SONOGRAPHY IN OBSTETRICS
TECHNOLOGY AND SAFETY
SECOND- AND THIRD-TRIMESTER SONOGRAPHY
NORMAL AND ABNORMAL FETAL ANATOMY
THREE- AND FOUR-DIMENSIONAL SONOGRAPHY
MAGNETIC RESONANCE IMAGING
SONOGRAPHY IN OBSTETRICS
A great hallmark in obstetrical history began in the second half of the 20th century with the ability to image the pregnant uterus and its contents. Beginning with sonographic imaging and continuing through computed tomographic and magnetic resonance imaging, obstetrical practice was revolutionized and gave birth to the specialty of fetal medicine. Today’s practitioner can hardly imagine obstetrical care without these technical advances, which have become commonplace and regarded almost as a sixth sense.
Sonography in prenatal care includes first- and second-trimester fetal anatomic evaluation and specialized studies performed to characterize abnormalities. With improvements in resolution and image display, anomalies are increasingly diagnosed in the first trimester. Applications for three-dimensional sonography and Doppler continue to expand. A sonographic examination performed with the exacting recommended standards of the American Institute of Ultrasound in Medicine (2013a) offers vital information regarding fetal anatomy, physiology, growth, and well-being. Indeed, a National Institute of Child Health and Human Development (NICHD) workshop concluded that “every fetus deserves to have a physical examination” (Reddy, 2008).
Technology and Safety
The real-time image on the ultrasound screen is produced by sound waves that are reflected back from fluid and tissue interfaces of the fetus, amnionic fluid, and placenta. Sector array transducers used in obstetrics contain groups of piezoelectric crystals working simultaneously in arrays. These crystals convert electrical energy into sound waves, which are emitted in synchronized pulses. Sound waves pass through tissue layers and are reflected back to the transducer when they encounter an interface between tissues of different densities. Dense tissue such as bone produces high-velocity reflected waves, which are displayed as bright echoes on the screen. Conversely, fluid generates few reflected waves and appears dark—or anechoic. Digital images generated at 50 to more than 100 frames per second undergo postprocessing that yields the appearance of real-time imaging.
Ultrasound refers to sound waves traveling at a frequency above 20,000 hertz (cycles per second). Higher-frequency transducers yield better image resolution, whereas lower frequencies penetrate tissue more effectively. Transducers use wide-bandwidth technology to perform over a range of frequencies. In the second trimester, a 4- to 6-megahertz abdominal transducer is often in close enough proximity to the fetus to provide precise images. By the third trimester, however, a lower frequency 2- to 5-megahertz transducer may be needed for penetration, but can lead to compromised resolution. This explains why resolution is often poor when imaging obese patients and why low-frequency transducers are needed to reach the fetus through maternal tissues. In early pregnancy, a 5- to 10-megahertz vaginal transducer may provide excellent resolution, because the early fetus is close to the transducer.
Sonography should be performed only for a valid medical indication, using the lowest possible exposure setting to gain necessary information—the ALARA principle—as low as reasonably achievable. It should be performed only by those trained to recognize medically important conditions such as fetal anomalies, artifacts that may mimic pathology, and techniques to avoid ultrasound exposure beyond what is considered safe for the fetus (American Institute of Ultrasound in Medicine, 2008a, 2013a). Prolonged ultrasound exposure may affect brain cell migration in fetal mice (Rakic, 2006). However, no causal relationship has been demonstrated between diagnostic ultrasound and recognized adverse effects in human pregnancy (American Institute of Ultrasound in Medicine, 2010).
All sonography machines are required to display two indices: the thermal index and the mechanical index. The thermal index is a measure of the relative probability that the examination may raise the temperature, potentially enough to induce injury. That said, it is extremely unlikely that fetal damage could occur using commercially available ultrasound equipment in routine practice. The potential for temperature elevation is higher with longer examination time and is greater near bone than in soft tissue. Also, theoretical risks are greater during organogenesis than later in gestation. The thermal index is higher with pulsed Doppler applications than with routine B-mode scanning (p. 219). In the first trimester, if pulsed Doppler is needed for a clinical indication, the thermal index should be ≤ 1.0, and exposure time should be kept as short as possible, usually no longer than 5 to 10 minutes (American Institute of Ultrasound in Medicine, 2011; Salvesen, 2011). To document the embryonic or fetal heart rate, M-mode imaging should be used instead of pulsed Doppler imaging (American Institute of Ultrasound in Medicine, 2013a).
The mechanical index is a measure of likelihood of adverse effects related to rarefractional pressure, such as cavitation—which is relevant only in tissues that contain air. Microbubble ultrasound contrast agents are not used in pregnancy for this reason. No adverse effects have been reported in mammalian tissues that do not contain gas bodies over the range of diagnostically relevant exposures. Because fetuses cannot contain gas bodies, they are not considered at risk (American Institute of Ultrasound in Medicine, 2008b).
The use of sonography for any nonmedical purpose, such as “keepsake fetal imaging,” is considered contrary to responsible medical practice and is not condoned by the Food and Drug Administration (Rados, 2007), the American Institute of Ultrasound in Medicine (2012, 2013a), or the International Society of Ultrasound in Obstetrics and Gynecology (2011).
The reported prevalence of work-related musculoskeletal discomfort or injury among sonographers and sonologists is as high as 70 to 80 percent (Janga, 2012; Magnavita, 1999; Pike, 1997). According to the National Institute for Occupational Safety and Health, the main risk factors for injury during transabdominal ultrasound are awkward posture, sustained static forces, and various pinch grips while maneuvering the transducer (Centers for Disease Control and Prevention, 2006). Another possible contributory factor is maternal habitus—as more force may be employed when imaging obese patients.
The following guidelines may help avert injury:
1. Position the patient on the examination table close to you, so that your elbow is close to your body, with less than 30 degrees shoulder abduction, keeping your thumb facing up.
2. Adjust the table or chair height so that your forearm is parallel to the floor.
3. If seated, use a chair with back support, support your feet, and keep ankles in neutral position. Do not lean toward the patient or monitor.
4. Face the monitor squarely and position it so that it is viewed at a neutral angle, such as 15 degrees downward.
5. Avoid reaching, bending, or twisting while scanning.
6. Frequent breaks may avoid muscle strain. Stretching and strengthening exercises can be helpful.
Indications for sonography before 14 weeks’ gestation are listed in Table 10-1. Early pregnancy can be evaluated using transabdominal or transvaginal sonography, or both. The components listed in Table 10-2should be assessed. The crown-rump length (CRL) is the most accurate biometric predictor of gestational age (Appendix, p. 1294). The CRL should be obtained in a sagittal plane and include neither the yolk sac nor a limb bud. If carefully performed, it has a variance of only 3 to 5 days.
TABLE 10-1. Some Indications for First-Trimester Ultrasound Examination
Confirm an intrauterine pregnancy
Evaluate a suspected ectopic pregnancy
Define the cause of vaginal bleeding
Evaluate pelvic pain
Estimate gestational age
Diagnose or evaluate multifetal gestations
Confirm cardiac activity
Assist chorionic villus sampling, embryo transfer, and localization and removal of an intrauterine device
Assess for certain fetal anomalies such as anencephaly, in high-risk patients
Evaluate maternal pelvic masses and/or uterine abnormalities
Measure nuchal translucency when part of a screening program for fetal aneuploidy
Evaluate suspected gestational trophoblastic disease
Modified from the American Institute of Ultrasound in Medicine, 2013a.
TABLE 10-2. Components of Standard Ultrasound Examination by Trimester
First-trimester sonography can reliably diagnose anembryonic gestation, embryonic demise, ectopic pregnancy, and gestational trophoblastic disease. Multifetal gestation can be identified early, and this is the optimal time to determine chorionicity (Chap. 45, p. 896). The first trimester is also the ideal time to evaluate the uterus, adnexa, and cul-de-sac. Cervical length and the relationship of the placenta to the cervical os are best evaluated in the second trimester.
An intrauterine gestational sac is reliably visualized with transvaginal sonography by 5 weeks, and an embryo with cardiac activity by 6 weeks. The embryo should be visible transvaginally once the mean sac diameter has reached 20 mm—otherwise the gestation is anembryonic (Chap. 18, p. 355). Cardiac motion is usually visible with transvaginal imaging when the embryo length has reached 5 mm. If an embryo less than 7 mm is not identified to have cardiac activity, a subsequent examination is recommended in 1 week (American Institute of Ultrasound in Medicine, 2013a). At Parkland hospital, first-trimester demise is diagnosed if the embryo has reached 10 mm without cardiac motion, taking into consideration the standard error of the ultrasound measurements.
Nuchal Translucency (NT)
Nuchal translucency evaluation, a component of first-trimester aneuploidy screening, has had a major impact on the number of pregnancies receiving late first-trimester ultrasound examination. It represents the maximum thickness of the subcutaneous translucent area between the skin and soft tissue overlying the fetal spine at the back of the neck (Fig. 14-5, p. 290). It is measured in the sagittal plane between 11 and 14 weeks using precise criteria (Table 10-3). When the nuchal translucency is increased, the risk for fetal aneuploidy and various structural anomalies—including heart defects—is significantly elevated. Aneuploidy screening using nuchal translucency measurement in conjunction with assessment of maternal serum human chorionic gonadotropin and pregnancy-associated plasma protein A levels is discussed in Chapter 14 (p. 290).
TABLE 10-3. Guidelines for Nuchal Translucency (NT) Measurement
The margins of NT edges must be clear enough for proper caliper placement
The fetus must be in the midsagittal plane
The image must be magnified so that it is filled by the fetal head, neck, and upper thorax
The fetal neck must be in a neutral position, not flexed and not hyperextended
The amnion must be seen as separate from the NT line
Electronic calipers must be used to perform the measurement
The + calipers must be placed on the inner borders of the nuchal space with none of the horizontal crossbar itself protruding into the space
The calipers must be placed perpendicular to the long axis of the fetus
The measurement must be obtained at the widest space of the NT
From the American Institute of Ultrasound in Medicine, 2013a, with permission.
First-Trimester Fetal Anomaly Detection
Assessment for selected fetal abnormalities in an at-risk pregnancy is another indication for first-trimester sonography (see Table 10-1). Research in this area has focused on anatomy visible at 11 to 14 weeks, to coincide with sonography performed as part of aneuploidy screening (Chap. 14, p. 289). With current technology, it is not realistic to expect that all major abnormalities detectable in the second trimester may be visualized in the first trimester. A study of systematic anatomy evaluation between 11 and 14 weeks in more than 40,000 pregnancies yielded a detection rate of approximately 40 percent for nonchromosomal abnormalities (Syngelaki, 2011). This detection rate is nearly identical to that from a review of more than 60,000 pregnancies from 15 studies and is also comparable with other reports (Pilalis, 2012; Syngelaki, 2011). Identification varies considerably according to the specific abnormality. For example, reported detection rates are extremely high for anencephaly, alobar holoprosencephaly, and ventral wall defects. However, only one-third of major cardiac anomalies have been identified, with no detected cases of microcephaly, agenesis of the corpus callosum, cerebellar abnormalities, congenital pulmonary airway malformations, or bowel obstruction (Syngelaki, 2011). Thus, as first-trimester sonography is unreliable for detection of many major abnormalities, it should not replace second-trimester anatomical evaluation.
Second- and Third-Trimester Sonography
The many indications for second- and third-trimester sonography are listed in Table 10-4. There are three types of examinations: standard, specialized, and limited.
TABLE 10-4. Indications for Second- or Third-Trimester Ultrasound Examination
Suspected uterine abnormality
Suspected ectopic pregnancy
Suspected molar pregnancy
Suspected placenta previa and subsequent surveillance
Suspected placental abruption
Preterm premature rupture of membranes and/or preterm labor
Adjunct to cervical cerclage
Adjunct to amniocentesis or other procedure
Adjunct to external cephalic version
Gestational age estimation
Significant uterine size/clinical date discrepancy
Suspected multifetal gestation
Fetal anatomical evaluation
Fetal anomaly screening
Assessment for findings that may increase the aneuploidy risk
Abnormal biochemical markers
Fetal presentation determination
Suspected hydramnios or oligohydramnios
Fetal well-being evaluation
Follow-up evaluation of a fetal anomaly
History of congenital anomaly in prior pregnancy
Suspected fetal death
Fetal condition evaluation in late registrants for prenatal care
Adapted from the American Institute of Ultrasound in Medicine, 2013a.
1. Standard sonographic examination is the most commonly performed. Components are listed in Table 10-2. The fetal anatomical structures that should be evaluated during the examination, which are listed in Table 10-5, may be adequately assessed after approximately 18 weeks. When examining twins or other multiples, documentation also includes the number of chorions and amnions, comparison of fetal sizes, estimation of amnionic fluid volume within each sac, and fetal sex determination (Chap. 45, p. 912).
2. There are several types of specialized examinations. The targeted examination is a detailed anatomical survey performed when an abnormality is suspected on the basis of history, screening test result, or abnormal findings from a standard examination (American Institute of Ultrasound in Medicine, 2013a). A targeted examination is performed and interpreted by an experienced operator. It includes the anatomical structures listed in Table 10-5, along with additional views of the brain and cranium, neck, profile, lungs and diaphragm, cardiac anatomy, liver, shape and curvature of the spine, hands and feet, and any placental abnormalities. The physician performing the examination further determines whether other examination components will be needed on a case-by-case basis (American College of Obstetricians and Gynecologists, 2011). Other specialized examinations include fetal echocardiography and Doppler evaluation (discussed below), biophysical profile (Chap. 17, p. 341), and additional biometric measurements.
3. A limited examination is performed to address a specific clinical question. Examples include amnionic fluid volume assessment, placental location, or evaluation of fetal presentation or viability. In most cases, a limited examination is appropriate only when a prior standard or targeted examination has previously been performed (American Institute of Ultrasound in Medicine, 2009, 2013a).
TABLE 10-5. Minimal Elements of a Standard Examination of Fetal Anatomy
Head, face, and neck
Lateral cerebral ventricles
Cavum septum pellucidi
Consideration of nuchal fold measurement at 15–20 weeks
Four-chamber view of the heart
Left ventricular outflow tract
Right ventricular outflow tract
Stomach—presence, size, and situs
Umbilical cord insertion into fetal abdomen
Umbilical cord vessel number
Cervical, thoracic, lumbar, and sacral spine
Legs and arms
In multifetal gestations and when medically indicated
Summarized from the American Institute of Ultrasound in Medicine, 2013a.
Equipment software derives the estimated gestational age from the crown-rump length. Formulas are similarly used to calculate estimated gestational age and fetal weight from measurements of the biparietal diameter, head and abdominal circumference, and femur length (Fig. 10-1). The estimates are most accurate when multiple parameters are used and when nomograms derived from fetuses of similar ethnic or racial background living at similar altitude are selected. Even the best models may over- or underestimate fetal weight by as much as 15 percent (American Institute of Ultrasound in Medicine, 2013a). Various nomograms for other fetal structures, including the cerebellum diameter, ear length, interocular and binocular distances, thoracic circumference, and kidney, long bones, and feet lengths, may be used to address specific questions regarding organ system abnormalities or syndromes. These nomograms may be found in the Appendix (p. 1298).
FIGURE 10-1 Fetal biometry. A. Transthalamic view. A transverse (axial) image of the head is obtained at the level of the cavum septum pellucidum (arrows) and thalami (asterisks). The biparietal diameter is measured perpendicular to the sagittal midline, from the outer edge of the skull in the near-field to the inner edge of the skull in the far-field. By convention, the near-field is that which is closer to the sonographic transducer. The head circumference is measured circumferentially around the outer border of the skull. B. Femur length. The femur is measured perpendicular to the femoral shaft, from each diaphyseal end, excluding the epiphysis. C. Abdominal circumference. This is a transverse measurement at the level of the stomach (S). The J-shaped structure (arrowheads) indicates the confluence of the umbilical vein and the right portal vein. Ideally, only one rib is visible on each side of the abdomen, indicating that the image was not taken at an oblique angle.
In the second trimester, the biparietal diameter (BPD) most accurately reflects the gestational age, with a variation of 7 to 10 days. The BPD is measured in the transthalamic view, at the level of the thalami and cavum septum pellucidum (CSP), from the outer edge of the skull in the near field to the inner edge of the skull in the far field (see Fig. 10-1A). The head circumference (HC) is also measured in the transthalamic view, either by placing an ellipse around the outer edge of the skull, or by measuring the occipital-frontal diameter (OFD) and calculating the circumference from the BPD and OFD. The cephalic index, which is the BPD divided by the OFD, is normally approximately 70 to 86 percent. If the head shape is flattened—dolichocephaly, or rounded—brachycephaly, the HC is more reliable than the BPD. Dolichocephaly and brachycephaly may be normal variants or may be secondary to positional changes or oligohydramnios. However, dolichocephaly can occur with neural-tube defects, and brachycephaly may be seen in fetuses with Down syndrome (Chap. 13, p. 262). Whenever the skull shape is abnormal, craniosynostosis and other craniofacial abnormalities are a consideration.
The femur length (FL) correlates well with both BPD and gestational age. It is measured with the beam perpendicular to the long axis of the shaft, excluding the epiphysis. For gestational age estimation, it has a variation of 7 to 11 days in the second trimester (see Fig. 10-1B). A mildly foreshortened femur—one that is 90 percent or less than that expected for gestational age—has been used as a minor marker for Down syndrome (Chap. 14, p. 292). A femur length that is dramatically foreshortened prompts an evaluation for a skeletal dysplasia, as discussed on page 217. In general, the normal range for the FL to abdominal circumference (AC) ratio is 20 to 24 percent. A FL/AC < 16 percent suggests a lethal skeletal dysplasia, particularly if other skeletal abnormalities are present (Rahemtullah, 1997; Ramus, 1998).
The abdominal circumference has the greatest variation, up to 2 to 3 weeks, for gestational age estimation. The AC is measured around the outer border of the skin. This is a transverse image at the level of the stomach and the confluence of the umbilical vein with the portal sinus (see Fig. 10-1C). Of the biometric parameters, AC is most affected by fetal growth. As discussed in Chapter 44 (p. 875), a small abdominal circumference has been used as an early indicator of fetal-growth restriction (Baschat, 2011).
Variability of the estimated gestational age and of fetal weight increases with advancing gestation. Individual measurements are least accurate in the third trimester. Although estimates are improved by averaging multiple parameters, if one parameter differs significantly from the others, consideration is given to excluding it from the calculation. The outlier could result from poor visibility, but it could also indicate a fetal abnormality or growth problem. Reference tables such as the one in the Appendix (p. 1296) are used to estimate fetal weight percentiles. Menstrual dates are generally considered confirmed if an estimated gestational age (EGA) based on a sonographic first-trimester crown-rump length is within 1 week or if the EGA from biometry at 14 to 20 weeks is within 10 days (American College of Obstetricians and Gynecologists, 2011). In the third trimester, the accuracy of sonography is only within 3 to 4 weeks. Sonographic evaluation performed to monitor fetal growth should typically be performed at least 2 to 4 weeks after a prior examination (American Institute of Ultrasound in Medicine, 2013a).
Amnionic fluid volume evaluation is a component of every second- or third-trimester sonogram. Oligohydramnios indicates that the volume is below normal range, and subjective crowding of the fetus is often noted. Hydramnios—also called polyhydramnios—is defined as amnionic fluid volume above normal (Fig. 11-3, p. 234). Although it is considered acceptable for an experienced examiner to assess the amnionic fluid volume qualitatively, fluid is usually assessed semiquantitatively (American Institute of Ultrasound in Medicine, 2013a). Measurements include either the single deepest vertical fluid pocket or the sum of the deepest vertical pockets from each of four equal uterine quadrants—the amnionic fluid index (Phelan, 1987). Reference ranges have been established for both measurements from 16 weeks’ gestation onward (Fig. 11-1, p. 233). The single deepest vertical pocket is normally between 2 and 8 cm, and the amnionic fluid index normally ranges between 8 and 24 cm. Amnionic fluid volume is discussed further in Chapter 11 (p. 232).
Fetal Anatomical Evaluation
An important goal of second- and third-trimester sonography is to systematically evaluate fetal anatomy and determine whether specific anatomical components appear normal or abnormal. If a single ultrasound examination is planned for the purpose of evaluating fetal anatomy, the American College of Obstetricians and Gynecologists (2011) recommends that it be performed at 18 to 20 weeks. At this gestational age range, complex organs such as the fetal brain and heart can be imaged clearly enough to visualize many major malformations. Technical factors such as maternal habitus, abdominal wall scarring, fetal size, and fetal position may limit adequate visualization, and these limitations should be noted in the report. If imaging is suboptimal, a follow-up examination may be helpful. If an abnormality is identified or suspected during a standard examination of fetal anatomy, specialized sonography is indicated.
Second-Trimester Fetal Anomaly Detection. The sensitivity of sonography for detecting fetal anomalies varies according to factors such as gestational age, maternal habitus, fetal position, equipment features, examination type, operator skill, and the specific abnormality in question. For example, maternal obesity has been associated with a 20-percent reduction in the fetal anomaly detection rate, regardless of examination type (Dashe, 2009).
Imaging technological advances have contributed to dramatic improvements in anomaly detection. In a review of more than 925,000 pregnancies evaluated between 1978 and 1997, Levi (2002) identified an overall anomaly detection rate of 40 percent. The single largest trial, the EUROFETUS study, included 170,800 pregnancies and identified 55 percent with severe malformations before 24 weeks (Grandjean, 1999). The most recent data are available from a network of population-based registries from 21 European countries, termed EUROCAT, found at: www.eurocat-network.eu.
Between 2006 and 2010, EUROCAT prenatal detection rates for selected anomalies were as follows: anencephaly, 97 percent; spina bifida, 84 percent; hydrocephaly, 77 percent; cleft lip, 54 percent; hypoplastic left heart, 73 percent; diaphragmatic hernia, 59 percent; gastroschisis, 94 percent; omphalocele, 84 percent; bilateral renal agenesis, 91 percent; posterior urethral valves, 81 percent; limb-reduction defects, 52 percent; and clubfoot, 43 percent (EUROCAT, 2012). Importantly, however, the overall anomaly detection rate, excluding aneuploidy, was only 34 percent. This reflects inclusion of anomalies with minimal or no sonographic detection, such as microcephaly, anotia, choanal atresia, cleft palate, bile duct atresia, Hirschsprung disease, anal atresia, and congenital skin disorders. These are mentioned because clinicians tend to focus on abnormalities amenable to sonographic detection, whereas families may find those not readily detectable no less devastating. Every sonographic examination should include a frank discussion of examination limitations.
The sensitivity of specialized sonography in experienced centers is considered to be at least 80 percent (American College of Obstetricians and Gynecologists, 2011). Most anomalous infants—approximately 75 percent—occur in pregnancies that are otherwise low-risk, that is, without an indication for specialized sonography. Thus, the quality of a standard screening sonogram greatly affects overall anomaly detection from a population perspective (Dashe, 2009; Levi, 2002). Practice guidelines and standards established by organizations such as the American Institute of Ultrasound in Medicine (2013a) and the International Society of Ultrasound in Obstetrics and Gynecology (Salomon, 2011) have undoubtedly contributed to improvements in anomaly detection rates.
NORMAL AND ABNORMAL FETAL ANATOMY
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.
Brain and Spine
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, p. 289). 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 page 202.
FIGURE 10-2 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.
FIGURE 10-3 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.
FIGURE 10-4 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 (p. 223).
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, p. 181), and their prenatal diagnosis is discussed in Chapter 14 (p. 283). 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.
FIGURE 10-5 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, p. 121).
FIGURE 10-6 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.
FIGURE 10-7 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 (p. 285), 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, p. 287), 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 (p. 325).
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.
FIGURE 10-8 Ventriculomegaly. In this transverse view of the cranium, the yellow 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, p. 1245).
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.
FIGURE 10-9 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.
FIGURE 10-10 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 (p. 202).
FIGURE 10-11 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 (red 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 (p. 327).
FIGURE 10-12 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.
Face and Neck
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, p. 235). Use of the ex-utero intrapartum treatment (EXIT) procedure for severe micrognathia is discussed in Chapter 16 (p. 331).
FIGURE 10-13 Midline face. This view demonstrates the integrity of the upper lip.
FIGURE 10-14 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).
FIGURE 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).
FIGURE 10-16 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, p. 1299). Various abnormalities may be seen sonographically as cystic or solid space-occupying lesions. Fetal therapy for thoracic abnormalities is discussed in Chapter 16 (p. 329).
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, p. 277). 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.
FIGURE 10-17 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 (p. 328).
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).
FIGURE 10-18 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 (p. 323), 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 (p. 323).
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, p. 329). 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, p. 316). 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, p. 316). 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 (p. 331).
FIGURE 10-19 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.
FIGURE 10-20 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.
FIGURE 10-21 Fetal echocardiography gray-scale imaging planes. A. Four-chamber view. B. Left ventricular outflow tract view. The white arrow illustrates the mitral valve becoming the wall of the aorta. The yellow arrow marks 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.
Four-Chamber View. 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 10-6. 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
aPulsed-wave Doppler sonography should be used as an adjunct to evaluate these structures.
Cardiac biometry and functional assessment are optional but should be considered for suspected structural/functional abnormalities.
Adapted from the American Institute of Ultrasound in Medicine, 2013b.
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).
FIGURE 10-22 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 (p. 322), this confers a poor prognosis.
FIGURE 10-23 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 (p. 331).
Tetralogy of Fallot. 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.
Cardiac Rhabdomyoma. 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 (p. 223).
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 (p. 321). M-mode can also be used to assess ventricular function and atrial and ventricular outputs.
FIGURE 10-24 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 (p. 285), both are associated with maternal serum alpha-fetoprotein elevation.
FIGURE 10-25 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-Muoz, 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-Muoz, 2007).
FIGURE 10-26 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- Muoz, 2007). Whereas Nicholas and colleagues (2009) reported an association between growth restriction and adverse outcome with gastroschisis, Santiago-Muoz 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.
FIGURE 10-27 Omphalocele. Transverse view of the abdomen showing an omphalocele as a large abdominal wall defect with exteriorized liver covered by a thin membrane.
Body Stalk Anomaly
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, p. 236).
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 (p. 201) (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.
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.
FIGURE 10-28 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.
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.
FIGURE 10-29 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, p. 231). 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.
Renal Pelvis Dilatation
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.
FIGURE 10-30 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, p. 293).
TABLE 10-7. Risk for Postnatal Urinary Abnormality According to Degree of Renal Pelvis Dilatationa
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.
FIGURE 10-31 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).
FIGURE 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 (p. 1058), 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 (p. 330).
FIGURE 10-33 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, p. 1299). 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, p. 1299) (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, p. 1298). 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, p. 269). Another skeletal dysplasia that results in severe hypomineralization is hypophosphatasia, which is inherited in an autosomal recessive fashion.
FIGURE 10-34 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).
FIGURE 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 the standard 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, p. 252). 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, p. 121). They have also been associated with chorionic villus sampling when performed before 10 weeks’ gestation (Chap. 14, p. 300).
THREE- AND FOUR-DIMENSIONAL SONOGRAPHY
During the last two decades, three-dimensional (3-D) sonography has gone from a novelty to a standard feature of most modern ultrasound equipment (Fig. 10-36). 3-D sonography is not routinely used during a standard examination nor considered a required modality. However, it may be a component of various specialized evaluations.
FIGURE 10-36 Fetal face. Surface rendered three-dimensional image of a normal fetal face and hand at 32 weeks.
Most 3-D scanning uses a special transducer developed for this purpose. After a region of interest is identified, a 3-D volume is acquired that may be rendered to display images of any plane—axial, sagittal, coronal, or even oblique—within that volume. Sequential “slices” can be generated, similar to computed tomographic (CT) or MR images. Technique applications include evaluation of intracranial anatomy in the sagittal plane, for example, the corpus callosum, and imaging of the palate and skeletal system (Benacerraf, 2006; Pilu, 2008; Timor-Tritsch, 2000).
Unlike 2-D scanning, which appears to be in “real time,” 3-D imaging is static and obtained by processing a volume of stored images. There is also four-dimensional (4-D) sonography, also known as real-time 3-D sonography. This enhancement allows rapid reconstruction of the rendered images to convey the impression that the scanning is in real time. One application of 4-D imaging has been to improve visualization of cardiac anatomy. Postprocessing algorithms and techniques take advantage of real-time image volumes, with and without color Doppler mapping. An example is spatiotemporal image correlation—STIC, used to evaluate complex cardiac anatomy and function (DeVore, 2003; Espinoza, 2008). Addition of an inversion-mode algorithm may aid imaging of blood flow within the heart and great vessels and may even permit measurement of ventricular blood volume (Goncalves, 2004). Systematic approaches or protocols for using these new techniques to evaluate cardiac anatomy and physiology are under development (Espinoza, 2007; Turan, 2009).
For selected anomalies, such as those of the face and skeleton, 3-D sonography may provide additional useful information (Goncalves, 2005). That said, comparisons of 3-D with conventional 2-D sonography for the diagnosis of most congenital anomalies have not demonstrated an improvement in overall detection (Goncalves, 2006; Reddy, 2008). The American College of Obstetricians and Gynecologists (2011) currently recommends that 3-D ultrasound be used only as an adjunct to conventional sonography.
When sound waves strike a moving target, the frequency of the waves reflected back is shifted proportionate to the velocity and direction of that moving target—a phenomenon known as the Doppler shift. Because the magnitude and direction of the frequency shift depend on the relative motion of the moving target, Doppler can be used to evaluate flow within blood vessels. The Doppler equation is shown in Figure 10-37.
FIGURE 10-37 Doppler equation. Ultrasound emanating from the transducer with initial frequency fo strikes blood moving at velocity v. Reflected frequency fd is dependent on angle θ between beam of sound and vessel.
An important component of the equation is the angle of insonation, abbreviated as theta (θ), which is the angle between the sound waves from the transducer and flow within the vessel. Measurement error becomes large when θ is not close to zero, in other words, when blood flow is not coming directly toward or away from the transducer. For this reason, ratios are often used to compare different waveform components, allowing cosine θ to cancel out of the equation. Figure 10-38 is a schematic of the Doppler waveform and describes the three ratios commonly used. The simplest is the systolic-diastolic ratio (S/D ratio), which compares the maximal (or peak) systolic flow with end-diastolic flow to evaluate downstream impedance to flow.
FIGURE 10-38 Doppler systolic–diastolic waveform indices of blood flow velocity. S represents the peak systolic flow or velocity, and D indicates the end-diastolic flow or velocity. The mean, which is the time-average mean velocity, is calculated from computer-digitized waveforms.
Continuous wave Doppler equipment has two separate types of crystals—one transmits high-frequency sound waves, and another continuously captures signals. In M-mode imaging, continuous wave Doppler is used to evaluate motion through time, however, it cannot image individual vessels.
Pulsed-wave Doppler uses only one crystal, which transmits the signal and then waits until the returning signal is received before transmitting another one. It allows precise targeting and visualization of the vessel of interest. Pulsed-wave Doppler can be configured to allow color-flow mapping—such that blood flowing toward the transducer is displayed in red and that flowing away from the transducer appears in blue. Various combinations of pulsed-wave Doppler, color-flow Doppler, and real-time sonography are commercially available.
As discussed in Chapter 17 (p. 344), umbilical artery Doppler has been subjected to more rigorous assessment than has any previous test of fetal health. The umbilical artery differs from other vessels in that it normally has forward flow throughout the cardiac cycle. Moreover, the amount of flow during diastole increases as gestation advances—a function of decreasing placental impedance. The S/D ratio normally decreases from approximately 4.0 at 20 weeks to 2.0 at term, and it is generally less than 3.0 after 30 weeks. Because of downstream impedance to flow, more end-diastolic flow is observed at the placental cord insertion than at the fetal ventral wall. Thus, abnormalities such as absent or reversed end-diastolic flow will appear first at the fetal cord insertion site. The International Society of Ultrasound in Obstetrics and Gynecology recommends that umbilical artery Doppler measurements be made in a free loop of cord (Bhide, 2013). However, the Society for Maternal Fetal Medicine has recommended that assessment be performed close to the ventral wall insertion to optimize reproducibility (Berkley, 2012).
The waveform is considered abnormal if the S/D ratio is above the 95th percentile for gestational age. In extreme cases of growth restriction, end-diastolic flow may become absent or even reversed (Fig. 10-39). Such reversal of end-diastolic flow has been associated with greater than 70-percent obliteration of the small muscular arteries in placental tertiary stem villi (Kingdom, 1997; Morrow, 1989).
FIGURE 10-39 Umbilical artery Doppler waveforms. A. Normal diastolic flow. B. Absence of end-diastolic flow. C. Reversed end-diastolic flow.
Umbilical artery Doppler is a useful adjunct in the management of pregnancies complicated by fetal-growth restriction, and it has been associated with improved outcome in such cases (American College of Obstetricians and Gynecologists, 2013). It is not recommended for complications other than growth restriction. Similarly, it is not recommended as a screening tool for identifying pregnancies that will subsequently be complicated by growth restriction (Berkley, 2012). Abnormal umbilical artery Doppler findings should prompt a complete fetal evaluation if not already done, as such findings are associated with major fetal anomalies and aneuploidy (Wenstrom, 1991). The Society for Maternal Fetal Medicine has recommended that so long as fetal surveillance remains reassuring, pregnancies with fetal-growth restriction and absent end-diastolic flow in the umbilical artery may be managed expectantly until delivery at 34 weeks, and those with reversed end-diastolic flow managed expectantly until delivery at 32 weeks (Berkley, 2012).
Doppler evaluation of the ductus arteriosus has been used primarily to monitor fetuses exposed to indomethacin and other nonsteroidal antiinflammatory agents (NSAIDs). Indomethacin, which is used by some for tocolysis, may cause ductal constriction or closure, particularly when used in the third trimester (Huhta, 1987). The resulting increased pulmonary flow may cause reactive hypertrophy of the pulmonary arterioles and eventual development of pulmonary hypertension. In a review of 12 randomized controlled trials involving more than 200 exposed pregnancies, Koren and colleagues (2006) reported that NSAIDs increased the odds of ductal constriction 15-fold. They also concluded that this was a low estimate because most of the pregnancies were exposed only briefly. Fortunately, ductal constriction is often reversible after NSAID discontinuation. Because ductal constriction is a potentially serious complication that should be avoided, the duration of NSAID administration is typically limited to less than 72 hours, and women taking NSAIDs are closely monitored so that these can be discontinued if ductal constriction is identified.
Uterine blood flow is estimated to increase from 50 mL/min early in gestation to 500 to 750 mL/min by term (Chap. 4, p. 47). The uterine artery Doppler waveform is characterized by high diastolic flow velocities and by highly turbulent flow. Increased resistance to flow and development of a diastolic notch are associated with later development of gestational hypertension, preeclampsia, and fetal-growth restriction. Zeeman and coworkers (2003) also found women with chronic hypertension who had increased uterine artery impedance at 16 to 20 weeks were at increased risk to develop superimposed preeclampsia. Even so, the predictive value of uterine artery Doppler testing is low, and screening is not recommended in either high-risk or low-risk pregnancies (Sciscione, 2009). The technique has not been standardized, frequency of assessment has not been established, and criteria for an abnormal test have not been determined. In a report from a workshop on prenatal imaging held by the NICHD, Reddy and associates (2008) concluded that perinatal benefits of uterine artery Doppler screening have not yet been demonstrated.
Middle Cerebral Artery
Doppler interrogation of the middle cerebral artery (MCA) has been investigated and applied clinically for fetal anemia detection and fetal-growth restriction evaluation. Anatomically, the path of the MCA is such that flow often approaches the transducer “head-on,” allowing for accurate determination of flow velocity (Fig. 10-40). The MCA is imaged in an axial view of the head at the base of the skull, ideally within 2 mm of the internal carotid artery origin. Velocity measurement is optimal when the insonating angle is close to zero, and no more than 30 degrees of angle correction should be used. In general, velocity assessment is not performed in other fetal vessels, because a larger insonating angle is needed and confers significant measurement error.
FIGURE 10-40 Middle cerebral artery (MCA) Doppler. A. Color Doppler of the circle of Willis, demonstrating the correct location to sample the MCA. B. The waveform demonstrates a peak systolic velocity exceeding 70 cm/sec in a 32-week fetus with severe fetal anemia secondary to Rh alloimmunization.
When fetal anemia is present, the peak systolic velocity is increased due to increased cardiac output and decreased blood viscosity (Segata, 2004). This has permitted the reliable, noninvasive detection of fetal anemia in cases of blood-group alloimmunization. More than a decade ago, Mari and colleagues (2000) demonstrated that an MCA peak systolic velocity threshold of 1.50 multiples of the median (MoM) could reliably identify fetuses with moderate or severe anemia. In most referral centers, MCA peak systolic velocity has replaced invasive testing with amniocentesis for fetal anemia detection (Chap. 15, p. 310).
MCA Doppler has also been studied as an adjunct in the evaluation of fetal-growth restriction. Fetal hypoxemia is believed to result in increased blood flow to the brain, heart, and adrenal glands, leading to increased end-diastolic flow in the MCA. This phenomenon, “brain-sparing,” is actually a misnomer, as it is not protective for the fetus but rather is associated with perinatal morbidity and mortality (Bahado-Singh, 1999; Cruz-Martinez, 2011). The utility of MCA Doppler to aid the timing of delivery is uncertain. It has not been evaluated in randomized trials nor adopted as standard practice in the management of growth restriction (American College of Obstetricians and Gynecologists, 2013; Berkley, 2012).
The ductus venosus is imaged as it branches from the umbilical vein at approximately the level of the diaphragm. Fetal position poses more of a challenge in imaging the ductus venosus than it does with either the umbilical artery or the middle cerebral artery. The waveform is biphasic and normally has forward flow throughout the cardiac cycle. The first peak reflects ventricular systole, and the second is diastolic filling. These are followed by a nadir during atrial contraction—termed the a-wave.
It is believed that there is a progression of Doppler findings in preterm fetuses with growth restriction, such that umbilical artery Doppler abnormalities occur first, followed by those in the middle cerebral artery and then the ductus venosus. However, there is wide variability in manifestation of these abnormalities (Berkley, 2012). When severe fetal-growth restriction is present, cardiac dysfunction may lead to flow in the a-wave that is decreased, absent, and eventually reversed, along with pulsatile flow in the umbilical vein (Reddy, 2008).
Thus, ductus venosus abnormalities have potential to identify preterm growth-restricted fetuses that are at greatest risk for adverse outcomes (Baschat, 2003, 2004; Bilardo, 2004; Figueras, 2009). As noted by the Society for Maternal-Fetal Medicine, however, they have not been sufficiently evaluated in randomized trials (Berkley, 2012). The American College of Obstetricians and Gynecologists (2013) recently concluded that Doppler assessment of vessels other than the umbilical artery has not been shown to improve perinatal outcome and that its role in clinical practice remains uncertain.
MAGNETIC RESONANCE IMAGING
The fetus was first studied with MR imaging in the mid-1980s, when image acquisition was slow and motion artifact was problematic (Lowe, 1985). Since then, technological advances that allow fast-acquisition MR protocols have been developed. These newer protocols permit image acquisition in 1 second or less, which significantly reduces motion artifact and eliminates the need for sedation.
Image resolution with MR is often superior to that with sonography because it is not as hindered by bony interfaces, maternal obesity, oligohydramnios, or an engaged fetal head. MR may be a useful adjunct to sonography in evaluating and further characterizing suspected fetal abnormalities. MR imaging, however, is not portable, it is time-consuming, and its use is generally limited to referral centers with expertise in fetal imaging. It may be helpful in the evaluation of complex abnormalities of the fetal CNS, thorax, gastrointestinal system, genitourinary system, and musculoskeletal system. MR has also been used in the evaluation of maternal pelvic masses, placental invasion, and abnormalities of the pelvic floor and cervix.
The American College of Radiology and Society for Pediatric Radiology (2010) have developed a practice guideline for fetal MR imaging. This guideline acknowledges that sonography is the screening modality of choice. Moreover, it recommends that fetal MR imaging be used for problem solving to ideally contribute to prenatal diagnosis, counseling, treatment, and delivery planning. Specific indications for fetal MR imaging are listed in Table 10-8and are discussed subsequently.
TABLE 10-8. Fetal Conditions for Which Magnetic Resonance Imaging May Be Indicated
Brain and spine
Agenesis of the corpus callosum
Posterior fossa abnormalities
Cerebral cortical malformations
Monochorionic twin pregnancy complications
Caudal regression sequence
Skull, face, and neck
Other abnormalities with potential airway obstruction
Congenital cystic adenomatoid malformation
Extralobar pulmonary sequestration
Congenital diaphragmatic hernia
Evaluation of pulmonary hypoplasia secondary to oligohydramnios, chest mass, or skeletal dysplasia
Abdomen, pelvis, and retroperitoneum
Assess the size and location of tumors (such as sacrococcygeal teratoma, neuroblastoma, suprarenal or renal masses)
Assess renal anomalies with oligohydramnios
Diagnose bowel anomalies
Complications of monochorionic twins
Determine vascular anatomy prior to laser treatment
Assess morbidity after death of a monochorionic cotwin
Evaluate conjoined twins
Fetal surgery assessment
Fetal brain anatomy before and after surgical intervention
Fetal anomalies for which surgery is planned
Adapted from American College of Radiology–Society of Perinatal Radiologists Practice Guideline, 2010.
MR imaging uses no ionizing radiation. Theoretical concerns include the effects of fluctuating electromagnetic fields and high sound-intensity levels. The strength of the magnetic field is measured in tesla (T), and all imaging studies during pregnancy are currently performed using 1.5 T or less.
Human studies and tissue studies support the safety of fetal MR imaging. Repetitive exposure of human lung fibroblasts to a static 1.5-T magnetic field has not been found to affect cellular proliferation (Wiskirchen, 1999). Fetal heart rate patterns have been evaluated before and during MR imaging, with no significant differences observed (Vadeyar, 2000). Children exposed to MR as fetuses have not been found to have an increased incidence of disease or disability when tested at age 9 months or 3 years (Baker, 1994; Clements, 2000).
Glover and associates (1995) attempted to mimic the sound level experienced by the fetal ear by having an adult volunteer swallow a microphone while the stomach was filled with a liter of fluid to represent the amnionic sac. There was at least 30-dB attenuation in intensity from the body surface to the fluid-filled stomach, reducing the sound pressure from 120 dB to below 90 dB. This level is considerably less than the 135 dB experienced from vibroacoustic stimulation (Chap. 17, p. 341). Cochlear function testing has been performed in infants who were exposed to 1.5-T MR imaging as fetuses. Such testing has not demonstrated evidence of hearing impairment (Reeves, 2010).
The Expert Panel on MR Safety of the American College of Radiology (2013) has concluded that based on available evidence, there are no documented deleterious effects of MR imaging exposure on the developing fetus. Therefore, MR can be performed in pregnancy if the data are needed to care for the fetus or mother. Health-care providers who are pregnant may work in and around an MR unit, but it is recommended that they not remain in the MR scanner magnet room—known as Zone IV—while an examination is in progress (American College of Radiology, 2013).
Gadolinium-based MR contrast agents should be avoided during pregnancy because of the potential for dissociation of the chelate molecule in the amnionic fluid (American College of Radiology, 2013). These readily enter the fetal circulation and are excreted into the amnionic fluid via fetal urine. Here, they may remain for an indeterminate period before being reabsorbed. The longer the gadolinium-chelate molecule remains in a protected space such as the amnionic sac, the greater the potential for dissociation of the toxic gadolinium ion (American College of Radiology, 2013). In adults with renal disease, this contrast agent has been associated with development of nephrogenic systemic fibrosis, a potentially severe complication.
All women complete a written MR safety screening questionnaire before the examination. This includes information regarding metallic implants, pacemakers, or other metal- or iron-containing devices that may alter the study (American College of Radiology, 2013). Iron supplementation may cause artifact in the colon but does not usually affect the fetal resolution. In more than 2000 MR procedures in pregnancy performed at Parkland Hospital during the last 10 years, maternal anxiety secondary to claustrophobia and/or fear of the MR equipment has occurred in fewer than 1 percent of our patients. To reduce maternal anxiety in this small group, a single oral dose of diazepam, 5 to 10 mg, or lorazepam, 1 to 2 mg, is given.
Women are placed in the supine or left lateral decubitus position. A torso coil is used in most circumstances, with the occasional use of either the body or cardiac coil depending on maternal or fetal size and area of interest. A series of three-plane localizers are obtained relative to the maternal coronal, sagittal, and axial planes. The gravid uterus is imaged in the maternal axial plane (7-mm slices, 0 gap) with a T2-weighted fast acquisition. Typically, these may be a single-shot fast spin echo sequence (SSFSE), half-Fourier acquisition single-shot turbo spin echo (HASTE), or rapid acquisition with relaxation enhancement (RARE), depending on the brand of machine and manufacturer. Next, a fast T1-weighted acquisition such as spoiled gradient echo (SPGR) is performed (7-mm thickness, 0 gap). These acquisitions are particularly good for identifying fetal and maternal anatomy.
Orthogonal images of targeted fetal or maternal structures are then obtained. In these cases, 3- to 5-mm slice thickness, 0 gap T2-weighted acquisitions are performed in the coronal, sagittal, and axial planes. Depending on the anatomy and underlying suspected abnormality, T1-weighted images can be performed to evaluate for subacute hemorrhage, fat, or location of normal structures that appear bright on these sequences, such as liver and meconium in the colon (Brugger, 2006; Zaretsky, 2003b).
Short TI inversion recovery images (STIR) may provide differentiation in cases in which the water content of the abnormality is similar to the normal structure. An example is a thoracic mass compared with normal lung. Occasionally, fluid attenuated inversion recovery (FLAIR) images may be obtained for CNS abnormalities to evaluate the ventricular system and other CSF-containing spaces. Diffusion-weighted imaging may be employed to evaluate for restricted diffusion and ischemia (Brugger, 2006; Zaretsky, 2003b). Our series also includes an axial brain 3- to 5-mm T2-weighted sequence to obtain head biometry for gestational age estimation using the biparietal diameter and head circumference (Reichel, 2003).
Fetal Anatomical Evaluation
Whenever a fetal abnormality has been identified, findings from the affected organ as well as other organ systems should be thoroughly characterized. Accordingly, a fetal anatomical survey is generally completed during each MR examination. In a recent prospective study, nearly 95 percent of the anatomical components recommended by the International Society of Ultrasound in Obstetrics and Gynecology were visible at 30 weeks (Millischer, 2013). The aorta and pulmonary artery were the structures most difficult to evaluate. Zaretsky and coworkers (2003a) similarly found that with the exclusion of cardiac structures, fetal anatomical evaluation was possible in 99 percent of cases.
Central Nervous System
With MR imaging, the brain can be visualized in the axial, coronal, and sagittal planes, without the near-field attenuation caused by the fetal skull during sonography. This makes MR a valuable adjunct in the evaluation of selected intracranial anomalies. Very fast T2-weighted images produce excellent tissue contrast, and CSF-containing structures are hyperintense or bright. This allows exquisite detail of the posterior fossa, midline structures, and cerebral cortex. T1-weighted images are occasionally used to differentiate between fat and hemorrhage.
CNS biometry obtained with MR imaging has been found to be comparable with that obtained using sonography (Twickler, 2002). Nomograms have been published for multiple intracranial structures, including corpus callosum and cerebellar vermis lengths (Garel, 2004; Tilea, 2009).
Levine and colleagues (1999a) demonstrated that MR imaging accurately portrays cerebral gyration and sulcation patterns (Fig. 10-41). This is important because fetuses with a cerebral abnormality may have a significant lag in cortical development. Sonography permits limited evaluation of subtle migrational abnormalities, and MR imaging provides greater accuracy, particularly later in gestation.
FIGURE 10-41 Sagittal images of the fetal brain at 25 weeks (A) and at 37 weeks (B) demonstrate the normal increase in gyration and sulcation that occurs during fetal development. These images were obtained using a Half Fourier Acquisition Single Shot Turbo Spin Echo (HASTE) sequence.
Indications. There have been numerous studies of second-opinion MR examination for a cerebral abnormality detected or suspected sonographically (Benacerraf, 2007; Li, 2012). Levine and associates (1999b) found that MR imaging changed the diagnosis in 40 percent of cases and affected management in 15 percent. Simon and coworkers (2000) reported that MR-imaging findings changed management in almost half of cases. Twickler and colleagues (2003) also reported that fetal CNS MR imaging changed the diagnosis in half of fetuses and altered clinical management in a third. Additional information was more likely to be gained when the examination was performed beyond 24 weeks’ gestation.
Ventriculomegaly is a common fetal MR imaging indication, if used to determine whether this finding is truly isolated or associated with other CNS dysmorphology (p. 202). For example, MR may demonstrate that severe ventriculomegaly is secondary to aqueductal stenosis, shown in Figure 10-42, or that it is actually hydranencephaly. In the case of mild ventriculomegaly, MR may identify agenesis of the corpus callosum or migrational abnormalities (Benacerraf, 2007; Li, 2012; Twickler, 2003).
FIGURE 10-42 Aqueductal stenosis. A. An axial transventricular image at 22 weeks using a HASTE sequence demonstrates severe ventriculomegaly. B. A coronal image of the same fetus shows that the third ventricle (arrow) is dilated. C. An axial image at the level of the posterior fossa reveals that the fourth ventricle (arrowhead) appears normal, consistent with a diagnosis of aqueductal stenosis.
Another fetal MR imaging indication is the evaluation of possible intraventricular hemorrhage (IVH), such as shown in Figure 10-43. Fetal IVH risk factors may include an atypical appearance of ventriculomegaly, neonatal alloimmune thrombocytopenia, and a monochorionic multifetal gestation complicated by demise of one fetus or by severe twin-twin transfusion syndrome (Hu, 2006). If hemorrhage is identified, MR imaging characteristics may indicate which structures are involved and approximately when bleeding occurred.
FIGURE 10-43 Intraventricular hemorrhage. Axial images through the brain a 24-week fetus. Arrows denote an area of abnormal signal in the left lateral ventricle. On the HASTE image (A), the irregularity is well delineated but of nonspecific low signal intensity. The T1-weighted image (B) demonstrates increased signal intensity within this area of concern, suggesting an intraventricular hemorrhage. Diffusion-weighted image (C) and Apparent Diffusion Coefficient map (D) demonstrate true restricted diffusion associated with the hemorrhage.
Thoracic abnormalities are readily visualized with targeted sonography. MR imaging, however, may help delineate the location and size of space-occupying thoracic lesions and quantify remaining lung tissue volumes. MR imaging may aid in characterizing the type of cystic adenomatoid malformation and in visualizing the blood supply of extralobar pulmonary sequestration (p. 208). With congenital diaphragmatic hernia, MR imaging may be used to verify and quantify the abdominal organs within the thorax. This includes the volume of herniated liver as well as compressed lung tissue volumes (Fig. 10-44) (Debus, 2013; Lee, 2011; Mehollin-Ray, 2012). MR imaging has also been used to identify other organ-system abnormalities in fetuses with diaphragmatic hernia. This may greatly clarify fetal prognosis (Kul, 2012). MR imaging similarly has been used for lung volume evaluation in cases of skeletal dysplasia and prolonged oligohydramnios secondary to renal disease or ruptured membranes (Messerschmidt, 2011; Zaretsky, 2005).
FIGURE 10-44 Congenital diaphragmatic hernia A. A HASTE image of a 26-week fetus with congenital diaphragmatic hernia involving the liver (arrows). B. Coronal STIR image through a 33-week fetal chest demonstrates multiple loops of bowel filling the left chest (dashed lines).
When sonographic visualization is limited by oligohydramnios or maternal obesity, MR imaging may be useful (Caire, 2003). Hawkins and associates (2008) found that lack of signal in a contracted fetal bladder on T2-weighted sequences was associated with lethal renal abnormalities. Differences in signal characteristics between meconium in the fetal colon and urine in the bladder may permit characterization of cystic abdominal abnormalities (Farhataziz, 2005).
Adjunct to Fetal Therapy
As indications for fetal therapy have increased, MR imaging has been become more routinely used to outline abnormalities preoperatively. At some centers, before laser ablation of placental anastomoses for twin-twin transfusion syndrome, MR imaging is performed to assess the brain for IVH or periventricular leukomalacia (Chap. 34, p. 656) (Hu, 2006; Kline-Fath, 2007). Because of its precision in visualizing brain and spine findings in cases of myelomeningocele, it is often used before fetal spina bifida surgery (Fig. 10-45). If fetal surgery is considered for sacrococcygeal teratomas, MR imaging may identify tumor extension into the fetal pelvis (Avni, 2002; Neubert, 2004). With a fetal neck mass for which an EXIT procedure is considered, MR imaging may help delineate the lesion extent and its effect on the oral cavity and hypopharynx (Hirose, 2003; Ogamo, 2005; Shiraishi, 2000). Finally, MR imaging has also been used when an EXIT procedure may be needed for severe micrognathia (MacArthur, 2012; Morris, 2009). Fetal therapy is discussed in Chapter 16 (p. 331).
FIGURE 10-45 Myelomeningocele. A. A sagittal balanced TruFisp image at 32 weeks demonstrates herniation of the cerebellum into the cervical canal (arrow) and a small sacral neural-tube defect with a thin covering membrane (arrowhead). B. A sagittal TruFisp image of a different fetus demonstrates a neural-tube defect (arrowheads) and prominent myelomeningocele (arrows). B = fetal bladder.
The clinical importance of identifying women with placenta accreta is discussed in Chapter 41 (p. 804). Sonography is generally used to identify placental invasion into the myometrium, however, MR evaluation has been used as an adjunct in indeterminate cases. Findings concerning for invasion include uterine bulging, dark intraplacental bands on T2-weighted images, and placental heterogeneity (Leyendecker, 2012). When used in a complementary role, MR imaging sensitivity for detection of placental invasion has been high, although the depth of invasion has been difficult to predict. Clinical risk factors and sonographic findings should be taken into account when interpreting MR placental images (Leyendecker, 2012). Identification of placenta percreta with bladder wall invasion has been a challenge, even when both sonography and MR imaging are used.
As MR acquisition times improve and technology allows for better resolution of structures and movement, there are three potential directions that fetal imaging may proceed. One is volume acquisition and 3-D postprocessing. This would occur in a manner similar to spiral CT with multiple channel detectors, in which one large high-resolution image can be processed in any plane. Applying this to the fetal structure of interest would require faster acquisition times, the ability to correct for fetal motion, and improved field-of-view options—which are in development.
The second direction is real-time MR imaging for evaluation of the fetal heart and other moving structures. A feasibility study reviewed MR evaluations of the chest to ascertain specific fetal heart components (Gorincour, 2007). These authors found, among other things, that balanced fast imaging with steady-state precession (TruFISP) was helpful in defining atrial, ventricular, conotruncal, and venous relationships.
A third direction is further assessment of already established acquisitions of fetal physiological functions. This includes spectroscopy for brain maturity, which has been discussed in small series (Fenton, 2001; Kok, 2002). Other possibilities include diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) for fetal CNS evaluation (Chung, 2009; Garel, 2008). The latter has the added advantage of white matter tract imaging. These emerging technologies are still experimental and will require rigorous investigation before clinical application.
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