Trisomy 18 is a chromosomal abnormality that results from the presence of an extra copy of chromosome 18. It is the second most common autosomal trisomy in liveborn infants. The clinical features associated with the abnormality were first described by Edwards in 1960. The condition is also known as Edwards syndrome or trisomy E. Of patients with trisomy 18, 80% to 85% have a full extra copy of chromosome 18 in all of their cells, 10% have mosaicism, with a normal cell line in some of their cells, and 5% have the long arm of chromosome 18 translocated onto another chromosome (Hill, 1996).

The incidence of trisomy 18 varies from approximately 1 in 3000 to 1 in 7000 livebirths. The specific incidence of trisomy 18 in Leicestershire, England, was studied during the years 1980 through 1985. At that time the incidence was noted to be 1 in 3086 livebirths (Young et al., 1986). A less frequent incidence of 1 in 6806 livebirths was noted during a 10-year period in Denmark (Goldstein and Nielsen, 1988). The incidence of trisomy 18 mosaicism is approximately 1 in 70,000 livebirths (Bass et al., 1982). Interestingly, the sex ratio of fetuses and livebirths with trisomy 18 differs. Sex ratios are defined as the number of males divided by the number of females. In prenatal normal controls, the ratio is 1.07. The sex ratio for fetal cases of trisomy 18 is 0.90 and for livebirths it is 0.63. Therefore, a clear-cut differential natural selection against males with trisomy 18 exists after 16 weeks of gestation (Huether et al., 1996). Females with trisomy 18 are more likely to be born alive and survive longer than males (Rasmussen et al., 2003; Lin et al., 2006; Niedrist et al., 2006).

Nyberg et al. (1993) reviewed prenatal sonographic findings in 47 consecutive fetuses with trisomy 18. They documented that the type and frequency of sonographic abnormalities varies with gestational age (Table 130-1). Excluding choroid plexus cysts, one or more sonographic abnormalities were found in 39 of 47 (83%) of fetuses with trisomy 18, including 21 of 29 fetuses examined between 14 and 24 weeks of gestation and 100% of fetuses examined at greater than 24 weeks of gestation. Intrauterine growth restriction (IUGR) was the most common abnormality. It was observed in 51% of all fetuses with trisomy 18 and in 89% of fetuses after 24 weeks of gestation. The most common abnormalities seen before 24 weeks of gestation included cystic hygroma, nuchal thickening, and meningomyelocele. After 24 weeks of gestation, IUGR, cardiac defects, and enlarged cisterna magna were more commonly detected. In this study, choroid plexus cysts were seen in 25% of fetuses with trisomy 18 (Nyberg et al., 1993).

A variety of sonographic abnormalities are seen in fetuses with trisomy 18 (Table 130-2). IUGR occurs as early as the first trimester (Lynch and Berkowitz, 1989). The long bones of the extremities are significantly shortened in trisomy 18 (Droste et al., 1990). This affects the lower extremities more than the upper extremities and this begins before the 18th week of gestation. In addition, Droste et al. (1990) documented a poor correlation between fetal foot length and gestational age by menstrual dating. The results of this study imply a significant effect of this chromosomal abnormality on fetal bone growth. Two sonographic markers, the biparietal diameter (BPD) to femur length (FL) ratio and nuchal translucency measurement were found to be sensitive indicators for the prenatal detection of trisomy 18. A BPD:FL ratio of greater than 1.5 SD above the mean identified three of four fetuses with trisomy 18, whereas nuchal thickening identified two of four fetuses with trisomy 18 (Ginsberg et al., 1990). Combining these sonographic markers gave a positive predictive value of 1 in 47 for the detection of trisomy 18.

A variety of cranial abnormalities are seen in trisomy 18. There is an unusually shaped head with a wide occipitoparietal and narrow frontal diameter. This has been called the “strawberry sign” by Nicolaides et al. (1992). Nicolaides and colleagues hypothesized that the narrowed frontal cranium is due to hypoplasia of the face and underdevelopment of the frontal lobes. The presence of choroid plexus cysts has elicited much debate over the association between this finding and trisomy 18. Choroid plexus cysts are present in 50% of fetuses with trisomy 18, but these are never an isolated finding (Seoud et al., 1994; Snijders et al., 1994; Hill, 1996; DeVore, 2000; Yeo et al., 2003). Another cranial sonographic finding associated with trisomy 18 is the presence of an enlarged cisterna magna due to cerebellar hypoplasia. Thurmond et al. (1989) described five fetuses with enlarged cisterna magna, which prompted a search for additional fetal anomalies. These five fetuses had a predicted biparietal diameter less than the measured biparietal diameter, and all turned out to have trisomy 18 (Thurmond et al., 1989).

Although echogenic bowel is more characteristic of fetuses with trisomy 21, it has also been described in fetuses with trisomy 18 (Hamada et al., 1996). Hamada et al., described a normal-appearing fetus during the second trimester, but echogenic bowel developed during the third trimester. They hypothesized that the mechanisms for the echogenic bowel included decreased fetal swallowing, hypoperistalsis, and a hypercellular meconium. They also noted that this fetus was growth-restricted, which potentially caused redistribution of regional blood flow, further causing ischemia of the mesentery and the impairment of bowel motility. These abnormalities resulted in thickened echogenic meconium.

Cardiovascular abnormalities are present in 73% to 90% of fetuses with trisomy 18. Most commonly, these include large ventricular septal defects (VSD), atrial septal defects (ASD), tetralogy of Fallot, and left heart disease (Moyano et al., 2005). Diagnosis of heart malformations can be made reliably in the first trimester. One study suggested that male fetuses with trisomy 18 have more complex congenital heart disease than female fetuses (Chen, 2006). This may be the underlying basis for the increased mortality seen in affected males.

Wladimiroff et al. (1989) described the antenatal sonographic markers in 16 fetuses with trisomy 18. All fetuses had a cardiac abnormality. The majority of these were due to VSDs, double outlet right ventricle, or complete atrioventricular septal defect. The extracardiac structural pathology consisted of abnormal hands and feet, symmetrical IUGR, and polyhydramnios. It is thought that the increased nuchal translucency (see Chapter 2) seen in 90% of affected fetuses with trisomy 18 may be due to the cardiac abnormalities. The increased fluid collection at the back of the neck may be an early sign of congestive heart failure.

A variety of limb abnormalities are also a characteristic of trisomy 18, including the typical overlapping flexed fingers, positional abnormalities of the wrist or fingers, and rocker-bottom feet. Overlapping of the fingers occurs sometime between 12 and 14 weeks (Quintero et al., 1999). The prenatal detection of preaxial upper limb reduction facilitated the diagnosis of trisomy 18 in three cases (Sepulveda et al., 1995). In a report of 7 cases of fetal radial ray reduction malformations, three fetuses had trisomy 18 (Brons et al., 1990).

A single umbilical artery (see Chapter 109) is seen in 38% to 50% of fetuses with trisomy 18 (Baty et al., 1994a). Yeo et al. (2003) showed that a short ear length (<10% for gestational age) was present in 96% of fetuses with trisomy 18.

Several investigators have described findings that in combination tend to predict a high risk of trisomy 18. These include the combination of polyhydramnios, abnormal hand posturing, and other major structural abnormalities (Carlson et al., 1992), and abnormalities of the fetal face and extremities (Figures 130-1 and 130-2) (Benacerraf et al., 1986, 1988). Benacerraf and colleagues (1994) developed a scoring system to identify fetuses with trisomy 18 based on the presence of certain sonographic findings. Her group specifically looked for the presence of nuchal translucency, long-bone shortening, choroid plexus cysts, echogenic bowel, and other major anatomic defects. They prospectively evaluated 60 fetuses with various autosomal trisomies between 14 and 21 weeks of gestation and 106 normal fetuses at the same gestational age. A sonographic score of 2 or more enabled the prospective identification of trisomy 18 in 11 of 13 affected fetuses. DeVore (2000) identified six sonographic markers (choroid plexus cysts, central nervous system malformations, abnormal nuchal skin fold, ventricular septal defect, outflow tract abnormalities, and right to left chamber disproportion of the heart) that collectively identify 93% of fetuses with trisomy 18 at a false-positive rate of 8.9%. Snijders et al. (1994) calculated a risk of trisomy 18 relative to maternal age and the number of additional sonographic abnormalities present.

First trimester sonographic findings observed in fetuses with trisomy 18 include increased nuchal translucency thickness and pulsatile blood flow in the umbilical vein (Sherod et al., 1997; Brown et al., 1999).