Sonographic Evaluation of the Normal and Abnormal Placenta

Introduction
The placenta evolves rapidly over a short period of time. Its response to injury is limited. Fortunately, the placenta has significant reserve capacity; the fetus may be relatively unaffected until 30% of the placenta is no longer functional1.

Placental Development
The placenta evolves both structurally and functionally throughout pregnancy. In the first half of the 1st trimester, the embryo develops in an environment with a lower oxygen concentration than the fetus. The formation of villi begins around day 13 after conception; fetal placental capillaries are detectable by 3 weeks post conception. A transudate from maternal plasma bathes the trophoblastic plugs2. A true intervillus blood flow is not well established until 12 weeks' gestation. By 14 weeks' gestation uterine artery velocity increases; there is continuous intervillous flow; and end diastolic flow appears in the umbilical artery3.

The eventual position and shape of the normal placenta is due to the degeneration of villi from all areas, except those with the best blood supply. As a result, villi in the lower uterine segment tend to atrophy, while villi develop within the uterine fundus. This process is referred to as trophotropisim (tropho [Greek], to feed; tropic [Greek], turn toward) 4 .

Placental Volume

The placenta should be considered a fetal organ. Intrauterine growth restriction (IUGR) is preceded by reduced placental growth in the first half of pregnancy 5 . In early onset IUGR there is a failure to develop a normal placental villous tree, as well as a failure by the placenta to respond to hypoxia with trophoblastic proliferation and angiogenesis 6 .

Enlarged "jelly-like" Placenta

Enlarged "jelly-like" placentas have a prevalence of 0.6 to 7.6% 7 (Fig. 1). The range in the estimated frequency is due to variation in terminology between authors. In general, these placentas contain numerous sonolucent spaces with turbulent flow; the placental weight is < 10th percentile. They are associated with IUGR, pre-eclampsia and elevated 2nd trimester maternal serum alphafetoprotein 8 . Defective transformation of the spiral arteries results in a globular "jelly-like" placenta. Because of the poor vascularity, the majority of jelly-like placentas are located laterally.

Figure 1 - Jelly-like globular placenta associated with 2nd trimester intrauterine growth restriction.

Intervillous Thombosis

The intervillous space varies in size (0.3 to 3.0 cm) 9 . With uterine contractions, spiral artery flow is altered, resulting in a change in the shape of the intervillous space. The slow turbulent flow within the intervillous space, as well as the spiral artery's entrance into the intervillous space can be appreciated with color Doppler. One or more intervillous spaces are visualized in 2.2% of placentas between 15 and 34 weeks' gestation 10 .

An intervillous thrombus (Fig. 2), therefore, consists of coagulated maternal and fetal blood within an intervillous space. These lesions occur in up to 40% of placentas; they are not associated with an increase in fetal morbidity. Sonographically, they are initially isoechoic. As fibrin accumulates around its periphery, an intervillous thrombus becomes increasingly echogenic 11,12 .

Figure 2 - Intervillous thrombus (arrow).

 Subamniotic Cysts

These cysts are frequently located close to the placental cord insertion (Fig. 3). The cysts may be simple or complex. If the cysts are larger than 4.5 cm or > 3 in number, the frequency of intrauterine growth restriction may be increased 13 .

Figure 3 - Subamniotic cyst (arrow) at the placental cord insertion (a, longitudinal; b, transverse).

Placenta Previa

In mid-gestation the placenta occupies 50% of the uterine surface. By 40 weeks' gestation, the placenta occupies 17 - 25% of the uterine volume 14 . This, in part, explains the decreasing prevalence of placenta previa as gestation advances.

The incidence of placenta previa is approximately 6% in the 1 st trimester 15 and 0.5% at term 15 .

Predisposing factors for placenta previa are outlined on Table I. The recurrence risk for placenta previa increases with each cesarean section (Table II) 16 . A prior cesarean section does not affect the site of placental implantation. The association between a prior cesarean section and placenta previa is due to a lack of resolution of a previa, suggesting that trophotropism is affected by lower uterine segment scarring 17 .

Table I. Predisposing factors for placenta previa.

Advanced maternal age Multiparity Prior cesarean section Uterine curettage Maternal cigarette smoking

Table II. Prevalence of placenta previa after cesarean sections 16
Cesarean Sections	Prevalence Placenta Previa (%)
1	0.65
2	1.80
3	3.00
4	10.00

With transvaginal sonography, Farine et al 18 reported a 100% sensitivity and negative predictive value for the sonographic diagnosis of placenta previa (Fig. 4). If the placenta extends over the internal cervical os by >= 2.5 cm at 20 - 23 weeks' gestation, Becker et al 19 had a 100% cesarean delivery rate (12 cases) (Fig. 5).

Figure 4 - Placenta previa. The placeta extends over the internal cervical os by 2.6 cm (+. . .+).		Figure 5 - Complete placenta previa (PL = placenta; cx = cervix).

Low-lying Placenta

Transvaginal sonography has been used to define a low-lying placenta as < 2.0 cm from the internal cervical os 20 (Fig. 6). Openheimer et al 20 did not have to perform any cesarean sections for vaginal bleeding when the placenta was > 2 cm from the internal cervical os (14 cases). However, 7 of 8 patients with a placental edge < 2 cm from the internal cervical os required a cesarean section for bleeding. The only patient in this group who did not have a cesarean section had a scan to delivery interval of 11 weeks. If the lower edge of a low-lying placenta is thick (> 1 cm) there is a higher risk of hemorrhage, emergency cesarean section and placenta accreta 21 .

Figure 6 - Low-lying placenta. The placental edge is 18 mm (+. . .+) from the internal cervical os. .

Placental Abruption

Placental abruption has been defined as the premature separation of a normally implanted placenta after 20 to 24 weeks' gestation. External vaginal bleeding is not always present; approximately 40% of cases have concealed retroplacental hemmorhage (Fig. 7). The incidence of placental abruption is determined by the prevalence of high-risk patients at a given institution and is between 1/50 and 1/270 deliveries. The recurrence risk after 1 or 2 prior placental abruptions is 5.6% and 17%, respectively 22,23,24 . Factors that have been associated with placental abruption are outlined in Table III 25 .

Figure 7 - There is a 9.2 x 2.8 x 5.4 cm anterior retroplacental abruption between the markers. To view an enlargement, click on the image.

Table III. Factors associated with placental abruption.

Advanced maternal age Multiparity Maternal vascular disease Smoking Prior placental abruption External trauma Cocaine use Prolonged rupture of membranes Uterine leiomyomas Severe growth restriction

The sensitivity of an ultrasound examination for detecting placental abruption is between 25% and 50% 24,26,27 . However, if a retroplacental clot is visualized, the positive predictive value is quite high. In one study, if the delivery was within 2 weeks of positive ultrasound finding, the diagnosis was confirmed in every case. Because of its low sensitivity, the primary role of an ultrasound examination is to exclude a diagnosis of placenta previa.

Some of the numerous sonographic manifestations of placental abruption are outlined in Table IV 24,28,29 . Retroplacental abruptions generally have a worse prognosis than abruptions without a contained hemorrhage. Chronic or recurrent abruption with subsequent placental insufficiency can result in fetal growth restriction 30 .

Table IV. Sonograhic signs of placental abruption.

Retroplacental mass Intraplacental mass Diffuse placental thickness Rounded placental edge Separation of placental edge Intra-amniotic hemorrhage Preplacental or subamniotic mass Blood in the fetal stomach Intermembranous clot in twins

Succenturiate Placental Lobe

There may be one to several succenturiate or accessory placental lobes (Fig. 8). They each would have a vascular connection to the main body of the placenta. The incidence of succenturiate placental lobes is approximately 5% 31 . Villous atrophy results in the isolation of a placental lobe from the main body of the placenta. The primary concern with a succenturiate placental lobe is that the vessel connecting to the main placental body traverses the cervix (vasa previa). The second complication associated with a succenturiate placental lobe is the potential retention of the accessory lobe within the uterus after delivery 32 .

Figure 8 - Posterior succenturiate placental lobe.

Placenta Accreta

With placenta accreta the decidua basalis does not separate the myometrium and trophoblast. As a result the placenta adheres directly to the myometrium (accreta), grows into the myometrium (increta); or grows completely through the myometrium (percreta).

The incidence of placenta accreta has increased markedly over the past 70 years. In the 1930's the reported incidence was approximately 1 case/30,000 deliveries 33,34 . Wu 35 has recently reported an incidence in 1/533 deliveries. This marked increase is due to the increase in cesarean sections. With the increase in cesarean sections, there has also been an increased incidence of placenta previa - an additional risk factor for placenta accreta 34 . Usta et al 36 have reported a 6.3% rate of placenta accreta with placenta previa.

The loss of the hypoechoic interface between the placenta and myometrium was one of the first sonographic signs associated with placenta accreta. However, the isolated loss of this clear space as the only sign of placenta accreta has subsequently been found to have a low positive predictive value for placenta accreta between 15 weeks' gestation and term 37 .

When placenta accreta is present, the placenta has irregularly shaped vascular sinuses (lacunae) that have detectable low velocity blood flow (Fig. 9). Placental lacunae have been detected in cases of placenta accreta as early as 15 weeks' gestation. Placental lacunae have been reported to have a 93% sensitivity and positive predictive value for placenta accreta 38 .

Figure 9 - Placenta accreta. Irregularly shaped vascular lacunae (arrows) are present within the placenta. To view an enlargement, click on the image.

The interface between the bladder and uterus is usually fairly thick. In patients with placenta accreta, varicies give the appearance that the bladder wall is interrupted (Fig. 10). This sonographic sign has a 93% sensitivity for detecting placenta accreta 38 .

Figure 10 - Placenta accreta. The interface between the bladder and uterus appears interrupted because of the bladder wall varicies

The presence of a gestational sac in the lower uterine segment at 10 weeks or earlier is a 1 st trimester sonographic sign associated with palcenta accreta 37 .

Placental Chorioangioma

Chorioangiomas are detected in 1% of placentas evaluated pathologically after delivery. However, those that are large enough to be clinically significant occur only once in every 3,500 to 9,000 pregnancies 39,40 . In the past, only chorioangiomas > 5 cm were considered large enough to produce fetal complications 41 . More recently, it has been determined that the vascularity of a tumor, rather than its size, determines the likelihood of fetal complications 42 . Chorioangiomas are most commonly detected around the placental cord insertion. As they enlarge, chorioangiomas protrude into the amniotic cavity (Fig. 11).

Figure 11 - Placental chorioangioma. The feeding vessel to the chorioangioma can be appreciated with color Doppler.

Color Doppler should be used to evaluate a placental mass for blood flow. Chorioangiomas that produce fetal effects have either significant internal flow or a large feeding vessel 41 (Fig. 11). Their echo pattern may vary from isoechoic with the placenta to having a mixed echodense/echospared appearance due to the type and degree of degenerative changes that may have occurred. Fibrotic degeneration of a chorioangioma reduces the amount of blood flow through the lesion and is, therefore, considered a good prognostic sign.

The fetal effects from a vascularized chorioangioma are outlined in Table V. Non-immune hydrops results from the shunting of blood to the tumor and secondary high-output failure. Hemolytic anemia may also contribute to fetal hydrops 43 . Polyhydramnios is associated with the amount of vascular flow to the chorioangioma rather than to its size 42 . It has been hypothesized that the associated polyhydramnios is due to a transudate through the walls of the abnormal vessels within the chorioangioma. The fluid then passes through the placenta to the amniotic cavity.

Table V. Potential fetal effects of placental chorioangiomas.

Non-immune hydrops   •  Anemia   •  Thromocytopenia   •  Cardiomegaly   •  Pleural effusions   •  Ascites   •  Anasarca Polyhydramnios Pre-term labor Intrauterine growth restriction

Conclusion

The placenta should be evaluated, not only as a necessary organ for fetal growth the development, but also as a potential source of fetal disease and/or compromise.

NON TROPHOBLASTIC PLACENTAL TUMORS

Chorioangioma - Teratoma - Metastasis

CHORIOANGIOMA (1-5)

• The chorioangioma or placental hemangioma is the most common benign tumor of the placenta, followed by hydatidiform mole and choriocarcinoma..
• Most common non trophoblastic placental tumor and has a reported incidence of between 0.2‑139:10,000 births (Large tumors, those greater than 5 cm, have been reported to occur from 0.2‑4:10,000 births. Smaller chorioangiomas occur more frequently with an incidence of 14‑139:10,000 deliveries) (22,23).
• Reported incidence in pathological series is as high as 1%, however not all tumors are sonographically visible (24).
• The recurrence risk is not yet known but appears to be very small.
• Chorioangiomas are hamartoma, which arise as a malformation of the primitive angioblastic tissue of the placenta.
• Small tumors are essentially asymptomatic.
• Large, clinically significant chorioangiomas occur much less frequently, with a reported incidence ranging from 1 in 3500 to 1 in 9000 births.
• Large chorioangiomas (>5cm) are thought to act as peripheral arteriovenous shunts resulting in cardiac overload, complications associated with them include congestive heart failure, polyhydramnios, hydrops fetalis, premature labor, maternal and fetal coagulopathies and hemolytic anemia (5,8,40,41).

 

PATHOGENESIS

A chorioangioma originates from primitive chorionic mesenchyme. It develops when blood vessels and stroma proliferate independently of the surrounding tissue.

Marchetti (25) describes three histological tumor types (believed to represent various phases of tumor development)

·         One type is less differentiated or more immature with a compact structure of mostly cellular elements.

·         The second type is the mature angiomatous or vascular type. This is the most common type of chorioangioma composed of numerous small blood vessels and capillaries.

·         The last type is characterized by degenerative changes.

Although tumors tend to be of one type, some may exhibit a combination of the characteristics described above.

Chorioangiomas are believed to originate at about the 16^th day after fertilization, although there has been no documentation of chorioangiomas during the first trimester.

ULTRASOUND

The specific findings of chorioangioma are variable, and depend largely on the histological composition of the tumor (angiomatous, cellular or degenerative).

Histological classification correlates well with the sonographic features.

·         If the mass is predominantly vascular, color flow imaging reveals a hypervascularization pattern.

·         Cellular and degenerative types are solid or cystic tumors with little vascularity and the gray-scale appearance ranges from echogenic to hypoechogenic.
 

• Rounded, primarily hypoechoic or mixed echogenic mass. It is well circumscribed and has a different echogenicity from the rest of the placental tissue.

• Most chorioangiomas are small, single, circular, encapsulated and intraplacental. Ultrasound appearances that have been described include:
• Multicystic (12) – the case below demonstrates the rare multicentric angiomatous form (target lesions with hypoechoic central portion and echogenic rim). All lesions demonstrated peripheral arterial inflow and venous outflow on color doppler.

• Echogenic mass with dilated vascular channels (13).
• Complex (14,15).
• Uniformly and non-uniformly solid (16-18).
• Multitumoral (19).
• Usually situated near the umbilical cord insertion site.
• They are surrounded by a capsule or pseudocapsule.
• Location:

• These tumors are usually a single, well-circumscribed mass within the placental substance, but they can present as multiple separate masses that usually bulge into the amniotic cavity.
• Less often they can be located in the membranes and attached to the placenta by a vascular pedicle.
• They have also been described on the umbilical cord  (22).

• Rarely they may present as diffuse mass lesions. Our case presented as “target lesions” with a hyperechogenic periphery and central hypoechoic central portion.
• Usually on the surface of the placenta.
• Usually 1-5 cm in size.
• Mild to moderate blood flow on color doppler (helps distinguish chorioangioma from an intraplacental hematoma).
• Non-immune hydrops (6), thought to be caused by shunting of blood through a large arteriovenous malformation (seen with large tumors)
• Calcification seen sonographically has not been reported (7).
• Polyhydramnios (14-33%) independent of tumor size and is probably related to the vascularity of the tumor and fluid leakage. Polyhydramnios and fetal hydrops may spontaneously regress when the chorioangioma degerates (8,20,21).
• Color doppler pattern is dependent on the histological type of the tumor. Cellular tumors consisting of mixed mesenchymal tissue are relatively avascular whereas the angiomatous type is vascular. Lesions above 7-8 cm may get shunting of fetal blood through the tumor (arterio-venous fistula). Janiaux and Ogle (8) suggest that vascularization of the tumor is an important determining factor of pregnancy outcome. No specific complications should be expected in avascular tumors whereas vascular tumors containing numerous large vessels may result in polyhydramnios and fetal congestive cardiac failure.
• CDI plays an essential role in the differential diagnosis and management of chorioangiomas. Where the tumor is avascular, no specific complications should be expected. Where the tumor is vascularized, and in particular if it contains numerous large vessels, serial ultrasound and Doppler examinations is warranted to detect fetal complications and polyhydramnios (8).
• Color Doppler imaging has contributed greatly to the prenatal differentiation between placental chorioangiomas and other nonvascular tumors such as hematoma, infarcts, intervillous thrombosis, teratoma and partial mole (42,43).
• The angioarchitecture revealed by 3D power Doppler confirms that the vascular channels in the tumor were continuous with the fetal circulation. This rules out other vascularized lesions such as placental hemorrhage (44), maternal lakes, degenerated myoma or placenta accrete (45,46).
• Using color Doppler ultrasound, Jauniaux and Ogle (47) categorized various vascular patterns of chorioangiomas and further identified that tumor vascularization is a pivotal determinant factor of pregnancy outcome.
• Hsieh and Soong (48) illustrated how changes on intracardiac Doppler, rather than a change in tumor size, could reflect the pathophysiological situation in the presence of a chorioangioma. However, detection of such subtle changes requires a high level of expertise.

• Pulsed doppler – waveform usually shows a typical fetal pattern.
• An increase in the echogenicity of the tumor as pregnancy advances is a good prognosis as this appearance is related to fibrotic degeneration of the lesion, reducing the amount of fetal blood shunted through the tumor (8).

COMPLICATIONS

• Chorioangiomas >5 cm are more frequently associated with fetal and maternal complications (hydrops, thrombocytopenia, elevated maternal serum Afp. Large tumors require 1-2 week serial ultrasounds to monitor growth and the development of hydrops.
• Fetal anemia with or without associated hydrops (7).
• Polyhydramnios - incidence of polyhydramnios has been found to be related to the size of the tumor. It occurs in 18‑35% of patients with large tumors (26).
• Oligohydramnios has been reported to be associated with chorio­angioma. This diagnosis was made subjectively at the time of birth in a term gestation without the benefit of sonography. This association has not been confirmed by subsequent literature (27).
• Obstructed labor, which were attributed to the size and location of the chorioangioma (25). These reports have not been substantiated by more recent literature and appear to have been a coincidental rather than a causal finding.
• The incidence of preeclampsia is believed to be increased by some (23,28), but others (22,26,29) believe the incidence is similar to that of the general population. Froehlich, using ColLaborative Research Study data, has documented an increased incidence of preeclampsia of 16.4% vs 4.8% when comparing a group of 76 women with chorioangioma to a control group of 44,994 women (28).

• Antepartum bleeding is believed to be caused by a premature separation of the placenta as a result of bleeding from the tumor bed or a rupture of the vascular pedicle.
• Froehlich reported a 4.0% incidence of abruptio placenta in the group with chorioangioma vs 1.2% in the control group (28).
• Postpartum hemorrhage has been reported to occur on occasions secondary to the over‑distension of the uterus and subsequent uterine atony. Rarely the tumor has been reported to remain in the uterine cavity after delivery of the placenta and has caused postpartum hemorrhage (22).
• There is a case report of ovarian theca lutein cysts and high levels of hCG being associated with chorioangioma (30). The cause of these cysts is unknown but may occur either as a result of high hCG levels or as an abnormal ovarian response to normal hCG levels. The authors believe that the source of hCG in their case may be either the enlarged placenta or the chorioangioma itself.
• Elevated serum alpha‑fetoprotein levels associated with chorio­angioma. It is believed that this elevation is caused by feto‑maternal hemorrhage.
• Arteriovenous shunts have been reported in large chorioanfiomas, which can result in fetal tachycardia, cardiomegaly and hypervolemia (31). As a result, there is the possibility of high output cardiac failure, edema, hydrops, and stillbirth (32-34). Fetal anemia can also lead to hydrops through compensatory production of red cells by the liver, which causes hepatomegaly, portal hypertension, and hepatic cell dysfunction, resulting in hypoproteinemia.
• The abnormal tortuous vascular channels in these tumors may cause red cell destruction and platelet sequestration, resulting in thrombocytopenia, microangiopathic hemolytic anemia, and disseminated intravascular coagulation (35). Feto‑maternal hemorrhage may also cause fetal anemia (36,37).
• There appears to be a connection between chorioangiomas and other vascular anomalies such as skin hemangiomas and single umbilical artery. The incidence of single umbilical artery in pregnancies complicated by chorioangioma is 2.7% compared to 0.7% in the control group, and the incidence of skin lesions is 12.2% versus 2.1% in the control group (28).
• Although there have been some reports of chromosome abnormalities associated with chorioangiomas (28,38,39), this does not seem to be a true association.
• Higher incidence of velamentous insertion of the cord (4.1% vs 1.5%) (28). 
• Chazotte and colleagues (48) first reported a case of spontaneous infarction of a chorioangioma, which was evident from decreasing tumor size and gradual transition to an echolucent appearance on ultrasound.

DIFFERENTIAL DIAGNOSIS

• Placental hemorrhage may be sonographically indistinguishable (6). Placental hemorrhage may show some diminution in size over a period.
• Placental metastasis from a primary maternal tumor (very rare).
• Submucus fibroids – located on the maternal side rather than the placental side.

·         Partial hydatidiform moles are characterized by localized swelling of chorionic villi with focal trophoblastic hyperplasia and, on ultrasound, appear as multiple diffuse sonoluscent intraplacental areas.

TERATOMA

• Rare tumor.
• There is a controversy as to whether they actually arise from abnormal fetal development in a twin pregnancy. The distinction between placental teratoma and fetus amorphous (blighted fetus in a twin pregnancy) is controversial (9).
• Fox's criteria (10) - teratomas are characterized by a lack of development of skeletal parts and absence of an umbilical cord. Fox postulates that because germ cells are capable of multifarious differentiation and have migratory capabilities, they are able to implant at various sites and can develop into teratomas.
• During the first three months of fetal development, primordial germ cells migrate out through the wall of the envaginated gut into the umbilical cord. With further migrations these cells could land up in the placenta and thus form a nidus for placental teratoma. Therefore histological analysis is required to differentiate a teratoma from fetus amorphous (9).

ULTRASOUND

• Mixed cystic and solid masses that resemble a chorioangioma.
• 10-20% are purely cystic (10).
• Calcification occurs in 40% of cases.