and Marcelo Zugaib4
São Paulo University, Bauru, Brazil
Parisian University, Bauru, France
Member of International Fetal Medicine and Surgery Society, Bauru, Brazil
Obstetrics, University of São Paulo, Bauru, Brazil
The ultrasound evaluation of the fetal skeleton begins with the correct assessment of gestational age, based on early fetal ultrasound and evaluation of biometrics in the current examination. Measurement of long bones using normograms for different gestational ages is of utmost importance to the diagnostic certitude of skeletal involvement.
In most cases, suspicion of skeletal abnormalities is obtained during a routine scan, fetal biometry, and morphological analysis in low-risk pregnancies. Other times, the study is directed to this diagnosis by previous ultrasound findings or the presence of malformations in other organs (e.g., central nervous system changes).
The ideal gestational age for the best fetal bone assessment is between 16 and 24 weeks’ gestation; however, when there is a high risk for skeletal disorders, bone evaluation can be performed from the 13th week of pregnancy. It is important to obtain long bone measurements in the third trimester, as for many cases of osteochondrodysplasia, bone alterations are best demonstrated later during gestation.
In the assessment of the bones, the following should be analyzed:
Numerical errors such as the absence of a limb or a portion of it, and the presence of supernumerary bones (e.g., polydactyly).
Bone position (e.g., clubfoot, misplaced hands).
Bone shape (e.g., curvature, telephone receiver shape).
Movement of limbs.
Details of the fetal face profile (e.g., frontal bossing), analysis of the head (e.g., brachycephaly), face, the spine in all its segments, and the chest, noting its size and proportionality in relation to the cardiac area and abdominal circumference.
The study of skeletal anomalies is certainly among the more complex fetal analyses because of the large number of likely diagnostic diseases, constituting one of the most challenging phases of prenatal diagnosis.
The two main groups of skeletal disorders are osteochondrodysplasia, resulting from dominant and recessive inheritance, dysostosis, resulting from exposure to teratogenic substances (e.g., thalidomide, phenytoin, diabetes).
When distinguishing the various types of dysostosis, anomalies are classified according to the degree of limb impairment. Amelia means the absence of one or both extremities. Meromelia indicates the presence of only the hands and feet.
In assessing osteochondrodysplasia, when shortening involves the entire limb, this is called micromelia. When the proximal segment is affected, it is named rhizomelia, the intermediate segment mesomelia, and the distal segment acromelia.
Abnormalities of the hands and feet are important clues to the type of skeletal dysplasia. Polydactyly is more often observed at the cubital edge of the upper limb or the fibular side of the fetal foot and may be part of a syndromic condition. It is classified in the group of appendicular anomalies along with syndactyly, which refers to bone fusion of fingers or toes, and clinodactyly, which corresponds to deviation of the axis of the fingers.
In the study of bone disorders, other aspects besides those already mentioned should be taken into account in an attempt to classify the type of skeletal dysplasia found and its lethality, as follows:
Degree of limb shortening and bone shape: in lethal anomalies, limbs are often shortened. The evaluation of the femoral size is the best parameter for distinguishing the most common bone malformations. Short bone and sometimes in the form of a telephone receiver may be characteristic of campomelic dysplasia. The limb shortening is an important parameter in distinguishing among different forms of skeletal dysplasia, in which there is disproportion, and intrauterine growth restriction, which presents with proportional shortening.
Anatomy of the thorax: shortening, narrowing chest with relative cardiomegaly and the presence of rib fractures are important in determining lethality.
Evaluation of nomograms for bone biometrics in relation to gestational age: the study of the circumferences of the head, chest, and abdomen may be useful in the diagnosis of macrocephaly, narrow chest, hypertelorism, etc. Femur-to-foot length ratio is an important parameter for suspecting an isolated short femur.
Evaluation of other organs: the presence of heart disease is important for the prognosis and the possibility of a syndromic condition, in addition to evaluation of the face, as most of the fetuses with facial defects has some sort of skeletal anomaly.
Amniotic fluid evaluation: the presence of polyhydramnios is the most common finding in skeletal dysplasia. The oligohydramnios may be associated with other anomalies that occur with skeletal disorders, such as amniotic band syndrome.
The evaluation of bone mineralization is carried out by echogenicity at ultrasound and the homogeneity of the bone image (no fractures), which sometimes demonstrated calluses. These parameters are best studied by X-ray imaging of the uterine content, which should be performed after the 32nd week of pregnancy.
Gestational age at the time of diagnosis is another important aspect in determining lethality, as the lethal abnormalities are diagnosed earlier.
The most frequent forms of lethal skeletal dysplasia are described below.
Thanatophoric dysplasia has an incidence estimated to be 1:4000–1:15,000 births. On ultrasound, it is characterized by marked shortening of the long bones with rhizomelic predominance, curving and enlargement of the long bones, cloverleaf skull, hydrocephalus, macrocephaly, flattened vertebral bodies, “platyspondyly.”
Osteogenesis imperfecta is characterized by collagen synthesis disorder and by severe bone fragility, leading to multiple fractures. It is subdivided into three groups (types I, II, and III). Type II, the more severe form, is most often diagnosed in the prenatal period. Its ultrasound findings include micromelia with significant bowing of the long bones, diffuse hypomineralization, and multiple fractures. Diagnosis in the fetus is made by the presence of callus formation in the long bones and fetal ribs (heterogeneous and wrinkled appearance with hypo- and hyperechoic areas along the bone, giving it a grainy appearance).
In the group of non-lethal skeletal dysplasia and other pathological conditions that can be individualized, achondroplasia is the most common. It is characterized by moderate rhizomelia, macrocephaly, prominent frontal bossing, low nasal bridge, thoracolumbar kyphosis, lordosis exaggerating the coccygeal segment, and trident hands. The discrepancy between the biparietal diameter and femur length, particularly in the third trimester, is the most frequent sonographic finding in prenatal diagnosis.
Longitudinal section of the hand with four fingers (2, 3, 4, and 5) and normal phalanges. Note that often, particularly at later gestational ages, the thumb can only be viewed on the same plane as the other four fingers when the fetal hands are open
Clinodactyly: short fifth finger (5) with axis deviation (1 = thumb)
Longitudinal section of the hand presenting clinodactyly of the fifth finger (5), with distal phalanx overlapping the fourth finger (4). 2 = index finger, 3 = middle finger
Hand (M) next to the cephalic pole (PC). A malpositioned, clenched hand with overlapping fingers is observed
Badly positioned fingers, clenched hand (the fifth finger overlapping the fourth finger and the second finger overlapping the third), a typical finding of trisomy 18
Coronal view of hands at 25 weeks’ gestation where clenched or clawed hands with overlapping fingers are demonstrated (arrows)
Thumb is in contact with the palm–thumb adduct (1, black arrow) in a case of X-linked hydrocephalus (Bicker Adams). 2 = index finger, 5 = little finger
Syndactyly of the fourth and fifth fingers (arrows)
Ectrodactyly observed in the longitudinal plane of the arm. Hand bones (P) and ectrodactylous fingers (D) in a fetus at 12 weeks and 4 days
Ectrodactyly: right and left hands (MD, ME) with only two ectrodactylous fingers (D). Age = 1756 days
Same fetus as in Fig. 12.11, with an increased view. M = hand, D = ectrodactylous fingers
Postaxial polydactyly: supernumerary finger (6) seen as a protuberance at the ulnar edge
Postaxial membranous polydactyly. Observe the circular echogenic mass corresponding to the appendix of the sixth finger (6) on the ulnar side of the hand. 1, 2, 3, 4, and 5 = normal fingers
Child with polydactyly in both hands