Imaging of the Fetal Zygomatic Bone: A Key Role in Prenatal Diagnosis of First Branchial Arch Syndrome.

OBJECTIVES: First arch syndromes are congenital defects caused by failure of neural crest cells to migrate into the first branchial arch. First arch syndrome is classified into 2 main clinical manifestations: Treacher Collins syndrome, characterized by bilateral underdevelopment of the zygomatic bones; and Pierre Robin sequence. The aim of this study was to describe the feasibility of visualization of the fetal zygomatic bone and assess its application in cases referred for features suggestive of first arch syndrome. METHODS: A prospective cohort study was conducted. The feasibility of visualization of the zygomatic bone was performed in 50 sequential fetuses with a normal anatomic scan between 12 and 24 weeks' gestation using 3-dimensional sonography. Following this, cases referred for targeted scans for suspected first branchial arch syndrome were assessed for the presence or absence of the zygomatic bones. RESULTS: Visualization of the fetal zygomatic bone was feasible in all low-risk cases. Cases referred for targeted scans included 11 isolated cases of micrognathia or retrognathia, 3 cases of microtia, and 3 cases of auricular or facial vestiges. Within this group, the zygomatic bones were visualized in all but 2 cases. No associated extrafacial malformations were detected; therefore, this phenotype was consistent with Treacher Collins syndrome. CONCLUSIONS: Prenatal imaging of the zygomatic bones offers a clinically based sonographic approach to cases referred for features suggestive of first arch syndrome and enables differentiation between the 2 main clinical manifestations: Treacher Collins syndrome and Pierre Robin sequence.

The added value of detailed early anomaly scan in fetuses with increased nuchal translucency.

OBJECTIVE: This study aims to assess the utility of a detailed early fetal anatomy scan prior to karyotyping in the management of pregnancies with an increased nuchal translucency (NT). METHODS: The study included fetuses with NT above the 99th centile. These women were offered the option of an early detailed fetal anatomy scan prior to genetic evaluation. The presence or absence of major sonographic findings was analyzed for its predictive value for fetal aneuploidy. RESULTS: An increased NT >99th centile was detected in 43 fetuses (1.8%). Mean NT was 4.5 mm (range 3.4-9.0), and gestational age at the early fetal anatomy survey was 12.4 weeks (12-13.6). Major sonographic findings were present in 30 fetuses (69.8%); 24 of them underwent karyotyping, and it was abnormal in 14. Among the 13 fetuses without major sonographic findings, 12 had normal karyotype results, and 1 had aneuploidy, yielding a positive predictive value of 58.3% of early fetal anatomy scan for abnormal karyotype results. Multivariate logistic regression analysis showed that the presence of major sonographic findings was as an independent predictor of fetal aneuploidy (adjusted odds ratio 8.15). CONCLUSION: A detailed early anatomy scan upon detection of increased NT has an important value in the prediction of fetal aneuploidy. © 2016 John Wiley & Sons, Ltd.

Prenatal sonographic features of triploidy at 12-16 weeks.

OBJECTIVE: The purpose of our study was to describe the sonographic appearance of triploidy in early pregnancy. METHODS: We report the sonographic characteristics of a cohort of fetal triploid cases detected at targeted ultrasonographic vaginal examinations between 12 and 16 weeks of gestation from 2008 to 2014. Indications for fetal karyotype following ultrasound were maternal request, advanced maternal age, increased nuchal translucency, and/or fetal abnormalities. RESULTS: Triploidy was detected in 25 cases during the 6 years of the study period with an estimated incidence of ~1 in 5000 pregnancies. Four cases had molar changes in the placenta. Among the remaining 21 cases, a consistent sonographic pattern was noted, which included the combination of asymmetric growth restriction with abdominal circumference lagging 2 weeks behind head circumference in 21/21, oligohydramnios in 20/21, abnormal posterior fossa or enlarged fourth ventricle in 20/21, and absent gall bladder in 17/21. Other findings present in more than 50% of cases included cardiac (70%) and renal (55%) abnormalities, clenched hands (55%), and hypoplastic lungs (67%). CONCLUSION: Fetal triploidy can manifest at 12-16 weeks with molar changes in the placenta or with a cluster of unusual sonographic findings whose presence should prompt appropriate testing for diagnosis in early pregnancy. © 2016 John Wiley & Sons, Ltd.

Sonographic Evaluation of the Fetal Thymus Using the Thy-Box Technique Between 13 and 16 Weeks' Gestation.

OBJECTIVES: The purposes of this study were to assess the feasibility of fetal thymus measurement between 13 and 16 weeks' gestation, to evaluate the potential difference using color Doppler sonography with the thy-box technique, and to construct normal percentile ranges. METHODS: This retrospective study included 287 healthy singleton pregnancies. The fetal thymus was shown in an axial plane of the upper mediastinum. Color Doppler imaging was applied to outline the thy-box: ie, the area between the brachiocephalic artery posteriorly and internal mammary arteries laterally. Measurements of the lateral and anteroposterior diameters of the thymus with and without color Doppler imaging were compared. RESULTS: The thymus was shown in 95% of the cases (273 of 287) between 13 and 16 weeks' gestation. The mean lateral thymus diameter ± SD with color Doppler imaging (5.30 ± 0.7 mm) was significantly longer in comparison to the measurement without color Doppler imaging (5.06 ± 0.8 mm; P < .001), whereas the anteroposterior diameter was significantly shorter (3.19 ± 0.9 versus 3.26 ± 0.8 mm; P = .044). Normal percentiles of thymus measurements for gestational age were constructed. CONCLUSIONS: The fetal thymus can be clearly and accurately shown as early as 13 weeks' gestation by using the thy-box. Measurements with color Doppler imaging were significantly different from those without and hence are preferable, as color Doppler imaging can delineate the thymus borders more accurately.

Umbilical vein insertion into the inferior vena cava: an ominous sign of chromosomal abnormalities?

This series describes the sonographic characteristics and pregnancy outcomes of fetuses with abnormal insertion of the umbilical vein (UV) into the inferior vena cava (IVC). We conducted a retrospective study that described the sonographic features of 6 patients who underwent a routine anatomic scan during early pregnancy. Six patients had a diagnosis of abnormal insertion of the UV to the IVC; in 3, the diagnosis was made at 12 weeks' gestation. Cardiac anomalies were detected in 3 patients, including ventricular septal defects, pericardial effusion, tricuspid and mitral regurgitation, and an aberrant right subclavian artery. Four had noncardiac anomalies, including cystic hygroma and skeletal, brain, and abdominal anomalies. Only 1 fetus who presented with UV insertion into the IVC as an isolated finding had a normal karyotype, resulting in term vaginal delivery. Four other patients had chromosomal abnormalities, including trisomies 13 and 21, Turner mosaicism of 45,XO/46,XY, and Robertsonian translocation, and 1 patient terminated the pregnancy without a karyotype evaluation. Abnormal insertion of the UV into the IVC with agenesis of the ductus venosus can be seen as early as the first trimester. When detected, a detailed anatomic examination should be performed, as well as a fetal karyotype evaluation. Isolated cases of insertion of the UV into the IVC at a position lower than usual may have a good prognosis.

Sonographic examination of the fetal vermis: tricks for obtaining the narrow midline target with 3-dimensional volume contrast imaging in the C plane.

Prenatal imaging of the fetal cerebellar vermis is challenging even for experienced examiners. We found that by aiming the ultrasound beam through the mastoid fontanel and then rotating the data set in a multiplanar reconstruction and applying volume contrast imaging in the C plane, we were consistently able to obtain images of the vermis in the standard midsagittal plane. Images of the fetal vermis suitable for morphologic evaluation were obtained in 408 of 414 cases (98.5%) at gestational ages of 18 weeks to 31 weeks 6 days; the examination time was only minimally increased.

Fetal brain asymmetry: in utero sonographic study of normal fetuses.

OBJECTIVE: The objective of the study was to evaluate the magnitude of normal fetal brain asymmetry. STUDY DESIGN: This was a prospective study. Normal fetuses between 19-28 weeks of gestation were studied. The cerebral atria, occipital cortex, and hemispheres in both sides were measured. The difference between each side was evaluated and was correlated with sex, head biometry, and estimated weight. RESULTS: Four hundred six fetuses were studied. Mean atrial width was larger in the males and on the left side (5.2% and 6.5%, respectively). Mean cortical width was 2.6% larger in males but 5.5% thinner on the left side. Mean hemisphere width was larger in males and on the left side (2.3% and 1.5%, respectively). The atria and the cortex presented an inverse relationship regarding fetal growth parameters. CONCLUSION: Brain asymmetry represents normal fetal brain developmental phenomena. It is sex dependent and lateralized in most cases to the left. Lateralization was more accentuated in males.

Three-dimensional ultrasonography of the fetal vermis at 18 to 26 weeks' gestation: time of appearance of the primary fissure.

OBJECTIVE: The purpose of this study was to establish the normality of the fetal vermis, ie, the time of appearance of the primary fissure, as well as its measurements between 18 and 26 weeks' gestation, using 3-dimensional (3D) ultrasonography. METHODS: A prospective cross-sectional study of normal singleton pregnancies was conducted. Examinations were performed with high-resolution transabdominal ultrasonography using the axial plane in 173 fetuses between 18 and 26 weeks' gestation. Postprocessing measurements of the fetal vermis were done with 4-dimensional software using static volume contrast imaging and tomographic ultrasound imaging in the C-plane. Detection of the primary fissure was evaluated in all cases, and the time of appearance was documented. RESULTS: Adequate vermis measurements were obtained in 173 fetuses. Vermian length as a function of gestational age was expressed by regression equations, and the correlation coefficients were found to be highly statistically significant (P < .001). The normal mean +/- 2 SD for each gestational week was defined. The primary fissure was observed at 24 weeks' gestation in all cases, at 22 weeks in 94% of cases, and as early as 18 weeks in 40%. CONCLUSIONS: This 3D study documents the appearance of the primary fissure and presents the normal range of vermian measurements, confirming normal development of the fetal vermis starting as early as 18 weeks' gestation. It also shows an easy method for visualizing the vermis with 3D ultrasonography at every gestational week regardless of fetal presentation.

Ultrasonographic diagnosis of glossoptosis in fetuses with Pierre Robin sequence in early and mid pregnancy.

OBJECTIVE: This study was undertaken to describe the sonographic features of fetal glossoptosis in the Pierre Robin sequence. STUDY DESIGN: Fetal sonography was prospectively performed in 8000 consecutive pregnancies at 14 to 24 weeks' gestation. In addition we retrospectively reevaluated ultrasound recordings of 4 fetuses from other hospitals, in which the diagnosis of Pierre Robin sequence was overlooked at 22 weeks' gestation. Glossoptosis was defined as a posteriorly displaced tongue that never reached the anterior mandibular alveolar ridge while watching the fetal profile. Micrognathia, which is a component of the sequence, was subjectively defined. RESULTS: Glossoptosis with micrognathia was detected in 2 fetuses in the prospective group at 14 and 15 weeks' gestation. Both pregnancies were terminated; the diagnosis was confirmed in 1 case where postmortem examination was performed. There were no false-negative diagnoses in the other 7.998 fetuses. Glossoptosis and micrognathia were observed in the 4 retrospective cases. CONCLUSION: Sonographic identification of glossoptosis with fetal micrognathia suggests the possibility of Pierre Robin sequence.

The influence of prothrombotic polymorphisms and obstetrical and medical variables on the length of secondary postpartum hemorrhage.

OBJECTIVE: To determine if the presence of prothrombotic polymorphisms, such as factor V G1691A (factor V Leiden) or factor II G20210A, affect the length of secondary postpartum bleeding. METHODS: We conducted a prospective and blind study that enrolled primiparous healthy women following singleton pregnancy. Whole blood was taken for determining the presence of factor V G1691A or prothrombin G20210A by PCR and specific restriction enzymes. RESULTS: We enrolled 638 women, of whom 524 had vaginal delivery, 34 had planned cesarean delivery, and 80 had emergency cesarean delivery. Seventy-nine of 524 women with vaginal delivery required vacuum, 19 women needed forceps, and 2 women required both vacuum and forceps. Seventy parturients had prothrombotic polymorphisms: 31 were heterozygote to factor V G1691A, 34 were heterozygote to prothrombin G20210A, and 1 was homozygote for the mutation. Another 4 women had both mutations. Women who gave birth by planned cesarean deliveries bled 4.9 days longer on average than women who gave birth vaginally or had emergency cesarean delivery (p = 0.03), after adjustment for length of pregnancy. The weight of the newborn and the length of the pregnancy affected the duration of bleeding. The presence of prothrombotic polymorphisms did not affect the duration of postpartum bleeding. CONCLUSIONS: The duration of secondary postpartum hemorrhage is related to length of pregnancy, neonate weight, and planned cesarean delivery but is not affected by the presence of factor V G1691A or prothrombin G20210A mutation in the primiparous women.

Prenatal diagnosis of sex differentiation disorders: the role of fetal ultrasound.

We describe our experience with prenatal diagnosis of sex differentiation disorders, with focus on the role of ultrasound scans for coherent assessment of prenatal diagnosis. Over a 5-yr period all cases suspected of sexual ambiguity based on abnormal ultrasonographic scans (US) or US/genotype US discrepancy were evaluated prenatally by three modalities: 1) repeated fetal US; 2) genetic studies, primarily karyotype and fluorescence in situ hybridization analysis of sex-determining region on the Y gene (SRY); and 3) hormonal assays of amniotic fluid. Of approximately 10,000 gestations, 16 fetuses underwent prenatal evaluation. Twelve were referred because of an abnormal US and 4 because of genotype-phenotype discrepancy. Five fetuses were diagnosed with female pseudohermaphroditism (21-hydroxylase deficiency in 3 and urorectal septum malformation sequence in 2). Four fetuses were diagnosed with male pseudohermaphroditism (1 with steroid sulfatase deficiency, 1 with presumed camptomelic dysplasia, and 2 undetermined). Five cases had chromosomal abnormalities, and 2 had 46,XX+SRY sex reversal. In all genetic females the uterus was observed on US. In 11 cases initial US scan was performed at 13-15 wk; in 7 of 11, although the initial scan was normal, a repeated scan later in gestation revealed an abnormality. Repeated US scans performed at 13-15 and 22-24 wk gestation are a helpful tool in prenatal diagnosis of sex differentiation disorders. Our data suggest that both size and structure anomalies of the reproductive structures may evolve throughout pregnancy, and that they represent a developmental biological process rather than a single nonprogressive pathological event. US scan after approximately 19 wk enables detection of the uterus and provides pivotal information in cases of ambiguity. If the uterus appears normal, the most likely diagnosis is a virilized karyotypic female. Prenatal diagnosis allows for early parental counseling and anticipation of medical management postnatally.

Outcome of pregnancies with vertical transmission of primary cytomegalovirus infection.

OBJECTIVE: To study the outcome of 50 pregnancies with documented vertical transmission of cytomegalovirus infection. METHODS: We recruited 50 pregnant women (51 fetuses) with primary cytomegalovirus infection and confirmed in utero transmission. Prenatal evaluation included diagnostic amniocentesis and repeated ultrasound examinations. Fetal diagnosis was made after 21 weeks' gestation by amniocentesis and based on virus isolation by culture, shell vial, and polymerase chain reaction (PCR). Cytomegalovirus infection in neonates was determined by urinary viral isolation after birth or histologic examination of tissue from aborted fetuses. Cerebral ultrasound, hearing assessment, and psychomotor development were investigated for all 18 live-born neonates. RESULTS: Thirty-three of the 50 women (66%) elected termination of pregnancy. Ultrasonographic abnormalities associated with in utero fetal infection were observed in 11 (21.5%) fetuses. Two of them continued to term; both were congenitally infected, and one had neurologic abnormalities. The positive predictive values of the PCR and virus isolation assessments performed in all 50 pregnancies (51 gestational sacs) were 92% and 93.7%, respectively. Seventeen pregnancies (18 fetuses) continued to term: four fetuses had neurologic abnormalities, of which three had normal prenatal ultrasound findings. The remaining 14 had normal neonatal assessments. CONCLUSION: Positive isolation of cytomegalovirus accompanied by positive PCR values in amniotic fluid provided approximately 94% certainty of in utero cytomegalovirus infection. The risk of postnatal neurologic abnormalities was 19% (three of 16) when there were no prenatal ultrasonographic abnormalities.

The resistance index in the fetal middle cerebral artery by gestational age and ventricle size in a normal population.

OBJECTIVE: To study the association between fetal middle cerebral artery flow and the lateral cerebral ventricular width throughout gestation. METHODS: The study is a prospective cohort evaluation of 430 singleton male and female fetuses between 20 and 40 weeks' normal gestation. Abdominal ultrasonography and Doppler measurements were performed to measure the fetal atrial ventricular size and resistance index (RI) of the middle cerebral artery. RESULTS: The mean (+/- standard deviation) ventricular width was 6.2 +/- 1.2 mm. The modification in the RI of the middle cerebral artery throughout gestation showed a biphasic mode, increasing gradually to a peak at 30 weeks' gestation and decreasing progressively thereafter. No significant correlation was found between the middle cerebral artery flow and the lateral cerebral ventricular width (r =.11). In addition to the 430 cases studied, three cases of mild ventriculomegaly and three cases of hydrocephalus were evaluated. The RI of the middle cerebral artery was within the normal range in all six of these cases. CONCLUSION: Fetal middle cerebral artery blood flow is not affected by the width of the lateral ventricles, even in enlarged ventricles.

The "lasso sign": an early sonographic sign of posterior meningocele.

Posterior meningocele is an uncommon form of spina bifida. We present a case of unique posterior meningocele diagnosed at the early second trimester anatomical scan using 2D and 3D ultrasound. The sonographic appearance resembled "lasso". The prenatal follow-up was uneventful, with no demonstration of tethered cord. Clinical, neurological and radiological examinations following delivery and at the age of four months were unremarkable.

Isolated fetal umbilical vein varix--prenatal sonographic diagnosis and suggested management.

OBJECTIVE: To present our experience with fetuses with umbilical vein varix (UVV), to investigate possible risk factors and to suggest a management scheme of evaluation. STUDY DESIGN: A study of 14 pregnancies complicated with isolated UVV was performed. Data collected included sonographic characteristics of the UVV, pregnancy outcome including induction of labour, mode of delivery, birthweight, and neonatal complications. RESULTS: UVV was diagnosed at a median gestational age of 27.5 weeks' gestation (range: 22-34 weeks). The average diameter of the UVV at diagnosis was 10.6 mm (range: 8-15 mm), and the maximal diameter during follow-up was 12.8 mm (range: 10-18 mm). The median gestational age at delivery was 36.1 weeks (range: 34-40 weeks), with an average birthweight of 2834 g (range: 1725-3715 g). Five women underwent emergent cesarean section. In fetuses with turbulent flow in the UVV there was a tendency to larger maximal sizes of the UVV, earlier gestational age at delivery and smaller birthweight. There were no cases of fetal or neonatal demise. CONCLUSIONS: We suggest that fetuses with UVV should be followed weekly from diagnosis to 28 weeks, and twice a week afterwards. Induction of labour should be considered at 36-37 weeks' gestation or at signs of fetal distress.

The fetal mandible: an in utero sonographic evaluation between 11 and 31 weeks' gestation.

OBJECTIVE: To construct a growth chart of the mandible throughout gestation. METHODS: A prospective cross-sectional study of normal singleton pregnancies was conducted. Measurements of the fetal mandibular transverse and antero-posterior diameters were performed with high-resolution transvaginal and transabdominal ultrasonography in 490 pregnant women with singleton low-risk pregnancies between 11 and 31 weeks' gestation. RESULTS: The mandibular transverse and antero-posterior diameters were recorded by week of gestation and the ratio was calculated: mandibular ratio (MR) = 1.7759 - 0.01047 x gestational week. There was a negative linear correlation (-1.047%) for each incoming week of gestation. Normal values (+/-1SD and 2SD) were established. CONCLUSION: The present data provides a normal range of fetal mandibular diameters during normal pregnancies and introduces a new parameter, the mandibular ratio, for the intrauterine assessment of the fetal mandibular development.

Development of the fetal spinal cord: time of ascendance of the normal conus medullaris as detected by sonography.

OBJECTIVE: The purpose of this study was to perform high-resolution sonographic examinations to determine the normal anatomic relationship of the conus medullaris (CM) of the spinal cord with the vertebral column during different stages of gestation. METHODS: In this prospective study, fetal sonographic evaluations were performed between 13 and 40 weeks' gestation. Transvaginal probes (7.5-8 MHz) or abdominal probes (5-8 MHz) were used, depending on gestational age and position of the fetus. The CM was located in coronal longitudinal sections. The positions of the kidneys and lumbosacral junction and the origin of the ribs determined the location of the vertebrae. The locations of the CM were divided into 5 groups according to their positions relative to the vertebrae. RESULTS: A total of 110 fetuses between 13 and 40 weeks' gestation were studied. Between 13 and 18 weeks' gestation, the CM was situated at the level of the L4 vertebra, or more caudally, in 100% of the fetuses. At term, all fetuses showed the CM above L2. A distinct ascent of the CM was detected between 13 and 40 weeks' gestation. The results were statistically significant (P < .0001). CONCLUSIONS: A distinguishable ascent of the CM in relation to the vertebral column during fetal life was detected.

The development of the fetal thymus: an in utero sonographic evaluation.

OBJECTIVES: To establish a nomogram for fetal thymus size during gestation. METHODS: The study is a prospective, cross sectional evaluation of 403 male and female fetuses between 14 and 38 weeks of normal singleton pregnancies. Measurements of fetal thymus size were performed by high resolution transvaginal ultrasonography between 14 and 17 weeks' gestation, and by transabdominal ultrasonography after 18 weeks' gestation. RESULTS: Adequate thymus size measurements were obtained in all 403 fetuses. Thymus size as a function of gestational age was expressed by the regression equation: (square root) thymus size (mm)= -39.39+4.41 x gestational age (weeks). The correlation coefficient, r=0.965, was found to be highly statistically significant (p<0.0001). The normal mean and the 90% prediction limits were defined. CONCLUSION: The present data offer the normal range of fetal thymus size from early stages of gestation that may allow intrauterine assessment of its development. It may be helpful in the prenatal diagnosis of thymic pathologies.