Chapter 56
Techniques of Prenatal Diagnoses
Main Menu   Table Of Contents



The development of prenatal diagnosis has been an important advance in the field of clinical genetics.1 Techniques in prenatal diagnosis have made it possible for genetic counselors and parents to transform risks of certain genetic diseases from purported intermediate risks (5%, 25%, or 50%) to 0% or 100%. Although it is impossible currently to identify all genetic abnormalities, screening and diagnostic programs are available to detect the most common chromosomal defects prenatally. The techniques of prenatal diagnosis include maternal serum screening, amniocentesis, ultrasound, chorionic villi sampling, and cordocentesis.
Back to Top
Down syndrome and other autosomal trisomies increase with maternal age (Table 1).1,2 Genetic amniocentesis is generally offered to women who will be 35 years or older at delivery. At this age, the incidence of trisomy starts to increase rapidly. However, 87.1% of children are born to women who are less than 35 years of age at delivery, so the majority of children with Down syndrome are born to younger women.2 Because of advances in ultrasound techniques and biochemical markers, noninvasive methods of prenatal diagnosis are becoming more prevalent.

TABLE 1. Risk of Having a Live-Born Child with Chromosomal Abnormalities

Maternal ageMidtrimesterTerm liveborn
DSAll aneuploidiesDSAll aneuploidies

Adapted from Hook EB, Cross PK, Schreinemachers DM: Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA 249:2034, 1983.
DS, Down syndrome.


Back to Top
The most common indication for prenatal diagnosis is the routine screening of the general population.2 The most common methods of screening include ultrasound and maternal serum biochemistry. Table 2 lists the indications for which a couple should be offered prenatal testing. The incidence of Down syndrome increases as maternal age increases. The relationship between the incidence of Down syndrome and maternal age was noted long before the chromosomal etiology of the syndrome was known. Other chromosomal trisomies, such as trisomy 13; trisomy 18; 47, XXY; 47XXX; and 47XYY, may also increase with age.3,4

TABLE 2. Indications for Prenatal Diagnosis

Routine screening of the general population
Advanced maternal age (a patient who will be age 35 years or older at delivery)
Women with a previous trisomy
Major structural defect on ultrasound
Women with a previous pregnancy complicated by a gender chromosome aneuploidy
Male or female chromosomal translocation
Male or female carrier of a chromosomal inversion
Parental aneuploidy


In 1952, metabolic disorders were first demonstrated to be the result of an absence of a normally functioning enzymatic or structural protein.5 Most of these metabolic disorders are inherited in an autosomal-recessive manner; approximately 0.8% of newborns have such a disorder.6 Couples who are both heterozygous carriers of an autosomal-recessive genetic trait have a 25% risk of a homozygous affected fetus in each pregnancy. The metabolic conditions amenable to prenatal diagnosis include mucopolysaccharidoses, mucolipidoses, sphyngolipidoses, lysosomal-storage forms of carbohydrate metabolic disorders, aminoacidopathies with cultured cell expression of a known enzymatic defect, and a growing list of heterogeneously classified disorders.1,7

Women who are either known or suspected carriers of an X-linked recessive disorder may wish to use prenatal diagnosis because of the potential risk of 50% of male offspring having the disorder in question. Carrier tests for X-linked conditions are difficult and in many cases are not completely reliable. Therefore, many women may choose to consider themselves carriers when test results are in doubt. Presently, only a few X-linked conditions (e.g., Fabry's syndrome, Hunter's syndrome, Menkes ' kinky hair syndrome, and Lesch-Nyhan syndrome) can be diagnosed by enzymatic analysis.1,5 Duchenne-type muscular dystrophy and classic hemophilia can be diagnosed by fetal blood aspiration and serum creatine phosphokinase determination.8 Other mothers may choose to undergo amniocentesis in order to identify the fetal gender by chromosomal study or to determine testosterone levels, electing to bear only girls, who will be unaffected.9

Back to Top


Maternal Screening

Maternal serum screening can identify pregnant women who are at an increased risk for having a baby with certain birth defects. Patient-specific risks for open spina bifida, Down syndrome and trisomy 18 (Edwards syndrome) (Fig. 1) can be determined by measuring the levels of certain proteins in maternal serum and combining those data with the patient's maternal age and clinical information.10 Women with a positive screen should be offered a definitive diagnostic test.

Fig. 1. Three-dimensional ultrasound showing typical pattern of trisomy 18. A clenched fist with the index finger overlapping the third and fourth fingers is distinctive of this disorder. Image courtesy of GE Medical Systems.

Serum Alpha-Fetoprotein

Until the mid-1980s, there was no way to identify younger women at risk of having children with Down syndrome. Down syndrome screening for younger women was initiated when researchers discovered that the mean level of maternal serum alpha-fetoprotein (AFP) in pregnancies complicated by Down syndrome is 0.7 multiples of the normal medium (MOM).2 AFP can also be used to detect at least 80% of open neural tube defects, such as spina bifida.

Alpha-Fetoprotein P X-tra/Triple Screen Test

Shortly after the associated between AFP and Down syndrome was established, it was found that higher levels of human chorionic gonadotropins (hCG) and lower levels of unconjugated estriol levels (uE3) were also associated with Down syndrome.2 These three markers were combined to make the Triple Screen Test. Together, these markers are combined with gestational age, maternal age, weight, race, number of fetuses (up to twins), and presence of maternal diabetes to provide patient-specific risks for open spina bifida, Down syndrome, and trisomy 18. The Triple Screen Test detects at least 80% of open neural tube defects and at least 60% of Down syndrome and trisomy 18.10 Although serum screening does not detect other aneuploidies with great frequency, the aneuploidies likely to be missed by serum screening usually are ultimately lethal (e.g., trisomy 13) or are gender-chromosome abnormalities not associated with profound mental retardation or other severe physical or developmental limitations.

Maternal blood sampling can be performed between 15 and 20 weeks of gestation but is most accurate when performed between 16 and 18 weeks of gestation. Accurate pregnancy dating is essential.

Alpha-Fetoprotein Tetra/Quad Screen

AFP tetra adds a fourth marker, dimeric inhibin A (DIA), to the AFP X-tra. AFP Tetra increases the detection efficiency of Down syndrome by approximately 15%, while slightly lowering the false-positive rate. DIA is a glycol protein hormone made by the ovary and placenta. DIA levels are twice as high in Down syndrome pregnancies.11 Unlike AFP, hCG, and uE3, DIA does not vary with gestational age, resulting in greater screening accuracy.

Pregnancy-Associated Plasma Protein-A and β-Human Chorionic Gonadotropin

Many maternal serum analytes have been evaluated for possible use for first-trimester Down syndrome screening.12 Pregnancy-associated plasma protein-A (PAPP-A) is a highly glycosylated, high molecular weight protein and is produced by the human placenta and released into maternal circulation during pregnancy.13 Maternal serum concentrations of PAPP-A have been found to be reduced in pregnancies affected by Down syndrome in the first trimester when compared to normal, unaffected pregnancy at the same gestational period. This reduction is most pronounced before the twelfth week of gestation. Later, serum concentrations in Down syndrome gradually reach the control range and, in the second trimester, PAPP-A does not distinguish between normal and Down syndrome pregnancy. Therefore, accurate gestational dating is needed.

In the less frequent cases of fetal trisomy 18 and 13, first trimester maternal serum PAPP-A is even more strongly reduced than in Down syndrome, and preliminary results indicate that in fetal trisomy 18 PAPP-A continues to be below the normal range, including in the early second trimester (weeks 15 to 20).

Early pregnancy maternal serum PAPP-A is also reduced in nonviable pregnancies and threatened abortion and is absent in the very rare Cornelia de Lange syndrome. In ectopic pregnancies, PAPP-A has also been found to be reduced.

β Subunit of hCG is also produced by the placenta. When combined with PAPP-A, a 65% detection rate for Down syndrome can be achieved, with a 5% false-positive rate. When PAPP-A and β-hCG are combined with an ultrasound obtained nuchal translucency (to be discussed later in the text), an 86% detection rate for Down syndrome with a 5% false-positive rate can be achieved, while providing results earlier in the pregnancy so that a woman may have the choice of chorionic villus sampling (CVS) or amniocentesis.14–18 Both of these procedures will be discussed in depth later in the chapter. The first trimester only screen also affords the chance for women to make personal decisions regarding prenatal diagnosis and termination earlier in the pregnancy.

Back to Top
Amniocentesis was introduced in the 1930s as a diagnostic aid for placental localization by amniography.19 It gained widespread acceptance as a technique in the prenatal diagnosis of genetic diseases in the 1950s, after successful reports of amniotic fluid analysis in cases of Rh isoimmunization.20–22

In 1956, Fuchs and Riis23 demonstrated the feasibility of fetal sex determination by examining X-chromatin bodies in amniotic fluid cells. The ability to culture amniotic fluid cells in tissue culture and to acquire sufficient viable cells for karyotype analysis and biochemical studies was demonstrated in 1966.24 A partial list of conditions that lend themselves to prenatal diagnosis by amniocentesis is found in Table 3; all of these disorders have ocular manifestations.

TABLE 3. Disorders Diagnosed by Amniocentesis with Ocular Manifestations

Chromosomal abnormalities
Down syndrome
Klinefelter's syndrome
Turner's syndrome
Neural tube defects
Metabolic diseases
Arginosuccinic aciduria
Fabry's disease
Farber's disease
Galactosemia, type I
Galactokinase deficiency
Gaucher's disease
GM1 (generalized) gangliosidosis
Glucose-6-phosphate dehydrogenase deficiency
Glycogen storage disease, type I
GM2 gangliosidosis, type I (Tay-Sachs)
GM2 gangliosidosis, type II (Sandhoff's)
Hunter's syndrome
Hurler's syndrome
Juvenile GM1 gangliosidosis
Krabbe's disease
Maple syrup urine disease
Maroteaux-Lamy syndrome
Metachromatic leukodystrophy (two forms)
Morquio's syndrome
Neimann-Pick disease (four types)
Refsum's disease
Sandhoff's disease
Sanfilippo's syndrome
Scheie's syndrome
Tay-Sachs disease
Xeroderma pigmentosum

From Spaeth GL, Nelson LB, Beadoin AR: Ocular teratology. In Duane TD, Jaeger EA, eds. Biomedical Foundations of Ophthalmology. Philadelphia, JB Lippincott, 1982.


Traditional genetic amniocentesis is usually offered between 15 and 20 weeks' gestation. Amniocentesis performed earlier has a higher complication rate, as well as more amniotic culture failures. It may be offered when prenatal maternal screening results are high risk for a genetic abnormality or as an elective diagnostic test such as in advanced maternal age or prior history of an aneuploidy (see Fig. 2).

Fig. 2. Left midabdomen of neonate shows indented area probably resulting from contact of the amniocentesis needle with the abdominal skin.

Many large, multicenter studies have confirmed the safety of genetic amniocentesis, as well as its cytogenetic diagnostic accuracy (greater than 99%).2 The fetal loss rate is approximately 0.5%, and minor complications occur infrequently. Table 4 lists known complications for amniocentesis.

TABLE 4. Complications and Their Incidence in Amniocentesis

Fetal loss 0.5%
Vaginal spotting 1%–2 %
Amniotic fluid leakage 1%–2%
Chorioanmionitis 0.1%
Needle injury rare (Fig. 2)
Amniotic fluid cell culture failure rare


The procedure is performed under ultrasound guidance. After obtaining informed consent, an ultrasound examinations is performed to establish fetal viability, placental and fetal location, and depth to the largest pocket of amniotic fluid (Fig. 3). The maternal abdomen is prepped aseptically and a local anesthetic may be administered. A small gauge needle is then used to aspirate approximately 10 to 20 mL of amniotic fluid. The availability of the results is dependent on the amount of time needed for cell culture growth but usually is available within 7 to 10 days. The results received are a full cytogenic karyotype.

Fig. 3. A and B: Withdrawal of amniotic fluid with 20-gauge needle and 30-mL syringe.

Fluorescent in situ hybridization (FISH) is a new technology utilizing fluorescently labeled DNA probes to detect or confirm gene or chromosome abnormalities.25,26 The sample DNA is first denatured, a process that separates the complementary strands within the DNA double helix structure. The fluorescently labeled probe of interest is then added to the denatured sample mixture and hybridizes with the sample DNA at the target site as it reforms itself back into a double helix. The probe signal can then be seen through a fluorescent microscope and the sample DNA scored for the presence or absence of the signal.

FISH can be used in interphase cells to determine the chromosome number or more chromosomes, as well as detect some specific chromosome rearrangements that are characteristic for certain cancers. The primary advantage of interphase FISH is that it can be performed rapidly if necessary, usually within 24 hours, because cell growth is not required.

A good example is the Aneuploid Screen Test that is performed on amniotic fluid cells when there is a strong clinical indication for one of the common trisomies. The sample nuclei are denatured and hybridized with DNA probes for chromosomes 13, 18, 21, X, and Y.


The indications for CVS are similar for amniocentesis, except for a few rare genetic conditions that require chorionic villi for diagnosis.2 CVS is generally performed at 10 to 12 weeks' gestation. Similar to other first trimester methods, CVS allows for results earlier that can provide reassurance or allow for earlier and safer methods of pregnancy termination. Similar to amniocentesis, CVS is performed under ultrasound guidance. It can be performed either transabdominally or transcervically (Fig 4). Table 5 lists the contraindications and relative contraindications for CVS.

TABLE 5. Contraindications and Relative Contraindications for Chorionic Villus Sampling

Active cervical infection (Chlamydia or herpes)—contraindicated
Vaginal infection—relative contraindication
Vaginal bleeding or spotting—relative contraindication
Extreme anteversion or retroversion of the uterus—relative contraindication
Patient body habitus linking visualization—relative contraindication


Fig. 4. Aspiration method of chorionic villi sampling. Ultrasound is used to localize the chorionic frondosum and guide the aspirating catheter into position. Syringe suction is used to trap and withdraw villi into the catheter.

Patients considering CVS should be counseled that there may be a slightly higher risk of pregnancy loss associated with CVS than with traditional amniocentesis. Pregnancy loss rates are reported to be 0.6% to 0.8% for CVS in excess of traditional amniocentesis. Loss may result from the procedure itself, but may incorporate the expected spontaneous loss rate between 9 and 16 weeks of gestation. According to the World Health Organization, the incidence of limb reduction defects are approximately 6 per 10,000, which is not significantly different from the incidence in the general population.2 Oromandibular-limb hypogenesis appeared to be more common with CVS, although highest when CVS is performed before 9 weeks' gestation.27–29 Similar to amniocentesis, cytogenetics can be available in 7 to 10 days (Fig. 5). FISH can also be used to provide a limited aneuploid screen in 24 hours.

Fig. 5. Freshly aspirated chorionic villi in tissue culture medium in a Petri dish. Note the branched structure.


Cordocentesis is also known as percutaneous umbilical blood sampling (PUBS). Under direct ultrasound guidance, the umbilical vein is punctured. This procedure cannot be performed before 18 weeks' gestation. A karyotype of fetal blood can be available within 24 to 48 hours. Procedure-related pregnancy loss is less than 2%. Cordocentesis is rarely used for cytogenetics. This procedure is utilized more to evaluate fetal platelets, Rh sensitivity, and to administer fetal medications.2


Diagnostic ultrasound is widely used in the assessment of pregnancy and the fetus. Although clinical benefits of routine ultrasonography during pregnancy have not been established, approximately 70% of pregnancies in the United States undergo ultrasound evaluation.30 Because most instruments used in diagnostic ultrasonography produce energies no greater than 10 to 20 mW cm2 (safety defined as less than 100 mW cm2), ultrasound is considered generally safe. No harmful biologic effects on instrument operators, pregnant women, fetuses, or other patients have been found. Infants exposed in utero have shown no significant differences in birth weight or length, childhood growth, cognitive function, acoustic or visual ability, or rates of neurologic deficits (see Fig. 6).

Fig. 6. A: First-trimester twin intrauterine gestations. Ultrasound examination of the pregnant uterus (arrowheads) shows the “owl eyes” characteristic of early twin pregnancies. B: Maternal urinary bladder. (Courtesy of Alfred B. Kurtz, MD)

Indications for ultrasound are listed in Table 6. There are several levels of ultrasound. A basic ultrasound suffices for most obstetric patients. Table 7 lists the components of a basic ultrasound. A comprehensive ultrasound may be indicated for a patient who is suspected of carrying a physiologically or anatomically defective fetus by history, clinical evaluation, or prior ultrasound examination. Because of the level of expertise needed, comprehensive examinations are usually performed at a tertiary center.

TABLE 6. Indications for Ultrasonography During Pregnancy

Estimation of gestational age for patients with uncertain clinical dates, or verification of dates for patients who are to undergo scheduled elective repeat cesarean delivery, indicated induction of labor, or other elective termination of pregnancy
Evaluation of fetal growth
Vaginal bleeding of undetermined etiology in pregnancy
Determination of fetal presentation
Suspected multiple gestation
Adjunct to amniocentesis
Significant uterine size/clinical dates discrepancy
Pelvic mass
Suspected hydatidiform mole
Adjunct to cervical cerclage placement
Suspected ectopic pregnancy
Adjunct to special procedures
Suspected fetal death
Suspected uterine abnormality
Intrauterine contraceptive device localization
Biophysical evaluation for fetal well-being
Observation of intrapartum events
Suspected polyhydramnios or oligohydramnios
Suspected abruption placentae
Adjunct to external version from breech to vertex presentation
Estimation of fetal weight and/or presentation in premature rupture of membranes and/or premature labor
Abnormal serum alpha-fetoprotein value
Follow-up evaluation of placental location for identified placenta previa
History of previous congenital anomaly
Serial evaluation of fetal growth in multiple gestation
Evaluation of fetal condition in late registrants for prenatal care

Adapted from U.S. Department of Health and Human Services. Diagnostic ultrasound in pregnancy. National Institutes of Health publication no. 84-667. Bethesda: National Institutes of Health, 1984.


TABLE 7. Components of Basic Ultrasound Examination

Fetal number (Fig. 6)
Fetal presentation
Documentation of fetal life
Placental location
Assessment of amniotic fluid volume
Assessment of gestation age
Survey of fetal anatomy for gross malformations
Evaluation for maternal pelvic masses



First trimester ultrasound may be performed transabdominally or transvaginally. Table 7 lists the components of a first trimester ultrasound. A crown–rump length, done between 7 and 13 weeks, can define a gestational age to within 5 days (Fig. 7).

Fig. 7. First trimester ultrasound showing crown–rump length.

Nuchal edema is an echo-free space between the skin line and the soft tissue overlying the cervical spine. Nuchal edema is caused by subcutaneous accumulation of fluid and has diverse etiology, including aneuploidies, cardiovascular and pulmonary defects, skeletal dysplasias, congenital infections, and hematologic and metabolic disorders. A nuchal translucency (NT) is obtained between 10 and 13 weeks' 6 days' gestational age (Fig. 8).31 A study at King's College Hospital in London found an NT of 3 mm was associated with a 4-times increase in the maternal age related risk for aneuploidy. An NT greater than 4 mm resulted in a 29 times increased risk for trisomies 21, 18, and 13. Additionally, with a 4 mm or more NT, there was a high incidence of other anomalies and poor prognosis, whereas with just 3 mm and a normal karyotype, the outcome was usually normal. Table 8 lists the disorders associated with an increased nuchal translucency thickness.

Fig. 8. Normal nuchal translucency of 0.19 cm at 11 weeks' gestation.

TABLE 8. Disorders Associated with Increased Nuchal Translucency

Down syndrome
Trisomy 18, 13
Turner syndrome
Cardiac septal defect
Diaphragmatic hernia
Noonan's syndrome
Smith-Lemli-Opitz syndrome
Stickler syndrome
Jarco-Levine syndrome
Miller-Dieker syndrome
Amnion disruption sequence
Various skeletal dysplasias


The First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening Study is looking at combining NT, maternal age, gestational age, PAPP-A, and β-hCG to calculate a Down syndrome and trisomy 18 risk by using computer software. Currently still under investigation, this method is widely used in Europe. Women who screen positive are then offered CVS or amniocentesis.


A second trimester ultrasound is usually done at 20 to 22 weeks' gestational age. The most commonly used fetal measurements are biparietal diameter, length of the femur or other long bones, and abdominal and head circumference. In addition to measurements, an anatomic survey is also done to evaluate the fetal brain (Fig. 9), spine, stomach, heart, kidneys, placental location and assessment of amniotic fluid (Fig. 10). If maternal risk factors are present, tetra screening results are abnormal, or there are abnormal findings on the anatomic survey, the patient is sent for a comprehensive ultrasound. The components of a comprehensive ultrasound are shown in Table 9. The ultrasound findings associated with Down syndrome include cardiac defects or enlargement, cystic hygroma (Fig. 11), duodenal atresia (Fig. 12), omphalocele, polyhydramnios, choroids plexus cyst, and renal calyceal dilation.

Fig. 9. Transaxial ultrasound of fetal heads.

Fig. 10. Third trimester ultrasound image showing fetal ocular anatomy.

TABLE 9. Components of a Comprehensive (Level II) Ultrasound

Fetal numberLocation
GenderCord vessels and insertion
Cardiac activityFluid
Cranial signs of neural tube defectUmbilical artery
Choroid plexusLeft uterine artery
VentriclesRight uterine artery
Four-chamber heartMiddle cerebral artery
Left ventricular outflow tract 
Right ventricular outflow tractMeasurements
DiaphragmBiparietal diameter
StomachHead circumference
KidneysFoot length
SpineOuter orbital diameter
Bowel echogenecityCerebellar diameter
Abdominal wall 
Facial profile 
LensesUterine/adnexal pathology
Fifth digit 
 Biophysical profile


Fig. 11. Early second trimester ultrasound showing posterior neck cystic mass consistent with cystic hygroma. Image courtesy of GE Medical Systems.

Fig. 12. Duodenal atresia in a second trimester fetus. A: Ultrasound scan of fetal abdomen (arrowheads) showing two fluid-filled structures (arrows). Increased amniotic fluid (polyhydramnios) surrounds the fetus. B: Newborn radiograph of upper abdomen demonstrating gas-filled stomach (S) and duodenum (D), which are typical findings of duodenal atresia. (Courtesy of Alfred B. Kurtz, MD)


Three-dimensional ultrasound is currently investigational. It is most commonly used at tertiary care centers and is commercially available for patients to obtain a keepsake image of their unborn child. Potential advantages include the ability to visualize fetal anatomy better and possibly change a patient's diagnosis through improved visibility (Figs. 13 and 14). No confirmed adverse biologic effects on patients or instrument operators caused by exposure have been demonstrated.32

Fig. 13. Three-dimensional ultrasound image showing midline facial cleft. Image courtesy of GE Medical Systems.

Fig. 14. Three-dimensional ultrasound image of twin gestation. Image courtesy of GE Medical Systems.


Magnetic resonance imaging (MRI) is currently under investigation for use in prenatal diagnosis. Advantages of MRI over ultrasound include excellent tissue contrast, a large field of view, and relative operator independence.33 Table 10 lists the indications of fetal MRI. One of the most successful areas has been in the evaluation on the brain and central nervous system.

TABLE 10. Indications of Fetal Magnetic Resonance Imaging

Central nervous systemTumors
HydrocephalusCervical teratomas
Mild, borderline ventricular dilationSacrococcygeal teratomas
Posterior fossa abnormalitiesIntracranial tumors
Migration abnormalitiesOther tumors
Suspected ischemia 
Vascular accidents, thrombosisPlacental abnormalities
TumorsInvasive placenta (accrete, increta, percreta)
Spinal abnormalitiesChorioangioma
TumorsMolar pregnancy
Spinal abnormalities 
Follow-up of prenatal surgeryTwins
 Twin transfusion syndrome
Thoracic abnormalitiesConjoined twins
Diaphragmatic hernia 
Cystic adenomatoid malformationMaternal conditions
SequestrationUnusual fibroids
 dnexal masses
Extremity, posturing abnormalitiesLiver, CNS abnormalities, HELLP syndrome
Limb body wallEvaluation of fetal well-being
 Fetal weight assessment
Abdominal abnormalitiesFetal CNS ischemia
Bowel obstruction 
Liver abnormalities, tumorsOther conditions
Abdominal wall defectsAbdominal pregnancy
 Tumors of any origin
 As replacement for early postnatal MRI

CNS, central nervous system; HELLP syndrome, hemolysis, elevated liver enzymes, and low platelet count syndrome; MRI, magnetic resonance imaging.



Genetic counselors serve as the link between the medical communities' increasing knowledge of genetics and a patient's understanding of genetic risk. A genetic counselor helps a health care provider and a patient understand the risks associated with birth defects and hereditary disorders through interpreting family history, laboratory results, and other medical information. Often times, a couple proceeds no further with diagnostic testing after receiving a risk assessment. Ideally, the couple planning pregnancy meets with a health care provider prior to pregnancy in order to assess risk.

Decisions at this time are as difficult as those after diagnosis of a live-born child with a genetic handicap, and similar psychologic reactions can occur.34 After abortion of an affected fetus, both parents—especially the mother—may also require supportive psychological counseling.35

Properly applied, prenatal diagnosis with attendant genetic counseling can be a powerful preventive medical tool. In the more personal sense, it frequently allows at-risk couples to have healthy children when they might otherwise forfeit the opportunity.

Back to Top

1. Jackson LG, Schimke RN: Clinical Genetics: A Source Book for Physicians. New York: John Wiley & Sons, 1979.

2. American College of Obstetricians and Gynecologists: Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists. Number 27. Washington, DC: American College of Obstetricians and Gynecologists, May 2001.

3. Smith DW, Patau K, Therman E: Autosomal trisomy syndromes. Lancet 2:211, 1961

4. Smith D: Autosomal abnormalities. Am J Obstet Gynecol 90:1055, 1964

5. Mikkelson M, Steve J: Genetic counseling in Down's syndrome. Hum Hered 20:457, 1970

6. Polani PE: Incidence of developmental and other genetic abnormalities. Proc R Soc Lond 66:1118, 1973

7. Milunsky A: Current concepts in genetics: prenatal diagnosis of genetic disorders. N Engl J Med 295:377, 1976

8. Mahoney MJ, Haseltine FP, Hobbins JC, et al: Prenatal diagnosis of Duchenne's muscular dystrophy. N Engl J Med 297:968, 1977

9. Simpson JL, Golbus MS, Martin AO, et al: Genetics in Obstetrics and Gynecology. New York: Grune & Stratton, 1982

10. American College of Obstetricians and Gynecologists: Maternal Serum Screening. Educational Bulletin Number 228. Washington, DC: American College of Obstetricians and Gynecologists, 1996

11. Haddow JL, Palomaki GF, Kinght GJ, et al: Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A. J Med Screen 5:115, 1998

12. Palomaki GE, Haddow JE, Knight GJ, et al: Risk based prenatal screening for trisomy 18 using alpha-fetoprotein, unconjugated oestriol and human chorionic gonaditropin. Prenat Diagn 15:713, 1995

13. Yaron Y, Heifetz S, Ochshorn Y, et al: Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome. Prenat Diagn 22:778, 2002

14. De Blasio P, Siccardi M, Volpe G, et al “First trimester screening for Down syndrome using nuchal translucency measurement with free β-hCG and PAPP-A between 10 and 13 weeks of pregnancy—The combined test. Prenat Diagn 19;360, 1999

15. Krantz DA, Hallahan TW, Orlandi F, et al: First trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol 96:207, 2000

16. Wald NJ, Kennard A, Smith D: First trimester biochemical screening for Down's syndrome. Ann Med 26:23, 1994

17. Wald NJ, Kennard A, Hacksaw AK: First trimester serum screening for Down's syndrome. Prenat Diagn 15:1227, 1995

18. Wald NJ, George L, Smith D, et al: Serum Screening for Down's Syndrome between 8 and 14 weeks of pregnancy. Br J Obstet Gynaecol 103:407, 1996

19. Menees TD, Miller JD, Holly LE: Amniography: preliminary report. Am J Roentgenol 24:363, 1930

20. Bevis DCA: Composition of liquor amnii in haemolytic disease of newborn. Lancet 2:443, 1950

21. Bevis DCA: The antenatal prediction of haemolytic disease of the newborn. Lancet 1:395, 1952

22. Nadler HL, Gerbie AB: Role of amniocentesis in the intrauterine detection of genetic disorders. N Engl J Med 282:596, 1970

23. Fuchs F, Riis P: Antenatal sex determination. Nature 177:330, 1956

24. Steele MW, Breg WT: Chromosome analysis of human amniotic fluid cells. Lancet 1:383, 1966

25. American College of Medical Genetics (ACMG): Technical and clinical assessment of flourescentce in situ hybridization: An ACMG/ASHG Position Statement. I. Technical considerations. Genet Med 2:356, 2000

26. Thein ATA, Abdel-Fattah SA, Kyle PM, et al: An assesment of the Use of Interphase FISH with Chromosome Specific Probes as an Alternative to Cytogenetics In Prenatal Diagnosis. Prenat Diagn 20:275-280, 2000.

27. Firth HV, Boyd PA, Chamberlain P, et al: Severe limb abnormalities after chorion villus sampling at 56–66 days' gestation. Lancet 337:762, 1991

28. Mahoney MJ: for the USNICHD Collaborative CVS Study Group: Limb abnormalities and chorionic villus sampling. Lancet 337:1422, 1991

29. Jackson LG, Zachary JM, Fowler SE, et al: A randomized comparison of transcervical and transabdominal chorionic-villus sampling. The U.S. National Institute of Child Health and Human Development Chorionic-Villus Sampling and Amniocentesis Study Group. N Engl J Med 327:594, 1992

30. American College of Obstetricians and Gynecologists: Technical Bulletin: An Educational Aid to Obstetrician-Gynecologists. Number 187. Washington, DC: American College of Obstetricians and Gynecologists, Washington, DC: American College of Obstetricians and Gynecologists, December 1993

31. Pandya PP, Bizrot ML, Kuhn P, et al: First-trimesterfetal nuchal translucency thickness and risk for trisomies. Obstet Gynecol 84:40, 1994

32. The AIUM takes a stand against using ultrasound for entertainment. J Ultrasound Med 19:10, 2002

33. Blaicher W, Bernaschek G, Deutinger J, et al: Fetal and early postnatal magnetic resonance imaging—Is there a difference? J Perinat Med 32:53, 2004

34. Jackson LG: Prenatal genetic counseling. Prim Care 3:710, 1976

35. Blumberg BD, Golbus MS, Hanson KH: The psychological sequelae of abortion performed for a genetic indication. Am J Obstet Gynecol 122:799, 1975

Back to Top