS: The median gestation was 12 (11-14) weeks. The fetal profile was successfully examined in all cases. The fetal karyotype was normal in 955 pregnancies and abnormal in 137, including 79 cases of trisomy 21. In the chromosomally normal group, the fetal nasal bone length increased significantly with crown-rump length (CRL) from a mean of 1.3 mm at a CRL of 45 mm to 2.1 mm at a CRL of 84 mm. In 54 of the 79 (68.4%) cases of trisomy 21, the nasal bone was absent. In the 25 cases with present nasal bone, the nasal bone length for the CRL was not significantly different from normal. Similarly, there were no significant differences from normal in the nasal bone length of fetuses with other chromosomal defects. CONCLUSIONS: At 11-14 weeks of gestation, the nasal bone length of chromosomally abnormal fetuses is not significantly different from normal.