Protocols for High-Risk Pregnancies. Группа авторов
For a couple where one partner is Ashkenazi Jewish, the person of Ashkenazi Jewish background should be tested first. Counseling regarding residual risk should be performed, particularly whenever screening an individual without Ashkenazi Jewish ancestry, due to the potential to be a carrier of a rare mutation.
In the case of screening for Tay–Sachs disease, DNA‐based mutation analysis is highly effective for those in high‐risk populations. However, the serum or leukocyte hexosaminidase enzymatic activity (the enzyme that is deficient in those affected by Tay–Sachs disease) can be used to distinguish carriers from noncarriers in a manner that is not specific to ethnic background. Because it is not mutation specific, biochemical analysis is more sensitive and therefore preferred for screening for Tay–Sachs disease among individuals of nonhigh‐risk ancestry.
Table 10.1 Recommended carrier screening for individuals of Ashkenazi Jewish backgrounds
| American College of Obstetricians and Gynecologists | American College of Medical Genetics and Genomics |
|---|---|
| Cystic fibrosis | Cystic fibrosis |
| Tay–Sachs disease | Tay–Sachs disease |
| Familial dysautonomia | Familial dysautonomia |
| Canavan disease | Canavan disease |
| Fanconi anemia (group C) | |
| Niemann–Pick disease (type A) | |
| Bloom syndrome | |
| Mucolipidosis IV | |
| Gaucher disease |
Management and follow‐up
Carrier screening is optional. It is critical that patient counseling be performed and consent be obtained prior to screening. In the context of expanded panels, for which all conditions cannot be specifically addressed, this education should include a description of the general types of conditions being screened and their common clinical features. Patients should be informed of the potential benefits of acquiring information and the availability of preimplantation genetic diagnosis, donor gametes, prenatal diagnosis and management, coordination of postnatal care, pregnancy termination, and adoption services. There should be a clear process for post‐test counseling and offering of screening to the patient’s reproductive partner or diagnostic testing of the pregnancy in the setting of a positive result. The limitations of carrier screening, including the concept of residual risk and the evolving landscape of expanded panels, should be explained in advance of screening. Efforts should be made to ensure confidentiality of genetic screening results. It is important to note that carrier screening can complement, but does not replace, state‐mandated newborn screening.
Conclusion
Preconception carrier screening is being offered for an increasing number of genetic conditions and to a broadening population of patients. It is incumbent on providers to stay abreast of the types of screening offered through clinical and commercial laboratories. We must educate pregnant women and those considering pregnancy on the availability of screening. As screening expands, so must our pretest and post‐test counseling surrounding the potential benefits and risks of this screening and the implications and follow‐up for both positive and negative results. Professional guidelines should continue to be updated to reflect scientific developments and the changing role of carrier screening.
Suggested reading
1 American College of Obstetricians and Gynecologists. Carrier screening for genetic conditions. Committee Opinion 691. Obstet Gynecol 2017; 129:e41–55.
2 American College of Obstetricians and Gynecologists. Family history as a risk assessment tool. Committee Opinion 478. Obstet Gynecol 2011; 117:747–50.
3 American College of Obstetricians and Gynecologists. Carrier screening in the age of genomic medicine. Committee Opinion 690. Obstet Gynecol 2017; 129:e35–40.
4 Brennan ML, Schrijver I. Cystic fibrosis: a review of associated phenotypes, use of molecular diagnostic approaches, genetic characteristics, progress, and dilemmas. J Mol Diagn 2016; 18:3–14.
5 Edwards J, Feldman G, Goldberg J, et al. Expanded carrier screening in reproductive medicine – points to consider. A joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal‐Fetal Medicine. Obstet Gynecol 2015; 125:653–62.
6 Hoffman JD, Park JJ, Schreiber‐Agus N, et al. The Ashkenazi Jewish carrier screening panel: evolution, status quo, and disparities. Prenat Diagn 2014; 34:1161–7.
7 Hussein N, Weng SF, Kai J, Kleijnen J, Qureshi N. Preconception risk assessment for thalassemia, sickle cell disease, cystic fibrosis, and Tay–Sachs disease. Cochrane Database Syst Rev 2015;( 8):CD010849.
8 Kraft SA, Duenas D, Wilifond BS, Goddard KAB. The evolving landscape of expanded carrier screening: challenges and opportunities. Genet Med 2019; 21:790–7.
9 MacDonald WK, Hamilton D, Kuhle S. SMA carrier testing: a meta‐analysis of differences in test performance by ethnic group. Prenat Diagn 2014; 34:1219–26.
10 Nolin SL, Brown WT, Glicksman A, et al. Expansion of the fragile X CGG repeat in females with permutation or intermediate alleles. Am J Hum Genet 2003; 72:454–64.
11 Vrettou C, Kakourou G, Mamas T, Traeger‐Synodinos J. Prenatal and preimplantation diagnosis of hemoglobinopathies. Int J Lab Hematol 2018; 40:74–82.
PROTOCOL 11 Maternal Anemia
Elaine Duryea
Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA
A comprehensive review of all causes of anemia may be intimidating, and many available algorithms are not high yield when evaluating pregnant women. The protocol presented here provides an algorithm for the initial evaluation of anemia in pregnancy, with treatment algorithms for the most common causes in pregnancy. Women who do not meet one of the definitions provided below are best managed in consultation with a hematologist.
Definition
During a singleton gestation, plasma volume doubles (increasing approximately 1000 mL) and red blood cell (RBC) volume increases by 25% (300 mL), with RBC production lagging slightly behind plasma expansion. This results in a physiological dilutional anemia of pregnancy, which reaches a nadir during the late second to early third trimester (Table 11.1). The Centers for Disease Control and Prevention (CDC) define anemia as a hemoglobin (Hb) below the fifth centile for a healthy, iron‐supplemented population. This translates to a threshold of Hb less than 11 g/dL in the first and third trimesters, and less than 10.5 g/dL during the second trimester. Rates of anemia in pregnancy vary widely between different populations and socioeconomic classes.
Consequences