This Practice Advisory was developed by the American College of Obstetricians and Gynecologists with the assistance of Ahizechukwu C. Eke, MD, MPH, PhD; Manisha Gandhi, MD; Anjali J. Kaimal, MD, MAS; Michelle Moniz, MD, MSc; and Andrea Shields, MD, MS.
This Practice Advisory serves as an update to Practice Bulletin No. 78, Hemoglobinopathies in Pregnancy, originally published in 2007 1 .
The American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin No. 78, Hemoglobinopathies in Pregnancy, reviews the most common hemoglobinopathies and provides recommendations regarding screening and clinical management of hemoglobinopathies in pregnancy 1 . This Practice Advisory provides updated guidance regarding universal hemoglobinopathy testing, screening echocardiogram, and low-dose aspirin.
Universal Hemoglobinopathy Testing
Previous recommendations for hemoglobinopathy testing have used a race/ethnicity-based strategy 1 2 3 . However, race and self-identified ethnicity are poor proxies for genetics since self-identification with a specific race/ethnicity may be incompatible with genetic ancestry 4 . Given that approximately 1 in 66 people in the United States have a hemoglobinopathy trait 5 6 , ACOG recommends offering universal hemoglobinopathy testing to persons planning pregnancy or at the initial prenatal visit if no prior testing results are available for interpretation. This helps ensure that at-risk individuals receive counseling about genetic risks; learn their reproductive options, which include preimplantation genetic testing and prenatal diagnosis 5 7 ; and make informed decisions. Hemoglobinopathy testing may be performed using hemoglobin electrophoresis or molecular genetic testing (eg, expanded carrier screening that includes sickle cell disease [SCD] and other hemoglobinopathies). The use of noninvasive prenatal diagnosis for SCD with cell-free fetal DNA is still experimental 8 9 and currently not recommended.
Screening Echocardiogram
Sickle cell disease is characterized by complex chronic vascular disorders, pulmonary arterial hypertension (PAH), ventricular diastolic dysfunction, and heart failure 10 11 . Elevated peak tricuspid regurgitant jet velocity, as measured by Doppler (transthoracic echocardiogram tricuspid regurgitant jet velocity, 2.5 m/s or greater), is common among adults with SCD, can be predictive of PAH, and is associated with an increased risk of mortality in SCD 12 . The prevalence of PAH in pregnant individuals with SCD is not known. The American Society of Hematology guidelines recommend echocardiogram for patients with SCD who have dyspnea or hypoxemia at rest or with exertion, chest pain at rest or with exertion, exercise limitation, sleep disordered breathing with or without hypoxemia, a history of syncope or pre-syncope, signs of heart failure or fluid overload on examination, or a history of pulmonary embolism 13 . Based on this, ACOG recommends that reproductive-aged people with SCD with a personal history of pulmonary embolism or signs or symptoms of hypoxia undergo screening with transthoracic Doppler echocardiography due to the increased risk of pulmonary hypertension. For patients with symptoms, a screening echocardiogram before pregnancy is recommended because further evaluation, including right heart catheterization, is ideally performed prior to pregnancy and confirmation of PAH may impact the advisability of pregnancy. However, if a screening echocardiogram cannot be obtained prior to pregnancy, it can be performed in early pregnancy to estimate resting mean pulmonary arterial pressures. Abnormal echocardiographic findings should be co-managed by a multidisciplinary team, including consultants with expertise in SCD 14 .
Low-Dose Aspirin
The rate of preeclampsia in pregnant women with SCD is approximately 1 in 8 (12%) 15 compared with 1 in 25 (4%) for pregnancies not impacted by SCD in the United States 16 . Women with SCD also have an increased risk of gestational hypertension and eclampsia 17 . There is no specific evidence that aspirin decreases the risk of preeclampsia in persons with SCD, and therefore this population was not included in the most recent (2021) United States Preventive Services Task Force (USPSTF) systematic review on aspirin use to prevent preeclampsia 18 . However, the USPSTF guideline recommends giving low-dose aspirin after 12 weeks of gestation to pregnant individuals with an absolute risk of preeclampsia of at least 8%, the lowest incidence of preeclampsia in control groups of studies included in their review. In view of the increased risk of hypertensive diseases in pregnant individuals with SCD, low-dose aspirin prophylaxis (81 mg/d) may be considered and initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) for those individuals with no contraindications to aspirin. Aspirin therapy should be continued until the time of delivery.
References
- Hemoglobinopathies in pregnancy. ACOG Practice Bulletin No. 78. American College of Obstetricians and Gynecologists. Obstet Gynecol 2007;109:229-37. doi: 10.1097/00006250-200701000-00055.
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- Carrier screening for genetic conditions. Committee Opinion No. 691. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e41-55. doi: 10.1097/AOG.0000000000001952.
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- Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e35-40. doi: 10.1097/AOG.0000000000001951.
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- Duello TM, Rivedal S, Wickland C, Weller A. Race and genetics versus 'race' in genetics: a systematic review of the use of African ancestry in genetic studies [published erratum appears in Evol Med Public Health 2021;9:289-91]. Evol Med Public Health 2021;9:232-45. doi: 10.1093/emph/eoab018.
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- Pecker LH, Naik RP. The current state of sickle cell trait: implications for reproductive and genetic counseling. Blood 2018;132:2331-8. doi: 10.1182/blood-2018-06-848705.
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- Gregg AR, Aarabi M, Klugman S, Leach NT, Bashford MT, Goldwaser T, 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 erratum appears in Genet Med 2021;23:2015]. Genet Med 2021;23:1793-806. doi: 10.1038/s41436-021-01203-z.
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- Early ML, Strodel RJ, Lake IV, Ruddy JA, Saba JA, Singh SM, et al. Acceptable, hopeful, and useful: development and mixed-method evaluation of an educational tool about reproductive options for people with sickle cell disease or trait. J Assist Reprod Genet 2022;39:183-93. doi: 10.1007/s10815-021-02358-z.
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- Erlich HA, López-Peña C, Carlberg KT, Shih S, Bali G, Yamaguchi KD, et al. Noninvasive prenatal test for β-thalassemia and sickle cell disease using probe capture enrichment and next-generation sequencing of DNA in maternal plasma. J Appl Lab Med 2022;7:515-31. doi: 10.1093/jalm/jfab118.
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- van Campen J, Silcock L, Yau S, Daniel Y, Ahn JW, Ogilvie C, et al. A novel non-invasive prenatal sickle cell disease test for all at-risk pregnancies. Br J Haematol 2020;190:119-24. doi: 10.1111/bjh.16529.
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- Gordeuk VR, Castro OL, Machado RF. Pathophysiology and treatment of pulmonary hypertension in sickle cell disease. Blood 2016;127:820-8. doi: 10.1182/blood-2015-08-618561.
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- Wood KC, Gladwin MT, Straub AC. Sickle cell disease: at the crossroads of pulmonary hypertension and diastolic heart failure. Heart 2020;106:562-8. doi: 10.1136/heartjnl-2019-314810.
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- Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 2011;365:44-53. doi: 10.1056/NEJMoa1005565.
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- Liem RI, Lanzkron S, D Coates T, DeCastro L, Desai AA, Ataga KI, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease. Blood Adv 2019;3:3867-97. doi: 10.1182/bloodadvances.2019000916.
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- Pecker LH, Sharma D, Nero A, Paidas MJ, Ware RE, James AH, et al. Knowledge gaps in reproductive and sexual health in girls and women with sickle cell disease. Br J Haematol 2021;194:970-9. doi: 10.1111/bjh.17658.
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- Chang JN, Magann EF, Novotny SA, Cooley CE, Gauss CH, Parrish MR, et al. Maternal/perinatal outcome in women with sickle cell disease: a comparison of two time periods. South Med J 2018;111:742-5. doi: 10.14423/SMJ.0000000000000900.
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- Henderson JT, Thompson JH, Burda BU, Cantor A. Preeclampsia screening: evidence report and systematic review for the US Preventive Services Task Force. JAMA 2017;317:1668-83. doi: 10.1001/jama.2016.18315.
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- Lari NF, DeBaun MR, Oppong SA. The emerging challenge of optimal blood pressure management and hypertensive syndromes in pregnant women with sickle cell disease: a review. Expert Rev Hematol 2017;10:987-94. doi: 10.1080/17474086.2017.1379895.
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- Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, Davis EM, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force. JAMA 2021;326:1186-91. doi: 10.1001/jama.2021.14781.
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The American College of Obstetricians and Gynecologists recognizes and supports the gender diversity of all patients who seek obstetric and gynecologic care. In original portions of this document, authors seek to use gender-inclusive language or gender-neutral language. When describing research findings, this document uses gender terminology reported by investigators. To review ACOG's policy on inclusive language, see www.acog.org/clinical-information/policy-and-position-statements/statements-of-policy/2022/inclusive-language.
A Practice Advisory is a brief, focused statement issued to communicate a change in ACOG guidance or information on an emergent clinical issue (eg, clinical study, scientific report, draft regulation). A Practice Advisory constitutes ACOG clinical guidance and is issued only on-line for Fellows but may also be used by patients and the media. Practice Advisories are reviewed periodically for reaffirmation, revision, withdrawal or incorporation into other ACOG guidelines. This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary. This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It is not intended to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology. The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its publications may not reflect the most recent evidence. Any updates to this document can be found on www.acog.org/clinical.
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