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.
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 .
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.