Congenital Anomalies
Jill Berkin
Melissa L. Russo
Congenital anomalies are among the most common causes of neonatal morbidity and mortality. According to the Centers for Disease Control and Prevention, they occur in 3% of live births and account for 25% of all pediatric hospital admissions. Birth defects can involve an isolated organ system or multiple organ systems; multiple anomalies may encompass a syndrome. The causes of congenital anomalies are genetic, environmental, or unknown etiology. There are multiple risk factors that have been associated with increased risk of congenital anomalies.
ETIOLOGY
Causes of congenital anomalies may be chromosomal, familial, multifactorial, or idiopathic; hence, obtaining a thorough family history and screening of low-risk populations are important.
Genetic etiologies include the following: chromosomal disorders such as trisomy (e.g., Down syndrome), deletion (e.g., DiGeorge syndrome), or monosomy (e.g., Turner syndrome); monogenic disorders such as Noonan syndrome and Smith-Lemli-Opitz syndrome; and multifactorial disorders such as isolated congenital heart disease, cleft lip and palate, and arthrogryposis which result from interactions of several genes and environmental factors.
Nongenetic/environmental etiologies include the following teratogens: ethanol, certain medications such as tretinoin (Retin-A) and warfarin (Coumadin), illicit
drugs, maternal nutritional deficiencies, and maternal medical conditions such as diabetes and maternal infections such as toxoplasmosis or syphilis (see Chapter 11).
TABLE 12-1 Factors Associated with Increased Risk for Congenital Abnormalities
Advanced maternal age (maternal age ≥35 years at time of delivery)
Pregestational diabetes
Exposure to a known teratogen
History of having a child with birth defect
Personal or family history of a known genetic abnormality (e.g., balanced translocation, mutation, or aneuploidy)
Abnormal serum screening
Multiple gestation
Assisted reproductive technology
Ninety percent of infants with congenital anomalies are born to women with no risk factors (Table 12-1).
SCREENING AND MANAGEMENT
Given the significant morbidity and mortality of congenital defects, all patients should be offered screening for fetal chromosomal abnormalities preferably during the first trimester and a level II anatomy ultrasound at 18 to 22 weeks. Detailed ultrasonography by an experienced technician can detect up to 80% of fetal anomalies, allowing the full range of management options: expectant management, in utero therapy, further workup (e.g., karyotyping, microarray and/or viral studies), and pregnancy termination.
Management should include counseling that takes into consideration the fetus, the mother, and the family. Treatment options and prognosis should be discussed. With a fetal congenital anomaly, multidisciplinary approach facilitates a unified plan of care. The obstetrician or maternal fetal medicine (MFM) specialist can coordinate care with genetic counselors, neonatologists, and other pediatric specialists such as surgeons, cardiologists, urologists, and neurosurgeons. Social work and bereavement counseling can also be part of the care plan if indicated. The care plan must be timely, unbiased, and sensitive to the concerns and values of the patient and her family.
Ultrasonography can be used to diagnose many major anomalies. The other clinical uses for ultrasound entail confirmation of gestational age, definition of placental location, determination of amniotic fluid volume, and evaluation of fetal growth.
Optimal timing for the anatomic survey is between 18 and 20 weeks’ gestation. At this gestational age, organogenesis is complete, bony ossification in the skull does not yet obscure sonography, and structures are large enough for accurate assessment but still small enough to visualize within a single ultrasound window. With a detected anomaly, a patient can pursue a genetic workup and has a full set of options available to her at the time the anomaly is discovered.
The structures that are assessed in the level II anatomy screen include the following:
Head: The biparietal diameter and head circumference are measured, both in the same view at the level of the thalamus and cavum septum pellucidum. The intracranial contents, ventricular structures, cerebellar diameter, and cisterna magna are evaluated.
Spine: Sagittal, transverse, or coronal views are obtained at all levels to screen for neural tube defects.
Heart: Four-chamber view and visualization of left and right outflow tracts are required. If an abnormality is suspected, fetal echocardiography should be performed.
Abdomen: The stomach and umbilical vein should be visualized in the same plane for the abdominal circumference measurement. Abdominal wall defects are ruled out by verifying normal cord insertion and the absence of bowel loops in the amniotic fluid. The kidneys, renal pelvises, and bladder are evaluated for location, structure, and evidence of obstruction.
Limbs: The four limbs should be imaged to their distal ends and the humerus and femur measured. The hands should be seen to open and close and the feet examined for normal positioning and appearance.
Several sonographic “soft markers” occur more frequently in fetuses with aneuploidy, specifically trisomy 21. These markers include increased nuchal translucency, renal pelvis dilation, echogenic intracardiac focus (small bright spot within the fetal heart on ultrasound), echogenic bowel, and short long bones. Aneuploidy risk increases with an increased number of markers identified; previous studies have reported likelihood ratios for the individual markers.
CHROMOSOMAL ABNORMALITIES WITH ASSOCIATED CONGENITAL ANOMALIES
In many specific chromosomal syndromes, there are characteristic findings prenatally that assist in prenatal diagnosis. Common aneuploidies will be discussed with their associated findings (Table 12-2A, 12-2B).
Trisomy 21 (Down syndrome)
Down syndrome is the most common aneuploidy where the fetus survives, with a frequency of 1:660 to 1:800 births. With trisomy 21, there is an extra copy of chromosome 21. The frequency of nondisjunction increases with increasing maternal age.
Down syndrome can be complete trisomy 21 in which all cells have three copies of chromosome 21 (94% of cases) or mosaic trisomy 21 in which only some cells in the body have an abnormal number of chromosome 21 (2% to 3%). A third etiology of Down syndrome results from a mother who has a balanced translocation, in which an extra piece of chromosome 21 is attached to another chromosome and is given to the fetus.
The finding of an echogenic intracardiac focus is not an indication for a fetal echocardiogram, as this is not a structural defect, but should prompt a search for other markers of Down syndrome and a discussion of a potential increased risk in the pregnancy. If Down syndrome is suspected, a fetal echocardiogram is recommended, as these fetuses have a higher incidence of congenital heart defects.
Children with Down syndrome have some degree of intellectual disability, and in prenatal counseling, it is important to discuss that there is a spectrum of disease and the severity of disease cannot be predicted prenatally or by genetic testing.
TABLE 12-2A Common Aneuploidies with Associated Findings | ||||||||||||||
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TABLE 12-2B Common Aneuploidies with Associated Findings | ||||||||
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Trisomy 13 and 18
Trisomy 13 (Patau syndrome) is usually due to meiotic primary nondisjunction giving rise to a 47 +13, XX or XY genotype. Trisomy 13 is invariably fatal; approximately 50% of newborns die in the first month of life and 90% die by 1 year. Of those that survive, they have multiple anomalies and severe intellectual disability.
Trisomy 18 (Edwards syndrome) is most commonly due to meiotic primary nondisjunction giving rise to a 47 +18, XX or XY genotype. Life expectancy for these infants is usually very limited.
Turner Syndrome
Turner syndrome (monosomy X) is usually 45, X genotype. Some individuals are mosaic, with both 45, X and 46, XX cell lines, with resultant variable characteristics. These individuals can have some degree of learning disability.
Triploidy
Triploidy has one extra haploid set of chromosomes (i.e., 69 chromosomes). Most cases are 69, XXY (60%) or 69, XXX (37%). Only 3% of cases are 69, XYY. Triploidy is uniformly fatal within the first few months of life.
COMMON SPECIFIC CONGENITAL ANOMALIES
Congenital Heart Abnormalities
Congenital heart abnormalities are among the most common birth defects (Table 12-3). There are some known etiologies for congenital heart disease (CHD), namely maternal diabetes, teratogen exposure, and certain genetic causes such as 22q11 microdeletion (i.e., DiGeorge syndrome). There is a long-established association between congenital heart defects and aneuploidy. The frequency of chromosomal abnormalities with a congenital heart defect has been estimated to be 16% to 45% prenatally and 5% to 10% postnatally; the discrepancy in these rates is secondary to antenatal death occurring in fetuses with chromosomal abnormalities. The likelihood of a cardiac defect exceeds 50% for Down syndrome and is 90% for trisomies 13 and 18.
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