Prenatal diagnosis of congenital anomalies


On completion of this chapter, you should be able to:

  • Describe the methods of genetic testing, including maternal serum markers, chorionic villus sampling, and amniocentesis

  • Describe the ultrasound technique of amniocentesis

  • Discuss how anomalies are transmitted genetically

  • Detail the prevalence and prognosis of the most common chromosomal anomalies

  • Describe the sonographic features of chromosomal anomalies

Chromosomal disorders

Prenatal ultrasound has become the investigative tool for the obstetrician to access the developing fetus, and it is likely that the fetus with an anomaly will be subjected to ultrasound at some time during pregnancy. The role of the sonographer is to screen for the unsuspected anomaly and to study the fetus at risk for an anomaly. The benefits of the examination are greatest when the sonographer is adept at detecting congenital anomalies and understands the cause, progression, and prognosis of the common congenital anomalies, including chromosomal anomalies.

When a fetal anomaly is found antenatally, a multidisciplinary team approach to managing the fetus, mother, and family is preferable because the fetus may need special monitoring (e.g., serial ultrasound), delivery, postnatal care, and surgery. This multidisciplinary team includes the perinatologist (maternal-fetal medicine specialist), neonatologist (specialist for critically ill infants), sonologist, perinatal sonographer, pediatric surgeon, other pediatric specialists, geneticist, obstetrician, perinatal and pediatric social workers, and other support personnel. Consultation with specialists is recommended when diagnosis is uncertain. Once an anomaly is found, these specialists can work as a team to optimize clinical management, to prepare the patient and family for possible surgery, to provide the patient and family with emotional support, and to plan for delivery. Most fetuses with major birth defects are delivered in perinatal regional centers where the specialized physicians, nurses, equipment, treatment, and postnatal surgery are available.

Genetic testing

The role of genetic testing is to provide noninvasive prenatal testing and invasive testing, which may include screening tests and diagnostic tests, when needed, to identify chromosomal anomalies. Paired with sonographic evaluation, the risk for a chromosomal anomaly may be increased based on these findings. The number and type of screening and diagnostic tests continue to increase, most recently with the addition of cell-free DNA screening and chromosomal microarray analysis.

Chorionic villus sampling

Chorionic villus sampling (CVS) is an ultrasound-directed biopsy of the placenta or chorionic villi (chorion frondosum). The chorion frondosum is the active trophoblastic tissue that becomes the placenta. Because the chorionic villi are fetal in origin, chromosomal abnormalities may be detected when cells from the villi are grown and analyzed. Other conditions, such as biochemical or metabolic disorders, thalassemia, and sickle cell disease (hemoglobinopathies), may also be diagnosed using chorionic villi.

CVS is an alternative test used to obtain a fetal karyotype by the culturing of fetal cells similar to amniocentesis. The advantages of CVS include the following: (1) it is performed early in pregnancy (10 to 14 weeks), (2) results are available within 1 week, and (3) earlier results allow more options for parents.

CVS is performed transcervically or transabdominally ( Figure 55-1 ). Ultrasound performed before the actual procedure aids in a number ways: (1) It determines the relationship between the lie of the uterus and cervix and path of the catheter. Bladder fullness influences this relationship. Filling or emptying of the bladder may be necessary to facilitate the catheter route. (2) It assesses the fetus in terms of life, normal morphology, and age. (3) It identifies uterine masses or potential problems that may interfere with passage of the catheter.


A, Transabdominal chorionic villus sampling. B, Transcervical chorionic villus sampling.

Transvaginal CVS is performed in the dorsolithotomy position (pelvic examination position). The sonographer aids the obstetrician in determining the correct route to pass the catheter through the cervix to the placenta. A guiding stylet is initially introduced to check uterine and placental position. A flexible catheter is then introduced and directed into the placental tissue ( Figure 55-2 ). The placental cells are aspirated through the catheter. The villi are collected and transported to the cytogenetics technician for analysis. Additional retrievals often are necessary. The sonographer should monitor the fetal heart rate and check for procedural bleeding.


A, Transcervical chorionic villus sampling at 10 weeks of gestation demonstrating the placement of the sampling catheter (arrowheads) within an anterior placenta (P) or chorion frondosum. a, Amniotic cavity. B, Transcervical chorionic villus sampling at 11 weeks of gestation showing the placement of the sampling catheter (arrowheads) within a posterior placenta (P). Note the fetal abdomen (f) within the amniotic cavity (a).

The transabdominal CVS approach entails using a syringe and needle inserted into the placenta to withdraw the villi. The procedure is performed in a manner similar to amniocentesis (see the discussion of amniocentesis).

The risk of fetal loss because of CVS is approximately 0.05% to 1.0%. There has been some association with limb reduction defects when CVS is performed before 8 weeks of gestation. Rh o (D) immune globulin (RhoGAM) should be administered to Rh-negative unsensitized women to prevent sensitization problems in subsequent pregnancies.


Amniocentesis was first used as a technique to relieve polyhydramnios, to predict Rh isoimmunization, and to document fetal lung maturity. In the mid-1960s amniocentesis was used to study fetal cells from amniotic fluid that allowed the analysis of fetal chromosomes ( Figure 55-3 ). Normal and abnormal chromosomal patterns ( Figures 55-4 and 55-5 ) could be identified.


Normal karyotype demonstrating 46 chromosomes in a female fetus (46,XX).


Karyotype of trisomy 21 (Down syndrome) in a male fetus (47,XY,21). Note the extra chromosome at the 21st position (arrow). Note the sex chromosomes indicating a male fetus.


Karyotype of trisomy 13 (47,XY,13) (arrow) male fetus.

Amniocentesis is a test offered to expectant patients who are at risk for a chromosomal abnormality or biochemical disorder that may be prenatally detectable. The results are available between 1 and 3 weeks; however, if rapid results are desired, fluorescence in situ hybridization (FISH) provides a limited analysis within 24 hours for the most common chromosomal anomalies. The FISH assay most commonly evaluates for numeric abnormalities of chromosomes 21, 13, 18, X, and Y.

Advanced maternal age is a common reason for performing amniocentesis. All pregnant women are at risk for having a child with a chromosomal defect, but the risk is greater in a woman of advanced maternal age.

Other indications for genetic amniocentesis include a history of a balance rearrangement in a parent or previous child with a chromosomal abnormality, a history of an unexplained abnormal alpha-fetoprotein (AFP) level or an abnormal screening test, and a fetus with a congenital anomaly.

Amniocentesis for genetic reasons is ideally performed between 15 and 20 weeks of gestation. Amniocentesis may be done as early as 12 weeks, but it may lead to the development of fetal scoliosis or clubfoot secondary to the reduced amount of amniotic fluid. The rate of miscarriage in early amniocentesis is not clearly defined. Some studies have shown that the loss rate is similar to midtrimester amniocentesis, whereas others have shown a higher loss rate. The fetal loss rate of midtrimester amniocentesis was reported at 1 in 769 in one study. Amniocentesis performed beyond 20 weeks of gestation is possible but may be associated with poor cell growth.

The amniocentesis procedure should include a fetal survey to exclude congenital anomalies. A fetal examination should be performed, and targeted areas of anatomy should be documented to exclude the physical features that would suggest a chromosomal anomaly (e.g., hand clenching, hypoplasia of the fifth middle phalanx, choroid plexus cysts, ventriculomegaly, thickened nuchal fold, cardiac anomalies, omphalocele, spina bifida, or foot anomalies).

The sonographer will also assist the physician in the amniocentesis procedure. The optimal collection site for amniotic fluid should be away from the fetus, away from the central portion of the placenta, away from the umbilical cord, and near the maternal midline to avoid the maternal uterine vessels.

Technique of genetic amniocentesis

Ultrasound-monitored amniocentesis is a technique that allows the continuous monitoring of the needle during the amniocentesis procedure. Using this technique, the maternal skin is prepared with a povidone-iodine solution.

The transducer is placed in a sterile cover or sterile glove to allow monitoring on the sterile field during the procedure. Sterile coupling gel may be applied to the maternal skin to ensure good transmission of the sound beam. The amniocentesis site is rescanned to confirm the amniotic pocket, and then the site and pathway for the introduction of the needle are determined. The distance to the amniotic fluid may be measured with electronic calipers, which may be useful in obese patients in whom a longer needle may be necessary. In many instances, a new site is chosen as a result of fetal movement or a myometrial contraction in the proposed site, and the transducer is moved to a new sterile area. On successful identification of the amniocentesis site, a finger is placed between the transducer and the skin to produce an acoustic shadow. The needle is then inserted under continuous ultrasound observation ( Figure 55-6 ). Inserting the needle in a plane perpendicular to the transducer will allow for a bright reflection of the needle tip, so that it can be easily observed ( Figure 55-7 ) at the edge of the uterine wall and then as it punctures the uterine cavity. When incorrectly directed, the needle may be repositioned.


If the needle is inserted parallel to the transducer, only the tip will be represented. If the needle is inserted at an angle with the transducer, the beam will intersect the needle, but it will not demonstrate its tip, which could be in a harmful position. Notice that in both cases the image on the screen is the same. Angling the needle is a dangerous procedure that should be avoided.


A, Genetic amniocentesis at 15.6 weeks of gestation using direct visualization method. The needle tip (t) is identified within the amniotic cavity. F, Fetus. B, Genetic amniocentesis at 16 weeks of gestation in a twin pregnancy. The needle tip (t) is identified within the sac above the amniotic membrane (arrows). F, Fetus; P, placenta. 1, Umbilical cord insertion into placenta.

Amniotic fluid is aspirated through a syringe connected to the needle hub. Approximately 20 ml of amniotic fluid will be collected for chromosomal analysis and AFP evaluation. In advanced pregnancies, additional amniotic fluid may be required. When amniocentesis is performed because of a known fetal anomaly, acetylcholinesterase and viral studies ( TORCH titers) may be ordered. Following aspiration of amniotic fluid, the needle is removed from the uterus under sonographic guidance.

After the amniocentesis has been completed, fetal cardiac activity should be identified and documented. If the placenta has been traversed, the site should be monitored for bleeding. The use of videotaping can allow for continuous recording and documentation of the fetal examination, the amniocentesis, and postamniocentesis ultrasound evaluation.

The continuous monitoring with ultrasound during amniocentesis is invaluable in cases of oligohydramnios, anterior placental position, and premature rupture of membranes. Ultrasound imaging can help achieve a successful amniocentesis when only small pockets of fluid are available.

Genetic amniocentesis and multiple gestations

Amniocentesis in multiple gestations warrants special consideration. Preliminary sonographic examination for each fetus should be performed to include a survey of fetal anatomy and growth profiles. Determination of whether the pregnancy is monozygotic or dizygotic should be made. It should be determined whether there are multiple sacs, and the amount of amniotic fluid within each sac should be assessed.

The amniocentesis technique for multiple gestations is similar to the singleton method, except that each fetal sac is entered. To be certain that amniotic fluid is obtained from each sac, indigo carmine dye can be injected into the first sac. The presence of clear amniotic fluid indicates that the second sac has been penetrated when the second pass is made. If dye-stained fluid is visible, it indicates that the first sac has been penetrated a second time. Documentation of each amniocentesis and meticulous labeling of fluid samples are recommended. It is desirable to avoid the placenta in patients who are Rh-negative. In all Rh-negative patients, RhoGAM is administered within 72 hours of the procedure.


Cordocentesis is another method in which chromosomes are analyzed. Fetal blood is obtained through needle aspiration of the umbilical cord. Karyotype results can be processed within 2 to 3 days; however, the availability of FISH has decreased the need for cordocentesis for chromosomal analysis. Cordocentesis is more commonly used for guidance for transfusions to treat fetal isoimmunization

Maternal serum markers


Alpha-fetoprotein (AFP) is the major protein in fetal serum and is produced by the yolk sac in early gestation and later by the fetal liver. AFP is found in the fetal spine, gastrointestinal tract, liver, and kidneys. This protein is transported into the amniotic fluid by fetal urination and reaches maternal circulation or blood through the fetal membranes ( Figure 55-8 ). AFP may be measured in the maternal serum (MSAFP) or from amniotic fluid (AFAFP).


Schematic drawing showing the production and distribution of alpha-fetoprotein (AFP) into its three components: fetal tissues, amniotic fluid, and maternal serum. AF-AFP, Amniotic fluid AFP; FS-AFP, fetal serum AFT; MS-AFP, maternal serum AFP.

AFP levels are considered abnormal when elevated or low. Neural tube defects, such as anencephaly and open spina bifida, are common reasons for high AFP levels. In both instances, AFP leaks from the defect to enter the amniotic fluid and then diffuses into the maternal bloodstream (see Figure 55-8 ). AFP elevations will not be found when there is closed spina bifida (occulta) because there is no opening to allow leakage.

Monitoring of AFP is a screening test for neural tube defects and other conditions ( Box 55-1 ). Evaluation is usually based on 2.0 to 2.5 multiples of the median (MOM), but false positives do occur. MSAFP screening detects approximately 75% to 90% of open neural tube defects and may also detect up to 85% of abdominal wall defects.

BOX 55-1

Reasons for Elevation of Alpha-Fetoprotein and Acetylcholinesterase

Neural tube defects

  • Anencephaly

  • Exencephaly (acrania)

  • Encephalocele (including Meckel-Gruber syndrome)

  • Spina bifida

  • Sacrococcygeal teratoma

Abdominal wall defects

  • Omphalocele

  • Gastroschisis

  • Limb–body wall complex

  • Amniotic band syndrome

  • Bladder or cloacal exstrophy

  • Ectopia cordis

Multiple gestation

  • Twin with a co-twin death

  • Acardiac twin

  • Fetus papyraceous

Gastrointestinal obstruction

  • Annular pancreas

  • Duodenal atresia

  • Esophageal atresia

Renal anomalies

  • Congenital nephrosis

  • Hydronephrosis

  • Polycystic kidney disease (including Meckel-Gruber syndrome)

  • Urinary tract obstruction

  • Prune-belly syndrome

  • Urethral atresia

Placental and cord abnormalities

  • Chorioangioma

  • Placental or cord hematoma

  • Umbilical cord hemangioma

  • Hydatidiform mole

Fetal heart failure

  • Hydrops or ascites

  • Lymphangiectasia

  • Rh isoimmunization

Neck masses

  • Cystic hygroma

  • Noonan’s syndrome (with hygroma)

Liver disease

  • Hepatitis

  • Maternal herpes virus (fetal liver necrosis and skin lesions)

  • Hepatocellular carcinoma

  • Hamartoma of liver

Miscellaneous causes

  • Incorrect dates

  • Fetal demise

  • Oligohydramnios

  • Unexplained

  • Hereditary overproduction of alpha-fetoprotein

  • Blood in amniotic fluid

  • Chromosome abnormalities (trisomies 18 and 13, Turner’s syndrome, triploidy)

  • Cystadenomatoid malformation

  • Epignathus

  • Intracranial tumor

  • Pilonidal cyst

  • Skin defects

  • Hydrocephalus

  • Congenital heart defects

  • Viral infections (cytomegalovirus, parvovirus)

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May 29, 2019 | Posted by in ULTRASONOGRAPHY | Comments Off on Prenatal diagnosis of congenital anomalies
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