Prenatal screening and testing for hemoglobinopathy
- Amber M Yates, MD
Amber M Yates, MD
- Assistant Professor of Pediatrics
- Baylor College of Medicine
- Section Editors
- Louise Wilkins-Haug, MD, PhD
Louise Wilkins-Haug, MD, PhD
- Section Editor — Prenatal Diagnosis and Genetics
- Professor of Obstetrics, Gynecology, and Reproductive Biology
- Harvard Medical School
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
The hemoglobinopathies can be divided into two general types: the thalassemias (which are disorders of decreased globin chain production) and the hemoglobin structural variants (eg, hemoglobin S, hemoglobin C); a combination of the two is also possible.
The purpose of prenatal hemoglobinopathy screening is to identify and counsel asymptomatic individuals whose offspring are at risk of an inherited hemoglobinopathy. Prenatal diagnosis of fetal hemoglobinopathy is offered when the fetus is at risk of being affected. The purpose is to allow parents to make reproductive choices based on this information and, in the case of alpha-thalassemia major, to monitor the pregnancy for nonimmune hydrops fetalis and potentially intervene. The clinical sequelae of other hemoglobinopathies manifest later in life and have no adverse effects on the fetus, mother, or neonate.
Sickle cell disease and thalassemia are among the most common genetic diseases worldwide. Over 1 percent of couples are at risk for having an affected newborn . (See "Methods for hemoglobin analysis and hemoglobinopathy testing", section on 'Types of abnormalities'.)
United States — The frequency of carrier conditions for hemoglobinopathies is higher in blacks than in whites, but all racial/ethnic populations in the United States have individuals who carry sickle cell trait . Data from state newborn screening programs showed that 1.5 percent of all infants screened in 2010 had sickle cell trait . The incidence of sickle cell trait was 73.1 per 1000 African American infants, 6.9 per 1000 Hispanic infants, 3 per 1000 white infants, and 2.2 per 1000 Asian, Native Hawaiian, or other Pacific Islander infants screened. Approximately 30 percent of African Americans have alpha thalassemia minor .
In the US, the incidence of sickle cell disease has remained relatively stable (SS disease 1 in 3721 newborns, SC disease 1 in 7386 newborns ); however, the prevalence of individuals with hemoglobinopathy, particularly thalassemia, is changing because of the immigration of new ethnic groups, some of whom are carriers of hemoglobinopathies that had been rare in the United States, and the increasing number of pregnancies among couples with different ethnicities in this country [5-7]. This has led to births of infants with hemoglobinopathies that previously had not been seen and from diverse ethnicities.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86:480.
- Ojodu J, Hulihan MM, Pope SN, et al. Incidence of sickle cell trait--United States, 2010. MMWR Morb Mortal Wkly Rep 2014; 63:1155.
- Pierce HI, Kurachi S, Sofroniadou K, Stamatoyannopoulos G. Frequencies of thalassemia in American blacks. Blood 1977; 49:981.
- Therrell BL, Hannon WH. National evaluation of US newborn screening system components. Ment Retard Dev Disabil Res Rev 2006; 12:236.
- Pearson HA, Cohen AR, Giardina PJ, Kazazian HH. The changing profile of homozygous beta-thalassemia: demography, ethnicity, and age distribution of current North American patients and changes in two decades. Pediatrics 1996; 97:352.
- Michlitsch J, Azimi M, Hoppe C, et al. Newborn screening for hemoglobinopathies in California. Pediatr Blood Cancer 2009; 52:486.
- Vichinsky EP, MacKlin EA, Waye JS, et al. Changes in the epidemiology of thalassemia in North America: a new minority disease. Pediatrics 2005; 116:e818.
- Lorey FW, Arnopp J, Cunningham GC. Distribution of hemoglobinopathy variants by ethnicity in a multiethnic state. Genet Epidemiol 1996; 13:501.
- Cao A, Saba L, Galanello R, Rosatelli MC. Molecular diagnosis and carrier screening for beta thalassemia. JAMA 1997; 278:1273.
- Vichinsky EP. Changing patterns of thalassemia worldwide. Ann N Y Acad Sci 2005; 1054:18.
- Piel FB, Patil AP, Howes RE, et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet 2013; 381:142.
- Colah R, Surve R, Nadkarni A, et al. Prenatal diagnosis of sickle syndromes in India: dilemmas in counselling. Prenat Diagn 2005; 25:345.
- Wang X, Seaman C, Paik M, et al. Experience with 500 prenatal diagnoses of sickle cell diseases: the effect of gestational age on affected pregnancy outcome. Prenat Diagn 1994; 14:851.
- Kaufmann JO, Demirel-Güngör G, Selles A, et al. Feasibility of nonselective testing for hemoglobinopathies in early pregnancy in The Netherlands. Prenat Diagn 2011; 31:1259.
- Committee on Genetics. Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol 2017; 129:e41.
- Ahmed S, Saleem M, Modell B, Petrou M. Screening extended families for genetic hemoglobin disorders in Pakistan. N Engl J Med 2002; 347:1162.
- Sirichotiyakul S, Maneerat J, Sa-nguansermsri T, et al. Sensitivity and specificity of mean corpuscular volume testing for screening for alpha-thalassemia-1 and beta-thalassemia traits. J Obstet Gynaecol Res 2005; 31:198.
- Lafferty JD, Barth DS, Sheridan BL, et al. Prevalence of thalassemia in patients with microcytosis referred for hemoglobinopathy investigation in Ontario: a prospective cohort study. Am J Clin Pathol 2007; 127:192.
- Ryan K, Bain BJ, Worthington D, et al. Significant haemoglobinopathies: guidelines for screening and diagnosis. Br J Haematol 2010; 149:35.
- de Montalembert M, Guilloud-Bataille M, Ducros A, et al. Implications of prenatal diagnosis of sickle cell disease. Genet Couns 1996; 7:9.
- Rowley PT, Loader S, Sutera CJ, et al. Prenatal screening for hemoglobinopathies. III. Applicability of the health belief model. Am J Hum Genet 1991; 48:452.
- Li Y, Di Naro E, Vitucci A, et al. Detection of paternally inherited fetal point mutations for beta-thalassemia using size-fractionated cell-free DNA in maternal plasma. JAMA 2005; 293:843.
- Ho SS, Chong SS, Koay ES, et al. Noninvasive prenatal exclusion of haemoglobin Bart's using foetal DNA from maternal plasma. Prenat Diagn 2010; 30:65.
- Phylipsen M, Yamsri S, Treffers EE, et al. Non-invasive prenatal diagnosis of beta-thalassemia and sickle-cell disease using pyrophosphorolysis-activated polymerization and melting curve analysis. Prenat Diagn 2012; 32:578.
- Zafari M, Kosaryan M, Gill P, et al. Non-invasive prenatal diagnosis of β-thalassemia by detection of the cell-free fetal DNA in maternal circulation: a systematic review and meta-analysis. Ann Hematol 2016; 95:1341.
- Leung KY, Cheong KB, Lee CP, et al. Ultrasonographic prediction of homozygous alpha0-thalassemia using placental thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone or in combination? Ultrasound Obstet Gynecol 2010; 35:149.
- Li X, Zhou Q, Zhang M, et al. Sonographic markers of fetal α-thalassemia major. J Ultrasound Med 2015; 34:197.
- Kuliev A, Rechitsky S, Verlinsky O, et al. Preimplantation diagnosis of thalassemias. J Assist Reprod Genet 1998; 15:219.
- Kuliev A, Rechitsky S, Verlinsky O, et al. Preimplantation diagnosis and HLA typing for haemoglobin disorders. Reprod Biomed Online 2005; 11:362.
- GENE FREQUENCY
- United States
- Global data
- - Thalassemia
- - Hemoglobin S, C, E
- RATIONALE FOR PRECONCEPTIONAL HEMOGLOBINOPATHY COUNSELING, PRENATAL SCREENING, AND PRENATAL DIAGNOSIS
- IDENTIFYING AT-RISK PARENTS
- Candidates for screening
- PRENATAL DIAGNOSIS
- During pregnancy
- Prior to implantation
- GENETIC COUNSELING
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS