Like much of medicine, ultrasound diagnosis of fetal anomalies is both a science and an art. Part 1 of this article will detail, within the text and with images, the anomalies that should not be missed when performing ultrasound during the first and second trimesters of pregnancy. Part 2, in a future issue, will deal with multifetal gestations. This series will discuss and show the appearance of anomalies in the first and second trimesters, and in multifetal gestations (anomalies unique to multiples) to enhance the ob/gyn’s knowledge of pitfalls that can lead to errors in diagnosis.
Ultrasound and prenatal diagnosis of structural fetal anomalies
Ultrasound can identify the majority of major structural fetal abnormalities. Prenatal diagnosis can lead to improved outcomes by ensuring that delivery occurs in a hospital with the necessary personnel to manage newborns who may require surgery or other specialized care. In rare cases, prenatal diagnosis can lead to fetal intervention, although most anomalies do not require any treatment in utero. Some structural anomalies are associated with genetic conditions, and recognition can lead to prenatal genetic diagnosis. In cases in which prenatal diagnosis reveals a major structural abnormality, some patients may choose to terminate the pregnancy.
Patients who present early for pre- natal care typically undergo 2 ultrasound fetal assessments. At 11 to 14 weeks, when nuchal translucency (NT) is measured as a component of Down syndrome screening, a brief fetal anatomic scan is performed. A first-trimester ultrasound is a valuable tool to confirm viability, rule out multiple pregnancy, and evaluate anatomy, even if genetic screening is not desired. The main ultrasound used to screen for structural anomalies is in the second trimester, generally at 18 to 20 weeks
In the first trimester, some major anomalies can be diagnosed or excluded. In other cases, there may be findings that are not diagnostic but that may suggest a structural anomaly. In these patients, second-trimester ultrasound before 18 weeks can lead to earlier prenatal diagnosis. Abnormal NT in a fetus with a normal karyotype is associated with a higher rate of structural abnormalities. When NT is abnormal, it is reasonable to assess fetal anatomy early in the second trimester, as some structural anomalies can be identified prior to 18 weeks’ gestation.
Late in the first trimester, the brain can be imaged in the transverse plane, identifying both hemispheres and midline structures. Major anomalies that can be identified include anencephaly (absent skull and brain; Figure 1), acrania (absent skull), and holoprosencephaly (no division into separate hemispheres, with absence of midline structures; Figure 2). If a transverse view through the fetal brain identifies a normal midline, representing the falx cerebri, and lateral ventricles, these 3 conditions can be excluded. A large skull defect (cephalocele; Figure 3) can be identified as well.
In the same image used to assess NT, the profile can be evaluated. A profile view can identify a small mandible, or micrognathia (Figure 4). Large median or bilateral cleft lip can also be suspected based on profile views. Coronal imaging can identify the orbits, and large clefts may be visible. Rarely, facial masses representing teratomas or lymphangiomas may be visible.
NT measurements require proper fetal position, image magnification, and caliper placement. All individuals measuring NT as a component of screening for genetic abnormalities must undergo the requisite training, credentialing and quality review.1 An extreme variant of abnormal NT is the cystic hygroma, characterized by midline septations and edema extending to the fetal thorax. While studies looking at outcomes of this condition have identified high rates of genetic and structural abnormalities, it is not clear that the prognosis is poorer compared to fetuses with comparable NT measurements not categorized as cystic hygroma.2
Evaluation of the chest is very limited in the first trimester. The heart should be visible in the midline, and lung tissue should be present on both sides. Mediastinal shift can represent evidence of a chest mass or diaphragmatic hernia, although those are uncommon diagnoses early in pregnancy. Late in the first trimester, it should be possible to distinguish the left from the right side of the heart, and normal situs can be verified. While structural cardiac anomalies rarely can be suspected, diagnosis before the second trimester is uncommon.
An abnormal-appearing cardiac axis may reflect underlying structural abnormalities.3
In the first trimester, visible structures include the ventral wall, umbilical cord insertion, stomach bubble, and urinary bladder. The most common abnormalities identified are the ventral wall defects omphalocele (Figure 5), gastroschisis (Figure 6 and discussed in detail in our February 2017 issue), and more extensive defects including body-stalk anomaly and limb-body-wall complex. Physiologic midgut herniation is common prior to 12 weeks’ gestation and should not be confused with an omphalocele. An enlarged urinary bladder (megacystis; Figure 7) can represent early evidence of bladder outlet obstruction. Kidneys are generally not imaged at < 14 weeks, and because amniotic fluid does not consist primarily of fetal urine until the second trimester, absent or dysfunctional kidneys will not result in oligohydramnios earlier in pregnancy.
The spine is not easy to evaluate in the first trimester, and most abnormalities will go undetected. Spina bifida involving multiple levels can be suspected in rare cases, as can large masses such as sacrococcygeal teratoma.
At a minimum, all limbs should be documented, including proximal long bones (humerus and femur) and distal long bones (radius/ulna and tibia/fibula). Severe skeletal dysplasias, such as thanatophoric dysplasia, can have features such as small limbs and narrow chest even in the first trimester. Hands and feet can also be imaged, although abnormalities of the digits cannot always be identified. In some cases, polydactyly (Figure 8) may be suspected.
Risk factors for structural abnormalities
Abnormal NT is associated with a higher rate of structural abnormalities in fetuses with normal and abnormal karyotypes. Abnormal NT at 11-14 weeks is an indication for genetic counseling, and early second trimester ultrasound at 14-16 weeks should be considered. Abnormal NT is also an indication for fetal echocardiography in the second trimester.
In some cases, first-trimester ultrasound findings may be suspicious, but not diagnostic, for abnormalities of certain structures. In these cases, early second-trimester ultrasound can lead to prenatal diagnosis prior to the routine 18- to 20-week scan. In our experience, early second-trimester ultrasound in such cases contributed to lower gestational age at abortion in women undergoing ultrasound at 11 to 14 weeks.4
At 18 to 20 weeks, detailed ultrasound can evaluate most anatomic structures. Earlier second-trimester anatomic evaluation at < 18 weeks should be limited to high-risk patients and/or specialized centers.
Imaging in the transverse plane at the level where the biparietal diameter (BPD) and head circumference (HC) are measured allows identification of the cavum septum pellucidum, third ventricle, and thalami. An oblique/transverse view will image structures in the posterior fossa. Finally, a transverse view superior to the midbrain can identify the lateral ventricles. Realtime scanning should evaluate the integrity of the calvarium. Anomalies that should not be missed in the first trimester should not be missed in the second trimester, such as holoprosencephaly (Figure 9), cephalocele (Figure 10), and anencephaly (Figure 11).
Enlarged ventricles, or ventriculomegaly can indicate several conditions (Figure 12). As an isolated finding, ventriculomegaly can represent obstruction of the flow of cerebrospinal fluid (CSF), and can indicate hydrocephalus. Abnormal cortical development can result in ventricular enlargement in the absence of obstruction.
Ventriculomegaly is also present in the Dandy-Walker malformation (Figure 13), a malformation characterized by absence of the middle portion of the cerebellum, known as the vermis, with cystic dilation of the fourth ventricle visible in the posterior fossa. Ventriculomegaly is also part of the Arnold-Chiari Type II malformation, which is present in most cases of spina bifida. The spinal defect with herniated tissue, or meningomyelocele, has a negative pressure effect on the brain, with herniation of the hindbrain into the spinal canal. This causes the cerebellum to be elongated and distorted into a “banana” shape” (Figure 14), the frontal bones of the calvarium to collapse, causing a “lemon shaped” skull (Figure 15), and obstruction of CSF flow leading to ventriculomegaly. Evaluation of the spine in sagittal and transverse views is necessary to confirm the presence and level of the spinal defect.
Ventriculomegaly, whether isolated or with associated structural abnormalities, is associated with genetic abnormalities. Mild ventriculomegaly is associated with Down syndrome. Hydrocephalus in a male fetus with no associated finding could reflect a mutation in the L1CAM gene associated with X-lined hydrocephalus. Dandy-Walker Malformation is associated with chromosomal abnormalities, as well as single gene disorders. While open neural tube defects are usually multifactorial in origin, they may be a feature of Trisomy 18. Genetic counseling is indicated when ventriculomegaly is identified.
Another diagnosis that can be suspected based on second-trimester ultrasound is agenesis of the corpus callosum (Figure 16), a condition in which the large midline bundle of white matter connecting neurons in the 2 hemispheres is absent. Agenesis of the corpus callosum should be suspected when the cavum septum pellucidum is not visible, the third ventricle appears prominent, and the lateral ventricles have a teardrop-shaped configuration, with dilation of the posterior horns.
A profile view in the first and second trimester can identify a small mandible, or micrognathia (Figure 17). Median or bilateral cleft lip (Figures 18, 19) can also be suspected based on profile views. The lips and palate are best evaluated with coronal imaging and transverse views at the level of the palate. The most common clefts are unilateral, and generally will not be identified until the second trimester. Cleft-palate in the presence of a cleft-lip involves the bony palate, and it can generally be suspected. Isolated cleft palate typically affects the soft palate, and it is rarely detected. Real-time imaging of the entire face can identify masses, including teratomas and lymphangiomas.
The nuchal skin fold is visible in the same plane as the posterior fossa. A thickened nuchal skin fold is associated with chromosomal and cardiovascular abnormalities. The neck can also be evaluated and neck masses identified in the profile view. Persistent hyperextension of the neck can also indicate presence of an anterior neck mass.
In the second trimester, the heart should be visible in the middle of the chest with its axis pointed toward the fetal left, with lung surrounding the heart on both sides, left smaller than right. When the heart is not in the midline position, a mediastinal shift can indicate a unilateral lung mass or diaphragmatic hernia. Congenital pulmonary airway malformations are more echogenic or bright than normal lung tissue, and can appear solid or contain cysts. Diaphragmatic hernia should be suspected if abdominal contents are visible in the chest in the presence of a mediastinal shift (Figures 20, 21). In the absence of significant mediastinal shift, smaller right-sided lesions are less likely to be detected. The echotexture of herniated liver in the right thorax may appear similar to that of lung, while the stomach bubble or small intestine in the chest with left-sided lesions is usually obvious. When transverse imaging of the chest is suggestive of diaphragmatic hernia, sagittal and coronal images can directly identify the defect in the affected hemi-diaphragm in most cases.
Heart and cardiac outflow tracts
A 4-chamber view can identify defects of the ventricular septum (or VSDs) (Figure 22), and abnormalities of chamber size such as hypoplastic right or left ventricles. Small VSDs are commonly missed, however, and atrial septal defects (ASDs) are generally not diagnosed in utero due to the presence of the foramen ovale, a physiologic connection between the atria. Obstruction of the aorta, such as with coarctation or stenosis, will typically cause enlargement of the right ventricle, which supplies most of the aortic blood flow through the ductus arteriosus. Because of the fetal circulation, however, milder degrees of aortic coarctation may be missed.
While the 4-chamber view of the heart is very useful, it alone will not detect several major abnormalities. Evaluation of the outflow tracts, or the aorta and pulmonary artery as they exit the left and right ventricles, is recommended if possible. Major conditions such as Tetralogy of Fallot (Figure 23), Transposition of the great vessels (Figure 24), and Truncus arteriosus will have a normal 4-chamber view of the heart in most cases, but will usually be apparent if the outflow tracts are included.
Structures that should be imaged include the stomach bubble, in the left upper quadrant, ventral wall, umbilical cord insertion, bowel, and gall bladder. Gastrointestinal obstruction, including intestinal atresia, is often not apparent before the third trimester. Esophageal atresia should be suspected if the stomach bubble is persistently small or absent. A cystic mass medial to the gall bladder connecting to the cystic duct is likely to represent a choledochal cyst. Anomalies that should not be missed in the first trimester should not be missed in the second trimester, such as omphalocele (Figure 25) and gastroschisis (Figure 26).
The kidneys should be visible in the renal fossae. Unilateral renal agenesis or ectopic kidney (Figure 27) may be missed, as the adrenal gland or adjacent bowel can be mistaken for a kidney in the renal fossa. To avoid that, the renal cortex and pelvis should be identified before concluding that the kidney is present in the renal fossa. Disorders affecting both kidneys, such as renal agenesis, dysplastic kidneys (Figure 28), or autosomal-recessive polycystic kidney disease are associated with oligohydramnios (Figure 29), and are seldom missed.
The urinary bladder is visible inferior to the umbilical cord insertion, and the umbilical arteries can be seen laterally using color Doppler. Normal amniotic fluid with a persistently non-visualized bladder is suggestive of bladder exstrophy, a rare disorder.
The fetal genitalia can be evaluated starting early in the second trimester. Abnormalities in genitalia can include hypospadias and ambiguous genitalia. If the fetal genotype, based on karyotype or cell-free fetal DNA, is known, the appearance of the genitalia can be correlated with this information.
The cervical, thoracic, lumbar, and sacral spine should be imaged in sagittal and transverse planes. Real-time ultrasound can follow the spinal column from the base of the skull to the sacrum, evaluating each level. While spina bifida can be suspected based on sagittal imaging (Figure 30), smaller lesions may be apparent only with transverse imaging (Figure 31). Most cases will be associated with the Arnold-Chiari II malformation, with obvious abnormalities in the brain. Sagittal imaging can identify hemivertebra (Figure 32). The soft tissue superficial to the spine should be evaluated, and rare lesions such as sacrococcygeal teratoma can be identified.
Measurement of the femur and humerus are done to confirm adequate growth of long bones. Assessment should also include documenting presence of other long bones in all extremities, including radius and ulna in the forearms and tibia and fibula in the legs. Abnormalities of skeletal structures can be quantitative or qualitative. Quantitative abnormalities involve abnormal growth of the long bones of the arms and legs, such as limb reduction defects (Figure 33). Qualitative abnormalities of bones include conditions leading to abnormal appearance, such as bowing, fractures, or hypomineralization (Figure 34). While severe skeletal dysplasias are usually apparent in the second trimester, mild skeletal dysplasias, such as achondoroplasia, are often not diagnosed until later in pregnancy.
Assessment of hands should include attempts to rule out polydactyly and syndactyly (Figure 35), and to document presence of the thumb. Assessment of the feet should include their position relative to the tibia and fibula to rule out signs of clubfoot deformity (Figure 36). Real-time ultrasound assessment is important to document normal movement and tone in all extremities, including opening and closing of the hands. Abnormal tone, such as fixed extension of the legs or clenching of the fingers Figure 37), can indicate a neurologic, neuromuscular, or musculoskeletal abnormality.
Skeletal dysplasias can involve abnormalities of structures other than the arms and legs, including the skull, spine, and ribcage (Figure 38). Evaluation of these structures is important when skeletal dysplasia is suspected based on abnormalities of the extremities.
Fetal anomalies can be diagnosed by ultrasound in early pregnancy, though second-trimester ultrasound can identify or exclude more conditions. There are some anomalies that are difficult to diagnose or that do not lend themselves to ultrasound diagnosis and will be missed.
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4. Chasen ST, Kalish RB. Can early ultrasound reduce the gestational age at abortion for fetal anomalies? Contraception. 2013 Jan;87(1):63-6.