Carrier testing is part of routine prenatal care and is ideally done before conception. The extent of carrier testing is related to how the woman and her partner weigh factors such as
The probability of a fetal abnormality based on risk factors and the results of any previous testing
The probability of a complication from invasive fetal testing
The importance of knowing the results (eg, would the pregnancy be terminated if an abnormality was diagnosed, would not knowing the results cause anxiety)
For these reasons, the decision is individual, and recommendations often cannot be generalized to all women, even those with similar risk.
A screening history is part of the evaluation. The history is summarized as a pedigree (see figure ). Information should include the health status and presence of genetic disorders or carrier status of both parents, of first-degree relatives (parents, siblings, offspring), and of second-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.
Testing potential parents for a genetic carrier state that may result in affected offspring is best done before conception; however, many people wait until after conception to have carrier screening. Traditionally, screening tests are offered to parents at risk of being asymptomatic carriers for certain common mendelian disorders (see table ). Because parent ethnicity is often complex and not well-defined and because prenatal genetic testing is becoming much less expensive and quicker, some clinicians are starting to screen all potential (and expectant) parents, regardless of ethnicity (called universal carrier screening). Therefore, current approaches to carrier screening include offering all patients the same larger list of conditions to be evaluated. Often, dozens of genes and disorders (some with more severe phenotypic consequences than others) are included (1 General references Carrier testing is part of routine prenatal care and is ideally done before conception. The extent of carrier testing is related to how the woman and her partner weigh factors such as The probability... read more ). Increasing the amount of testing and evaluation is expected to increase the complexity of pre-test counseling. The American College of Medical Genetics and Genomics recommends a tiered carrier screening system based on carrier frequency and has provided tables listing disorders to be included in carrier screening panels (2 General references Carrier testing is part of routine prenatal care and is ideally done before conception. The extent of carrier testing is related to how the woman and her partner weigh factors such as The probability... read more ).
(See also Prenatal Genetic Counseling Prenatal Genetic Counseling Prenatal genetic counseling is provided for all prospective parents, ideally before conception, to assess risk factors for genetic disorders. In addition, prenatal counseling provides information... read more .)
General references
1. American College of Obstetricians and Gynecologists/Committee on Genetics: Committee opinion no. 690: Carrier Screening in the age of genomic medicine. Obstet Gynecol 129 (3):e35–e40, 2017. doi: 10.1097/AOG.0000000000001951
2. Gregg AR, Aarabi M, Klugman S, et al: Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: A practice resource of the American College of Medical Genetics and Genomics (ACMG). [published correction appears in Genet Med 2021 Aug 27]. Genet Med 23(10):1793-1806, 2021. doi:10.1038/s41436-021-01203-z
Prenatal Testing to Detect Fetal Genetic Abnormalities
After conception, pregnant women should be offered noninvasive screening tests for fetal chromosomal disorders using one of several methods (eg, ell-free DNA serum tests, analyte screening) (1 Testing references Carrier testing is part of routine prenatal care and is ideally done before conception. The extent of carrier testing is related to how the woman and her partner weigh factors such as The probability... read more ). If such a screening test is positive, it may be followed up with fetal diagnostic genetic testing, which are invasive tests using a sample of fetal cells (see table ). These diagnostic tests provide a definitive diagnosis of genetic abnormalities. Additionally, if screening of either parent (done before or after conception) detects a genetic abnormality, pregnant patients may choose to do fetal genetic diagnostic tests (eg, chorionic villous sampling or amniocentesis) without first doing a noninvasive fetal screening test (eg, cfDNA or serum screening).
Screening tests for fetal chromosomal disorders include screening for fetal Down syndrome Down Syndrome (Trisomy 21) Down syndrome is an abnormality of chromosome 21 that can cause intellectual disability, microcephaly, short stature, and characteristic facies. Diagnosis is suggested by physical anomalies... read more , trisomy 18 Trisomy 18 Trisomy 18 is caused by an extra chromosome 18 and is usually associated with intellectual disability, small birth size, and various congenital anomalies, including severe microcephaly, heart... read more , and trisomy 13 Trisomy 13 Trisomy 13 is caused by an extra chromosome 13 and causes abnormal forebrain, midface, and eye development; severe intellectual disability; heart defects; and small birth size. Diagnosis is... read more with analysis of cell-free DNA First-Trimester Screening Noninvasive prenatal screening for genetic disorders, unlike invasive testing, has no risk of test-related complications. Noninvasive maternal screening can help women decide whether to have... read more (cfDNA) in maternal plasma, which can be done as early as 10 weeks gestation. Another screening method, called analyte screening, uses multiple maternal serum markers Maternal serum screening for neural tube defects Noninvasive prenatal screening for genetic disorders, unlike invasive testing, has no risk of test-related complications. Noninvasive maternal screening can help women decide whether to have... read more (alpha-fetoprotein, beta-human chorionic gonadotropin [beta-hCG], estriol, inhibin A) to detect neural tube defects Maternal serum screening for neural tube defects Noninvasive prenatal screening for genetic disorders, unlike invasive testing, has no risk of test-related complications. Noninvasive maternal screening can help women decide whether to have... read more , Down syndrome Down Syndrome (Trisomy 21) Down syndrome is an abnormality of chromosome 21 that can cause intellectual disability, microcephaly, short stature, and characteristic facies. Diagnosis is suggested by physical anomalies... read more (and other chromosomal abnormalities), and some other birth defects. Analyte screening is done at 15 to 20 weeks gestation.
Fetal genetic diagnostic tests are usually recommended if risk of a fetal chromosomal abnormality is increased (see table ). Fetal genetic diagnostic tests, unlike screening tests, are usually invasive and involve fetal risk. Thus, in the past, these tests were not routinely recommended for women without risk factors or a known genetic abnormality in one of the parents. However, because fetal genetic diagnostic tests are now more widely available and safety has improved, it is recommended to offer fetal genetic testing to all pregnant patients, regardless of risk.
Fetal genetic diagnostic tests include chorionic villus sampling Chorionic Villus Sampling Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more , amniocentesis Amniocentesis Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more , or, rarely, percutaneous umbilical blood sampling Percutaneous Umbilical Blood Sampling Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more . In addition, for pregnancies conceived through assisted reproductive technologies (eg, in vitro fertilization), preimplantation genetic diagnosis is an option.
Fetal genetic diagnostic tests can detect all trisomies, many other chromosomal abnormalities, and several hundred mendelian abnormalities. Submicroscopic chromosomal abnormalities are missed by traditional karyotype testing and can be identified only by microarray technologies, such as array comparative genomic hybridization and single nucleotide polymorphism (SNP)-based arrays. Array comparative genomic hybridization in prenatal testing is most frequently used to evaluate fetuses with structural abnormalities. Arrays detect numeric chromosome abnormalities (eg, trisomies) as well as unbalanced structural chromosome disorders, such as microdeletions. Studies have reported about 6% incidence of array abnormalities that would have been missed with traditional karyotyping in structurally abnormal fetuses.
Preimplantation genetic diagnosis Preimplantation Genetic Testing (PGT) Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more may be available for partners who are using in vitro fertilization In vitro fertilization (IVF) Assisted reproductive technologies (ARTs) involve manipulation of sperm and ova or embryos in vitro with the goal of producing a pregnancy. For assisted reproductive technologies, oocytes and... read more .
Testing references
1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine: Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020;136(4):e48-e69. doi:10.1097/AOG.0000000000004084
Drugs Mentioned In This Article
Drug Name | Select Trade |
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human chorionic gonadotropin |
Novarel, Ovidrel, Pregnyl |