Many fetal anomalies and syndromes may be characterized with targeted sonography. Selected abnormalities of the anatomical components in Table 10-5 are discussed below. This list is not intended to be comprehensive but covers abnormalities that are relatively common and may be detectable with standard sonography, as well as those that are potentially amenable to fetal therapy. Sonographic features of chromosomal abnormalities are reviewed in Chapters 13 and 14, and fetal therapy is discussed in Chapter 16.
Standard sonographic evaluation of the fetal brain includes three transverse (axial) views. The transthalamic view is used to measure the BPD and HC and includes the midline falx, cavum septum pellucidum (CSP), and thalami (see Fig. 10-1A). The CSP is the space between the two laminae that separate the frontal horns. Inability to visualize a normal CSP may indicate a midline brain abnormality such as agenesis of the corpus callosum, lobar holoprosencephaly, or septo-optic dysplasia (de Morsier syndrome). The transventricular view includes the lateral ventricles, which contain the echogenic choroid plexus (Fig. 10-2). The ventricles are measured at their atrium, which is the confluence of their temporal and occipital horns. The transcerebellar view is obtained by angling the transducer back through the posterior fossa (Fig. 10-3). In this view, the cerebellum and cisterna magna are measured, and between 15 and about 20 weeks, the nuchal skinfold thickness may be measured (Chap. 14, First-Trimester Screening). From 15 until 22 weeks, the cerebellar diameter in millimeters is roughly equivalent to the gestational age in weeks (Goldstein, 1987). The cisterna magna normally measures between 2 and 10 mm. Effacement of the cisterna magna is present in the Chiari II malformation, discussed on Ventriculomegaly.
The transventricular view depicts the lateral ventricles, which contain the echogenic choroid plexus (CP). The lateral ventricle is measured at the atrium (arrows), which is the confluence of the temporal and occipital horns. A normal measurement is between 5 and 10 mm throughout the second and third trimesters. The atria measured 6 mm in this 21-week fetus.
Transcerebellar view of the posterior fossa, demonstrating measurement of the cerebellum (+), cisterna magna (X), and nuchal fold thickness (bracket). Care is taken not to angle obliquely down the spine, which may artificially increase the nuchal fold measurement.
Imaging of the spine includes evaluation of the cervical, thoracic, lumbar, and sacral regions (Fig. 10-4). Representative spinal images for record keeping are often obtained in the sagittal or coronal plane. However, real-time imaging should include evaluation of each spinal segment in the transverse plane, as this is more sensitive for abnormality detection. Transverse images demonstrate three ossification centers. The anterior ossification center is the vertebral body, and the posterior paired ossification centers represent the junction of vertebral laminae and pedicles. Ossification of the spine proceeds in a cranial-caudal fashion, such that ossification of the upper sacrum (S1-S2) is not generally visible sonographically before 16 weeks’ gestation. Ossification of the entire sacrum may not be visible until 21 weeks (De Biasio, 2003). Thus, detection of some spinal abnormalities may be challenging in the early second trimester.
Normal fetal spine. In this sagittal image of a 21-week fetus, the cervical (C), thoracic (T), lumbar (L), and sacral spine (S) are depicted. Arrows denote the parallel rows of paired posterior ossification centers—representing the junction of vertebral lamina and pedicles.
Examples of spinal abnormalities include spina bifida, caudal regression sequence, and sacrococcygeal teratoma. More subtle spinal abnormalities may be visible. These include diastematomyelia, which is a longitudinal cleft or splitting of the spinal cord itself, and hemivertebrae—a component of the vertebral, anal, cardiac, tracheo-esophageal fistula, renal, limb (VACTERL) association.
If a brain or spinal abnormality is identified, specialized sonography is indicated. The International Society of Ultrasound in Obstetrics and Gynecology (2007) has published guidelines for a “fetal neurosonogram.” Fetal magnetic resonance (MR) imaging may be helpful in further characterizing central nervous system (CNS) abnormalities (Hydramnios).
These result from incomplete closure of the neural tube by the embryonic age of 26 to 28 days. They are the second most common class of malformations after cardiac anomalies. Their prevalence was previously considered to be 1.4 to 2 per 1000 births. However, birth defect registries in the United States and Europe now report a prevalence of only 0.9 per 1000. In the United Kingdom, the prevalence is 1.3 per 1000 (Dolk, 2010). Neural-tube defects can be prevented with folic acid supplementation (Chap. 9, Folic Acid), and their prenatal diagnosis is discussed in Chapter 14 (Neural-Tube Defects). When isolated, neural-tube defect inheritance is multifactorial, and the defect recurrence risk without periconceptional folic acid supplementation is 3 to 5 percent.
Anencephaly is characterized by absence of the cranium and telencephalic structures, with the skullbase and orbits covered only by angiomatous stroma. Acrania is absence of the cranium, with protrusion of disorganized brain tissue. Both are generally grouped together, and anencephaly is considered to be the final stage of acrania (Bronshtein, 1991; McGahan, 2003). These lethal anomalies can be diagnosed in the late first trimester, and with adequate visualization, virtually all cases may be diagnosed in the second trimester (Fig. 10-5). An inability to view the biparietal diameter should raise suspicion. Hydramnios from impaired fetal swallowing is common in the third trimester.
Anencephaly/acrania. A. Acrania. This 11-week fetus has absence of the cranium, with protrusion of a disorganized mass of brain tissue that resembles a “shower cap” (arrows) and a characteristic triangular facial appearance. B. Anencephaly. This sagittal image shows the absence of forebrain and cranium above the skull base and orbit. The long white arrow points to the fetal orbit, and the short white arrow indicates the nose.
Cephalocele is the herniation of meninges through a cranial defect, typically located in the midline occipital region (Fig. 10-6). When brain tissue herniates through the skull defect, the anomaly is termed an encephalocele. Associated hydrocephalus and microcephaly are common. Surviving infants—those with smaller defects—have a high incidence of neurological deficits and developmental impairment. Cephalocele is an important feature of the autosomal recessive Meckel-Gruber syndrome, which includes cystic renal dysplasia and polydactyly. A cephalocele not located in the occipital midline raises suspicion for amnionic-band sequence (Chap. 6, Abnormalities of the Membranes).
Encephalocele. This transverse image depicts a large defect in the occipital region of the cranium (arrows) through which meninges and brain tissue have herniated.
Spina bifida is a defect in the vertebrae, typically the dorsal arch, with exposure of the meninges and spinal cord. The birth prevalence is approximately 1 per 2000 (Cragan, 2009; Dolk, 2010). Most cases are open spina bifida—the defect includes the skin and soft tissues. Herniation of a meningeal sac containing neural elements is termed a myelomeningocele (Fig. 10-7). When only a meningeal sac is present, the defect is a meningocele. Although the sac may be easier to image in the sagittal plane, transverse images more readily demonstrate separation or splaying of the lateral processes.
Myelomeningocele. In this sagittal image of a lumbosacral myelomeningocele, the arrowheads indicate nerve roots within the anechoic herniated sac. The overlying skin is visible above the level of the spinal defect but abruptly stops at the defect (arrow).
As discussed in Chapter 14 (MSAFP Elevation), spina bifida may be reliably diagnosed with second-trimester sonography, often because of two characteristic cranial findings. These are scalloping of the frontal bones—the lemon sign (Fig. 14-4, Management of the Fetus with Spina Bifida), and anterior curvature of the cerebellum with effacement of the cisterna magna—the banana sign (Fig. 14-5) (Nicolaides, 1986). These findings are manifestations of the Chiari II malformation (also called Arnold-Chiari malformation), which occurs when downward displacement of the spinal cord pulls a portion of the cerebellum through the foramen magnum and into the upper cervical canal. Ventriculomegaly is another frequent sonographic finding, particularly after midgestation, and more than 80 percent of infants with open spina bifida require ventriculoperitoneal shunt placement. A small biparietal diameter is often present as well. Children with spina bifida require multidisciplinary care to address problems related to the defect, shunt, swallowing, bladder and bowel function, and ambulation. They are also at increased risk for latex allergy. Fetal surgery for myelomeningocele is discussed in Chapter 16 (Open Fetal Surgery).
This distention of the cerebral ventricles by cerebrospinal fluid (CSF) is a nonspecific marker of abnormal brain development (Pilu, 2011). The atrium normally measures between 5 and 10 mm from 15 weeks until term (see Fig. 10-2). Mild ventriculomegaly is diagnosed when the atrial width measures 10 to 15 mm, and overt or severe ventriculomegaly when it exceeds 15 mm (Fig. 10-8). CSF is produced by the choroid plexus, which is an epithelium-lined capillary core and loose connective tissue found in the ventricles. A dangling choroid plexus characteristically is found with severe ventriculomegaly.
Ventriculomegaly. In this transverse view of the cranium, the white line depicts measurement of the atria, which measured 12 mm, consistent with mild ventriculomegaly.
Ventriculomegaly may be caused by various genetic and environmental insults, and prognosis is determined by etiology, degree, and rate of progression. In general, the larger the atrium, the greater the likelihood of abnormal outcome (Gaglioti, 2009; Joó, 2008). The finding of an enlarged ventricle may be due to another central nervous system abnormality—such as Dandy-Walker malformation or holoprosencephaly, due to an obstructive process—such as aqueductal stenosis, or secondary to a destructive process—such as porencephaly or an intracranial teratoma. Initial evaluation includes a specialized examination of fetal anatomy, fetal karyotyping, and testing for congenital infections such as cytomegalovirus and toxoplasmosis (Chap. 64, Fetal Infection).
Even when ventriculomegaly is mild and appears isolated, counseling may be a challenge because of the wide variability in prognosis. Devaseelan and colleagues (2010) conducted a systematic review of nearly 1500 pregnancies with apparently isolated mild ventriculomegaly. They found that 1 to 2 percent of cases were associated with congenital infection, 5 percent with aneuploidy, and 12 percent with neurological abnormality in the absence of infection or aneuploidy. Neurological abnormality was significantly more common if ventriculomegaly progressed, but asymmetry of ventricular size did not affect prognosis. As abnormalities associated with mild ventriculomegaly may not be detectable sonographically, fetal MR imaging may be considered.
Agenesis of the Corpus Callosum
The corpus callosum is the major fiber bundle connecting reciprocal regions of the cerebral hemispheres. With complete agenesis of the corpus callosum, a normal cavum septum pellucidum cannot be visualized sonographically, and the frontal horns are displaced laterally. Also, there is mild enlargement of the atria posteriorly—such that the ventricle has a characteristic “teardrop” appearance (Fig. 10-9). Callosal dysgenesis can also occur, in which absence involves only the caudal portions—the body and splenium—and is consequently more difficult to detect prenatally.
Agenesis of the corpus callosum. This image demonstrates a “teardrop” shaped ventricle with mild ventriculomegaly (dotted line) and laterally displaced frontal horns (arrow). A normal cavum septum pellucidum cannot be visualized.
In population-based studies, prevalence of agenesis of the corpus callosum is 1 in 5000 births (Glass, 2008; Szabo, 2011). In a recent review of apparently isolated cases of agenesis, fetal MR imaging identified additional brain abnormalities in more than 20 percent (Sotiriadis, 2012). If the anomaly was still considered isolated following MR imaging, normal developmental outcome was reported in 75 percent of cases, and severe disability in 12 percent. Agenesis of the corpus callosum is associated with other CNS and non-CNS anomalies, aneuploidy, and many genetic syndromes—more than 200—and thus genetic counseling can be challenging.
In early normal brain development, the prosencephalon or forebrain divides into the telencephalon and diencephalon. With holoprosencephaly, the prosencephalon fails to divide completely into two separate cerebral hemispheres and into underlying diencephalic structures. Main forms of holoprosencephaly are a continuum that contains, with decreasing severity, alobar, semilobar, and lobar types. In the most severe form—alobar holoprosencephaly—a single monoventricle, with or without a covering mantle of cortex, surrounds the fused central thalami (Fig. 10-10). In semilobar holoprosencephaly, partial separation of the hemispheres occurs. Lobar holoprosencephaly is characterized by a variable degree of fusion of frontal structures. Lobar holoprosencephaly should be considered when a normal cavum septum pellucidum cannot be visualized.
Alobar holoprosencephaly. A. Transverse cranial image of a 26-week fetus with alobar holoprosencephaly, depicting fused thalami (Th) encircled by a monoventricle (V). The midline falx is absent. B. In this profile view of the face and head, a soft tissue mass—a proboscis (arrow), protrudes from the region of the forehead.
Differentiation into two cerebral hemispheres is induced by prechordal mesenchyme, which is also responsible for differentiation of the midline face. Thus, holoprosencephaly may be associated with anomalies of the orbits and eyes—hypotelorism, cyclopia, or micro-ophthalmia; lips—median cleft; or nose—ethmocephaly, cebocephaly, or arhinia with proboscis (see Fig. 10-10).
The birth prevalence of holoprosencephaly is only 1 in 10,000 to 15,000. However, the abnormality has been identified in nearly 1 in 250 early abortuses, which attests to the extremely high in-utero lethality of this condition (Orioli, 2010; Yamada 2004). The alobar form accounts for 40 to 75 percent of cases, and approximately 30 to 40 percent have a numerical chromosomal abnormality, particularly trisomy 13 (Orioli, 2010; Solomon, 2010). Conversely, two thirds of trisomy 13 cases are found to have holoprosencephaly. Fetal karyotyping should be offered when this anomaly is identified.
Dandy-Walker Malformation—Vermian Agenesis
Originally described by Dandy and Blackfan (1914), this posterior fossa abnormality is characterized by agenesis of the cerebellar vermis, posterior fossa enlargement, and elevation of the tentorium. Sonographically, fluid in the enlarged cisterna magna visibly communicates with the fourth ventricle through the cerebellar vermis defect, with visible separation of the cerebellar hemispheres (Fig. 10-11). The birth prevalence is approximately 1 in 12,000 (Long, 2006). Associated anomalies and aneuploidy are very common in prenatal series. These include ventriculomegaly in 30 to 40 percent, other anomalies in approximately 50 percent, and aneuploidy in 40 percent (Ecker, 2000; Long, 2006). Dandy-Walker malformation is also associated with numerous genetic and sporadic syndromes, congenital viral infections, and teratogen exposure, all of which greatly affect the prognosis. Thus, the initial evaluation mirrors that for ventriculomegaly (Ventriculomegaly).
Dandy-Walker malformation. This transcerebellar image demonstrates agenesis of the cerebellar vermis. The cerebellar hemispheres (+) are widely separated by a fluid collection that connects the 4th ventricle (asterisk) to the enlarged cisterna magna (CM).
Inferior vermian agenesis, also called Dandy-Walker variant, is a term used when only the inferior portion of the vermis is absent. But, even when vermian agenesis appears to be partial and relatively subtle, there is a high prevalence of associated anomalies and aneuploidy, and the prognosis is often poor (Ecker, 2000; Long, 2006).
This germ cell tumor is one of the most common tumors in neonates, with a birth prevalence of approximately 1 per 28,000 (Derikx, 2006; Swamy, 2008). It is believed to arise from the totipotent cells along Hensen node, anterior to the coccyx. The American Academy of Pediatrics–Surgical Section classification for sacrococcygeal teratoma (SCT) includes four types. Type 1 is predominantly external with a minimal presacral component; type 2 is predominantly external but with a significant intrapelvic component; type 3 is predominantly internal but with abdominal extension; and type 4 is entirely internal with no external component (Altman, 1974). The tumor may be mature, immature, or malignant. Sonographically, SCT appears as a solid and/or cystic mass that arises from the anterior sacrum and usually extends inferiorly and externally as it grows (Fig. 10-12). Solid components often have varying echogenicity, appear disorganized, and may grow rapidly with advancing gestation. Internal pelvic components may be more challenging to visualize, and fetal MR imaging should be considered. Hydramnios is frequent, and hydrops may develop from high-output cardiac failure, either as a consequence of tumor vascularity or secondary to bleeding within the tumor and resultant anemia. Fetuses with tumors > 5 cm often require cesarean delivery, and classical hysterotomy may be needed (Gucciaro, 2011). Fetal surgery for SCT is discussed in Chapter 16 (Fetoscopic Surgery).
Sacrococcygeal teratoma. Sonographically, this tumor appears as a solid and/or cystic mass that arises from the anterior sacrum and tends to extend inferiorly and externally as it grows. In this image, a 7 × 6 cm inhomogeneous solid mass is visible below the normal-appearing sacrum. There is also an internal component to the tumor.
Caudal Regression Sequence—Sacral Agenesis
This rare anomaly is characterized by absence of the sacral spine and often portions of the lumbar spine. It is approximately 25 times more common in pregnancies with pregestational diabetes (Garne, 2012). Sonographic findings include a spine that appears abnormally short, lacks the normal lumbosacral curvature, and terminates abruptly above the level of the iliac wings. Because the sacrum does not lie between the iliac wings, they are abnormally close together and may appear “shield-like.” There may be abnormal positioning of the lower extremities and lack of normal soft tissue development. Caudal regression should be differentiated from sirenomelia, which is a rare anomaly characterized by a single fused lower extremity in the midline.
Normal fetal lips and nose are shown in Figure 10-13. A fetal profile is not a required component of standard examination but may be helpful in identifying cases of micrognathia—an abnormally small jaw (Fig. 10-14). Micrognathia should be considered in the evaluation of hydramnios (Chap. 11, Congenital Anomalies). Use of the ex-utero intrapartum treatment (EXIT) procedure for severe micrognathia is discussed in Chapter 16 (Ex-Utero Intrapartum Treatment).
Midline face. This view demonstrates the integrity of the upper lip.
Fetal profile. A. This image depicts a normal fetal profile. B. This fetus has severe micrognathia, which creates a severely recessed chin.
There are three main types of clefts. The first type, cleft lip and palate, always involves the lip, may also involve the hard palate, may be unilateral or bilateral, and has a birth prevalence of approximately 1 per 1000 (Cragan, 2009; Dolk, 2010). If isolated, the inheritance is multifactorial—with a recurrence risk of 3 to 5 percent for one prior affected child. If a cleft is visible in the upper lip, a transverse image at the level of the alveolar ridge may demonstrate that the defect also involves the primary palate (Fig. 10-15).
Cleft lip/palate. A. This fetus has a prominent unilateral (left-sided) cleft lip. B. Transverse view of the palate in the same fetus demonstrates a defect in the alveolar ridge (arrow). The tongue (T) is also visible.
In a recent systematic review of low-risk pregnancies, cleft lip was identified sonographically in only about half of cases (Maarse, 2010). Approximately 40 percent of those detected in prenatal series are associated with other anomalies or syndromes, and aneuploidy is common (Maarse, 2011; Offerdal, 2008). The rate of associated anomalies is highest for bilateral defects that involve the palate. Using data from the Utah Birth Defect Network, Walker and associates (2001) identified aneuploidy in 1 percent with cleft lip alone, 5 percent with unilateral cleft lip and palate, and 13 percent with bilateral cleft lip and palate. It seems reasonable to offer fetal karyotyping when a cleft is identified.
The second type of cleft is isolated cleft palate. It begins at the uvula, may involve the soft palate, and occasionally involves the hard palate—but does not involve the lip. The birth prevalence is approximately 1 per 2000 (Dolk, 2010). Identification of isolated cleft palate has been described using specialized 2- and 3-dimensional sonography (Ramos, 2010; Wilhelm, 2010). However, it is not expected to be visualized during a standard ultrasound examination (Maarse, 2011; Offerdal, 2008).
A third type of cleft is median cleft lip, which is found in association with several conditions. These include agenesis of the primary palate, hypotelorism, and holoprosencephaly. Median clefts may also be associated with hypertelorism and frontonasal hyperplasia, formerly called the median cleft face syndrome.
This is a venolymphatic malformation in which fluid-filled sacs extend from the posterior neck (Fig. 10-16). Cystic hygromas may be diagnosed as early as the first trimester and vary widely in size. They are believed to develop when lymph from the head fails to drain into the jugular vein and accumulates instead in jugular lymphatic sacs. Their birth prevalence is approximately 1 in 5000, but given the high in-utero lethality of this condition, the incidence is much higher (Cragan, 2009).
Cystic hygromas. A. This 9-week fetus with a cystic hygroma (arrow) was later found to have Noonan syndrome. B. Massive multiseptated hygromas (arrowheads) in the setting of hydrops fetalis at 15 weeks.
Up to 70 percent of cystic hygromas are associated with aneuploidy. Of those diagnosed in the second trimester, approximately 75 percent of aneuploid cases are 45,X—Turner syndrome (Johnson, 1993; Shulman, 1992). When cystic hygromas are diagnosed in the first trimester, trisomy 21 and 45,X are both common, followed by trisomy 18 in frequency (Kharrat, 2006; Malone, 2005). In a review of more than 100 cystic hygroma cases from the First And Second Trimester Evaluation of Risk (FASTER) trial, trisomy 21 was the single most common aneuploidy (Malone, 2005). First-trimester fetuses with cystic hygromas were five times more likely to be aneuploid than the fetuses with an increased nuchal translucency.
In the absence of aneuploidy, cystic hygromas confer a significantly increased risk for other anomalies, particularly cardiac anomalies that are flow-related. These include hypoplastic left heart and coarctation of the aorta. Cystic hygromas also may be part of a genetic syndrome. One is Noonan syndrome, an autosomal dominant disorder that shares several features with Turner syndrome, including short stature, lymphedema, high-arched palate, and often pulmonary valve stenosis.
Large cystic hygromas are usually found with hydrops fetalis, rarely resolve, and carry a poor prognosis. Small hygromas may undergo spontaneous resolution, and provided that fetal karyotype and echocardiography results are normal, the prognosis may be good. The likelihood of a nonanomalous liveborn infant with normal karyotype following identification of first-trimester hygroma is approximately 1 in 6 (Kharrat, 2006; Malone, 2005).
The lungs appear as homogeneous structures surrounding the heart and are best visualized after 20 to 25 weeks’ gestation. In the four-chamber view of the chest, they comprise approximately two thirds of the area, with the heart occupying the remaining third. The thoracic circumference is measured at the skin line in a transverse plane at the level of the four-chamber view. In cases of suspected pulmonary hypoplasia secondary to a small thorax, such as with severe skeletal dysplasia, comparison with a reference table may be helpful (Appendix, Length of Fetal Long Bones (mm) According to Gestational Age). Various abnormalities may be seen sonographically as cystic or solid space-occupying lesions. Fetal therapy for thoracic abnormalities is discussed in Chapter 16 (Percutaneous Procedures).
Congenital Diaphragmatic Hernia
This is a defect in the diaphragm through which abdominal organs herniate into the thorax. It is left-sided in approximately 75 percent of cases, right-sided in 20 percent, and bilateral in 5 percent (Gallot, 2007). The prevalence of congenital diaphragmatic hernia (CDH) is approximately 1 per 3000 to 4000 births (Cragan, 2009; Dolk, 2010; Gallot, 2007). Associated anomalies and aneuploidy occur in 40 percent of cases (Gallot, 2007; Stege, 2003). Targeted sonography and fetal echocardiography should be performed, and fetal karyotyping should be offered. Given the association with genetic syndromes, chromosomal microarray analysis is a consideration (Chap. 13, Chromosomal Microarray Analysis). In population-based series, the presence of an associated abnormality reduces the overall survival rate of neonates with diaphragmatic hernia from approximately 50 percent to about 20 percent (Colvin, 2005; Gallot, 2007; Stege, 2003). In the absence of associated abnormalities, the major causes of mortality are pulmonary hypoplasia and pulmonary hypertension.
Sonographically, the most frequent finding with a left-sided defect is repositioning of the heart to the mid or right hemithorax. With this, the axis of the heart points toward the midline (Fig. 10-17). Associated findings include the stomach bubble or bowel peristalsis in the chest and a wedge-shaped mass—the liver—located anteriorly in the left hemithorax. Liver herniation complicates at least 50 percent of cases and is associated with a 30-percent reduction in the survival rate (Mullassery, 2010). With large lesions, impaired swallowing and mediastinal shift may result in hydramnios and hydrops, respectively.
Congenital diaphragmatic hernia. In this transverse view of the thorax, the heart is shifted to the far right side of the chest by a left-sided diaphragmatic hernia containing stomach (S), liver (L), and bowel (B).
Efforts to predict survival have focused on indicators such as the sonographic lung-to-head ratio, MR imaging measurements of lung volume, and the degree of liver herniation (Jani, 2012; Mayer, 2011; Metkus, 1996; Worley, 2009). These and fetal therapy for CDH are reviewed in Chapter 16 (Complications).
Congenital Cystic Adenomatoid Malformation
This abnormality represents hamartomatous overgrowth of terminal bronchioles that communicates with the tracheobronchial tree. It is also called CPAM—congenital pulmonary airway malformation, based on an understanding that not all histopathologic types are cystic or adenomatoid (Azizkhan, 2008; Stocker, 1977, 2002). The prevalence is estimated to be 1 per 6000 to 8000 births, and the reported prevalence appears to be increasing with improved sonographic detection of milder cases (Burge, 2010; Duncombe, 2002).
Sonographically, congenital cystic adenomatoid malformation (CCAM) is a well-circumscribed thoracic mass that may appear solid and echogenic or may have one or multiple variably sized cysts (Fig. 10-18). It usually involves one lobe and has blood supply from the pulmonary artery, with drainage into the pulmonary veins. When the mass is large, hydrops and pulmonary hypoplasia may result. Lesions with cysts ≥ 5 mm are generally termed macrocystic, and lesions with cysts < 5 mm are termed microcystic (Adzick, 1985).
Transverse (A) and sagittal (B) images of a 26-week fetus with a very large left-sided microcystic congenital cystic adenomatoid malformation (CCAM). The mass (C) fills the thorax and has shifted the heart to the far right side of the chest, with development of ascites (asterisks). Fortunately, the mass did not continue to grow, the ascites resolved, and the infant was delivered at term and did well following resection.
In a review of 645 CCAM cases without hydrops, the overall survival rate was above 95 percent, and 30 percent of cases demonstrated apparent prenatal resolution. In the 5 percent complicated by hydrops, there typically were very large lesions with mediastinal shift, and the prognosis was poor without fetal therapy (Cavoretto, 2008). A subset of CCAMs demonstrate rapid growth between 18 and 26 weeks’ gestation, and a measurement called the CCAM volume ratio, discussed in Chapter 16 (Congenital Adrenal Hyperplasia), has been used to quantify size and hydrops risk. Corticosteroid therapy has been used for large microcystic lesions to forestall growth and potentially ameliorate hydrops (Curran, 2010). If a large dominant cyst is present, thoracoamnionic shunt placement may lead to hydrops resolution (Wilson, 2006). Fetal therapy for CCAM/CPAM is discussed in Chapter 16 (Congenital Adrenal Hyperplasia).
Extralobar Pulmonary Sequestration
Also called a bronchopulmonary sequestration, this abnormality is an accessory lung bud “sequestered” from the tracheobronchial tree, that is, a mass of nonfunctioning lung tissue. Most cases diagnosed prenatally are extralobar, which means they are enveloped in their own pleura. Overall, however, most sequestrations present in adulthood and are intralobar—within the pleura of another lobe. Extralobar pulmonary sequestration (ELS) is considered significantly less common than CCAM, and no precise prevalence has been reported. Lesions have a left-sided predominance and most often involve the left lower lobe. Approximately 10 to 20 percent of cases are located below the diaphragm, and associated anomalies have been reported in about 10 percent of cases (Yildirim, 2008).
Sonographically, ELS presents as a homogeneous, echogenic thoracic mass. Thus, it may resemble a microcystic CCAM. However, the blood supply to an ELS is from the systemic circulation—from the aorta rather than the pulmonary artery. In approximately 5 to 10 percent of cases, a large ipsilateral pleural effusion develops, and this may result in pulmonary hypoplasia or hydrops without treatment (Chap. 16, Magnetic Resonance Imaging). Hydrops may also result from mediastinal shift or high-output cardiac failure due to the left-to-right shunt imposed by the mass (Chap. 15, Diagnostic Evaluation). In the absence of a pleural effusion, the reported survival rate exceeds 95 percent, and 40 percent of cases demonstrate apparent prenatal resolution (Cavoretto, 2008).
Congenital High Airway Obstruction Sequence (CHAOS)
This rare anomaly usually results from laryngeal or tracheal atresia. The normal egress of lung fluid is obstructed, and the tracheobronchial tree and lungs become massively distended. Sonographically, the lungs appear brightly echogenic, and the bronchi are dilated with fluid (Fig. 10-19). Flattening and eversion of the diaphragm is common, as is compression of the heart. Venous return is impaired and ascites develops, typically followed by hydrops (Chap. 15, Diagnostic Evaluation). In one series, associated anomalies were reported in three of 12 cases (Roybal, 2010). This anomaly is a feature of the autosomal recessive Fraser syndrome. In some cases, spontaneous perforation of the obstructed airway can occur, potentially conferring a better prognosis. The EXIT procedure has also been used to treat this anomaly, as discussed in Chapter 16 (Ex-Utero Intrapartum Treatment).
Congenital high airway obstruction sequence (CHAOS). The lungs appear brightly echogenic, and one is marked by an “L.” The bronchi, one of which is noted by an arrow, are dilated with fluid. Flattening and eversion of the diaphragm is common, as is ascites (asterisks).
Cardiac malformations are the most common class of congenital anomalies, with an overall prevalence of 8 per 1000 births (Cragan, 2009). Almost 90 percent of cardiac defects are multifactorial or polygenic in origin; another 1 to 2 percent result from a single-gene disorder or gene-deletion syndrome; and 1 to 2 percent are from exposure to a teratogen such as isotretinoin, hydantoin, or maternal diabetes. Based on data from population-based registries, approximately 1 in 8 liveborn and stillborn neonates with a congenital heart defect has a chromosomal abnormality (Dolk, 2010; Hartman, 2011). The most frequent chromosomal abnormality found in those with a heart defect is trisomy 21. This accounts for more than half of cases and is followed by trisomy 18, 22q11.2 microdeletion, trisomy 13, and monosomy X (Hartman, 2011). Approximately 50 to 70 percent of aneuploid fetuses have extracardiac anomalies that are identifiable sonographically. Fetal karyotyping should be offered, and 22q11.2 microdeletion testing should be offered for conotruncal defects.
Traditionally, detection of congenital cardiac anomalies has been more challenging than anomalies of other organ systems. In recent series, routine second-trimester sonography identified approximately 40 percent of those with major cardiac anomalies before 22 weeks, and specialized sonography identified 80 percent (Romosan, 2009; Trivedi, 2012). There is evidence that prenatal detection of selected cardiac anomalies may improve neonatal survival rates. This may be particularly so with ductal-dependent anomalies—those requiring prostaglandin infusion after birth to keep the ductus arteriosus open (Franklin, 2002; Mahle, 2001; Tworetsky, 2001).
Basic Cardiac Examination
Standard cardiac assessment includes a four-chamber view (Fig. 10-20), evaluation of rate and rhythm, and evaluation of the left and right ventricular outflow tracts (Fig. 10-21) (American Institute of Ultrasound in Medicine, 2013a). Evaluation of the cardiac outflow tracts may aid in detection of abnormalities not initially appreciated in the four-chamber view. These may include tetralogy of Fallot, transposition of the great vessels, or truncus arteriosus.
The four-chamber view. A. Diagram demonstrating measurement of the cardiac axis from the four-chamber view of the fetal heart. B. Sonogram of the four-chamber view at 22 weeks demonstrates the normal symmetry of the atria and ventricles, normal position of the mitral and triscuspid valves, pulmonary veins entering the left atrium, and descending aorta (Ao). L = left; LA = left atrium; LV = left ventricle; R = right; RA = right atrium; RV = right ventricle.
Fetal echocardiography grayscale imaging planes. A. Four-chamber view. B. Left ventricular outflow tract view. The white arrow marks the mitral valve becoming the wall of the aorta. The arrow with an asterisk illustrates the interventricular septum becoming the opposing aortic wall. C. Right ventricular outflow tract view. D. Three vessel and trachea view. E. High short-axis view (outflow tracts). F. Low short-axis view (ventricles). G. Aortic arch view. H. Ductal arch view. I. Superior and inferior vena cavae views. Ao = aorta; IVC = inferior vena cava; LA = left atrium; LV = left ventricle; PA = pulmonary artery; RA = right atrium; RV = right ventricle; SVC superior vena cava.
This is a transverse image of the fetal thorax at a level immediately above the diaphragm. It allows evaluation of cardiac size, position in the thorax, cardiac axis, atria and ventricles, foramen ovale, atrial septum primum, interventricular septum, and atrioventricular valves (see Fig. 10-20). The atria and ventricles should be similar in size, and the apex of the heart should form a 45-degree angle with the left anterior chest wall. Abnormalities of cardiac axis are frequently encountered with structural cardiac anomalies and occur in more than a third (Shipp, 1995). Smith and coworkers (1995) found that 75 percent of fetuses with congenital heart anomalies had an axis angle that exceeded 75 degrees.
This is a specialized examination of fetal cardiac structure and function designed to identify and characterize abnormalities. Guidelines for its performance have been developed collaboratively by the American Institute of Ultrasound in Medicine (2013b), American College of Obstetrics and Gynecology, Society of Maternal-Fetal Medicine, American Society of Echocardiography, and American College of Radiology. Echocardiography indications include suspected fetal cardiac anomaly, extracardiac anomaly, or chromosomal abnormality; fetal arrhythmia; hydrops; increased nuchal translucency; monochorionic twin gestation; first-degree relative to the fetus with a congenital cardiac defect; in vitro fertilization; maternal anti-Ro or anti-La antibodies; exposure to a medication associated with increased cardiac malformation risks; and maternal metabolic disease associated with cardiac defects—such as pregestational diabetes or phenylketonuria (American Institute of Ultrasound in Medicine, 2013a). Components of the examination are listed in Table 10-6, and examples of the nine required gray-scale imaging views are shown in Figure 10-21. Examples of selected cardiac anomalies are reviewed below.
TABLE 10-6Components of Fetal Echocardiography ||Download (.pdf) TABLE 10-6 Components of Fetal Echocardiography
|Basic imaging parameters |
Evaluation of atria
Evaluation of ventricles
Evaluation of great vessels
Cardiac and visceral situs
|Scanning planes, gray scale |
Left ventricular outflow tract
Right ventricular outflow tract
Three-vessel and trachea view
Short-axis view, low (ventricles)
Short-axis view, high (outflow tracts)
Superior and inferior vena cavae
|Color Doppler evaluation |
Systemic veins (vena cavae and ductus venosusa)
Atrial and ventricular septae
Aortic and pulmonary valvesa
Umbilical artery and vein (optional)a
|Cardiac rate and rhythm assessment |
Ventricular Septal Defect
This is the single most common congenital cardiac anomaly and occurs in approximately 1 per 300 births (Cragan, 2009; Dolk, 2010). Even with adequate visualization, the prenatal detection rate of ventricular septal defect (VSD) is low. A defect may be appreciated in the membranous or muscular portion of the interventricular septum in the four-chamber view, and color Doppler demonstrates flow through the defect. Imaging of the left ventricular outflow tract may demonstrate discontinuity of the interventricular septum as it becomes the wall of the aorta (Fig. 10-22). Fetal VSD is associated with aneuploidy, particularly with coexistent other congenital abnormalities, and fetal karyotyping should be offered. That said, the prognosis for an isolated defect is good—more than a third of prenatally diagnosed VSDs close in utero, and another third close in the first year of life (Axt-Fliedner, 2006; Paladini, 2002).
Ventricular septal defect. A. In this four-chamber view of a 22-week fetus, a defect (arrow) is noted in the superior (membranous) portion of the interventricular septum. B. The left-ventricular outflow tract view of the same fetus demonstrates a break (arrow) in continuity between the interventricular septum and the anterior wall of the aorta.
Endocardial Cushion Defect
This is also called an atrioventricular (AV) septal defect or AV canal defect. It develops in approximately 1 per 2500 births and is associated with trisomy 21 in more than half of cases (Cragan, 2009; Dolk, 2010). The endocardial cushions are the crux of the heart, and defects jointly involve the atrial septum primum, interventricular septum, and medial leaflets of the mitral and tricuspid valves (Fig. 10-23). In addition to trisomy 21 and other aneuploidies, an endocardial cushion defect may develop with heterotaxy syndrome. In this condition, which is also called atrial isomerism, the heart and/or abdominal organs are on the incorrect side. Endocardial cushion defects associated with heterotaxy are more likely to have conduction system abnormalities resulting in third-degree AV block. As discussed in Chapter 16 (Bradyarrhythmia), this confers a poor prognosis.
Endocardial cushion defect. A. During ventricular systole, the lateral leaflets of the mitral and triscuspid valves come together in the midline. But the atrioventricular valve plane is abnormal, a common atrium (A) is observed, and there is a visible defect (arrow) in the interventricular septum. B. During diastolic filling, opening of the atrioventricular valves more clearly demonstrates the absence of their medial leaflets.
Hypoplastic Left Heart Syndrome
This anomaly occurs in approximately 1 per 4000 births (Cragan, 2009; Dolk, 2010). Postnatal treatment consists of a three-stage palliative repair or a cardiac transplantation. Once considered a lethal prognosis, it is now estimated that 70 percent of infants may survive to adulthood (Feinstein, 2012). Morbidity remains high, and developmental delays are common. Sonographically, the left side of the heart may appear so small that it is difficult to appreciate a ventricular chamber. There may be no visible inflow or outflow and may be reversal of flow in the ductus arteriosus. Fetal therapy for hypoplastic left heart is discussed in Chapter 16 (Fetoscopic Surgery).
This anomaly occurs in approximately 1 per 3500 births (Cragan, 2009; Dolk, 2010). It is characterized by four components: ventricular septal defect, an overriding aorta, pulmonary valve abnormality, and right ventricular hypertrophy. The last does not present before birth. Due to the location of the ventricular septal defect, it is often not visible in the four-chamber view, which may appear normal. The prognosis following postnatal repair is usually excellent, and 20-year survival rates exceed 95 percent (Knott-Craig, 1998). Cases with pulmonary atresia have a more complicated course, however. There is also a variant in which the pulmonary valve is absent. Affected fetuses are at risk for hydrops and for tracheomalacia from compression of the trachea by the enlarged pulmonary artery.
This is the most common cardiac tumor. Approximately 50 percent of cases are associated with tuberous sclerosis, an autosomal dominant disease with multiorgan system manifestations caused by mutations in the hamartin (TSC1) and tuberin (TSC2) genes. Cardiac rhabdomyomas appear as well-circumscribed echogenic masses, usually within the ventricles or outflow tracts. There may be one or multiple; they may increase in size during gestation; and occasionally, inflow or outflow obstruction may result. In the absence of obstruction or very large size, the prognosis is relatively good from a cardiac standpoint. These tumors are largest in the neonatal period and tend to regress as children grow. It is problematic, however, that other findings of neurofibromatosis, including growth of benign tumors in the brain, kidney, and skin, may not be apparent prenatally or may develop later in gestation. If a fetal rhabdomyoma is identified, in the absence of a family history, evaluation of the parents for clinical manifestations of neurofibromatosis should be considered. Fetal MR imaging may be considered to evaluate CNS anatomy (Technique).
Motion-mode or M-mode imaging is a linear display of cardiac cycle events, with time on the x-axis and motion on the y-axis. It is used frequently to measure fetal heart rate (Fig. 10-24). If there is an abnormality of heart rate or rhythm, M-mode imaging permits separate evaluation of atrial and ventricular waveforms. Thus, it is particularly useful for characterizing arrhythmias and their response to treatment, which is discussed in Chapter 16 (Medical Therapy). M-mode can also be used to assess ventricular function and atrial and ventricular outputs.
M-mode, or motion mode, is a linear display of the events of the cardiac cycle, with time on the x-axis and motion on the y-axis. M-mode is used commonly to measure the fetal heart rate. In this image, there is normal concordance between atrial (A) and ventricular contractions (V). Movement of the tricuspid valve (T) is also shown. There is also a premature atrial contraction (arrow) and a subsequent early ventricular contraction, followed by a compensatory pause.
Premature Atrial Contractions
Also called atrial extrasystoles, these are the most common fetal arrhythmia and a frequent finding. They represent cardiac conduction system immaturity and typically resolve later in gestation or in the neonatal period. Premature atrial contractions (PACs) may be conducted—and sound like an extra beat. However, they are more commonly blocked, and with handheld Doppler or fetoscope, they sound like a dropped beat. As shown in Figure 10-24, the dropped beat may be demonstrated with M-mode evaluation to be the compensatory pause that follows the premature contraction.
Premature atrial contractions are not associated with major structural cardiac abnormalities, although they sometimes occur with an atrial septal aneurysm. In case reports, they have been associated with maternal caffeine consumption and hydralazine (Lodeiro, 1989; Oei, 1989). In a small percentage of cases, about 2 percent, affected fetuses are later identified to have a supraventricular tachycardia (SVT) that requires urgent treatment (Copel, 2000). Given the importance of identifying SVT, pregnancies with fetal PACs are often followed with fetal heart rate assessment as often as every 1 to 2 weeks until ectopy resolution.
The integrity of the abdominal wall at the level of the cord insertion is assessed during the standard examination (Fig. 10-25). Gastroschisis and omphalocele, collectively termed ventral wall defects, are relatively common fetal anomalies. As discussed in Chapter 14 (MSAFP Elevation), both are associated with maternal serum alpha-fetoprotein elevation.
Normal ventral wall. Transverse view of the abdomen in a second-trimester fetus with an intact anterior abdominal wall and normal cord insertion.
This is a full-thickness abdominal wall defect typically located to the right of the umbilical cord insertion. Bowel herniates through the defect into the amnionic cavity (Fig. 10-26). The prevalence is 1 per 2000 to 4000 pregnancies (Canfield, 2006; Dolk, 2010). Gastroschisis is the one major anomaly more common in fetuses of younger mothers, and the average maternal age is 20 years (Santiago-Mu˜noz, 2007). Bowel abnormalities such as jejunal atresia are found in 15 to 30 percent of cases. Gastroschisis is not associated with an increased risk for aneuploidy, and the survival rate approximates 90 percent (Kitchanan, 2000; Nembhard, 2001; Santiago-Mu˜noz, 2007).
Gastroschisis. This 18-week fetus has a full-thickness ventral wall defect to the right of the cord insertion (arrowhead), through which multiple small bowel loops (B) have herniated into the amnionic cavity.
Fetal-growth restriction develops with gastroschisis in 15 to 40 percent of cases (Nicholas, 2009; Puligandla, 2004; Santiago-Mu˜noz, 2007). Whereas Nicholas and colleagues (2009) reported an association between growth restriction and adverse outcome with gastroschisis, Santiago-Mu˜noz and associates (2007) found that such newborns did not have increased mortality rates or longer hospitalizations compared with those of normally grown neonates. In a series of 75 infants with gastroschisis, Ergün and coworkers (2005) reported that the only risk factor associated with longer hospitalization was delivery before 36 weeks.
This anomaly complicates approximately 1 per 3000 to 5000 pregnancies (Canfield, 2006; Dolk, 2010). It forms when the lateral ectomesodermal folds fail to meet in the midline, leaving the abdominal contents covered only by a two-layered sac of amnion and peritoneum into which the umbilical cord inserts (Fig. 10-27). In more than half of cases, omphalocele is associated with other major anomalies or aneuploidy. It also is a component of syndromes such as Beckwith–Wiedemann, cloacal exstrophy, and pentalogy of Cantrell. Smaller defects confer an even greater risk for aneuploidy (De Veciana, 1994). Like other major anomalies, identification of an omphalocele mandates a complete anatomical evaluation, and fetal karyotyping is recommended.
Omphalocele. Transverse view of the abdomen showing an omphalocele as a large abdominal wall defect with exteriorized liver covered by a thin membrane.
Also known as limb-body-wall complex or cyllosoma, this is a rare, lethal anomaly characterized by abnormal formation of the body wall. Typically, no abdominal wall is visible, and there is extrusion of the abdominal organs into the extraamnionic coelom. There is close approximation or fusion of the body to the placenta, and an extremely short umbilical cord. Acute-angle scoliosis is another feature. Amnionic bands are often identified.
The stomach is visible in nearly all fetuses after 14 weeks’ gestation. The liver, spleen, gallbladder, and bowel can be identified in many second- and third-trimester fetuses. If the stomach is not seen on an initial evaluation, the examination should be repeated, and targeted sonography should be considered. Nonvisualization of the stomach may be secondary to impaired swallowing. And, underlying causes may include esophageal atresia, a craniofacial abnormality, or a CNS or musculoskeletal abnormality such as arthrogryposis. Fetuses with oligohydramnios or with severe illness from various causes—such as hydrops, may also have impaired swallowing.
Bowel appearance changes with fetal maturation. Occasionally, it may appear bright or echogenic, which may indicate small amounts of swallowed intraamnionic blood, particularly in the setting of maternal serum alpha-fetoprotein elevation. Bowel that appears as bright as fetal bone confers a slightly increased risk for underlying gastrointestinal malformations, cystic fibrosis, trisomy 21, and congenital infection such as cytomegalovirus.
Bowel atresia is characterized by obstruction and proximal bowel dilatation. In general, the more proximal the obstruction, the more likely it is to be associated with hydramnios. The hydramnios associated with proximal small bowel obstruction may be severe enough to result in maternal respiratory compromise or preterm labor. This may at times necessitate large-volume amniocentesis, also termed amnioreduction (Chap. 11, Oligohydramnios).
Esophageal atresia occurs in approximately 1 in 4000 births (Cragan, 2009; Pedersen, 2012). It may be suspected when the stomach cannot be visualized, and hydramnios is present. That said, in up to 90 percent of cases, a concomitant tracheoesophageal fistula allows fluid to enter the stomach, such that prenatal detection is problematic. More than half have associated anomalies and/or genetic syndromes. Specifically, multiple malformations are present in 30 percent, and aneuploidy are found in 10 percent, particularly trisomies 18 and 21 (Pedersen, 2012). Cardiac, urinary tract, and other gastrointestinal abnormalities are the most frequent. Approximately 10 percent of cases of esophageal atresia occur in the setting of the VACTERL association (Neural-Tube Defects) (Pedersen, 2012).
Duodenal atresia occurs in approximately 1 in 10,000 births (Best, 2012; Dolk, 2010). It is characterized by the sonographic double-bubble sign, which represents distention of the stomach and the first part of the duodenum (Fig. 10-28). This finding is usually not present before 22 to 24 weeks’ gestation and thus would not be expected to be identified during an 18-week standard sonographic examination. Demonstrating continuity between the stomach and proximal duodenum confirms that the second “bubble” is the proximal duodenum. Approximately 30 percent of affected fetuses have an associated chromosomal abnormality or genetic syndrome, particularly trisomy 21. In the absence of a genetic abnormality, a third of cases have associated anomalies, most commonly cardiac defects and other gastrointestinal abnormalities (Best, 2012). Obstructions in the more distal small bowel usually result in multiple dilated loops that may have increased peristaltic activity.
Duodenal atresia. The double-bubble sign represents distension of the stomach (S) and the first part of the duodenum (D), as seen on this axial abdominal image. Demonstrating continuity between the stomach and proximal duodenum confirms that the second “bubble” is the proximal duodenum.
Large bowel obstructions and anal atresia are less readily diagnosed by sonography, because hydramnios is not a typical feature, and the bowel may not be significantly dilated. A transverse view through the pelvis may show an enlarged rectum as a fluid-filled structure between the bladder and the sacrum.
Kidneys and Urinary Tract
The fetal kidneys are visible adjacent to the spine, frequently in the first trimester and routinely by 18 weeks’ gestation (Fig. 10-29). The length of the kidney is about 20 mm at 20 weeks, increasing by approximately 1.1 mm each week thereafter (Chitty, 2003). With advancing gestation, the kidneys become relatively less echogenic, and a rim of perinephric fat aids visualization of their margins.
Normal fetal kidneys. The kidneys are visible adjacent to the fetal spine in this 29-week fetus. With advancing gestation, a rim of perinephric fat facilitates visualization of the margins of the kidney. A physiological amount of urine is visible in the renal pelves and is marked in one kidney by an arrow.
The placenta and membranes are the major sources of amnionic fluid early in pregnancy. However, after 18 weeks’ gestation, most of the fluid is produced by the kidneys (Chap. 11, Normal Amnionic Fluid Volume). Fetal urine production increases from 5 mL/hr at 20 weeks to approximately 50 mL/hr at term (Rabinowitz, 1989). Unexplained oligohydramnios suggests a placental or urinary tract abnormality, whereas normal amnionic fluid volume in the second half of pregnancy suggests urinary tract patency with at least one functioning kidney.
This finding is present in 1 to 5 percent of fetuses. In 40 to 90 percent of cases, it is transient or physiological and does not represent an underlying abnormality (Ismaili, 2003; Nguyen, 2010). In approximately a third of cases, a urinary tract abnormality is confirmed in the neonatal period. Most frequently, this is either ureteropelvic junction (UPJ) obstruction or vesicoureteral reflux (VUR).
During evaluation, the renal pelvis is measured anterior-posterior in the transverse plane (Fig. 10-30). Although various thresholds have been defined, the pelvis is typically considered dilated if it exceeds 4 mm in the second trimester or 7 mm in the third trimester. Usually, the second-trimester threshold is used to identify pregnancies that warrant third-trimester evaluation.
Renal pelvis dilatation. This common finding is identified in 1 to 5 percent of pregnancies. A. In this 34-week fetus with mild renal pelvis dilatation, the anterior-posterior diameter of the renal pelvis measured 7 mm in the transverse plane. B. Sagittal image of the kidney in a 32-week fetus with severe renal pelvis dilatation secondary to ureteropelvic junction obstruction. One of the rounded calyces is marked (arrow).
Based on a metaanalysis of more than 100,000 screened pregnancies, the Society for Fetal Urology has categorized dilatation according to renal pelvis measurements and gestational age (Table 10-7) (Lee, 2006; Nguyen, 2010). The degree of renal pelvic dilatation correlates with the likelihood of underlying abnormality. Other findings that suggest pathology include calyceal dilatation, cortical thinning, or dilatation elsewhere along the urinary tract. Mild pyelectasis in the second trimester is associated with a slightly increased risk for Down syndrome (Chap. 14, Second-Trimester Sonographic Markers or “Soft Signs” Associated with Down Syndrome Fetuses).
TABLE 10-7Risk for Postnatal Urinary Abnormality According to Degree of Renal Pelvis Dilatationa ||Download (.pdf) TABLE 10-7 Risk for Postnatal Urinary Abnormality According to Degree of Renal Pelvis Dilatationa
|Dilatation ||Second Trimester ||Third Trimester ||Postnatal Abnormality |
|Mild ||4 to < 7 mm ||7 to < 9 mm ||12% |
|Moderate ||7 to ≤ 10 mm ||9 to ≤ 15 mm ||45% |
|Severe ||> 10 mm ||> 15 mm ||88% |
Ureteropelvic Junction Obstruction
This condition is the most common abnormality associated with renal pelvis dilatation. The birth prevalence approximates 1 per 1000 to 2000, and males are affected three times more often than females (Williams, 2007; Woodward, 2002). Obstruction is generally functional rather than anatomical, and it is bilateral in up to a fourth of cases. The likelihood of UPJ obstruction increases from 5 percent with mild renal pelvis dilatation to more than 50 percent with severe dilatation (Lee, 2006).
Duplicated Renal Collecting System
This occurs when the upper and lower poles of the kidney—called moieties—are each drained by a separate ureter (Fig. 10-31). Duplication is more common in females and is bilateral in 15 to 20 percent of cases (Whitten, 2001). It is recognized in approximately 1 per 4000 pregnancies (James, 1998; Vergani, 1998). Sonographically, an intervening tissue band separates two distinct renal pelves. These are typically cases in which hydronephrosis and/or ureteral dilatation develops, due to abnormal implantation of one or both ureters within the bladder—a relationship described by the Weigert-Meyer rule. The upper pole ureter often develops obstruction from a ureterocele within the bladder, whereas the lower pole ureter has a shortened intravesical segment that predisposes to vesicoureteral reflux (see Fig. 10-31). Thus, both moieties may become dilated from different etiologies, and both are at risk for loss of function. In the neonatal period, additional testing such as voiding cystourethrography will determine whether antimicrobial treatment is needed to minimize urinary infections and will assist with follow-up or surgical intervention.
Duplicated renal collecting system. The upper and lower moieties of the kidney are each drained by a separate ureter. A. Renal pelvis dilation is visible in both the upper (U) and lower (L) pole moieties, which are separated by an intervening band of renal tissue (arrowhead). B. The bladder, encircled by the highlighted umbilical arteries, contains a ureterocele (arrowhead).
The prevalence of bilateral renal agenesis is approximately 1 per 8000 births, whereas that of unilateral renal agenesis is 1 per 1000 births (Cragan, 2009; Dolt, 2010; Sheih, 1989; Wiesel, 2005). When a kidney is absent, the ipsilateral adrenal gland typically enlarges to fill the renal fossa, termed the lying down adrenal sign (Hoffman, 1992). In addition, color Doppler imaging of the descending aorta will demonstrate absence of the renal artery.
If renal agenesis is bilateral, no urine is produced. The resulting anhydramnios leads to pulmonary hypoplasia, limb contractures, and a distinctively compressed face. When this combination of abnormalities results from renal agenesis, it is called Potter syndrome, after Dr. Edith Potter who described it in 1946. When these abnormalities result from severely decreased amnionic fluid volume from another etiology, such as bilateral multicystic dysplastic kidney or autosomal recessive polycystic kidney disease, it is called Potter sequence.
Multicystic Dysplastic Kidney
This severe form of renal dysplasia results in a nonfunctioning kidney. The nephrons and collecting ducts do not form normally, such that primitive ducts are surrounded by fibromuscular tissue, and the ureter is atretic (Hains, 2009). Sonographically, the kidney contains numerous smooth-walled cysts of varying size that do not communicate with the renal pelvis and are surrounded by echogenic cortex (Fig. 10-32).
Multicystic dysplastic kidneys. Coronal view of the fetal abdomen demonstrates markedly enlarged kidneys containing multiple cysts of varying sizes that do not communicate with a renal pelvis.
Unilateral multicystic dysplastic kidney (MCDK) has a prevalence of 1 per 4000 births. It is associated with contralateral renal abnormalities in 30 to 40 percent of cases—most frequently vesicoureteral reflux or ureteropelvic junction obstruction (Schreuder, 2009). Nonrenal anomalies have been reported in 25 percent of cases, and cystic dysplasia may occur as a component of many genetic syndromes (Lazebnik, 1999; Schreuder, 2009). If MCDK is isolated and unilateral, the prognosis is generally good.
Bilateral MCDK develops in approximately 1 per 12,000 births. It is associated with severely decreased amnionic fluid volume from early in gestation. This leads to Potter sequence and a poor prognosis (Lazebnik, 1999).
Polycystic Kidney Disease
Of the hereditary polycystic diseases, only the infantile form of autosomal recessive polycystic kidney disease (ARPKD) may be reliably diagnosed prenatally. ARPKD is a chronic, progressive disease that involves the kidneys and liver. It results in cystic dilatation of the renal collecting ducts and congenital hepatic fibrosis (Turkbey, 2009). The carrier frequency of a disease-causing mutation in the PKHD1 gene approximates 1 in 70, and the disease prevalence is 1 in 20,000 (Zerres, 1998). ARPKD has wide phenotypic variability. This ranges from lethal pulmonary hypoplasia at birth to presentation in late childhood or even adulthood with predominantly hepatic manifestations. Infantile polycystic kidney disease is characterized by abnormally large kidneys that fill and distend the fetal abdomen and have a solid, ground-glass texture. Severe oligohydramnios confers a poor prognosis.
As discussed in Chapter 53 (Polycystic Kidney Disease), autosomal dominant polycystic kidney disease (ADPKD), which is far more common, usually does not manifest until adulthood. Even so, some fetuses with ADPKD have mild renal enlargement, increased renal echogenicity, and normal amnionic fluid volume. The differential diagnosis for these findings includes several genetic syndromes, aneuploidy, or normal variant.
Bladder Outlet Obstruction
Distal obstruction of the urinary tract is more frequent in male fetuses, and the most common etiology is posterior urethral valves. Characteristically, there is dilatation of the bladder and proximal urethra, termed the “keyhole” sign, and the bladder wall is thick (Fig. 10-33). Oligohydramnios, particularly before midpregnancy, portends a poor prognosis because of pulmonary hypoplasia. Unfortunately, the outcome may be poor even with normal amnionic fluid volume. Evaluation includes a careful search for associated anomalies, which may occur in 40 percent of cases, and for aneuploidy, which has been reported in 5 to 8 percent (Hayden, 1988; Hobbins, 1984; Mann, 2010). If neither are present, affected male fetuses with severe oligohydramnios who have fetal urinary electrolytes suggesting a potentially favorable prognosis may be fetal therapy candidates. Evaluation and treatment of fetal bladder outlet obstruction is discussed in Chapter 16 (Urinary Shunts).
Posterior urethral valve. In this 19-week fetus with severe bladder outlet obstruction, the bladder is dilated and thick-walled, with dilatation of the proximal urethra that resembles a “keyhole.” Adjacent to the bladder is an enlarged kidney with evidence of cystic dysplasia, conferring a poor prognosis.
The 2010 revision of the Nosology and Classification of Genetic Skeletal Disorders includes an impressive 456 skeletal abnormalities in 40 groups that are defined by molecular, biochemical, and/or radiographic criteria (Warman, 2011). There are two types of skeletal dysplasias: osteochondrodysplasias—the generalized abnormal development of bone and/or cartilage, and dysostoses—which are abnormalities of individual bones, for example, polydactyly. In addition to these malformations, skeletal abnormalities include deformations, as with some cases of clubfoot, and disruptions such as limb-reduction defects.
The prevalence of skeletal dysplasias approximates 3 per 10,000 births. Two groups account for more than half of all cases: the fibroblast growth factor 3 (FGFR3) chondrodysplasia group and the osteogenesis imperfecta and decreased bone density group. Each has a prevalence of approximately 0.8 per 10,000 births (Stevenson, 2012).
Evaluation of a pregnancy with suspected skeletal dysplasia includes a survey of every long bone, as well as the hands and feet, skull size and shape, clavicles, scapulae, thorax, and spine. Reference tables are used to determine which long bones are affected and ascertain the degree of shortening (Appendix, Length of Fetal Long Bones (mm) According to Gestational Age). Involvement of all long bones is termed micromelia, whereas predominant involvement of only the proximal, intermediate, or distal long bone segments is termed rhizomelia, mesomelia, and acromelia, respectively. The degree of ossification should be noted, as should presence of bowing or fractures. Each of these may provide clues to narrow the differential diagnosis and occasionally suggest a specific skeletal dysplasia. Many, if not most, skeletal dysplasias have a genetic component, and knowledge of specific mutations has advanced rapidly (Warman, 2011).
Although precise characterization of a specific skeletal dysplasia may elude prenatal diagnosis, it is frequently possible to determine whether a skeletal dysplasia is lethal. Lethal dysplasias are frequently characterized by profound long bone shortening, with measurements below the 5th percentile and by femur length-to-abdominal circumference ratios < 16 percent (Appendix, Length of Fetal Long Bones (mm) According to Gestational Age) (Rahemtullah, 1997; Ramus, 1998). Evidence of pulmonary hypoplasia includes a thoracic circumference < 80 percent of the abdominal circumference, thoracic circumference below the 2.5th percentile, and a cardiothoracic circumference ratio > 50 percent (Appendix, Fetal Thoracic Circumference Measurements (cm) According to Gestational Age). Affected pregnancies also may develop hydramnios and/or hydrops.
The FGFR3 chondrodysplasias include achondroplasia and thanatophoric dysplasia. Achondroplasia, also called heterozygous achondroplasia, is the most common nonlethal skeletal dysplasia. It is inherited in an autosomal dominant fashion, with 80 percent of cases resulting from a new mutation. An impressive 98 percent are due to one mutation in the FGFR3 gene. Achondroplasia is characterized by long bone shortening that is predominantly rhizomelic, an enlarged head with frontal bossing, depressed nasal bridge, exaggerated lumbar lordosis, and a trident configuration of the hands. Intelligence is typically normal. Sonographically, the femur and humerus measurements may not be below the 5th percentile until the early third trimester. Thus, this condition is usually not diagnosed until late in pregnancy. In homozygotes, which represent 25 percent of the offspring of heterozygous parents, the condition is characterized by much more severe long bone shortening and is lethal.
The other major class of FGFR3 dysplasias, thanatophoric dysplasia, is the most common lethal skeletal disorder. It is characterized by severe micromelia, and affected fetuses—particularly those with type II—may develop a characteristic cloverleaf skull deformity (kleeblattschädel) due to craniosynostosis. More than 99 percent of cases may be confirmed with genetic testing.
Osteogenesis imperfecta represents a group of skeletal dysplasias characterized by hypomineralization. There are multiple types, and more than 90 percent of cases are characterized by a mutation in the COL1A1 or COL1A2 gene. Type IIa, also called the perinatal form, is lethal. It is characterized by profound lack of skull ossification, such that gentle pressure on the maternal abdomen from the ultrasound transducer results in visible skull deformation (Fig. 10-34). Other features include multiple in-utero fractures and ribs that appear “beaded.” Inheritance is autosomal dominant, such that all cases result from either new mutations or gonadal mosaicism (Chap. 13, Modes of Inheritance). Another skeletal dysplasia that results in severe hypomineralization is hypophosphatasia, which is inherited in an autosomal recessive fashion.
Osteogenesis imperfecta. Type IIa, which is lethal, is characterized by such profound lack of skull ossification that gentle pressure on the maternal abdomen from the ultrasound transducer results in visible deformation (flattening) of the skull (arrowheads).
This disorder is notable for a deformed talus and shortened Achilles tendon. The affected foot is abnormally fixed and positioned with equinus—downward pointing, varus—inward rotation, and forefoot adduction. Most cases are considered malformations, with a multifactorial genetic component. However, an association with environmental factors and with early amniocentesis suggests that deformation also plays a role (Tredwell, 2001). Sonographically, the footprint is visible in the same plane as the tibia and fibula (Fig. 10-35).
Foot position. A. Normal fetal lower leg, demonstrating normal position of the foot. B. With talipes equinovarus, the foot “print” is visible in the same plane as the tibia and fibula.
In population-based series, the prevalence of clubfoot is approximately 1 per 1000 births, with a male:female ratio of 2:1 (Carey, 2003; Pavone, 2012). Clubfoot is bilateral in approximately 50 percent of cases, and associated anomalies are present in at least 50 percent (Mammen, 2004; Sharma, 2011). Frequently associated anomalies include neural-tube defects, arthrogryposis, and myotonic dystrophy and other genetic syndromes. In the setting of associated anomalies, aneuploidy is present in approximately 30 percent, but it has been reported in less than 4 percent when clubfoot appears isolated (Lauson, 2010; Sharma, 2011). Thus, a careful search for associated anomalies is warranted, and fetal karyotyping may be considered.
Documentation of the arms and legs is a component of thestandard examination. A limb-reduction defect is the absence of all or part of one or more extremities. Absence of an entire extremity is termed amelia. Phocomelia, associated with thalidomide exposure, is an absence of one or more long bones with the hands or feet attached to the trunk (Chap. 12, Acitretin). Limb-reduction defects are associated with numerous genetic syndromes, such as Roberts syndrome, an autosomal recessive condition characterized by tetraphocomelia. A clubhand deformity, usually from an absent radius, is associated with trisomy 18 and is also a component of the thrombocytopenia-absent radius syndrome. Limb-reduction defects may occur in the setting of a disruption such as amnionic band sequence (Chap. 6, Abnormalities of the Membranes). They have also been associated with chorionic villus sampling when performed before 10 weeks’ gestation (Chap. 14, Chorionic Villus Sampling (CVS)).