Prevalence of aneuploidy and additional anatomic abnormalities in fetuses and neonates with cleft lip with or without cleft palate: a population-based study in Utah.

OBJECTIVE: To determine the prevalence of aneuploidy and additional major anatomic abnormalities in fetuses and neonates with cleft lip with or without cleft palate. METHODS: All cases of cleft lip with or without cleft palate (cleft lip/cleft palate) occurring in Utah from 1995 through 1999 were reviewed by using the Utah Birth Defect Network population-based surveillance system. All pregnancy outcomes are included (stillborn, live born, and termination) in this analysis. RESULTS: Of 263 cases of cleft lip/cleft palate, 72 (27.4%) were unilateral cleft lip, 112 (42.6%) were unilateral cleft lip and cleft palate, 12 (4.6%) were bilateral cleft lip, and 67 (25.5%) were bilateral cleft lip and cleft palate. Fifteen (5.7%) of the 263 fetuses and neonates were aneuploid. One (1.2%) with cleft lip (unilateral and bilateral combined) was aneuploid. Five (4.5%) of the fetuses and neonates with unilateral cleft lip and cleft palate were aneuploid compared with 9 (13.4%) of fetuses and neonates with bilateral cleft lip and cleft palate. In known or presumed euploid fetuses and neonates, additional sonographically occult major anatomic abnormalities occurred in 5 (7.0%) of 71 with unilateral cleft lip, 18 (16.8%) of 107 with unilateral cleft lip and cleft palate, 1 (8.3%) of 12 with bilateral cleft lip, and 12 (20.7%) of 58 with bilateral cleft lip and cleft palate. These abnormalities primarily involved the heart and the central nervous system. CONCLUSIONS: Amniocentesis for karyotype should be offered in all cases of cleft lip/cleft palate because of the risk of aneuploidy. Patients should be counseled that sonographically occult additional anatomic abnormalities might be present with all clefts.

MR, CT, and plain film imaging of the developing skull base in fetal specimens.

BACKGROUND AND PURPOSE: The developing fetal skull base has previously been studied via dissection and low-resolution CT. Most of the central skull base develops from endochondral ossification through an intermediary chondrocranium. We traced the development of the normal fetal skull base by using plain radiography, MR imaging, and CT. METHODS: Twenty-nine formalin-fixed fetal specimens ranging from 9 to 24 weeks' gestational age were examined with mammographic plain radiography, CT, and MR imaging. Skull base development and ossification were assessed. RESULTS: The postsphenoid cartilages enclose the pituitary and fuse to form the basisphenoid, from which the sella turcica and the posterior body of the sphenoid bone originate. The presphenoid cartilages will form the anterior body of the sphenoid bone. Portions of the presphenoid cartilage give rise to the mesethmoid cartilage, which forms the central portion of the anterior skull base. Ossification begins in the occipital bone (12 weeks) and progresses anteriorly. The postsphenoid (14 weeks) and then the presphenoid portion (17 weeks) of the sphenoid bone ossify. Ossification is seen laterally (16 weeks) in the orbitosphenoid, which contributes to the lesser wing of the sphenoid, and the alisphenoid (15 weeks), which forms the greater wing. CONCLUSION: MR imaging can show early progressive ossification of the cartilaginous skull base and its relation to intracranial structures. The study of fetal developmental anatomy may lead to a better understanding of abnormalities of the skull base.

Prevalence of aneuploidy and additional anatomic abnormalities in fetuses with open spina bifida: population based study in Utah.

Data were used to determine the population prevalence of aneuploidy and additional anatomic abnormalities in fetuses with open spina bifida. The ability of sonography to predict aneuploidy and identify additional anatomic abnormalities in euploid fetuses was assessed. All cases of spina bifida occurring in the state of Utah from 1995 through 1997 were reviewed using Utah Birth Defect Network data, including stillborn, liveborn, and terminated cases. Chromosomes were known in 45 of 51 cases of open spina bifida. Of the 45 fetuses, 6 (13%) were aneuploid. Major anatomic abnormalities were present in four of six (67%) cases, and two of six (33%) cases had additional anomalies that could be missed sonographically. Of 39 euploid fetuses, 12 (31%) had additional abnormalities, but only half likely would be detected sonographically. Our 4% risk of aneuploidy in sonographically isolated spina bifida is substantially higher than the risk associated with advanced maternal age (0.37%).

Effect of maternal hydration on mild fetal pyelectasis.

The aim of our study was to determine whether maternal hydration status prior to prenatal sonography affects fetal renal pelvic diameter. The renal pelvic diameters of fetuses from two different institutions were compared prospectively. At one institution 74 women were asked to drink 32 to 48 ounces of water prior to undergoing sonography (hydration group), whereas at the second institution, no specific hydration regimen was requested of 176 subjects. The inclusion criteria were as follows: greater than 15 weeks' gestation, otherwise normal obstetrical sonogram, normal amniotic fluid volume, and negative family history for renal disease. Renal pelvic diameter, degree of maternal bladder fullness, and gestational age were compared between the two groups using logistic regression analysis and log-linear analysis. A P value < 0.01 was considered significant. Bladder fullness in the two groups differed significantly (P < 0.001). Logistic regression analysis showed a very strong effect of maternal bladder fullness on fetal renal pelvic diameter (P < 0.001). The log-linear analysis model showed a highly significant association between maternal bladder fullness and fetal renal pelvic diameter (P < 0.001). We conclude that maternal hydration influences fetal renal pelvic diameter. The larger fetal renal diameters seen in the hydrated group support physiologic theories that the effects of maternal hydration on amniotic fluid volume are partially mediated via fetal urine production.

A magnetic resonance template for normal cerebellar development in the human fetus.

OBJECTIVE: Although ultrasound is the primary imaging modality for prenatal anatomic evaluation, some central nervous system malformations may be better defined with high-resolution magnetic resonance imaging (MRI). MRI allows us to visualize the features of brain development that were previously only seen histologically by embryologists and anatomists. Although there are several reports of the postnatal development of the cerebellum as revealed on magnetic resonance (MR) images, systematic MR studies of cerebellar development during the fetal period are lacking. Our objective was to use high-resolution MRI to provide a template of cerebellar development during the late first and early second trimesters, a period when the diagnosis of congenital malformations is most medicoethically relevant. The MR findings were then correlated with histological data. METHODS: Twenty-six normal formalin-fixed fetal specimens with a gestational age of 9 to 24 weeks were examined with high-resolution MRI using a conventional clinical magnet and pulse sequences. The MR findings were correlated with the whole-mount histological specimens catalogued in a well-known fetal atlas. RESULTS: Resolution of the morphological features of cerebellar development in fetuses greater than 10 weeks gestational age was possible. Development of the rhombic lips, vermis, fourth ventricular roof, foramen of Magendie, and the cerebellar fissures was documented. Development of the cerebellum as revealed on MR images lagged behind the known stages of development by as much as 5 weeks. Features of cerebellar histogenesis were beyond the resolution of MRI. However, differences in signal intensity between gray and white matter of the developing cerebellum were detected and are postulated to represent differences in cellularity and water content of the constituent tissues. CONCLUSION: Direct correlation of MR images of fetuses during the late first and early second trimesters with anatomic atlases could result in a mistaken diagnosis of delayed or abnormal development of the posterior fossa contents because of a time lag in the detection of structures on MR images. An MR template of normal cerebellar development would be useful to avoid confusion of normal development with abnormal development and to identify the expected developmental features when provided the estimated gestational age of a fetus.

Axial ultrasonographic imaging of the fetal maxilla for accurate characterization of facial clefts.

The purpose of this study was to determine whether scanning of the fetal midface in the axial plane allows accurate characterization of facial clefts. During fetal anatomic survey, facial clefts were identified in six fetuses. The midface anatomy was evaluated with ultrasonography in the coronal and axial planes, and the clefts were characterized prospectively as unilateral or bilateral and as involving the lip alone or both the lip and the palate. The integrity of the upper lip was assessed in the coronal and axial planes. The continuity of the normal C-shaped curve of the tooth-bearing alveolar ridge and the anterior six tooth sockets was assessed in the axial plane. The prospective prenatal diagnosis was correlated with postnatal findings in all cases. The clefts where characterized prospectively as unilateral cleft lip (one case), unilateral cleft lip and cleft palate (four cases), and bilateral cleft lip and cleft palate (one case). The prenatal characterization was confirmed to be correct postnatally in all cases. Prenatal sonographic evaluation of the axial view of the tooth-bearing alveolar ridge of the maxilla allows accurate determination of whether a cleft is confined to the lip or involves both the lip and the palate.

Spinal level of fetal myelomeningocele: does it influence ventricular size?

OBJECTIVE: Our objective was to determine whether the level of the spinal defect influences ventricular size in fetuses with myelomeningoceles. MATERIALS AND METHODS: Sonograms of 51 fetuses with open spina bifida were reviewed to determine the gestational age, ventricular atrial diameter, severity of posterior fossa deformity, and the level of the spinal defect. Four categories for spinal defect level were used: sacral, low lumbar, high lumbar, and thoracic. Regression models for ventricular atrial diameter were fit, adjusting for gestational age, posterior fossa deformity, and spinal defect level. A Fisher's exact test was used to investigate a relationship between the level of the spinal defect and the severity of the posterior fossa deformity. RESULTS: Spinal defect level was distributed among the four categories as follows: sacral (n = 7), low lumbar (n = 30), high lumbar (n = 10), and thoracic (n = 4). The level of the spinal defect did not significantly affect ventricular size (p > .1), and the level of the spinal defect did not show any relationship to the severity of the posterior fossa deformity (p > .8). CONCLUSION: The level of the spinal defect does not independently affect the degree of ventriculomegaly or severity of the posterior fossa deformity in fetuses with myelomeningoceles.

Evaluation of fetal midface anatomy related to facial clefts: use of US.

PURPOSE: To identify the sonographic appearance of normal fetal midface anatomy of in vitro fetal specimens and to correlate the appearance with that of in utero fetuses to determine which aspects of this anatomy can be evaluated clinically. MATERIALS AND METHODS: The midface structures of 12 normal fetal specimens were examined in the axial, sagittal, and coronal planes with ultrasound. The results were correlated with those of other modalities. One hundred consecutive, normal in utero fetuses were scanned in the same planes in an attempt to identify the same anatomic landmarks identified in the fetal specimens. RESULTS: In the fetal specimens, the upper lip (coronal plane), alveolar ridge, tooth sockets, point of fusion of primary and secondary palates (axial plane), and fusion line of the secondary palate (sagittal plane) were consistently observed. In the 100 in utero fetuses, the same anatomy was visualized in the coronal plane in 95 (95%), in the axial plane in 97 (97%), and in the sagittal plane in 26 (26%). The mean scanning time was 2.8 minutes. CONCLUSION: Important aspects of fetal midface anatomy that relate to facial clefts can be observed in utero at prenatal sonography in the coronal and axial planes.

Imaging findings of the developing temporal bone in fetal specimens.

PURPOSE: To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT. METHODS: Eighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed. RESULTS: The membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth. CONCLUSION: The study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning techniques may provide a method for in utero evaluation of the fetal temporal bone.

A magnetic resonance template for normal neuronal migration in the fetus.

OBJECTIVE: Although the features of neuronal migration have been known since the turn of the century, the serial features of neuronal migration as seen with magnetic resonance imaging (MRI) have not been described. Our objective was to provide a template of the normal appearance and the temporal pattern of neuronal migration in the human fetal brain early in the second trimester as seen with MR imaging and to correlate our findings with histological sections and atlases. METHODS: Twenty-eight normal fetal specimens, which ranged from 9 to 24 weeks of gestational age, were imaged with a 1.5 T clinical MRI unit by use of conventional spin echo, fast spin echo, and three-dimensional Fourier transformation spoiled gradient refocussed pulse sequences. RESULTS: The three-dimensional Fourier transformation spoiled gradient refocussed pulse sequence provided the highest resolution images of neuronal migration. At 13 weeks of gestational age, the germinal matrix was identified. A five-layer pattern of the fetal forebrain, which included layers of neuroblast formation and migration, could be identified at 16 to 18 weeks by MRI. The germinal matrix and layers of migrating neurons diminished considerably in size by 21 weeks. Histological studies and correlation with anatomic atlases confirmed the MRI findings. CONCLUSION: Images obtained by use of MRI with standard clinical pulse sequences can document the appearance and the temporal patterns of neuronal migration in postmortem fetal specimens. With the evolution of high-resolution MRI and faster scanning techniques, these findings may serve as a template for the in utero MRI appearance of neuronal migration and thereby compliment the antenatal ultrasonic investigation of congenital anomalies.

Sonographic anatomy of the developing cerebellum: normal embryology can resemble pathology.

OBJECTIVE: The aims of this study were to evaluate sonographically observable fetal cerebellar development by use of MR image and anatomic correlations to determine what aspects of this development can be visualized by sonography and to define the normal sonographic appearance of cerebellar development to assist in the differentiation of normal development from pathologic development during prenatal sonography. MATERIALS AND METHODS: The posterior fossae of 19 normal, whole, fixed fetal specimens of 11-21 weeks' gestational age were imaged by sonography and MR imaging. Images were correlated with anatomic atlases and anatomic sections. RESULTS: By 13-14 weeks, both sonography and MR imaging demonstrated the vermis between the hemispheres rostrally, but the caudal vermis was undeveloped. Although visualized on MR images, the caudal fourth ventricular roof was not yet appreciated on sonograms, giving the false impression of communication between the fourth ventricle and the cisterna magna. Separation of these CSF spaces was not appreciated at all levels sonographically until 16 weeks. CONCLUSIONS: The sonographic appearance of normal cerebellar development can resemble pathology early in the second trimester. Caution is warranted in making an early diagnosis of fetal cerebellar dysgenesis.

Ultrasound evaluation of prenatal and neonatal spina bifida.

Interest in studying the role of sonography in the evaluation of newborns and infants with spinal dysraphism waned with the advent of MR imaging. Sonographic evaluation of the neonatal spine, however, can be performed portably, is relatively inexpensive when compared with MR imaging, and does not require sedation. Its recognized utility in evaluating the neonatal spine in both open and occult spinal dysraphisms makes sonography an ideal diagnostic modality for this patient population. Its most valuable contribution probably lies in screening for closed dysraphisms, but comparative studies with MR imaging are necessary to clarify sonography's role.

Prenatally detected fetal myelomeningocele: is karyotype analysis warranted?

PURPOSE: To determine the prevalence of karyotype abnormalities in fetuses with prenatally detected spina bifida and evaluate the ability of prenatal sonography to enable prediction of chromosomal abnormalities. MATERIALS AND METHODS: Sonograms from 63 fetuses with prenatally detected spina bifida were reviewed, and associated sonographic abnormalities were recorded. Sonographic findings were correlated with autopsy or clinical findings when possible. RESULTS: Associated sonographic abnormalities were present in 15 (24%) of fetuses with spina bifida. Among 52 fetuses with known karyotypes, the prevalence of chromosome abnormalities was 17%. Karyotype abnormalities included trisomy 18, trisomy 13, triploidy, and translocation. Twenty-two percent of chromosomally abnormal fetuses had sonographically isolated spina bifida. CONCLUSION: Prenatal sonography can help predict most karyotypically abnormal fetuses with spina bifida, but approximately 20% will be missed with this technique alone in the second trimester. The authors believe cytogenetic analysis is justified in the setting of prenatally detected spina bifida.

Gastroschisis: can sonography of the fetal bowel accurately predict postnatal outcome?

To determine whether prenatal sonographic features of the small bowel can accurately predict postnatal outcome in fetuses with gastroschisis, the sonograms of 24 fetuses with prenatally detected gastroschisis were retrospectively reviewed for fetal bowel features including small bowel dilatation and bowel wall thickening. To identify a relationship between the sonographic features and neonatal outcome, each feature was analyzed against eight adverse clinical outcome measures including bowel obstruction or atresia, necrosis, and need for bowel resection, using chi-square analysis and Kendall's taub correlation. When a relationship was identified, the sensitivity and specificity of the sonographic feature for predicting adverse outcome were determined. Only maximum small bowel diameter was related to postnatal bowel complications. Significantly more fetuses with a maximum small bowel diameter of greater than 11 mm (7/12) had bowel complications than did fetuses with MBD 11 mm or less (2/12) P < 0.05). Using a cutoff point of greater than 11 mm for maximum small bowel diameter, the sensitivity was 78%, specificity 66%, and positive predictive value 71% for predicting postnatal bowel complications. However, in only seven of 24 cases did the two observers make the same maximum small bowel diameter measurement, and in 14 of 24 cases their measurements differed by 2 mm or more. The observers varied sufficiently in their measurements to shift three fetuses (13%) between categories (< or = 11 mm or > 11 mm). Although a maximum small bowel diameter of 11 mm stratified our fetuses, this measurement may not be clinically meaningful.

Sonography of ovarian masses: poor sensitivity of resistive index for identifying malignant lesions.

OBJECTIVE: Current research suggests that the resistive index of adnexal masses is a sensitive measure for distinguishing between benign and malignant ovarian masses. We devised a study to determine how morphologic findings on sonograms compare with the resistive index of benign and malignant lesions. SUBJECTS AND METHODS: Pelvic sonograms were obtained in 34 women with 36 adnexal masses that were likely neoplastic or non-self-limiting (such as an endometrioma). Transabdominal and transvaginal sonograms were obtained, and the resistive index was calculated. A threshold resistive index of 0.4 was used to differentiate benign from malignant lesions. Masses were characterized prospectively as probably benign or possibly malignant on the basis of their sonographic appearance. Pathologic proof was obtained for 35 masses, and one mass was diagnosed on the basis of CT findings. RESULTS: Seventeen lesions were deemed probably benign, and pathologic examination showed that all 17 were benign. The resistive index was greater than 0.4 in 14 of these 17 cases. Nineteen lesions were characterized as possibly malignant. On pathologic examination, six were benign neoplasms, five were nonneoplastic masses, and eight were malignant neoplasms. The resistive index was greater than 0.4 in 10 of the 11 benign lesions. It was less than 0.4 in only two of the eight lesions that were classified as malignant on the basis of both morphologic and pathologic findings. CONCLUSION: Sonography is sensitive but not specific for distinguishing between benign and malignant ovarian neoplasms. Although use of the resistive index might improve specificity in the assessment of possibly malignant lesions, reliance on this parameter is potentially misleading, as six of eight malignant lesions in this series were miscategorized on the basis of their resistive index.

Prevalence of ventriculomegaly in association with myelomeningocele: correlation with gestational age and severity of posterior fossa deformity.

PURPOSE: To investigate the relationship of ventriculomegaly (VM) with gestational age (GA) and the severity of the associated Chiari II malformation. MATERIALS AND METHODS: The sonograms of 51 fetuses with myelomeningoceles were retrospectively reviewed. VM was judged to be present when the transverse ventricular atrial diameter was greater than 10 mm. The severity of the posterior fossa (PF) deformity was subjectively graded as mild, moderate, or severe. Thirty-four fetuses were scanned at < or = 24 weeks GA, and 17 were scanned at > 24 weeks GA. RESULTS: The prevalence of VM was 61%. However, only 44% of fetuses < or = 24 weeks GA had VM, whereas 94% of fetuses > 24 weeks GA had VM. When compared with fetuses with mild PF deformities, fetuses with moderate or severe deformities had a higher prevalence of VM and the largest ventricles. CONCLUSION: The prevalence of VM in fetuses with myelomeningoceles varies with both GA and the severity of the associated PF deformity. These observations may provide additional prognostic information once a myelomeningocele is detected at sonography.

Effect of clinical history on the interpretation of chest radiographs in childhood bronchiolitis.

RATIONALE AND OBJECTIVES: This study assesses the effect of a clinical history of "bronchiolitis" versus "well child" on the interpretation of pediatric chest radiographs. METHODS: Radiologists reviewed radiographs previously identified as "definite bronchiolitis," "equivocal bronchiolitis," "definite normal," and "equivocal normal." They were asked to identify features of bronchiolitis and give a confidence level for their diagnosis. A correct clinical history of "bronchiolitis" or a "well child" was provided for all definite and half the equivocal radiographs. The other half of the equivocal radiographs were matched with incorrect histories. RESULTS: Given normal radiographs with a history of bronchiolitis, radiologists reported more features of bronchiolitis with increased confidence and also more features. CONCLUSIONS: The results suggest that the effect of history is not simply to provide additional confirmatory information, thereby increasing the diagnosis rating, but rather to change the interpretation of features, to the extent that features apparently are seen even on normal radiographs.

The correlation of feature identification and category judgments in diagnostic radiology.

Expert and novice radiologists were given films accompanied by clinical histories that supported a diagnosis either of bronchiolitis or of normal. To provide a plausible task context, some films were radiologically unambiguous and were accompanied by histories consistent with them. For a set of radiologically difficult films from confirmed normal or bronchiolitis patients, fictitious normal or abnormal histories were counterbalanced with the films. The clinical histories affected ratings both of diagnosis and of features present on the difficult films. Thus, uncertainty about individual features evidently was affected by history, and features did not act as an independent source of information. The dependence of feature calls on an overall judgment was also suggested by intra-observer agreement in another study in which an explicit diagnosis was not requested. It is unclear whether the history increased discrimination between normal and abnormal films, or indiscriminately added evidence for or against the disease. Factors are discussed that make it appropriate for feature identification to be partially dependent on category identification.

Observer variation in detecting the radiologic features associated with bronchiolitis.

Chest radiographs are commonly obtained to assess children for bronchiolitis, both to corroborate the diagnosis and to exclude other diagnostic possibilities. Their utility in this setting has not previously been examined. Using a blinded, randomized study design, we examined the interobserver and intraobserver variation in the detection of the radiologic features of bronchiolitis from the chest radiograph using "weighted kappa" statistics. This observer variation was compared with that found by other authors for other diagnoses. We also determined the reported presence of these radiologic features in radiographs from patients with bronchiolitis as compared with normal controls. Our study showed acceptable interobserver (kappa = 0.40-0.66) and intraobserver agreement (kappa = 0.50-0.78) on the radiologic features of bronchiolitis relative to other diagnoses. We demonstrated a higher reported presence of these accepted radiologic features in patients with bronchiolitis as compared to controls. Although kappa statistics are widely used in studies of observer variation, "weighted kappa" has received little attention in the radiologic literature. This statistical analysis allows observers to equivocate on the presence or absence of a feature and therefore allows the format of observer variation studies to simulate more closely the normal clinical setting.