Dandy-Walker malformation 1/12,000 40 18/ 13/21, triploidy Clet lip/palate 1/1000 5-15 18,13 Cardiac defects 5-8/1000 10-30 21; 18; 13; 45/X; 22q 11.2 microdeletion
Diaphragmatic hernia 1/3000-4000 5-15 18,l13,l21
Esophageal atresia 1/4000 10 18,l21
Duodenal atresia 1/10,000 30 21 Gastroschisis 112000-4000 No increase
Omphalocele 1/4000 30-50 18, 13, 21, triploidy autosomal trisomies except where indicated. For example, 45,X indicates Turner syndrome. Data from Best, 201l2; Canfield, 2006; Colvin, 2005; Cragan, 2009; Dolk/ 201l0; Ecker, 2000; Gallot/ 2007; Long, 2006; Orioli, 2010; Pedersen/ 2012; Sharma/ 201l1l; Solomon, 2010; Walker/ 2001l.
screens are specific for individual aneuploidies (Baer, 2015; Kazerouni, 2011). Women younger than 35 are at lower risk for the speciic autosomal trisomies for which cell-free DNA screening is typically performed. hus, if the goal is to select a screening test that will identiY the highest proportion of fetuses with any chromosomal abnormality, the yield may be comparable or even slightly higher with integrated or sequentil screening than with current cell-free DNA screening (Baer, 2015; Norton, 2014).
Sonography can augment aneuploidy screening by providing accurate gestational age assessment, by detecting multifetal gestations, and by identiYing major structural abnormalities and minor sonographic markers. s shown in Table 14-7, with rare exceptions, the aneuploidy risk associated with any major abnormality is high enough to warrant ofering prenatal diagnosis. Generally, chromosomal microarray analysis is recommended as the irst-line test. Importantly, a fetus with one abnormality may have others that are less likely to be detected sonographically but that greatly afect the prognosis. Aneuploidy screening-including cell-free DNA-is not recommended if a major abnormality has been identified. The fetal risk cannot be normalized with a normal screening result, not merely because screening results can be falsely negative, but also because major anomalies confer risk for genetic syndromes not identiied through screening tests.
If a major abnormlity is identified, targeted sonography is indicated. Sonography is not an alternative to prenatal diagnosis, but the aneuploidy risk is urther increased if additional findings are identified. An earlier study reported that only 25 to 30 percent of second-trimester fetuses with Down syndrome had a major malformation that could be identiied sonographically (Vintzileos, 1995). When both major anomalies and minor aneuploidy markers are considered, it is estimated that 50 to 60 percent of Down syndrome pregnancies can be detected sonographiclly (American College of Obstetricians and Gynecologists, 2016c). Fortunately, most fetuses with aneuploidy that is likely to be lethal in uterosuch as trisomy 18 and 13 and triploidy-usully have sonographic abnormalities that can be seen by the second trimester.