During pregnancy, recommended tests can include blood tests, ultrasounds, amniocentesis, and chorionic villus sampling. These screen for various conditions, primarily related to the fetus.
Prenatal diagnosis of fetal disorders and structural malformations is becoming increasingly important as approximately 3% of all pregnancies have a genetic disorder or birth defect. Such anomalies are also the biggest cause of infant mortality in the United States.
Genetic disorders are caused by changes in a person’s DNA, located on genes or chromosomes.
Aneuploidy is a condition in which there are missing or extra chromosomes. In a trisomy, there is an extra chromosome. In a monosomy, a chromosome is missing. Inherited disorders are caused by changes in genes called mutations. Inherited disorders include sickle cell disease, cystic fibrosis, Tay-Sachs disease, and many others. In most cases, both parents must carry the same gene to have an affected child.
Types of prenatal tests
There are two types of prenatal tests for genetic disorders. Both screening and diagnostic testing are offered to all pregnant women.
- Prenatal screening tests. These tests can tell you the chances that your fetus has aneuploidy and a few other disorders. They include tests to determine if one or more of the parents carry a gene defect – called carrier screening – and the other detects fetal gene mutations – called prenatal genetic screening tests.
- Prenatal diagnostic tests. These tests tell you whether your fetus actually has certain disorders. Maternal blood tests and ultrasounds to examine anatomy are two such tests. There are also tests done on cells from the fetus or placenta obtained through amniocentesis or chorionic villis sampling (CVS). They include first-trimester screening, second-trimester screening, combined first- and second-trimester screening, and cell-free DNA testing.
Prenatal screening tests
Screening tests look for various fetal metabolic, chromosomal, and anatomic defects.
First-trimester screening tests may include the following:
- Beta human chorionic gonadotropin (β-hCG) is the pregnancy hormone measured in the urine and blood to detect and diagnose pregnancy. β-hCG levels lower than expected for presumed gestation can be due to an ectopic pregnancy or threatened abortion.
- Pregnancy-associated plasma protein-A (PAPP-A) is used to detect trisomy 18 and 21 cases (in conjunction with β-hCG and ultrasonography for nuchal (neck) translucency.
Second-trimester screening tests may include the following:
- Maternal serum alpha-fetoprotein (MSAFP).
- Serum β-hCG.
- Unconjugated estriol (uE3).
- Inhibin A.
- Maternal hexosaminidase test.
- Fetal cells in maternal circulation.
The “triple screen” includes MSAFP, serum β-hCG, and uE3. Adding inhibin A results in the “quadruple screen.” The panel findings, along with gestational age, can suggest a number of fetal abnormalities.
Table 1. Patterns of Triple Screen Test Results and Their Interpretations (Medscape)
|Condition||MSAFP level||uE3 level||hCG level|
|Molar pregnancy||Low||Low||Very high|
|Fetal death (stillbirth)||Increased||Low||Low|
Prenatal diagnostic tests
Diagnostic tests are indicated when conditions that increase the risk of chromosomal anomaly are present or suspected which may be the case for advanced maternal age 35 and over), or abnormal findings on fetal ultrasonography (US). Genetic counseling is essential to prenatal diagnosis.
First-trimester diagnostic tests may include the following:
- Fetal US.
- Chorionic villus sampling-sampling of the placenta to evaluate chromosomes.
- Early amniocentesis-sampling of amniotic fluid to evaluate chromosomes.
- Pre-implantation biopsy: performed before implantation to diagnosis a fetus of parents with substantial risk of a known genetic disorder and in women with repeated miscarriages due to chromosomal translocation.
- Coelocentesis is performed around 10 weeks and is considered investigational because of reportedly high rates of pregnancy loss.
Second-trimester diagnostic tests may include the following:
- Mid-trimester amniocentesis.
- Percutaneous umbilical blood sampling or cordocentesis.
- Late chorionic villus sampling.
- Fetal muscle and liver biopsy.
Diagnostic imaging modalities include the following:
- US: Most valuable modality for identifying fetal and/or placental structural anomalies.
- Magnetic resonance imaging (MRI): Important adjunct to ultrasonography.
- Computed tomography (CT): Not used in most cases.
- Fetal magnetocardiography.
Causes of an elevated MSAFP level include the following:
- More advanced gestational age.
- Multiple gestations.
- Neural tube defects (NTDs) or spina bifida.
- Open abdominal wall defects.
- Renal diseases such as congenital nephrosis, infantile polycystic disease, and bilateral renal agenesis.
- Skin diseases such as ectodermal dysplasia and aplasia cutis congenital.
- Cystic adenomatoid malformation of the lung.
- Maternal liver and ovarian tumors.
- Uterine and placental anomalies.
- Uterine and placental anomalies. Fetomaternal hemorrhage.
- Fetal demise.
Causes of low MSAFP levels include the following:
- Trisomy 13.
- Trisomy 18.
- Trisomy 21.
Fetal disorders that require treatment include the following:
- Neural tube defects.
- Congenital adrenal hyperplasia.
- Thyroid excess.
- Low thyroid.
- Methylmalonic acidemia.
- Multiple carboxylase deficiency.
- Lung prematurity.
- Lung prematurity. Maternal HIV infection.
- Immune hydrops.
- Fetal thrombocytopenia (low platelets).
- Fetal hemoglobinopathies, immune deficiency diseases, inborn errors of metabolism.
- Congenital heart disease.
- Certain fetal arrhythmias-abnormal electrical pulses that trigger the pumping of the heart.
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