Anencephaly [congenital absence of a major portion of the brain, skull, and scalp (Medical Task Force on Anencephaly, 1990)] is the most severe and single most common prenatally detected neural tube defect (Goldstein and Filly, 1988). Although the cerebral hemispheres can develop in this condition, any exposed brain tissue is subsequently destroyed (see Chapter 13). This produces a hemorrhagic, fibrotic mass of neurons and glia, with no functional cortex. The brainstem and cerebellum may be spared. Despite the severe brain abnormalities, the facial bones and base of the skull are nearly normally formed. The frontal bone, however, is always absent and the brain tissue is always abnormal.

Anencephaly is sometimes divided into two subcategories. The milder form is known as meroacrania, which describes a small defect in the cranial vault covered by the area cerebrovasculosa. The more severe form is holoacrania, in which the brain is completely absent.

Van Allen et al. (1993) proposed that multisite neural-tube closure provides the best explanation for neural tube defects in humans. The closure sites are most likely controlled by separate genes expressed during embryogenesis. These authors hypothesized that the majority of neural tube defects could be explained by a failure of fusion of one of the closures or their contiguous neuropores. Anencephaly results from failure of closure site 2 for meroacranium and closures 2 and 4 for holoacranium. Folate deficiency is thought to affect the closures of sites 2 and 4. This hypothesis has been demonstrated in humans with more than one neural tube defect (Pantzar et al., 1993).

Anencephaly accounts for approximately one-half of all cases of neural tube defects (Chescheir et al., 2003). The incidence of anencephaly in livebirths and stillbirths has been estimated as 0.3 per 1000 by the Centers for Disease Control (Medical Task Force on Anencephaly, 1990). Female fetuses are more commonly affected. The ratio of affected females to males is 3:1 to 4:1 (Naidich et al., 1992). In one study, there was a 2.6 fold increased incidence of anencephaly in twins (Ben-Ami et al., 2005). There is also an increased incidence of anencephaly in Hispanic women, who are 45% more likely than white women to have an affected pregnancy (Feuchtbaum et al., 1999). Other risk factors include maternal pregestational diabetes, maternal obesity, and maternal hyperthermia (Mitchell, 2005). Unlike meningomyelocele, the risk of anencephaly is not increased in women who take valproic acid and/or carbamazepine (Mitchell, 2005). The most important environmental influence is diet. There is a well-documented protective effect of maternal periconceptual folic acid supplementation. Data from countries that have implemented mandatory folic acid fortification programs indicate a 30% to 50% reduction in the prevalence of neural tube defects postfortification (Mitchell, 2005).

In one study, Limb and Holmes (1994) documented that prenatal diagnosis and the availability of elective termination of pregnancy had significantly altered the birth status of infants with anencephaly. They noted a prevalence that varied between 1.0 and 0.4 per 1000 live and stillbirths during two different study periods (1972–1974 and 1979–1990, respectively). In the 1970s, half the infants with anencephaly were born alive at an average gestational age of 35.6 weeks. By 1988 to 1990, all affected infants were diagnosed by maternal serum α-fetoprotein screening or prenatal sonography. All parents elected to terminate, at an average gestational age of 19.6 weeks. These investigators, however, commented that their study population was potentially biased due to a higher percentage of mothers with epilepsy and diabetes delivering at their institution. More recent data, however, collected over the Internet, suggest that a larger proportion of women are opting to continue their pregnancies than would be suggested from the Limb and Holmes study (Jaquier et al., 2006).

The first trimester sonographic appearance of anencephaly differs significantly from the second trimester (Chatzipapas et al., 1999). In the first trimester, the cerebral hemispheres are present and in direct contact with the amniotic fluid. In the coronal section of the head, the exposed cerebral lobes resemble the face of Mickey Mouse. In addition, the crown-rump length is significantly reduced in affected fetuses.

In the second trimester, the ultrasound diagnosis of anencephaly is made on the basis of the absence of the upper portion of the cranial vault (Figures 7-1 to 7-3). Above the level of the orbits, where the cerebral hemispheres are normally seen, no tissue is present or an ill-defined mass of heterogeneous density is observed. The abnormality is best demonstrated on coronal views of the fetal face (Figure 7-2). The sonographic diagnosis of this condition is very accurate and there are almost no false-positive diagnoses.

Anencephalic fetuses are usually normal in terms of body weight for gestational age (Melnick and Myrianthopoulos, 1987). Thus, intrauterine growth restriction is uncommon in isolated anencephaly. Another sonographic finding that may be present is polyhydramnios.

Goldstein and Filly (1988) reviewed the spectrum of prenatal sonographic findings in 20 fetuses with anencephaly. The sonographic diagnosis was based on the absence of brain and calvarium superior to the orbits on coronal views of the fetal head. In 45% of cases, echogenic tissue was seen superior to the orbits. This corresponded to the area cerebrovasculosa and was quite large in four fetuses. In 35% of their cases, frank polyhydramnios was seen. There were no cases of oligohydramnios. These authors stated that anencephaly can be distinguished from cranial defects associated with the amniotic band syndrome on the basis of symmetry of the cranial defects and the absence of limb, body wall, and spinal anomalies that generally accompany amniotic bands. In this report, prenatal diagnosis was 100% accurate after 14 weeks of gestational age. These authors missed one case initially studied at 12.5 weeks of gestation, but the defect was diagnosed on a repeat study performed at 26 weeks (Goldstein and Filly, 1988). As stated above, more recently it has become appreciated that the first trimester signs of anencephaly are different, so accuracy of detection earlier in gestation is likely to improve.

In postnatal studies, 13% to 33% of anencephalic infants have additional major congenital anomalies. These include congenital heart disease (4% to 15% of cases), hypoplastic lungs (5% to 34%), congenital diaphragmatic hernia (2% to 6%), malrotation of the gut (1% to 9%), renal malformations (25%) including polycystic or dysplastic kidneys (1% to 3%), hypoplasia of the adrenal glands (94%), and omphalocele (16%) (Melnick and Myrianthopoulos, 1987; Medical Task Force on Anencephaly, 1990). Additional minor anomalies that have been observed in fetuses with anencephaly include a single umbilical artery, a patent ductus arteriosus, and a patent foramen ovale, seen in 2% to 31% of cases. In one study, four-dimensional (4-D) sonography was used to study the hand and body movements of an anencephalic fetus at 19 weeks (Andonotopo et al., 2005). These were compared to a normal fetus at the same gestational age. Movement of the hand occurred in only one direction, and it was abnormal, forceful, and “jerky.” In the normal fetus, movements were continuous and occurred in all directions. The anencephalic fetus showed a lack of positional changes.