Anomalies that result from failure or abnormal closure of the anterior cranial neuropore at around 26–32 days post conception result in cerebral, spinal or a combined cerebral and spinal defects or dysraphia among these exencephaly–anencephaly sequence, cephaloceles, and spina bifida are among the most common defects with a reported prevalence of 1/1000 pregnancies [11].

The exencephaly–anencephaly sequence is a lethal malformation. In exencephaly the typical sonographic features is acrania in which a relatively well formed brain is seen without the covering fetal cranium (Fig. 19.1). As the pregnancy continues the exposed fetal brain begins to disintegrate eventually, resulting in the typical sonographic features of anencephaly in which the cranium is absent and the fetal orbits prominent. Increasing the US gain the amniotic fluid appears speckled as the result of the sloughing off of the exposed brain tissue (Fig. 19.2) [12]. Reported detection rates at 11 to 13 6/7 weeks are 100 % [8, 13].

Cephalocele is a cranial defect that occurs along the bony sutures, through which brain and/or meninges or a combination of both herniates; this defect is thought to occur as a result of faulty cranial mesoderm development. Recent theories suggest that cephalocele is developmentally and genetically different from exencephaly–anencephaly sequence and should not be considered a neural tube defect [11]. Studies on posterior cephalocele occurring in fetuses with Meckel syndrome have found a relationship with ciliopathy syndromes [11]. Sonographic features are sac-like structures posterior to the head in cases of posterior cephalocele or anterior by the fetal face in cases of an anterior cephalocele (Fig. 19.3). The cephalocele may be small or large. They may contain only meninges (meningocele) or brain tissue (meningomylocele). The larger the cephalocele the more brain tissue it contains, the worse is the prognosis for the fetus. Microcephaly may be seen in as many as 20–25 % of the cases. Reported detection rates at 11 to 13 6/7 weeks are 100 % [8].

During normal fetal development the falx cerebri, a midline structure that separates the single cavity of the forebrain into two hemispheres, should be seen after 9–10 weeks in all normal brains. Lack of visualization of the falx cerebri is consistent with alobar holoprosencephaly (HPE) (Fig. 19.4). At 11 to 13 6/7 weeks the choroid plexus is seen on each side of the midline falx; this configuration has been likened to a butterfly with the wings open [14] (see Fig. 19.4a). Using the “butterfly sign” Sepulveda et al. [15] screened 11,068 live fetuses for HPE over a 9-year period. Among this cohort they diagnosed 11 cases of HPE, which demonstrated lack of visualization of the “butterfly sign.” Detection rate of HPE using the absent “butterfly sign” was 100 %. In addition, they noted that 40 % had a biparietal-diameter less than the fifth centile for gestational age (GA); which further aided in the diagnosis.

Holoprosencephaly is a common malformation involving the forebrain; this malformation results from complete or incomplete failure of the forebrain to divide during the second to the third week post-conception [16–18]. The prevalence of holoprosencephaly at 11 to 13 6/7 weeks has been reported as 1:1300 pregnancies; with approximately 66 % having a chromosomal abnormality of which 86 % have trisomy 13 and 4 % trisomy 18 [19]. This anomaly has a spectrum ranging from the most severe alobar HPE, to semilobar HPE, and to lobar HPE and the least severe middle interhemispheric variant (MIHV). In approximately 80 % of individuals affected with HPE [9] a craniofacial anomaly is also present [16]. The craniofacial anomalies range from cyclopia (single midline eye), synophthalmia (partial midline face fusion of the two eye), and a proboscis (nasal appendage with a single nostril located above the eyes) [17]. During the first trimester, most of the cases of HPE that are diagnosed are alobar; although the semilobar type can also be diagnosed; however, at 11 to 13 6/7 weeks, this presents a challenging task. Three-dimensional inversion rendering can be used to differentiate between a normal brain and HPE; this can be used as an additional tool in the diagnosis of HPE in the first trimester [20] (Fig. 19.5). Lobar HPE, which is a more subtle malformation and depends upon the appearance of the cava is diagnosed at or after the 18- to 20-week anatomy scan. Most fetuses affected by HPE do not survive. Detection rates of 50–100 % have been reported [8, 13].

The significance of thickened or increased nuchal translucency (NT) in the screening for aneuploidies, congenital heart defects and other malformations is well established. Thickened NT refers to a measurement that is greater than the 95th centile; which in turn increases with gestational age and is just about 2.5 mm; in contrast, its 99th centile is fixed at 3.5 mm (Fig. 19.6) [21, 22]. A thickened NT in itself is not an abnormality since it can be seen in both normal pregnancies as well as those with pathologies. Kagan et al. [23] looked at the relationship between thickened NT and chromosomal defect. With increasing NT from the 95th centile to 3.4 mm the incidence of chromosomal aneuploidy was 7 %; at an NT of 3.5–4.4 mm the incidence of chromosomal aneuploidy was 20 %; at a NT of 4.5–5.4 mm it was 45 %; at a NT of 5.5–6.4 mm, 50 %; at a NT of 6.5–7.4 mm, 70 %; and with NT of ≥8.5 mm, 75 %. Another interesting finding was that about half of the fetuses with trisomy 21 has NTs ≤ 4.5 mm; NT greater than 4.5 mm was seen in about 60 % of the cases with trisomy 13, 75 % of fetuses with trisomy 18 and 90 % of cases of Turner syndrome; moreover, fetuses with Turner tended to have the thickest NT ≥ 8.5 mm.

In euploid fetuses with thickened NT the association with congenital heart defects (CHD) is well known. In a 2003 meta-analysis by Makrydinas et al. [24] an NT > 95th centile had a sensitivity of 37 % and specificity of 96.6 %; and for NT > 99th centile they were 31 % and of 98.7 %, respectively, with a positive likelihood ratio of 24 for the diagnosis of major congenital heart defect [21, 24]. In a subsequent 2013 meta-analysis by Sotiriadis et al. [25] they found that approximately 45 % of chromosomally normal fetuses with CHD had an NT > 95th and 20 % had an NT > 99th centile.

Cystic hygroma refers to bilateral, septated, cystic, fluid-filled spaces located in the occipitocervical region [26]. This is a result of obstruction between the lymphatic and venous vessels in the neck resulting in accumulation of lymph in the jugular lymphatic sacs (Fig. 19.7). In fetuses with cystic hygroma between 11 and 13 6/7 weeks approximately 51 % [27] to 54.9 % [28] will have a chromosomal abnormality; of which trisomy 21 is the most common. In a recent retrospective cohort study of 944 fetuses with first trimester cystic hygroma; the prevalence of trisomy 21 was 21.4 %; followed by monosomy X (Turner syndrome) 12.1 %, trisomy 18 at 11.4 % and trisomy 13 at 3.6 % and other karyotypic abnormalities such as other trisomies, deletions, duplications, unbalanced translocations, inversions, and sex chromosome abnormalities [28]. Among the fetuses with normal karyotype 28.8 % had a major anomaly. Urinary, central nervous system, and cardiac were the most common accounting for 15 % of the anomalies [28]. In the same cohort six fetuses had genetic syndromes; Angelman and Noonan syndrome were among the genetic syndromes seen. Perinatal loss occurred in 39 % of ongoing pregnancies and the overall abnormal outcome ensued in 86.6 % of the fetuses [28].

During the early anatomical survey, similarly to the traditional second trimester anatomical survey, a profile view of the face should be obtained. This may reveal an absent or hypoplastic nasal bone, a cleft lip and/or palate, or micrognathia.

Absent nasal bone is not a fetal malformation per se however it is a marker of fetal aneuploidy; specifically of the common trisomies (Fig. 19.8). The nasal bones are actually paired structures, there is a right and a left nasal bone, and there can be unilateral as well as bilateral absence or hypoplasia. Absent nasal bone is seen in 60 % of fetuses with trisomy 21, 53 % of trisomy 18 and in 45 % of trisomy 13; its absence confers a likelihood ratio of 27.8 for Down syndrome; furthermore, it can be seen in 2.5 % of euploid fetuses [29]. Among euploid pregnancies absent nasal bone is seen more frequently in African American women (5.8 %) than in white women (2.6 %) or Asian women (2.1 %) [30]. In a recent publication among 57 fetuses with absent nasal bone and normal karyotype three fetuses had an adverse outcome and, in all, additional sonographic abnormalities were seen [30].

Cleft lip and/or palate (CLP) is a common facial anomaly with a reported incidence of 1.7 per 1000 live births; however, ethnic and geographic variation exist [31]. In up to 80 % of the cases cleft lip is unilateral, typically affecting the left side and most of the affected fetuses are male. However, isolated cleft palate is more commonly seen in females with a reported incidence of 1 in 2500 live births [31]. During development, a continuous upper lip is formed by 8 weeks when the medial nasal and maxillary processes fuse. Failure of fusion of the medial nasal and maxillary processes will result in a cleft lip affecting one or both sides. The palate develops from the primary and the secondary palate. Its development starts at 7 weeks, but is not completed until the 14th week. At 11 to 13 6/7 weeks a sagittal, coronal, and axial view using 2D and 3D sonography can detect a CLP (Fig. 19.9). In cases of bilateral cleft lip and palate a protuberance is seen anterior to the lips in the sagittal plane; in the axial plane the cleft lip and palate can be seen as a deep indentation. Three-dimensional ultrasound, specifically 3D reconstruction of the face using the coronal plane can help in evaluating the facial defects (see Fig. 19.9b). Detection rates of CLP in the first trimester are low, ranging from 5 to 50 % [8, 13]. The retronasal triangle (see Fig. 19.9e) can be imaged, using 2D or 3D sonography, by obtaining an anterior coronal view of the fetal face. The apex of the retronasal triangle is made up of the two nasal bones, the sides are the frontal process of the maxilla and the base of the triangle is the primary palate [32]. In cases of CLP, a defect can be imaged at the base of the triangle, at the site of the palate (Fig. 19.9b Box C) Boc C. The retronasal triangle view likely can improve the detection and diagnostic rates of CLP; however, no large prospective studies looking at efficacy of the retronasal triangle are available to date. Furthermore, this view has recently been reported as a new way to evaluate the presence or absence of the nasal bones [32–34].

Cataracts: the reported incidence is 1–6/10,000 births [35]. The fetal lens develops from the surface ectoderm before the sixth week of gestation [35]. Fetal cataracts may be the result of a very early in-utero fetal infection, such as rubella, varicella, herpes and CMV, exposure to a toxin (anti-psychotic drugs such as carbamazepine), idiopathic or genetic. A genetic cause is seen in 30 % of unilateral cases and in 50 % of bilateral cases [35]; genetic causes includes syndromes such as Walker–Warburg syndrome and karyotypic abnormalities such as trisomy 21, 18, and 13. The normal sonographic appearance of the fetal lens is that of a ring with an anechoic center and an outer echogenic rim (Fig. 19.10a). At times the hyaloid artery can be seen as a linear structure between the posterior aspect of the lens and the optic disc; however, the hyaloid artery typically regresses before birth. In fetal cataracts there is opacification of the anechoic center-core of the lens; at times, in conjunction with cataracts, there may be reduction in the size of the fetal eyes [36] (see Fig. 19.10b).