Процедури пренатальної діагностики

Some experts recommend ultrasonography routinely 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. 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. Ultrasonography is noninvasive and has no known risks to the woman or fetus.

Basic ultrasonography is done to

• Confirm gestational age

• Determine fetal viability

• Detect a multifetal pregnancy

• During the 2nd or 3rd trimester, possibly 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.

Targeted ultrasonography, with high-resolution ultrasonography equipment, is available at certain referral centers and provides more detailed images than basic ultrasonography. This test 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 the following:

• Renal malformations (eg, renal agenesis [Potter syndrome], polycystic kidney disease)

• Lethal forms of short-limbed skeletal dysplasias (eg, thanatophoric skeletal dysplasia, achondrogenesis)

• Gut malformations (eg, obstruction)

• Diaphragmatic hernia

• Microcephaly

• Hydrocephalus

During the 2nd trimester, identifying structures that are statistically associated with increased risk of fetal chromosomal abnormalities helps refine risk estimate.

In amniocentesis, a needle is inserted transabdominally, using ultrasonographic guidance, into the amniotic sac to withdraw amniotic fluid and fetal cells for testing, including measurement of chemical markers (eg, alpha-fetoprotein, acetylcholinesterase). The safest time for amniocentesis is after 14 weeks 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, Rho (D) immune globulin 300 mcg is given after the procedure to help prevent Rh sensitization.

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. However, with the widespread availability and improved safety of amniocentesis, the American College of Obstetricians and Gynecologists recommends all pregnant women be offered amniocentesis to assess the risk of fetal chromosomal disorders.

Occasionally, the amniotic fluid obtained is bloody. Usually, the blood is maternal, and amniotic cell growth is not affected; however, if the blood is fetal, it may falsely elevate amniotic fluid alpha-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 0.1 to 0.2%. Vaginal spotting or amniotic fluid leakage, usually self-limited, occurs in 1 to 2% of women tested. Amniocentesis done before 14 weeks gestation, particularly before 13 weeks, results in a higher rate of fetal loss and an increased risk of talipes equinovarus (clubbed feet) and is rarely done.

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 weeks 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, CVS does not enable clinicians to obtain amniotic fluid, and alpha-fetoprotein cannot be measured. Thus, women who have CVS should be offered maternal screening for serum alpha-fetoprotein at 16 to 18 weeks to assess risk of fetal neural tube defects.

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, Rho(D) immune globulin 300 mcg 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. Confined placental mosaicism is detected in about 1% of CVS specimens. 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, about 0.2%). Transverse limb defects and oromandibular-limb hypogenesis have been attributed to CVS but are exceedingly rare if CVS is done after 10 weeks gestation by an experienced operator.

Fetal blood samples can be obtained by percutaneous puncture of the umbilical cord vein (funipuncture) using ultrasound guidance. Chromosome analysis can be completed in 48 to 72 hours. For this reason, percutaneous umbilical blood sampling (PUBS) was formerly often done when results were needed rapidly. This test was especially useful late in the 3rd trimester, particularly if fetal abnormalities were first suspected at that time. Now, genetic analysis of amniotic fluid cells or chorionic villi via interphase fluorescent in situ hybridization (FISH) allows preliminary diagnosis (or exclusion) of more common chromosomal abnormalities within 24 to 48 hours, and PUBS is rarely done for genetic indications.

Procedure-related fetal loss rate with PUBS is about 1%.

Preimplantation genetic testing (PGT) is sometimes possible before implantation when in vitro fertilization is done; 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 expensive. However, newer techniques may reduce costs and make such tests more widely available.

There are 3 forms of PGT:

• PGT-M: Testing for monogenic (ie, single-gene) abnormalities

• PGT-A: Testing for aneuploidy

• PGT-SR: Testing for structural rearrangements such as unbalanced translocations

PGT-M is used primarily for couples when the risk of certain mendelian disorders (eg, cystic fibrosis) in the fetus is high. PGT-A or PGT-SR is used for couples when chromosomal abnormalities in the fetus is a risk.

PGT-A is used primarily for embryos from older women, but routine use is controversial (1). In a large multicenter randomized trial, ongoing pregnancy rates using frozen-thawed single embryo transfer after PGT-A or after morphologic evaluation did not differ significantly (2).