CHAPTER 10 • The Fetal Chest. First Trimester Ultr

 CHAPTER 10 • The Fetal Chest

INTRODUCTION

The examination of the fetal chest in the first trimester includes the assessment of the

right and left lung, the bony and cartilaginous thoracic cage, the diaphragm, and the heart

with surrounding vasculature. Because of the importance and prevalence of cardiac

anomalies, normal and abnormal anatomy of the heart and surrounding vasculature are

presented in Chapter 11. Normal and abnormal appearance of lungs, diaphragm, and rib

cage in the first trimester are discussed in this chapter. Pentalogy of Cantrell, involving

a sternal defect, and ectopia cordis are discussed in Chapter 12.

EMBRYOLOGY

The respiratory diverticulum or lung bud is first seen around day 22 from fertilization as

a ventral outgrowth of the primitive foregut. As the lung bud grows, it is surrounded by

mesoderm, which gives rise to the lung vasculature, connective tissue, and muscle

within the bronchial tree. The lengthening lung bud bifurcates on day 28 into the right

and left lung buds, which gives rise to the right and left lung, respectively. Growth and

bifurcation of the lung buds along with the surrounding mesenchyme continues

throughout pregnancy. The terminal bronchioles are seen by the 28th week of gestation

(menstrual) and the terminal sacs are formed by the 36th week of gestation. Maturation

of the alveoli occurs between the 36th week of gestation and term. Alveolar growth

continues into early childhood.

The four embryonic structures—septum transversum, pleuroperitoneal membranes,

mesoderm of body wall, and the esophageal mesoderm—coalesce to form the

diaphragm (Fig. 10.1). The central tendon of the diaphragm is primarily formed from the

septum transversum. The diaphragm is completely formed by the end of the 10th to 11th

week of gestation.Figure 10.1: Schematic drawing of the developing diaphragm. Note that the

diaphragm is formed by the fusion of the septum transversum, the

pleuroperitoneal membranes, the mesoderm of body wall and the esophageal

mesoderm, with the central tendon being primarily formed from the septum

transversum.

In the sixth week of embryogenesis, the sternum arises from the somatic mesoderm as

paired longitudinal sternal bars. These bars fuse in the midline to form a cartilaginous

sternum at around the 10th week. Sternal ossification starts at day 60 in a segmental

arrangement. The xiphoid process does not ossify until after birth. The vertebral bodies

and ribs are also derived from the paraxial mesoderm.

NORMAL SONOGRAPHIC ANATOMY

The systematic visualization of the fetal chest in the first trimester is generally achieved

from multiple sonographic planes. Axial views, at the level of the upper abdomen (Fig.

10.2A), the chest (Figs. 10.2B, 10.3, and 10.4A), and mediastinum (Fig. 10.4B), allow

for the evaluation of the diaphragm, right and left lungs, midline structures such as the

esophagus, trachea/bronchi, and the thymus gland. In the normal fetus, the lungs appear

slightly more echogenic than the liver and cardiac muscle (Fig. 10.2). At the fourchamber view plane, the right and left lungs are seen and the rib cage assessed (Figs.

10.2B, 10.3 and 10.4A). Comprehensive evaluation of the lungs in axial views requiresthe assessment at the level of the four-chamber view (Figs. 10.2B, 10.3 and 10.4A) and

superiorly into the upper mediastinum at the three-vessel-trachea view (Fig. 10.4B).

Assessment of cardiac position and axis in the chest (Fig. 10.4A) is helpful in the

identification of lung abnormalities.

Figure 10.2: A: Axial plane of the upper abdomen in a fetus at 13 weeks of

gestation showing the right (RL) and left (LL) lungs and the diaphragm (white

arrows), separating the lungs from the liver. Note that the lungs are slightly

more echogenic than the liver. B: Axial view of the thorax at the level of the

four-chamber view in the same fetus. Note the position of the heart in the left

hemithorax surrounded by the RL and LL. The ribs (yellow arrows) are seen

laterally in both A and B.Figure 10.3: Axial planes (A and B) of the fetal chest at the level of the fourchamber view in a fetus at 12 weeks of gestation. The four-chamber view plane

is optimal for the visualization of the right (RL) and left (LL) lungs. The lungs are

highlighted in B.Figure 10.4: Axial views in color Doppler at the four-chamber view (A) and the

three-vessel-trachea view (B) in a fetus at 13 weeks of gestation. Note that the

right (RL) and left (LL) lungs are seen in both planes (A and B).

Comprehensive evaluation of the fetal lungs in axial views requires an evaluation

at the level of the four-chamber view (A) and the three-vessel-trachea view (B).

The cardiac axis and position as evaluated in the four-chamber plane (A) is not

only important for detecting cardiac abnormalities, but also for suspecting lung

anomalies.

The right (Fig. 10.5A) and left (Fig. 10.5B) parasagittal views of the fetal chest are

important for assessment of individual lung lobes, the diaphragm, and the rib cage (Fig.

10.6A). The ribs can also be assessed from an axial plane of the chest at the level of the

four-chamber view (Fig. 10.6B). In our opinion, the evaluation of the diaphragm is best

achieved in coronal views (Fig. 10.7), starting from the posterior coronal view of the

spine and moving more anteriorly toward the sternum. In these planes the diaphragm

muscle and tendon on the right and left chest can be well visualized. The transvaginal

approach improves visualization of all chest structures due to higher resolution (Fig.

10.7B). Three-dimensional ultrasound in a surface (Fig. 10.8) or tomographic display

(Fig. 10.9) can help in demonstrating various chest structures, especially in transvaginal

scanning where transducer manipulation is limited. Clear visualization of the lungs can

be achieved from about the 12th week of gestation onward.Figure 10.5: Right (A) and left (B) parasagittal planes of the fetal chest at 13

weeks of gestation. Note in the right thorax (A) the slightly hyperechoic lung as

compared to the liver and the diaphragm in between. The bowel has the same

echogenicity as the lung. The parasagittal view on the left (B) shows the lung,

portion of the heart, the diaphragm, and the stomach (asterisk).Figure 10.6: A: A parasagittal plane of the thorax at the lateral chest wall in a

fetus at 12 weeks of gestation showing the rib cage laterally with the normal

arrangement of the ribs. B: An axial plane of the chest at the level of the fourchamber view in the same fetus demonstrating the ribs laterally.Figure 10.7: Coronal views of the fetal abdomen and chest at 13 weeks of

gestation obtained by the transabdominal (A) and transvaginal (B) approach in

the same fetus. Note in A, the right (RL) and left (LL) lung seen in a coronal

view with the diaphragm (arrows) separating the chest from the abdomen. The

kidneys (K) are seen in the abdomen in A. In the transvaginal approach (B), the

borders of the RL and LL are better seen and the diaphragm is clearly

delineated (arrows). The stomach is also seen in B as an anechoic structure in

the abdomen (asterisk).Figure 10.8: Surface display of a three-dimensional transvaginal ultrasound

volume of the chest in a fetus at 13 weeks of gestation showing the posterior

coronal plane (A) and right parasagittal plane (B). Note the full display of the

right (RL) and left (LL) lungs in A and the RL in B.Figure 10.9: Tomographic display of a three-dimensional transvaginal

ultrasound volume of the chest and abdomen in a fetus at 13 weeks of

gestation. The volume displays the coronal planes of the fetus showing in the

chest the thoracic cage with ribs (yellow arrows), lungs, heart, diaphragm, and

in the abdomen the stomach (asterisk), liver, and bowel.

CHEST ABNORMALITIES

Hydrothorax/Pleural Effusion

Definition

Hydrothorax (pleural effusion) is the accumulation of fluid in the pleural space between

the lungs and the thoracic cage. Hydrothorax may occur unilaterally or bilaterally and

may be primary or secondary. Primary hydrothorax is a diagnosis made after excluding

causes of hydrothorax, which are many, and involve fetal lung or cardiovascular

malformations, fetal arrhythmias, infections, chromosomal aneuploidy, and others. In a

prospective study between 7 and 10 weeks of gestation, hydrothorax was found in 1.2%

of embryos.1 The presence of bilateral hydrothorax in the first trimester is associated

with a poor prognosis. Follow-up of 14 fetuses with bilateral hydrothorax diagnosed in

the first trimester showed only one survivor. A high incidence of chromosomalaneuploidy, including monosomy X, was also reported.1 Isolated unilateral hydrothorax

with no other fetal abnormality may be a transient finding with disappearance of the

effusion upon follow-up ultrasound in the second trimester.

Ultrasound Findings

Accumulation of fluid around the lungs is relatively easy to detect on ultrasound on axial

(Figs. 10.10, 10.11, and 10.12A), coronal, or sagittal views (Fig. 10.12B). A typical

sign for hydrothorax involves the presence of fluid between the lateral borders of the

lungs and the ribs (Figs. 10.10 to 10.12). This sign allows for differentiating

hydrothorax from pericardial effusion, which can be difficult in some cases. In

pericardial effusion, the fluid surrounds the heart and is on the medial aspects of the

lungs (Fig. 10.13). The presence of severe hydrothorax results in lung compression with

the typical “butterfly” appearance of the lungs. The association of hydrothorax with fetal

hydrops is easily seen and is commonly noted with increased nuchal translucency (NT)

and genetic abnormalities (Figs . 10.10 and 10.11). Diagnostic or therapeutic

thoracocentesis is typically reserved for the second or third trimester of pregnancy.

Figure 10.12 shows a fetus with an isolated unilateral hydrothorax that resolved by the

second trimester of pregnancy.

Associated Abnormalities

Associated abnormalities are many and include cardiovascular and skeletal

malformations, fetal arrhythmias, chromosomal abnormalities including monosomy X,

trisomy 21, Noonan syndrome, and hematologic conditions. Persistence of hydrothorax

is later associated with pulmonary hypoplasia due to compression of lungs. Increased

pressure in the thoracic cavity, associated with bilateral hydrothorax, may lead in the

second trimester to reduction in venous return to the heart, resulting in fetal hydrops and

polyhydramnios due to compression of the esophagus.

Congenital Diaphragmatic Hernia

Definition

Congenital diaphragmatic hernia (CDH) results from a defect in the diaphragm with

protrusion of the abdominal organs into the thoracic cavity. The diaphragmatic defect is

most commonly located in the posterolateral part of the diaphragm (Bochdalek type).

Other types of diaphragmatic defects include the parasternal region of the diaphragm

(Morgagni type) located in the anterior portion of the diaphragm, the central tendinous

region of the diaphragm located in the central septum transversum region of the

diaphragm, and hiatal hernias occurring through a defective esophageal orifice. The

Bochdalek type is the most common and accounts for about 80% to 90% of CDHs.

CDHs are left-sided in about 85%, right-sided in about 13%, and bilateral in about 2%.

CDH is a fairly common malformation occurring in about 1:2,000 to 1:3,000

pregnancies.Figure 10.10: Axial views of the fetal chest in a fetus at 12 weeks (A) and

another fetus at 11 weeks (B) of gestation with pleural effusions (Pl.Eff.). Note

the location of pleural effusion on the lateral aspects of the lungs. Also note the

presence of skin edema in both fetuses (double headed arrows). Turner’s

syndrome was confirmed in both cases.Figure 10.11: Bilateral mild pleural effusions (Pl.Eff.) in two fetuses with

trisomy 21 at 12 (A) and 13 (B) weeks of gestation demonstrated in the axial

plane of the chest. Note in A that the heart shows a large atrioventricular septal

defect (AVSD), an echogenic focus (EF), and a shifted cardiac axis to the left.

Also note the presence of skin edema (double headed arrows) in both fetuses.

Both fetuses also had thickened nuchal translucencies (data not shown).

The embryologic development of the diaphragm is typically completed by the 12th

week of gestation (see section on Embryology) and thus CDH can be diagnosed in the

first trimester. It is reasonable to assume however that the timing of herniation of

intraabdominal content into the chest can be delayed to the second trimester or beyond,

as it is dependent upon the size of the diaphragmatic defect and intraabdominal

pressure. A normal ultrasound examination of the chest in the first trimester therefore

does not rule out the presence of a CDH.Figure 10.12: Axial (A) and left parasagittal (B) planes of a fetus with isolated

pleural effusion (Pl.Eff.) in the left hemithorax at 12 weeks of gestation. Note in

A that the effusion is on the lateral aspect of the lung. Compare with Figures

10.10 and 10.11. This effusion spontaneously resolved on follow-up ultrasound

in the second trimester of pregnancy.Figure 10.13: Axial plane of the chest at the level of the four-chamber view in a

fetus with pericardial effusion at 12 weeks of gestation. Note that the

pericardial effusion is located on the medial aspect of the lungs. Compare with

Figure 10.12. RL, right lung; LL, left lung.

Ultrasound Findings

CDH is first suspected on ultrasound in the first trimester by the presence of an

abnormal cardiac axis and mediastinal shift on the axial four-chamber view plane of the

chest (Figs. 10.14 and 10.15). The demonstration of the herniated stomach and other

intraabdominal organs into the chest confirms the diagnosis (Fig. 10.14), and this is

ideally visualized in a coronal view (Fig. 10.16). The diagnosis of CDH in the first

trimester is challenging, especially in isolated cases, as the typical signs of mediastinal

shift and the demonstration of intraabdominal content in the chest may not be evident. In

our experience, mild shifting of cardiac position in the four-chamber-view (Figs. 10.14

and 10.15), abnormal course of the ductus venosus in the abdomen, or a more cranial

position of the stomach in coronal views of the chest and abdomen (Fig. 10.16) provide

clues to the diagnosis. Polyhydramnios, a common association with CDH in the second

and third trimesters, is not seen in the first trimester. Observed/expected lung-to-head

ratio and liver herniation into the chest are ultrasound parameters that can stratifyseverity of CDH in the second and third trimesters of pregnancy. In the first trimester,

the presence of associated anomalies is most important for assessing prognosis.

Interestingly, the ipsilateral lung in CDH can be well identified in the first trimester

(Figs. 10.15 and 10.16), but the dynamics of its slow growth is not predictable. Followup ultrasound examination in the second trimester of pregnancy often reveals increased

severity of the diaphragmatic hernia with more herniation of abdominal content into the

chest (Fig. 10.17). Furthermore, the presence of severe CDH in the first trimester is

more commonly associated with chromosomal abnormalities (Fig . 10.18) and a

thickened NT.2 Some cases of CDH are not detectable in the first trimester due to

delayed organ herniation into the chest.3 In one study, only 50% of the CDH cases were

identified on first trimester ultrasound2 (see Table 5.2).

Figure 10.14: Axial planes of the chest at the level of the four-chamber view at

13 weeks of gestation in two fetuses (A,B) with left-sided congenital

diaphragmatic hernias. Note that the heart is shifted to the right chest in both

fetuses. Also note that the stomach (asterisk) is in the left hemithorax and the

right lung (RL) is compressed. R, right; L, left.Figure 10.15: Axial planes of the chest at the level of the four-chamber view at

13 weeks of gestation in a fetus (A) with left-sided congenital diaphragmatic

hernia (CDH) and another fetus (B) with right-sided CDH. Note that the heart is

shifted to the right in A and to the left in B. The liver is seen in the right

hemithorax in B. The right lung (RL) is seen compressed in both fetuses. R,

right; L, left.

Associated Abnormalities

CDH can be an isolated finding (60%) or can be associated with fetal structural and

genetic abnormalities (40%). The association with an enlarged NT is estimated to be

between 12%4 and 46%.5 The association of enlarged NT and CDH in the first trimester

suggests a poor neonatal outcome even after ruling out chromosomal or genetic

defects.3,4 CDH is considered a major fetal abnormality with postnatal mortality in the

range of 30% to 40% in isolated cases. Typical syndromes with CDH include trisomy

1 8 (Fig. 10.16), tetrasomy 12p (Pallister–Killian syndrome) (Fig . 10.19), Fryns

syndrome (Fig. 10.20), Cornelia de Lange syndrome, and other syndromic conditions.Figure 10.16: Coronal view of the chest and abdomen in a fetus at 13 weeks

of gestation with left-sided congenital diaphragmatic hernia and trisomy 18. The

stomach (asterisk) is seen herniated through the diaphragm (arrows) into the

left hemithorax, with no associated shift in the heart. At this early gestation, the

left lung (LL) appears normal in size and with advancing gestation; lung

compression and hypoplasia will develop. R, right; RL, right lung; L, left.

Pallister–Killian Syndrome

Pallister–Killian syndrome is a mosaic of tetrasomy for chromosome 12p, where in

addition to the two copies of chromosome 12, an extra isochromosome is present, made

from two p arms of chromosome 12 (see upper panel in Fig. 10.19). Typical anomalies

found in tetrasomy 12p include diaphragmatic hernia, facial dysmorphism, rhizomelic

limb shortening, and abdominal defects (omphalocele and anal atresia). The patient in

Figure 10.19 was referred due to advanced maternal age and the detection on

ultrasound of a thickened NT (Fig. 10.19A) and omphalocele (Fig. 10.19B), which was

initially suggestive of trisomy 18. Biometric assessment showed a normal crown-rump

length, head and abdominal circumference, and a short femur (Fig. 10.19C). Detailed

first trimester ultrasound examination revealed a left-sided CDH (Fig. 10.19D and E)with polydactyly (Fig. 10.19F), in addition to the short femur (Fig. 10.19C). CVS

revealed the presence of Pallister–Killian syndrome.

Fryns Syndrome

Fryns syndrome is an autosomal recessive disease with currently no identifiable gene

locus. Typical features include a diaphragmatic hernia in 90% of cases with multiple

anomalies including a coarse face with facial clefts, micrognathia, large mouth,

hypertelorism with occasionally microphthalmia and nuchal edema. In addition,

cerebral anomalies mainly of the posterior fossa (50% of cases), short hands, dysplastic

kidneys, and others are present. Figure 10.20 is a first trimester ultrasound of a patient

with a prior history of a fetus with multiple anomalies suggestive of Fryns syndrome.

Because of the autosomal recessive inheritance of Fryns syndrome, a detailed first

trimester ultrasound was performed and revealed the presence of a thickened NT (Fig.

10.20A and B), a dilated posterior fossa (Fig. 10.20B), abnormal profile with

maxillary gap, suggestive of facial clefting (Fig. 10.20B), short hands (Fig. 10.20C),

hyperechogenic kidneys with urinary tract dilation (Fig. 10.20D), and a left-sided CDH

(Fig. 10.20E and F). These findings were suggestive of recurrence of Fryns syndrome.

Figure 10.17: Axial planes of the chest at the level of the four-chamber view at

13 (A) and 20 (B) weeks of gestation in the same fetus. Note in A that the

heart is shifted to the right, suggesting the presence of a left-sided congenital

diaphragmatic hernia (CDH). The stomach is not yet visible in the chest at this

early gestation in A. At 20 weeks of gestation (B), the stomach (asterisk) is

clearly seen in the left chest, confirming the presence of a CDH with more

cardiac shifting into the right hemithorax. R, right; L, left.Figure 10.18: Axial plane of the chest at the level of the four-chamber view at

14 weeks of gestation in a fetus with left-sided congenital diaphragmatic hernia

(CDH) and chromosomal aneuploidy (trisomies 9 and 10). Note the severity of

the CDH with the heart severely shifted to the right hemithorax and the stomach

(asterisk) and abdominal content occupying the majority of the right chest. The

right lung (RL) is compressed. R, right; L, left.

Pulmonary Agenesis and Pulmonary Hypoplasia

Unilateral or bilateral agenesis of the lung(s) is an extremely rare condition that is

amenable to first trimester diagnosis. The true etiology is unknown and sporadic

occurrence is assumed in most cases; however, a genetic cause can also be present.

Several recurrences of bilateral pulmonary agenesis were reported in a single family.6

In this report, the diagnosis was performed in the second and third trimesters in two

fetuses and at 12 weeks of gestation in the third fetus.6 The authors reported that the

heart occupied almost the entire chest, whereas the thymus occupied the remaining

space, mimicking lung tissue.6 Agenesis of branching pulmonary arteries may be an

important clue to the presence of lung agenesis.

Unilateral lung agenesis can also be diagnosed in the first trimester as the heart is

shifted toward the empty hemithorax (Fig. 10.21). The diagnosis is first suspected by the

presence of dextrocardia or levocardia. Typically, the first impression is that a CDH is

present but the demonstration of normal liver, bowel, and diaphragm with highresolution transvaginal ultrasound can be of help in achieving the diagnosis of unilateral

lung agenesis. In right lung agenesis, there is absence of the right bronchus and right

pulmonary artery and upon follow-up ultrasound examinations, associated cardiac

anomalies as well as tracheoesophageal fistula with esophageal atresia can be

associated findings. Outcome can be good provided no additional anomalies are found.Figure 10.21 shows a case with an absent right lung with the heart completely

positioned in the right chest. The patient was referred to us at 14 weeks of gestation

with the suspected diagnosis of dextrocardia performed at 12 weeks by the referring

physician.

Unilateral pulmonary hypoplasia can be suggestive for the presence of Scimitar

syndrome with partial anomalous venous drainage into the inferior vena cava.7,8 The

diagnosis, similar to other venous anomalies, is very difficult to make in the first

trimester and a follow-up is recommended in the second trimester.

Figure 10.19: Fetus at 13 weeks of gestation with a tetrasomy 12p, also

called Pallister–Killian syndrome with a thickened nuchal translucency (NT) (A),

an omphalocele (B), a short femur (C), a left-sided diaphragmatic hernia (CDH)

(D and E) with the heart shifted to the right hemithorax and the stomach

(asterisk) seen in the chest (E). In addition, polydactyly is present (F). R, right;

L, Left. See text for more details.

Bilateral pulmonary hypoplasia is a challenging diagnosis to make prenatally and is

typically associated with other serious conditions such as preterm premature rupture ofmembranes, bilateral renal agenesis or dysplasia, CDH, bilateral pleural effusions,

lethal skeletal dysplasia with thoracic hypoplasia, and others.7 In all these conditions,

the lungs may appear normal in the first trimester and the prediction of lung hypoplasia

cannot be performed in early gestation. Follow-up ultrasound examinations in the

second and third trimesters are recommended in order to suspect the presence of

pulmonary hypoplasia.

Lung Abnormalities That are Not Detectable in the First

Trimester

In addition to bilateral pulmonary hypoplasia, several lung abnormalities that are

commonly seen in the second and third trimesters of pregnancy are currently not

detectable in the first trimester. These include bronchopulmonary sequestration (BPS),

cystic congenital adenomatoid malformation (CCAM) of the lung either with

macrocystic or microcystic lesions, isolated bronchogenic cyst and chronic high airway

obstructions.7 The diagnosis of these lung abnormalities is typically performed around

16 to 17 weeks of gestation.9 In a first trimester study on fetal malformations, CCAM

and BPS cases were not diagnosed in the first trimester2 (see Table 5.2) and the authors

thus classified these lesions in the group of “not detectable” anomalies. The authors

postulate that the production of pulmonary fluid and its retention within the abnormally

developed lung tissue occur after the onset of the canalicular phase of lung

development, typically at 16 weeks of gestation.2 This is possibly the reason why these

lung abnormalities are not visible in early gestation.Figure 10.20: Fetus at 12 weeks of gestation with Fryns syndrome, presenting

with a thickened nuchal translucency (NT) (A and B), a dilated fourth ventricle

(4V) and facial cleft with a maxillary gap (MG) in (B), short hand (C),

hyperechogenic kidneys (K) with renal track dilation (D), and the typical

diaphragmatic hernia (CDH) (E and F), with the heart shifted into the right

hemithorax (E) and liver and stomach (asterisk) shifted in the upper thorax (F).

R, right; L, Left. See text for more details.1.

Figure 10.21: Axial views of the chest in color Doppler (A), gray scale (B), and

three-dimensional (3D) ultrasound of a coronal view of the chest and abdomen

(C) in a fetus with right pulmonary agenesis at 14 weeks of gestation. The

heart is completely in the right chest (A and B) with normal diastolic filling (A).

Note the presence in A–C of a large-appearing left lung (LL) with no right lung

seen in the right hemithorax (?). There is no evidence of a stomach in the chest

in A and B. Note on the 3D ultrasound that the liver is in its normal anatomic

position in the right (R) abdomen and the stomach (asterisk) in the left (L)

abdomen. A well-delineated diaphragm (arrows) is also seen in C. This patient

was referred due to the prese

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