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A screening history is part of routine prenatal care. The history is summarized as a pedigree (see Fig. 1: General Principles of Medical Genetics: Symbols for constructing a family pedigree.). Information should include the health status and presence of genetic disorders or carrier status of both parents, of 1st-degree relatives (parents, siblings, offspring), and of 2nd-degree relatives (aunts, uncles, grandparents), as well as ethnic and racial background and consanguineous matings. Outcomes of previous pregnancies are noted. If genetic disorders are suspected, relevant medical records must be reviewed.

Genetic screening tests are offered to parents at risk of being asymptomatic carriers for certain common mendelian disorders (see Table 1: Prenatal Genetic Counseling and Evaluation: Genetic Screening for Some Ethnic Groups). Diagnostic tests for specific abnormalities are offered to parents when appropriate (see Table 2: Prenatal Genetic Counseling and Evaluation: Indications for Fetal Genetic Diagnostic Tests).

Table 1
Genetic Screening for Some Ethnic Groups Ethnic Group Disorder Screening Tests Prenatal Diagnosis All Cystic fibrosis* DNA analysis of 25 CFTR mutations, which are present in ≥ 0.1% of the US population CVS or amniocentesis for genotype determination† Ashkenazi Jews‡ Canavan disease DNA analysis to detect most common mutations CVS or amniocentesis for DNA analysis   Familial dysautonomia DNA analysis to detect most common mutations CVS or amniocentesis for DNA analysis   Tay-Sachs disease Measurement of serum hexosaminidase A to check for deficiency; possibly DNA analysis CVS or amniocentesis for enzymatic assays or molecular analysis to check for hexosaminidase A; DNA analysis Blacks Sickle cell anemia Screening tests for sickle cell hemoglobin, confirmatory hemoglobin electrophoresis CVS or amniocentesis for genotype determination (direct DNA analysis) Cajuns Tay-Sachs Measurement of serum hexosaminidase A to check for deficiency; possibly DNA analysis CVS or amniocentesis for enzymatic assays or molecular analysis to check for hexosaminidase A Mediterranean people β-Thalassemia MCV < 80%, followed by hemoglobin electrophoresis CVS or amniocentesis for genotype determination (direct DNA analysis or linkage analysis) Southeast Asians, Cambodians, Chinese, Filipinos, Laotians, Vietnamese α-Thalassemia MCV < 80%, followed by hemoglobin electrophoresis CVS or amniocentesis for genotype determination (direct DNA analysis or linkage analysis) *Should be offered to whites and Ashkenazi Jews; should be made available to other ethnic groups (eg, Asians, Hispanics, blacks). † Definitive diagnosis is not always possible; sensitivity varies by ethnic group. ‡For Ashkenazi Jews, some experts also recommend screening for Gaucher's disease, Niemann-Pick disease type A, Fanconi's anemia (syndrome) group C, Bloom syndrome, and mucolipidosis IV. Most (90%) Jews are Ashkenazi; thus, Jews who do not know whether they are Ashkenazi should be screened. CVS = chorionic villus sampling; MCV = mean corpuscular volume.

Table 2
Indications for Fetal Genetic Diagnostic Tests Indication Comment Maternal age > 35 at expected delivery   Recurrent previous spontaneous abortions Chromosomal analysis may be indicated for parents Chromosomal abnormality in a previous child Chromosomal analysis may be indicated for parents Paternal age > 50 Need for testing is controversial Parental chromosomal disorder Balanced parental chromosomal abnormalities may not require testing Parental sex-linked mendelian disorder   Autosomal recessive mendelian disorder diagnosed or suspected in both parents   Levels of maternal serum markers* suggesting trisomy 21 or 18 Chorionic villus sampling, sometimes with ultrasound measurement of nuchal translucency, during the 1st trimester or amniocentesis during the 2nd trimester is done Elevated maternal α-fetoprotein and indeterminate ultrasound results Amniocentesis is done *Measured during 1st or 2nd trimester.

Between 15 and 20 wk gestation, pregnant women should be offered screening using multiple maternal serum markers (α-fetoprotein, β-human chorionic gonadotropin, estriol, inhibin A—see Prenatal Genetic Counseling and Evaluation: Maternal Serum Screening) to detect neural tube defects, Down syndrome, and some other birth defects.

Fetal genetic diagnostic tests, unlike screening tests, are usually invasive and involve fetal risk. Genetic diagnostic tests are usually done via chorionic villus sampling, amniocentesis, or percutaneous umbilical blood sampling. These tests can detect all trisomies, many other chromosomal abnormalities, and > 100 mendelian abnormalities. Preimplantation diagnosis is not yet commonly used.

Ultrasonography

Some experts recommend conventional ultrasonography for all pregnant women. Others use ultrasonography only for specific indications, such as checking for suspected genetic or obstetric abnormalities or helping interpret abnormal maternal serum marker levels.

Ultrasonography is noninvasive and has no known risks to the woman or fetus. It can confirm gestational age, determine fetal viability, and detect multiple pregnancy. During the 2nd or 3rd trimester, ultrasonography may identify major malformations in the fetal intracranial structures, spine, heart, bladder, kidneys, stomach, thorax, abdominal wall, long bones, and umbilical cord. Although ultrasonography provides only structural information, some structural abnormalities strongly suggest genetic abnormalities. Multiple malformations may suggest a chromosomal disorder.

High-resolution ultrasonography may be indicated for couples with a family history of a congenital malformation (eg, congenital heart defects, cleft lip and palate, pyloric stenosis), particularly one that may be treated effectively before birth (eg, posterior urethral valves with megacystis) or at delivery (eg, diaphragmatic hernia). High-resolution ultrasonography may also be used if maternal serum marker levels are abnormal. High-resolution ultrasonography may allow detection of renal malformations (eg, renal agenesis [Potter's syndrome], polycystic kidney disease), lethal forms of short-limbed skeletal dysplasias (eg, thanatophoric skeletal dysplasia, achondrogenesis), gut malformations (eg, obstruction), diaphragmatic hernia, microcephalus, and hydrocephalus. If ultrasonography is done by skilled operators, sensitivity for major congenital malformations is high. However, some conditions (eg, oligohydramnios, maternal obesity, fetal position) interfere with obtaining optimal images.

Amniocentesis

In amniocentesis, a needle is inserted transabdominally into the amniotic sac to withdraw amniotic fluid and fetal cells for testing, including measurement of chemical markers (eg, α-fetoprotein, acetylcholinesterase—see Prenatal Genetic Counseling and Evaluation: Maternal Serum Screening). The safest time for amniocentesis is after 14 wk gestation. Immediately before amniocentesis, ultrasonography is done to assess fetal cardiac motion and determine gestational age, placental position, amniotic fluid location, and fetal number. If the mother has Rh-negative blood and is unsensitized, Rh₀(D) immune globulin 300 μg is given after the procedure to reduce the likelihood of sensitization (see Abnormalities of Pregnancy: Prevention). Amniocentesis has traditionally been offered to pregnant women > 35 because their risk of having an infant with Down syndrome or another chromosomal abnormality is increased.

Occasionally, the amniotic fluid obtained is bloody. Usually, the blood does not affect amniotic cell growth and is maternal; however, if the blood is fetal, it may falsely elevate amniotic fluid α-fetoprotein level. Dark red or brown fluid indicates previous intra-amniotic bleeding and an increased risk of fetal loss. Green fluid, which usually results from meconium staining, does not appear to indicate increased risk of fetal loss.

Amniocentesis rarely results in significant maternal morbidity (eg, symptomatic amnionitis). With experienced operators, risk of fetal loss is about 0.2 to 0.3%. Vaginal spotting or amniotic fluid leakage, usually self-limited, occurs in 1 to 2% of women tested.

Chorionic Villus Sampling

In chorionic villus sampling (CVS), chorionic villi are aspirated into a syringe and cultured. CVS provides the same information about fetal genetic and chromosomal status as amniocentesis and has similar accuracy. However, CVS is done between 10 wk gestation and the end of the 1st trimester and thus provides earlier results. Therefore, if needed, pregnancy may be terminated earlier (and more safely and simply), or if results are normal, parental anxiety may be relieved earlier. Unlike amniocentesis, amniotic fluid is not obtained at the time of CVS and measurement of α-fetoprotein cannot be performed.

Depending on placental location (identified by ultrasonography), CVS can be done by passing a catheter through the cervix or by inserting a needle through the woman's abdominal wall. After CVS, Rh₀(D) immune globulin 300 μg is given to Rh-negative unsensitized women.

Errors in diagnosis due to maternal cell contamination are rare. Detection of certain chromosomal abnormalities (eg, tetraploidy) may not reflect true fetal status but rather mosaicism confined to the placenta. Consultation with experts familiar with these abnormalities is advised. Rarely, subsequent amniocentesis is required to obtain additional information.

Rate of fetal loss due to CVS is similar to that of amniocentesis (ie, 0.2 to 0.3%). Transverse limb defects and oromandibular-limb hypogenesis have been attributed to CVS but are exceedingly rare if CVS is done after 10 wk gestation by an experienced operator.

Percutaneous Umbilical Blood Sampling

Fetal blood samples can be obtained by percutaneous puncture of the umbilical cord vein (funipuncture) via ultrasound guidance. Chromosome analysis can be completed in 48 to 72 h. This test is especially useful late in the 3rd trimester, particularly if fetal abnormalities are first suspected at this time. Procedure-related fetal loss rate is about 1%.

Preimplantation Diagnosis

Genetic diagnosis is sometimes possible before implantation; polar bodies from oocytes, blastomeres from 6- to 8-cell embryos, or a trophectoderm sample from the blastocyst is used. These tests are available only in specialized centers and are used primarily for couples with a high risk of certain mendelian disorders (eg, cystic fibrosis) or chromosomal abnormalities. Newer techniques may reduce costs and make such tests more widely available.

Last full review/revision November 2005

Content last modified November 2005