Major congenital abnormalities are identified during pregnancy or shortly after birth in 2 to 3 percent of pregnancies. They account for 20 percent of infant deaths in the United States, surpassing preterm birth as the most common cause (Kochanek, 2011). Prenatal diagnosis is the science of identifying malformations, disruptions, chromosomal abnormalities, and other genetic syndromes in the fetus. It encompasses routine screening tests for aneuploidy and neural-tube defects, invasive diagnostic tests such as chorionic villus sampling and amniocentesis, additional screening and diagnostic tests offered to those at risk for specific genetic disorders, and the diagnosis of structural malformations with specialized sonography and other fetal imaging techniques discussed in Chapter 10. The goal of prenatal diagnosis is to provide accurate information regarding short- and long-term prognosis, recurrence risk, and potential therapy and to thereby improve counseling and optimize outcomes.
Structural fetal abnormalities may develop in at least three ways. The most common mechanism is malformation—an intrinsic abnormality “programmed” in development, regardless of whether a precise genetic etiology is known. Examples include spina bifida and omphalocele. A second mechanism is deformation, by which a fetus develops abnormally because of extrinsic mechanical forces imposed by the uterine environment. An example is limb contractures that develop with oligohydramnios from bilateral renal agenesis. A third type is disruption, which is a more severe change in form or function that occurs when genetically normal tissue is modified as the result of a specific insult. An example is damage from an amnionic band, which can cause a limb-reduction defect.
Multiple structural or developmental abnormalities may also present together as a syndrome, sequence, or association. A syndrome is a cluster of several anomalies or defects that have the same cause—for example, trisomy 18. A sequence describes anomalies that all developed sequentially from one initial insult. An example is the Pierre-Robin sequence in which micrognathia causes posterior displacement of the tongue—glossoptosis—which leads to a posterior rounded cleft in the palate. An association is a group of specific abnormalities that occur together frequently but do not seem to be linked etiologically. Diagnosis of the VACTERL association, for example, includes three or more of the following: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. Because of overlap of anomaly patterns, it is readily apparent that classification of fetal malformations is challenging, and reclassification is required periodically.
These defects include anencephaly, spina bifida, cephalocele, and other rare spinal fusion (schisis) abnormalities. Features of these anomalies are detailed in Chapter 10 (Neural-Tube Defects), and fetal surgery for spina bifida is discussed in Chapter 16 (Open Fetal Surgery). Neural-tube defects (NTDs) are the second most common class of birth defect after cardiac anomalies, and their reported frequency is approximately 0.9 per 1000 births (Cragan, 2009; Dolk, ...