SMFM Consult Series

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Society for Maternal-Fetal Medicine Consult

Series #68: Sickle cell disease in pregnancy
Society for Maternal-Fetal Medicine; Rachel G. Sinkey, MD; Foluso J. Ogunsile, MD; Julie Kanter, MD; Cynthia Bean, MD;
and Mara Greenberg, MD; Society for Maternal-Fetal Medicine Publications Committee

Pregnant individuals with sickle cell disease have an increased risk of maternal and perinatal morbidity
and mortality. However, prepregnancy counseling and multidisciplinary care can lead to favorable
maternal and neonatal outcomes. In this consult series, we summarize what is known about sickle cell
disease and provide guidance for sickle cell disease management during pregnancy. The following are
Society for Maternal-Fetal Medicine recommendations:

1. We recommend that patients with sickle cell disease be managed by a multidisciplinary team
that includes maternal-fetal medicine, hematology (ideally a hematologist specializing in sickle
cell disease), genetics, pain management, and social work or behavioral health (as appropriate)
starting in early pregnancy (best practice).
2. We recommend that pregnant patients with sickle cell disease receive all routinely recom-
mended antenatal vaccinations in addition to meningococcal and pneumococcal vaccinations
if due (GRADE 1A).
3. We recommend prenatal vitamins without iron unless iron deficiency is confirmed and initiation
of 4 mg of folic acid for pregnant patients with sickle cell disease (GRADE 1B).
4. We recommend fetal growth surveillance every 4 weeks beginning in the 28th week of gestation
(GRADE 1C).
5. For patients with uncomplicated sickle cell disease and a normally grown fetus, we suggest
weekly or twice-weekly antenatal testing beginning at 32 to 34 weeks of gestation. For patients
with complicated sickle cell disease (i.e., maternal hypertension, vaso-occlusive crises, fetal
growth restriction, or other coexisting complication), we suggest initiating individualized
antenatal testing at diagnosis or at a gestational age when delivery would be considered if
results are abnormal (GRADE 2B).
6. We recommend following evidence-based guidelines for the management of chronic and acute
pain during pregnancy (best practice).
7. We suggest the use of prophylactic transfusions be individualized for high-risk patients with
sickle cell disease in accordance with American Society of Hematology guidelines and directed
by a hematologist and maternal-fetal medicine subspecialist in shared decision-making with
the patient (GRADE 2B).
8. We recommend shared decision-making occur regarding the use of hydroxyurea in pregnancy,
in conjunction with a sickle cell disease specialist and maternal-fetal medicine subspecialist,
accounting for the timing of use and individual disease severity (GRADE 1C).
9. We recommend that reliable contraception be offered to patients with sickle cell disease to
decrease the risk of an unintended pregnancy and associated maternal and perinatal risks
(GRADE 1B).
Key words: antenatal surveillance, disparities, fetal growth restriction, hemoglobinopathy, hydroxy-
urea, maternal morbidity, maternal mortality, pain management, perinatal outcomes, prepregnancy
counseling, transfusion, vaso-occlusive crisis

Introduction significant blood disorder.1,2 Pregnant individuals with SCD

Sickle cell disease (SCD) is an autosomal recessive hemo- have an increased risk of maternal and perinatal morbidity
globinopathy and the most common inherited, clinically and mortality.3 However, prepregnancy counseling and
multidisciplinary care can lead to favorable maternal and
Corresponding author: The Society for Maternal-Fetal Medicine neonatal outcomes.4 High-level evidence to guide SCD
Publications Committee. [email protected]

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management in pregnancy is sparse. This consult series How is sickle cell disease diagnosed?
presents the best available evidence to manage this com- The recommended laboratory techniques for detecting he-
plex disease process during pregnancy and outlines op- moglobinopathies are hemoglobin electrophoresis and
portunities for research to help enhance available evidence DNA molecular testing.7,12 Genetic testing of the beta-
for future advances in perinatal SCD care. globin gene is the most accurate method of diagnosis, but
it requires a specialized laboratory, is more expensive, and
What are the pathophysiologic and is usually reserved for special situations (i.e., conflicting
epidemiologic characteristics of sickle cell protein method results). The methods that only test for the
disease? presence of sickle cells (e.g., sickle cell prep) do not detect
SCD occurs as a result of a single amino acid change of noneS hemoglobin variants and are inadequate to distin-
glutamic acid to valine in the beta-globin subunit of hemo- guish between SCT, SCD, and compound heterozygous
globin.5 In stressful environments in those with SCD, red states, such as HbSC disease.13 There are many expanded
blood cells (RBCs) polymerize into a more elongated sickle carrier screening panels that evaluate for hemoglobinopa-
or S shape prone to hemolysis, endothelial adhesion, and thies; however, the preferred tests for the diagnosis of SCD
subsequent vaso-occlusion. or trait are a CBC with RBC indices and a hemoglobin
Approximately 100,000 persons in the United States have electrophoresis.13
SCD; globally, approximately 300,000 neonates are born
with SCD each year.2 SCD is particularly common among What are the manifestations of sickle cell
people whose ancestors came from sub-Saharan Africa; disease?
Spanish-speaking regions in the Western Hemisphere Vaso-occlusion and chronic hemolysis occur at baseline
(South America, the Caribbean, and Central America); Saudi resulting in anemia, endothelial dysfunction, and inflam-
Arabia; India; and Mediterranean countries (Turkey, Greece, mation. Repeated episodes of vaso-occlusion, hemolysis,
and Italy). In the United States, 1 in 365 neonates described and anemia can cause chronic organ complications for
as African American or Black are diagnosed with SCD.6 individuals with SCD (Figure). When vaso-occlusion results
Importantly, race should not be used in isolation as an in tissue ischemia, this is commonly called a “vaso-
assessment for genetic risk.7 Several genotypes result in the occlusive crisis (VOC)” or “acute painful episode.” VOCs
phenotypic expression of SCD. The most common form in are acute painful complications of SCD and the most
the United States is homozygous S or HbSS disease. Other commonly reported reason individuals with SCD present
common genotypes include the compound heterozygotes to emergency departments.14 Vaso-occlusive episodes
of HbS beta plus thalassemia (HbSbþ), HbS beta null thal- cost the US healthcare system more than $800 million in
assemia (HbSb0), and HbSC. Although people with HbSS 2016.15 Patients typically present with severe back, chest,
and HbSb0 often experience a more severe clinical course, or extremity pain. In general, triggers may include infec-
individuals with all types of SCD are at risk of severe tion, extreme temperatures, dehydration, acidosis, and
complications.8e10 hypoxia; however, the specific triggers for a VOC are often
If 2 unaffected carriers of an S allele (sickle cell trait [SCT]) unknown.16 Isolated vaso-occlusive events characterized
produce an offspring, the offspring has a 25% chance of by pain without evidence of organ dysfunction are referred
being unaffected (not a carrier), a 50% chance to be a car- to as uncomplicated VOC. In contrast, a complicated VOC
rier, and a 25% chance to have SCD. refers to pain in addition to an acute organ-based
complication of SCD, such as acute chest syndrome
Who should be screened for sickle cell (ACS), stroke, hepatic or splenic sequestration, or osteo-
disease? myelitis. Other acute complications of SCD are presented
In 1996, the US Preventive Services Task Force recom- in Table 1.
mended screening for SCD in all newborns.11 By 2006,
newborn screening was required and implemented in all What is the life expectancy of a person with
50 states and the District of Columbia. However, people sickle cell disease?
with SCT, thalassemia trait, or hemoglobin C disease Chronic organ complications, such as renal and cardiopul-
may be unaware of their status. As recommended by the monary disease, along with ACS, are the leading causes of
American College of Obstetricians and Gynecologists, all death for adults with SCD.20 Advances in management have
patients presenting for prepregnancy or prenatal care drastically increased the life span of persons with SCD.21
should be offered a complete blood count (CBC) with With the introduction of universal newborn screening,
RBC indices and hemoglobin electrophoresis testing.7 penicillin prophylaxis for children with SCD, and hydroxy-
Those diagnosed with SCT or disease should have urea, among other interventions, persons in the United
their partner undergo hemoglobinopathy evaluation to States with SCD have a median life expectancy of 58
assess the risk of SCD or other hemoglobinopathies to years.22 Since 1980, the life expectancy of persons with
their offspring. SCD has more than doubled, significantly increasing the

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FIGURE
SCD clinical complications

Reprinted with permission from Kato et al.17

SCD, sickle cell disease.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

prevalence of reproductive-aged women and pregnancy in age neonate (RR, 3.72),24 and preterm birth (RR, 2.21).24
this special population.21 Moreover, risks of stillbirth (OR, 4.05) and neonatal death
(OR, 2.71) are increased.25
What adverse maternal and perinatal In addition, individuals with SCD may be burdened by
outcomes are associated with sickle cell conditions, such as fatigue, depression, and anxiety, that
disease in pregnancy? negatively affect their quality of life and emotional well-be-
Pregnancies in patients with SCD are associated with adverse ing.28 These conditions may potentially be exacerbated
maternal and perinatal outcomes.23 Mortality is significantly during pregnancy and the postpartum period.
increased in pregnant patients with SCD compared with
pregnant patients without SCD. Worldwide maternal mortality Which patients with sickle cell disease face
for those with SCD has increased 10- to 18-fold compared the highest risk of mortality associated with
with those without SCD, with risk attenuated to a 3- to 4-fold pregnancy?
increase in high-income countries.24,25 ACS and pneumonia Pregnant patients with SCD have an increased risk of
occur in 6.5% of pregnant women with SCD, with pulmonary maternal and perinatal complications, including death.
causes contributing to 88% of maternal deaths in patients Given the unequivocal increased risk of maternal morbidity
with SCD.26 Severe morbidities are associated with SCD in and mortality, reproductive options (including abortion)
pregnancy, including bacterial infections (odds ratio [OR], should be discussed with all pregnant patients with
2.48),25 pulmonary thromboembolism (relative risk [RR], SCD.24-26 Patients with SCD should be supported in making
7.74),26 and pulmonary hypertension (OR, 6.3).26 In addition, an informed decision regarding their reproductive options in
obstetrical complications are increased in pregnant patients a shared decision-making process in consultation with
with SCD, including preeclampsia (RR, 2.06),24 eclampsia maternal-fetal medicine (MFM) subspecialists and hema-
(OR, 3.02),25 cesarean delivery (OR, 1.54),25 abruption (OR, tologists with expertise in SCD, as appropriate. Most preg-
1.6),27 and preterm labor (OR, 1.4).27 nant patients will have a successful outcome; however,
Perinatal risks are similarly increased in pregnancies there are certain patients with SCD in whom pregna-
complicated by SCD, including fetal growth restriction (OR, ncy significantly increases the risk of maternal death.
2.79),25 low birthweight (OR, 2.00),25 small-for-gestational- Specifically, pulmonary hypertension and significant

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TABLE 1
Clinical manifestations of sickle cell disease by organ system
Organ system Complication Clinical pearl
Neurologic Moyamoya disease, stroke Maintain high index of suspicion in the setting of
excruciating headaches, seizures, weakness, visual
disturbance, or altered mental status.
Ophthalmologic Visual changes, vitreous hemorrhage, retinal artery Urgently refer to ophthalmology in the setting of visual
stroke or occlusion changes.a
Pulmonary Pneumonia, pulmonary embolus, pulmonary O2 saturation, CXR, and/or CT pulmonary angiogram
hypertension, acute chest syndrome recommended for new pulmonary complaints.
Cardiac Cardiomegaly, cardiomyopathy, heart failure Low threshold to obtain echocardiogram for otherwise
unexplained cardiopulmonary complaints.
Hematologic Vaso-occlusive crises Hydration, O2 to keep O2 saturation 95%, investigate
and treat potential causes, treat pain per ASH guidelines
(Table 4).18
Vascular Deep venous thrombosis Evaluate complaints of calf pain or lower extremity size
discordance with venous Doppler ultrasound.
Skeletal Avascular necrosis, especially of the femoral head New pain with weight-bearing should be evaluated with a
radiograph; MRI without contrast may be considered if
radiograph normal.
Hepatic Hepatitis, cholecystitis, infarction, venous thrombosis Right upper quadrant pain and/or jaundice should be
evaluated with a comprehensive laboratory evaluation
(complete blood count with differential and either [1]
comprehensive metabolic panel or [2] basic metabolic
panel and liver function tests) and imaging, starting with a
right upper quadrant ultrasound with Doppler.
Abdominal Splenomegaly, splenic sequestration, splenic infarcts, Abdominal pain can be evaluated with an abdominal
thrombosis, pancreatitis examination and laboratory evaluation, including a
complete blood count, amylase or lipase, and liver and
renal panel. Imaging starting with abdominal ultrasound
is reasonable.
Genitourinary Hematuria, pyelonephritis Genitourinary symptoms should initially be evaluated with
a urinalysis and urine culture.
Skin Ulcerations Wound care should be provided to patients with
ulcerations; ulcers should be monitored for signs of
cellulitis with low threshold to prescribe antibiotics.
Obstetrical Preeclampsia, preterm labor, abruption Maintain high index of suspicion for obstetrical
complications. Use low-dose aspirin for preeclampsia risk
reduction.19
ASH, American Society of Hematology; CT, computed tomography; CXR, chest x-ray; MRI, magnetic resonance imaging.
a
If visual changes are attributed to preeclampsia, and if symptoms resolve after delivery, urgent ophthalmology referral can be deferred.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

cardiomyopathies classified as modified World Health What is the prepregnancy and pregnancy
Organization class IV diseases are contraindications to management for a patient with sickle cell
pregnancy.29 In addition, the inability to receive blood disease?
products because of severe alloimmunization and lack of There are 4 general categories of evaluation and counseling
available matched blood and other rare and severe com- for the patient with SCD who is pregnant or contemplating
plications of SCD that confer additional risks of morbidity pregnancy: prepregnancy counseling, baseline maternal
and mortality (e.g., moyamoya syndrome) should be assessment, medication assessment, and genetic coun-
identified and incorporated into individualized counseling seling. We recommend that patients with SCD be managed by a
with a high degree of caution against attempting or multidisciplinary team that includes maternal-fetal medicine,
continuing a pregnancy. hematology (ideally a hematologist specializing in SCD), genetics,

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pain management, and social work or behavioral health (as care may be needed, particularly for young patients with
appropriate) starting in early pregnancy (Best Practice).30-32 SCD previously managed by pediatric hematologists.

What prepregnancy and early pregnancy Baseline medication assessment

care specific to sickle cell disease should Many individuals with SCD are on several medications for
be provided? disease treatment and pain management. Many medica-
Prepregnancy counseling tions may be safely continued during pregnancy, whereas
Prepregnancy counseling allows a patient with SCD the others should be switched to a safer alternative or dis-
opportunity to make an informed decision regarding preg- continued. Table 3 outlines common medications used in
nancy after consideration of the maternal and fetal risks and SCD management and principles of management for the
the potential risks to the offspring. Reproductive planning pregnant patient. Recommendations regarding medication
options that reduce fetal risks include preimplantation ge- continuation must account for the patient’s disease severity
netics and using donor egg or sperm (screened for hemo- and desires after discussing risks, benefits, and alternatives.
globinopathies). However, in vitro fertilization and donor egg New evidence emerges regularly; referencing perinatal
or sperm are associated with a myriad of maternal risks, medication databases such as Reprotox
49,50 may provide
including preeclampsia and neonatal risks, including pre- current information on specific drug risks for individualized
maturity.33-35 Reproductive planning options that mitigate counseling.
maternal risk for individuals with SCD include surrogacy and
adoption. Referrals to MFM, genetics, and reproductive Genetic counseling
endocrinology specialists, as appropriate, should be made All patients with SCD should be offered genetic counseling,
in the prepregnancy period depending on individualized ideally before pregnancy, to be informed of their risk of
reproductive planning needs and desires. In addition, this is having offspring who are carriers or affected with SCD. Key
an opportunity to educate patients about disease man- components of genetic counseling include disease char-
agement and prenatal genetic counseling and testing op- acterization (i.e., HbSS, HBSC, and HbSbþ) for both patient
tions, which may improve informed decision-making, and partner. Individuals who are at risk of having a child with
healthcare utilization, and rates of depression associated SCD and present for prepregnancy counseling should be
with SCD.36 Prepregnancy counseling for patients with SCD informed about alternative reproductive options. Patients
should include baseline maternal assessment, medication with SCD who present during pregnancy should also be
assessment, and genetic counseling, as described in detail offered genetic counseling and informed of the risk of having
below.32 a child born with SCD, along with screening and testing
options (including newborn screening) for the current
Baseline maternal assessment pregnancy. Antenatal diagnostic options, including chori-
A thorough history should be obtained, including an onic villus sampling and amniocentesis should be offered.
assessment of previous SCD complications and current Newer noninvasive (cell-free DNA) screening tests that
medications. Laboratory evaluation includes assessing for report the fetal risk of SCD are commercially available,78,79
anemia, evaluating iron stores, obtaining a type and screen but not currently recommended in pregnancy.80 If, despite
to assess for alloimmunization, and assessing thoroughly this, a patient undergoes screening with positive cell-free
end-organ function, as outlined in Table 2. Understanding a DNA screening results for SCD, confirmatory diagnosis
patient’s current health status aids in counseling regarding should be offered. If not performed antenatally, the diag-
the likelihood of pregnancy complications. For example, a nosis can be confirmed postnatally.
patient without end-organ damage and previous uncom-
plicated term deliveries incurs a different level of risk in What vaccinations should patients with
pregnancy compared with a patient with severe anemia on sickle cell disease receive in pregnancy?
hydroxyurea with a history of ACS. Patients with SCD Pregnant patients with SCD should receive all routinely
should be optimized and comanaged by a hematologist recommended antenatal vaccinations.81-84 Patients can be
who is up to date on health maintenance screening reassured that the COVID-19 vaccines currently available in
according to the National Heart, Lung, and Blood Institute the United States do not appear to increase the rates of
(NHLBI)37 and American Society of Hematology VOC.85 Additional vaccines, which should be administered
(ASH)38,39,18,40,41 guidelines. Ideally, health maintenance (if due) during pregnancy for patients with SCD, include
should be optimized before pregnancy. For patients with a meningococcal vaccination (MenACWY) every 5 years86 and
lapse in care, pregnancy represents a unique window for pneumococcal vaccination (PPSV23) 5 years after the first
heightened adherence and, for some, access to healthcare dose.87 It is important to remember that many pregnant
that they did not have before. Therefore, referrals for SCD patients have significant barriers to care, and pregnancy
management should be expedited during pregnancy. A may represent a unique window whereby patients have
transition from pediatric specialty care to adult specialty access to lifesaving immunizations. We recommend that

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TABLE 2
Baseline maternal assessment for the prepregnancy or pregnant patient with sickle cell disease
Baseline
assessment Assessment and management principles
BP Baseline assessment of BP to permit BP assessment throughout gestation relative to patient’s baseline, acknowledging that BP in
patients with SCD is often lower than individuals without SCD.
Iron stores Baseline assessment of iron and iron stores (serum iron, transferrin, total iron-binding capacity, transferrin saturation, ferritin). Prenatal
vitamins without iron should be the default. Iron administration is strictly reserved for patients with iron deficiency.
Anemia Complete blood count to assess baseline hematocrit level and platelet count. Type and screen to assess for alloimmunization.
Leukocytes Patients with SCD often have elevated leukocytes. Noting the WBC count at baseline may assist later in pregnancy if a leukocyte
abnormality is noted; some data suggest a higher WBC is associated with poorer SCD outcomes.42,43
Neurologic Obtain thorough neurologic history, including history of headaches and strokes. Obtain past records where indicated. Understanding
patient’s headache history may assist later in pregnancy to differentiate between patient’s baseline headaches and a severe feature of
preeclampsia.
Ophthalmologic Baseline assessment of previous visual complications. Eye examinations are recommended every 1e2 y.37 If patient is not up to date,
expedited referral should occur during pregnancy.
Dental Patients with SCD have an increased risk of dental complications that can adversely affect the mother’s health and pregnancy
outcomes. Routine dental care during pregnancy is strongly recommended. Dental referral for routine maintenance should be
expedited during pregnancy if patient does not have a provider and/or if dental maintenance is not current.44,45
Cardiac In accordance with ASH guidelines, providers should have a low threshold to obtain a screening echocardiogram for patients with SCD
with comorbidities (chronic hypertension, lupus, etc.) and/or cardiopulmonary symptoms given the risks of pulmonary hypertension and
cardiomyopathy. Specific cardiopulmonary symptoms38 that should trigger screening with echocardiography include:
 Dyspnea at rest or with exertion that is out of proportion to known condition, increased compared with baseline or
unexplained
 Hypoxemia at rest or with exertion that is out of proportion to known condition, increased compared with baseline or
unexplained
 Chest pain at rest or with exertion that is out of proportion to known condition, increased compared with baseline or
unexplained
 Increase in exercise limitation compared with baseline that is unexplained by other factors
 History of recurrent hypoxemia at rest or with exertion
 Evidence for sleep-disordered breathing with or without hypoxemia
 History of syncope or presyncope
 Evidence for loud P2 component of second heart sound or unexpected or new murmur on examination
 Signs of heart failure and/or fluid overload on examination
 History of pulmonary embolism
Vascular Baseline assessment of previous thromboembolic events and anticoagulation, if indicated, per national guidelines.46,47
Pulmonary Baseline assessment of O2 saturation. If <95%, obtain CXR and echocardiogram. Consider pulmonary function tests if symptoms
persist.
Hepatic Baseline assessment of liver function panel. Note that most patients with SCD have unconjugated hyperbilirubinemia at baseline.48
Renal Baseline assessment of renal function and assessment of proteinuria.
Urine Baseline urine culture at the initial prenatal visit and a urine assessment (dipstick, urinalysis, or other) at each prenatal visit.
Vitamin D Baseline assessment of vitamin D.
ASH, American Society of Hematology; BP, blood pressure; CXR, chest x-ray; SCD, sickle cell disease; WBC, white blood count.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

pregnant patients with SCD receive all routinely recommended frequently in patients with SCD (and other hemolytic ane-
antenatal vaccinations in addition to meningococcal and pneu- mias), and folic acid supplementation repletes folate stores
mococcal vaccination if due (GRADE 1A).32 needed for hematopoiesis.88 Similar to all pregnant pa-
tients, prenatal vitamins are recommended for pregnant
In addition to routine prenatal care, what patients with SCD. However, iron-free prenatal vitamins
additional items should be considered for should be the default for patients with SCD unless iron
the pregnant patient with sickle cell deficiency is documented.89 We recommend prenatal vita-
disease? mins without iron unless iron deficiency is confirmed and
Daily folic acid supplementation is recommended for initiation of 4 mg of folic acid for pregnant patients with SCD
pregnant patients with SCD. RBC turnover occurs more (GRADE 1B).32,90-92

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TABLE 3
Common medications used in SCD management—management principles for the prepregnant or
pregnant patient with SCD
Medication Management principles
Anticoagulation For patients requiring lifelong anticoagulation or who have an indication for antepartum anticoagulation,
unfractionated or low-molecular-weight heparins are preferred as they do not cross the placenta. It may be
preferable to initiate or transition to heparin-based anticoagulation with early confirmation of an intrauterine
pregnancy.
ACE-i or ARBs ACE-i or ARBs are associated with increased risk of fetal anomalies, fetal renal failure, and perinatal death.51-53
Penicillin Patients entering pregnancy on daily prophylactic penicillin may safely continue this during pregnancy. Pregnancy
itself is not an indication to initiate penicillin prophylaxis.
Hydroxyurea Hydroxyurea induces production of hemoglobin F and reduces red cell sickling, pain crises, hospitalization, and
transfusion. As animal studies demonstrate an increased rate of fetal anomalies, it is generally discontinued in
pregnancy.54-56 Certain high-risk situations may warrant the use of hydroxyurea in pregnancy after
organogenesis. Shared decision-making should guide the use of hydroxyurea.
Iron chelators (deferoxamine, Iron chelators are commonly used in patients with sickle cell anemia to reduce iron overload as a result of
deferiprone, deferasirox) repeated blood transfusion. Data regarding the use of deferoxamine in pregnancy is reassuring and may be
considered.57-59
Crizanlizumab Crizanlizumab is a monoclonal antibody that reduces VOC.60 It has the potential to cause fetal harm and shared
decision-making should guide potential continuation.
L-glutamine oral powder L-glutamine oral powder (marketed as Endari) is an amino acid that reduces acute complications of SCD. The use
of Endari in pregnancy has not been reported. In the absence of data, shared decision-making should guide use of
Endari.
Voxelotor Prevents deoxygenated SS hemoglobin from polymerizing by increasing affinity for oxygen.61 No data in human
pregnancy. Shared decision-making should guide use of voxelotor.
Opioids Many patients with SCD are prescribed daily opioid therapy to manage painful effects of the disease. Pregnancy
should not prompt discontinuation of opioid therapy. Pregnancy increases the risk of pain and VOC. Patients with
SCD should be managed by a multidisciplinary team and a single pain provider when feasible.
NSAIDs NSAID use in the first trimester of pregnancy may be associated with fetal loss62 or congenital anomalies.63-65
Third-trimester use may be associated with premature closure of the ductus arteriosus and pulmonary
hypertension.66,67 Short courses of NSAIDs may be considered after shared decision-making for acute pain or
tocolysis before 32 wk of gestation.
Nonopioid or non-NSAID pain In addition to opioids and NSAIDs, many patients with SCD rely on other medications to treat pain, including
medications cyclobenzaprine, gabapentin, and pregabalin. Of these medications, cyclobenzaprine (Flexeril) has the most
favorable safety profile.68 Offspring of animals exposed to gabapentin had an increased risk of fetal growth
restriction and congenital anomalies,69,70 although this has not been replicated in observational human
studies.71,72 Congenital anomalies have been identified in patients taking pregabalin,73 although a definitive
association has not been established. In summary, cyclobenzaprine seems to be safe throughout gestation.
Gabapentin and pregabalin may be considered via shared decision-making after thorough counseling regarding
risks and benefits with the patient.
Antidepressants Patients with SCD and depression who enter pregnancy on antidepressants should have a thorough review of their
psychiatric history, as is recommended for all pregnant people. Mental health conditions are associated with
maternal morbidity,74 and psychiatric medications should not be withheld from pregnant patients.
Antiemetics Regular use of anti-emetics is common for the patient with SCD. Pregnancy poses additional challenges, including
an increased risk of nausea, vomiting, and dehydration. Patients with SCD and dehydration have an increased risk
VOC. Although the addition of doxylamine and vitamin B6 may provide a modicum of improvement, additional
antiemetics will likely be needed for patients who need them at baseline. Some reports suggest ondansetron
increases the risk of clefting and congenital heart disease,75 although more rigorous studies refute this.76
Promethazine is not thought to increase the risk of adverse perinatal outcomes.77 Shared decision-making should
guide the use of antiemetics.
ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; NSAID, nonsteroidal anti-inflammatory medication; SCD, sickle cell disease; VOC, vaso-occlusive crisis.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

Patients with SCD have an increased risk of urinary tract each trimester because of the increased risk of asymp-
infections.93-95 In addition to a baseline urine culture at the tomatic bacteriuria. Evidence to support this is lacking.
entry to prenatal care, many providers obtain urine cultures However, a baseline urine culture at the initial prenatal visit

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and some form of urine assessment, such as dipstick or and should take into account factors, such as fetal growth
urinalysis, at each prenatal visit are suggested. and disease severity.102
Patients with SCD have an increased risk of vitamin D
deficiency; therefore, checking a baseline vitamin D level is Management and treatment
suggested.96 Repletion of vitamin D at 1000 to 2000 inter- What is the general management of vaso-
national units daily seems safe in pregnancy.97 occlusive crises?
Individuals presenting with uncomplicated VOC (i.e., pain
What fetal surveillance is indicated for the without evidence of organ dysfunction) are typically
pregnant patient with sickle cell disease? managed with oral or intravenous (IV) fluids and analgesic
Pregnant patients with SCD should undergo an ultrasound medications. Pain caused by an uncomplicated VOC may
when they present for prenatal care to confirm the presence last up to 2 weeks. RBC transfusion is not recommended for
of a viable intrauterine pregnancy and to reliably date the uncomplicated VOC.41,18 Providers should observe for
pregnancy. Early confirmation of an intrauterine pregnancy acute complications of SCD in patients presenting with VOC
is important as this may affect medication management and alter the management plan accordingly. Complicated
concerning teratogen exposure. A detailed anatomic survey VOC should be treated in collaboration with a hematologist
should be performed 18 weeks of gestation to screen for and may require additional assessment, diagnostic evalu-
congenital anomalies, particularly among patients taking ation, and RBC transfusion in addition to pain management.
potential teratogens immediately before or during the first ACS deserves particular attention in the evaluation of
trimester of pregnancy. VOC as it is the leading cause of death among patients with
Fetal growth surveillance by ultrasound is indicated given SCD.105 ACS is diagnosed by imaging findings consistent
the increased risk of fetal growth restriction in patients with with a new pulmonary infiltrate and one additional item, which
SCD.25,32,98 Severe forms of SCD, including HbSS and may include oxygen desaturation, cough, temperature of
HbSb0 disease, confer the greatest risk.99 We recommend 101.3 F, tachypnea, or wheezing.106,107 ACS should be
fetal growth surveillance every 4 weeks beginning in the 28th kept on the differential diagnosis, and a hematologist, pul-
week of gestation (GRADE 1C).100 monologist, or other SCD specialist should be consulted for
Antenatal fetal surveillance is indicated for pregnant pa- prompt evaluation and treatment. The management of ACS
tients with an increased risk of stillbirth. A 2016 meta- includes pain control (at a dose that provides adequate pain
analysis, including data from 9 countries, found that pa- control but avoids sedation), IV fluids, broad-spectrum
tients with SCD have a significantly increased risk of stillbirth antibiotics, supplemental oxygen, and blood transfusions to
with an OR of 4.05.25 In contrast, a contemporary statewide decrease HbS to <30%.107,108 Incentive spirometry should
retrospective cohort study found no significant increase in be performed every 2 hours while the patient is awake.107,108
stillbirth among women with SCD.23 The authors hypothe-
sized that this finding reflected improved antenatal surveil- How should a vaso-occlusive crisis be
lance and management. It is unknown if third-trimester treated in pregnant patients?
antenatal fetal surveillance reduces stillbirth risk in preg- VOC in pregnant patients is initially treated with hydration
nancies complicated by SCD with normally grown fetuses; and aggressive pain management. Oxygen need not be
however, it is reasonable to consider antenatal fetal sur- initiated unless O2 saturation levels are <95%, in which
veillance for all patients with SCD given the above RR for case additional pulmonary assessment is needed. The
stillbirth and the unknown degree to which fetal growth re- threshold for oxygen supplementation in the pregnant pa-
striction is responsible for the increase in risk. Patients with tient is lower than in the nonpregnant patient with SCD to
SCD and a growth-restricted fetus should be assigned to maintain an effective gradient for fetal gas exchange.109 In
antenatal fetal surveillance according to guidelines for fetal addition, hydration should be administered, although the
growth restriction.100,101 For patients with uncomplicated SCD rate and volume of fluid administration must be balanced
and a normally-grown fetus, we suggest weekly or twice weekly with risks of volume overload and pulmonary edema.
antenatal testing beginning at 32 to 34 weeks of gestation. For Isotonic IV and oral fluids are preferred; hypertonic fluids are
patients with complicated SCD (i.e., maternal hypertension, VOC, not recommended. In the patient with dehydration, fluids
fetal growth restriction, or other coexisting complication), we may be continued until clinical improvement.
suggest initiating individualized antenatal testing at diagnosis or An evaluation for infectious etiology or trigger for VOC
at a gestational age when delivery would be considered if results should be performed and treatment initiated as indicated
are abnormal (GRADE 2B).102 and treated. The initial workup in pregnancy includes a CBC
Other forms of SCD (e.g., hemoglobin SC disease) have with differential, lactate dehydrogenase, comprehensive
less clear effects on the risk of perinatal death.103,104 metabolic panel, urinalysis, and urine culture. Routine radi-
Therefore, in the absence of other complications, ante- ography is not needed. A chest radiograph should be ob-
natal fetal surveillance for patients with hemoglobinopathies tained if the patient has respiratory symptoms, hypoxia, or a
other than HbSS or HbSb0 disease should be individualized significant decrease in hemoglobin level. Patients should be

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treated with IV opioids for acute VOC according to their written patient agreement can help establish informed
individualized pain plan (if present) or according to the ASH consent, improve adherence, and mitigate risk when initi-
guideline on management of pain (Table 4).18 ating opioid therapy.122 Referral to a pain specialist should
Anemia assessment is crucial for patients who present be considered for pregnant patients with chronic SCD
with a drop in hemoglobin level compared with their base- pain.123 Attention should be paid to the risk of bias when
line.41 Although transfusion may be considered for those assessing the opioid needs of an individual with chronic
whose hemoglobin level is significantly lower than baseline pain conditions, and an addiction medicine consultation
depending on the clinical context, it is important to exclude should be considered if there is a concern for the need to
causes of anemia other than splenic sequestration that differentiate opioid use disorder from chronic pain needs.124
might require different management strategies, such as
hemolysis, acute bleeding, or ACS. Exchange transfusions How should pregnant patients with sickle cell
are indicated in the acute setting for patients presenting with disease on opioid therapy be counseled
symptoms of acute ischemic stroke, severe ACS (or any regarding the risk of neonatal opioid
cause of hypoxic respiratory failure), or multisystem organ withdrawal syndrome?
failure.117 A hemoglobin electrophoresis may be obtained to Available evidence suggests that approximately 1 in 4 in-
determine the percentage of hemoglobin S but is not fants born to a mother with SCD will have neonatal opioid
needed in the acute setting and can be estimated on the withdrawal syndrome (NOWS). In one series, 4 of 15 infants
basis of the patient’s previous transfusion history. In gen- (27%) born to mothers with hemoglobin SS disease were
eral, the goal of an exchange transfusion is to decrease the diagnosed with NOWS. The risk factors included ante-
abnormal hemoglobin level (HbS or HbSþC) to <30%.118 partum admission, VOC, and exchange transfusion.125 In
another series, 5 of 23 mothers (22%) with SCD who
What principles of pain management should received opioids and 4 of 15 mothers (27%) with SCD who
be utilized in managing a patient with sickle received daily opioids had an infant with NOWS.126 Another
cell disease? review demonstrated that the risk of NOWS was associated
Outside of pregnancy, individuals with SCD are ideally with mean daily opioid dose; median maternal oral morphine
managed using principles of pain management outlined in doses were 416, 139, and 4 mg for infants with severe, mild,
the 2020 ASH guideline for SCD on the management of and no NOWS, respectively.127 Patients with SCD using
acute and chronic pain.18 With few exceptions, as outlined opioids during pregnancy should be counseled about the
in Table 4, we recommend following evidence-based guidelines risk of NOWS and should participate in shared decision-
for the management of chronic and acute pain during pregnancy making about an opioid dosing strategy to balance
(Best Practice).119 Table 4 summarizes key ASH recom- neonatal risks with the adequacy of pain management to
mendations and good practice statements for the man- maintain their well-being. Infants exposed to opioids in utero
agement of acute and chronic pain (left column) and should be monitored for signs and symptoms of NOWS.128
presents Society for Maternal-Fetal Medicine pregnancy- Prenatal consultation with pediatrics is encouraged to
specific modifications where applicable (right column). develop a monitoring and treatment plan. The Eat, Sleep,
Shared decision-making should guide pain management in Console treatment model prioritizes infant comfort and
pregnant patients with SCD, and all patients should have an family involvement in care and is associated with reduced
individualized pain management plan. length of hospital stay, exposure to pharmacologic agents,
Pregnant patients presenting with acute SCD pain should and overall cost of treatment.128e130 Patients can be reas-
receive rapid assessment and administration of analgesia sured that breastfeeding is beneficial for infants with
according to standard protocols and order sets to reduce NOWS.131,132
the risk of undertreating pain.119 Opioid dosing for acute
pain should be tailored to the patient with consideration of What is the role of transfusion in pregnant
their baseline opioid therapy and previous effective therapy. patients with sickle cell disease?
The dose of opioids needed to manage acute pain will vary Of note, 3 types of transfusions are used in the care of pa-
according to the patient and may be higher than standard tients with SCD: simple transfusions consisting of red cell
doses prescribed for postoperative pain. transfusion only, manual exchanges consisting of manual
Opioid therapy for chronic pain can be considered for phlebotomy before transfusion of 1 to 2 units of packed
pregnant patients with SCD after shared decision-making. RBCs, and automated exchange transfusions, which
Harm reduction strategies for chronic opioid therapy consist of the simultaneous removal of the patient’s full
include co-prescribing naloxone and prescribing the lowest blood volume with an infusion of blood products. Trans-
effective opioid dose. Morphine milligram equivalents (MME) fusions are indicated during pregnancy for acute compli-
should be documented.120 Many online MME calculators cations of SCD, such as stroke and ACS. In a 1988
exist, one of which is the Centers for Disease Control and randomized controlled trial, prophylactic transfusions dur-
Prevention (CDC) Opioid Guideline Mobile App.121 The ing pregnancy reduced the number of pain crises compared
usefulness of “pain contracts” is not known, but a well- with transfusions only when medically indicated but did not

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TABLE 4
ASH SCD guideline for the management of acute and chronic pain and SMFM pain management
principles for the pregnant patient
Select ASH recommendation18 SMFM principles for the pregnant patient
Acute pain
For adults and children with SCD presenting to an acute care setting Obstetrical triage units should develop protocols and/or EMR order
with acute pain related to SCD, the ASH guideline panel recommends sets to facilitate timely assessment and administration of analgesia to
rapid (within 1 h of ED arrival) assessment and administration of optimize pain control.
analgesia with frequent reassessments (every 30e60 min) to
optimize pain control.
For adults and children with SCD presenting to an acute care setting A tailored opioid dosing plan and controlled substance agreement
with acute pain related to SCD for whom opioid therapy is indicated, should be outlined in the medical record to facilitate optimal pain
the ASH guideline panel suggests tailored opioid dosing based on management in the obstetrical triage unit.
consideration of baseline opioid therapy and previous effective
therapy.
For adults and children with acute pain related to SCD, the ASH NSAID use in the first trimester of pregnancy may be associated with
guideline panel suggests a short course (5e7 d) of NSAIDs in miscarriage62 or congenital anomalies, specifically cardiac
addition to opioids for acute pain management. malformations63,64 and gastroschisis.65 Third-trimester use may be
associated with premature closure of the ductus arteriosus and
pulmonary hypertension.66,67 Short courses of NSAIDs may be
considered after shared decision-making for acute pain during the
second trimester of pregnancy.
For adults and children presenting for acute pain related to SCD, the Antenatal corticosteroids should be used for fetal lung maturity when
ASH guideline panel suggests against corticosteroids for acute pain a preterm birth is suspected according to national guidelines,110 but
management. should not be used for pain management.
For adults and children presenting with acute pain related to SCD Ketamine is not routinely used in obstetrics given adverse neurologic
who are hospitalized, the ASH guideline panel suggests a effects in animal offspring.111,112 Alternatives are preferred if
subanesthetic (analgesic) ketamine infusion as adjunctive treatment available.
of pain that is refractory or not effectively treated with opioids alone.
For adults and children presenting with acute pain related to SCD, the The use of regional anesthesia rarely applies to the pregnant patient
ASH guideline panel suggests regional anesthesia treatment outside of the intrapartum setting. If SCD pain requires regional
approaches for localized pain that is refractory or not effectively anesthesia treatment, multidisciplinary planning with MFM,
treated with opioids alone. obstetrical anesthesia and/or pain management should occur.
For adults and children who seek treatment of acute pain, the ASH These nonpharmacologic modalities are generally safe in pregnancy.
guideline panel suggests massage, yoga, TENS, VR, and guided AV Care should be taken in yoga or massage to avoid lying flat to prevent
relaxation in addition to standard pharmacologic management. compression of the great vessels impeding venous return.
For adults and children who develop acute pain episodes requiring Depending on gestational age, pregnant patients may need to
hospital care, the ASH guideline panel suggests using SCD-specific undergo assessment of well-being before transitioning to a
hospital-based acute care facilities (i.e., day hospitals and infusion specialized SCD-specific care facility.
centers, all with appropriate expertise to evaluate, diagnose, and
treat pain and other SCD complications) vs typical ED-based care.
Chronic pain
For adults with SCD who have chronic (as opposed to episodic) pain Duloxetine is not known to cause congenital anomalies but, as with
from the SCD-related identifiable cause of avascular necrosis of the other SNRIs, has been associated with other perinatal complications.
bone, the ASH guideline panel suggests use of duloxetine (and other Risks and benefits should be discussed, and this medication should
SNRI medications, because there is evidence of a class effect) as an not be withheld from pregnant patients.
option for management, in the context of a comprehensive disease
and pain management plan.
For adults with SCD who have chronic (as opposed to episodic) pain Shared decision-making should guide the use of NSAIDs. NSAIDs
from the SCD-related identifiable cause of avascular necrosis of should be avoided in the first and third trimesters of pregnancy; short
bone, the ASH guideline panel suggests the use of NSAIDs as an courses (i.e., 48e72 h) may be used in the second trimester of
option for management, in the context of a comprehensive disease pregnancy.
and pain management plan.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024. (continued)

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TABLE 4
ASH SCD guideline for the management of acute and chronic pain and SMFM pain management
principles for the pregnant patient (continued)
Select ASH recommendation18 SMFM principles for the pregnant patient
Given the prevalence of psychological comorbidities that are present Similar to all pregnant people, patients with SCD and chronic pain
in the context of pain, it is good practice to routinely screen for should undergo screening for depression and anxiety in the first
depression and anxiety and to perform targeted screening for other trimester of pregnancy, third trimester of pregnancy, and after
psychological comorbidities. delivery. Those with an identified mental health condition should be
screened monthly.113
For adults who have SCD-related chronic pain with no identifiable As above, duloxetine is not known to cause congenital anomalies in
cause beyond SCD, the ASH guideline panel suggests SNRIs (e.g., pregnancy, but care should be individualized.
duloxetine and milnacipran) as options for pain management.
For adults who have SCD-related chronic pain with no identifiable It is recommended to avoid amitriptyline in the first trimester of
cause beyond SCD, the ASH guideline panel suggests TCAs (e.g., pregnancy because of anomalies detected in animal models
amitriptyline) as an option for pain management. receiving high doses;114,115 second- and third-trimester use can be
considered after shared decision-making.
For adults who have SCD-related chronic pain with no identifiable It is not recommended to use pregabalin in the first trimester of
cause beyond SCD, the ASH guideline panel suggests pregnancy;73 second- and third-trimester use can be considered
gabapentinoids (e.g., pregabalin) as options for pain management. after shared decision-making.
For adults and children with SCD who have chronic pain related to This recommendation requires no modification for pregnancy.
SCD, the ASH guideline panel suggests cognitive and behavioral pain
management strategies in the context of a comprehensive disease
and pain management plan.
For adults with SCD who have chronic pain related to SCD, the ASH Massage therapy, with slight position modifications avoiding the
guideline panel suggests other provider-delivered integrative supine position, and acupuncture are safe in pregnancy.
approaches (e.g., massage therapy and acupuncture) as available,
as tolerated, and conditional upon individual patient preference and
response. These approaches should be delivered in the context of a
comprehensive disease and pain management plan.
For adults and children with SCD and emerging and/or recently After shared decision-making, initiation of COT during pregnancy
developed chronic pain, the ASH guideline panel suggests against may be considered for refractory pain. A clear plan should be made
the initiation of COT unless pain is refractory to multiple other regarding postpartum COT transition.
treatment modalities.
For adults and children with chronic pain from SCD who are receiving Shared decision-making regarding continuation of COT in pregnancy
COT, are functioning well, and have perceived benefit, the ASH is recommended.
guideline panel suggests shared decision-making for continuation of
COT.
Other considerations
For adults and children with chronic pain from SCD who are receiving SCD-related pain should be adequately treated, but patients at risk of
COT, are functioning poorly, or are at high risk of aberrant opioid use aberrant opioid use or toxicity may be more appropriately managed
or toxicity, the ASH guideline panel suggests against continuation of by a single pain or addiction provider.
COT.
It is good practice to implement harm reduction strategies for Patients receiving COT should receive the lowest effective dose along
patients on COT, including strongly considering co-prescribing with a prescription of naloxone.116 In addition, benzodiazepines
naloxone, avoiding co-prescribing opioids and benzodiazepines, and should be avoided in a patient receiving opioids.
prescribing the lowest effective opioid dose.
It is good practice to consider collaboration with pain medicine A multidisciplinary approach, including pain medicine specialists, is
specialists for the management of individuals living with SCD who recommended for the management of the pregnant patient with SCD.
have chronic pain. Involving pain medicine specialists who can provide continuity care
after delivery is preferred.
In cases in which the clinician has valid and substantial evidence of Pregnant patients with SCD and substantiated aberrant opioid use
aberrant opioid use, it is good practice to consider consulting an should be referred to an addiction specialist for treatment.
addiction medicine physician.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024. (continued)

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TABLE 4
ASH SCD guideline for the management of acute and chronic pain and SMFM pain management
principles for the pregnant patient (continued)
Select ASH recommendation18 SMFM principles for the pregnant patient
For adults and children with SCD and recurrent acute pain, the ASH Red blood cell transfusion is not recommended for the pregnant
guideline panel suggests against chronic monthly transfusion patient with acute pain in the absence of another indication.
therapy as a first-line strategy to prevent or reduce recurrent acute
pain episodes.
Shading indicates American Society of Hematology (ASH) recommendations that require significant modifications during pregnancy. ASH recommendations for which there are no major modifications
in pregnancy are unshaded.
ASH, American Society of Hematology; AV, audiovisual; COT, chronic opioid therapy; EMR, electronic medical record; ED, emergency department; MFM, maternal-fetal medicine; NSAID, nonsteroidal
anti-inflammatory medication; SCD, sickle cell disease; SMFM, Society for Maternal-Fetal Medicine; SNRI, serotonin and norepinephrine reuptake inhibitor; TAC, tricyclic antidepressant; TENS,
transcutaneous electrical nerve stimulation; VR, virtual reality.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

change other key maternal and perinatal outcomes. Con- pregnancy and those with a history of stroke.32,41 We suggest
cerns were raised by the authors regarding risks of alloim- the use of prophylactic transfusions be individualized for high-risk
munization, iron overload, hospital admissions, and excess patients with SCD in accordance with ASH guidelines and directed
healthcare costs.133 A 2015 systematic review and meta- by a hematologist and maternal-fetal medicine subspecialist in
analysis of studies of prophylactic transfusion in preg- shared decision-making with the patient (GRADE 2B).
nancy identified 12 studies with 1291 participants found a
moderate to high risk of bias among included studies and What are the risks and benefits of blood
found an association between prophylactic transfusion and transfusion in pregnancy?
reduction in maternal mortality, VOC, pulmonary compli- Blood transfusions in high-resource countries are consid-
cations, venous thromboembolism (VTE), pyelonephritis, ered safe and have low rates of adverse outcomes. The
perinatal mortality, neonatal death, and preterm birth.134 benefits of CTT, as described in a randomized trial, included
Subsequently, a 2016 Cochrane Review (which included reduced frequency of pain crises.133 In addition, observa-
only the 1988 randomized controlled trial [RCT]) concluded tional data consisting of a systematic review and meta-
that “prophylactic blood transfusion to pregnant women analysis found that CTT reduced maternal mortality, pul-
with sickle cell anemia confers no clear clinical benefit monary complications, pulmonary embolism, pyelonephri-
compared with selective transfusion.”135 In response to the tis, perinatal mortality, and preterm birth.134 Risks of blood
available evidence, the ASH recommends the following transfusion during pregnancy include those inherent to
regarding transfusion in pregnant patients with SCD: blood transfusions in all patients, plus added risks to the
pregnant patient and the developing fetus. Specifically,
 There is insufficient evidence to recommend a strategy of transfused blood should be cytomegalovirus (CMV) nega-
prophylactic transfusion rather than standard care. tive to avoid fetal CMV infection.136 Additional risks of blood
 Prophylactic transfusion at regular intervals at the onset transfusion include iron overload and alloimmunization.
of pregnancy should be considered for women with the Liver iron concentration monitoring and chelation therapy
following: are indicated to prevent the adverse consequences of iron
B A history of severe SCD-related complications before overload, which include fibrosis and cirrhosis.137,138 For
current pregnancy (including during previous preg- patients with alloimmunization, early communication with
nancies) to reduce recurrent pain episodes, incidence the local blood bank is important to ensure matched blood
of ACS, or other (SCD-related) comorbidities can be obtained if needed. Furthermore, the pregnant pa-
B Additional features of high-risk pregnancy (e.g., addi- tient with antibodies associated with hemolytic disease of
tional comorbidities: other medical conditions or the fetus and newborn should be managed according to
nephropathy) national guidelines.139,140
 Women who develop SCD-related complications during In addition, delayed hemolytic transfusion reactions
the current pregnancy would benefit from initiating reg- (DHTRs) should remain on the differential diagnosis for a
ular transfusions.41 pregnant person with SCD who presents with pain and dark
urine after a previous blood transfusion. The duration from
Practically speaking, there is insufficient evidence to red cell transfusion to DHTR can range from days to weeks
recommend routine chronic transfusion therapy (CTT) for and is typically, but not always, diagnosed by the identifi-
most pregnant patients with SCD; individualized consider- cation of new antibodies on their antibody screen.141 Sup-
ation should be given to patients with more severe historical portive care, steroids, and intravenous immunoglobulin are
features, such as those receiving chronic transfusion before likely the best approaches to treat a pregnant person with

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SCD and DHTR. Avoiding blood transfusions is ideal, is most likely (i.e., periconception to first trimester of preg-
although this can be challenging in a person with a low nancy), availability of cross-matched blood, likelihood of
hemoglobin level approaching delivery. Multidisciplinary developing severe morbidity if hydroxyurea is discontinued
planning is crucial in these challenging cases. MFM spe- (based on patient-level disease characteristics), and that
cialists should be vigilant to keep DHTR on the differential beneficial effects from hydroxyurea may take 6 months to
diagnosis as they manage patients with SCD in conjunction observe from initiation of treatment. Although hydroxyurea is
with a hematologist, preferably one who specializes in SCD. not indicated for most pregnant individuals with SCD, we
recommend shared decision-making occur regarding the use of
What is the role of disease-modifying hydroxyurea in pregnancy, in conjunction with a SCD specialist and
therapy, including hydroxyurea, in the maternal-fetal medicine subspecialist, accounting for the timing of
management of sickle cell disease? use and individual disease severity (GRADE 1C).
All individuals with SCD should be offered disease-
modifying therapy at baseline. For individuals with a his- What blood pressure and preeclampsia
tory of recurrent VOC, ACS, stroke, or other chronic organ management principles should be observed
complications, additional emphasis on disease-modifying for the pregnant patient with sickle cell
therapy is needed. Hydroxyurea is the best-studied dis- disease?
ease-modifying therapy in SCD, attenuating the number of Pregnant patients with SCD, especially those with HbSS or
VOC episodes and slowing the progression of end-organ HbSb0 disease, often have lower baseline blood pressure
disease.142 Chronic red cell transfusion is the only (BP) than pregnant patients without SCD.147e150 This may
disease-modifying therapy proven to decrease the risk of be due to lower body mass index, anemia, nitric oxide
ischemic stroke in patients with CNS vasculopathy. Newer deficiency, or other causes. Obstetrical providers should
therapies (L-glutamine, voxelotor, and crizanlizumab) note the patient’s baseline (prepregnancy) BP and first-
remain inconclusive in their potential for long-term efficacy trimester BPs so the relative change compared with the
and lack data on use during pregnancy.142 Of these thera- patient’s baseline can be noted throughout gestation. Pa-
pies, only CTT is considered safe in pregnancy.134 About tients with SCD have an increased risk of preeclampsia.95 In
these newer therapies, shared decision-making should help addition, individuals with SCD are at increased risk of
guide whether certain agents should be continued during microalbuminuria and chronic kidney disease, separate
pregnancy. from pregnancy.151 Therefore, baseline preeclampsia lab-
Hydroxyurea has historically not been recommended in oratory test results (which are included within the baseline
pregnancy primarily because of teratogenic effects found in assessment of end-organ damage shown in Table 2) should
animal models.54-56 Although available data are limited, a be obtained. The administration of low-dose aspirin should
thorough search did not locate any reported cases of in- be initiated at 12 weeks of gestation to reduce the risk of
dividuals taking hydroxyurea for SCD who had an infant with preeclampsia.7,152 Preeclampsia in patients with SCD
a birth defect,143,144 and a systematic review is ongoing.145 should be managed according to existing guidelines.19
A 2022 retrospective study of 1788 pregnancies, among Pregnant patients with SCD should be counseled about
which 241 (16%) were conceived while on hydroxyurea, did an increased risk of preeclampsia. Providers should remain
not demonstrate independent associations between use aware that new-onset hypertension in patients with SCD,
during conception and adverse pregnancy outcomes.146 even if mild, may represent a significant increase in mean
However, among patients with SCD using hydroxyurea arterial pressure from the patient’s baseline. Providers
during conception and continuing use during pregnancy, should recognize that a systolic BP of 30 mm Hg or a dia-
there were increased risks of miscarriage or stillbirth (OR, stolic BP of 15 mm Hg above baseline, even if it does not
2.21; 95% confidence interval [CI], 1.09e7.38) and reach “mild hypertension,” represents a significant physio-
increased risk of low birthweight (OR, 2.98; 95% CI, logical change and warrants assessment of maternal end-
1.09e7.38) among term infants, after adjustment for organ damage and continued close surveillance.153,154
markers of disease severity. Furthermore, the development of severe hypertension
Of note, one strategy for individuals of childbearing po- should be considered relatively more ominous in the preg-
tential is to recommend discontinuation of hydroxyurea if nant patient with SCD and low baseline BP and should be
planning to conceive within 3 months or to discontinue hy- evaluated and treated accordingly to reduce the risk of
droxyurea in the event of an unexpected pregnancy.32 How- stroke.
ever, this recommendation should be individualized and risk
stratified by trimester in collaboration with an expert in SCD. At what gestational age should the patient
Because of the limited available low-quality data balanced with sickle cell disease be delivered?
with maternal and perinatal risks, we recommend that prin- For patients with uncomplicated SCD, normal BP, and a
ciples of informed consent and shared decision-making be normally grown fetus, delivery is recommended between 39
applied to the use of hydroxyurea in pregnancy. Counseling 0/7 and 39 6/7 weeks of gestation, consistent with existing
should include animal model data, timing when teratogenicity guidelines for timing of delivery in patients with

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comorbidities associated with an increase in maternal and before cesarean delivery, whereas a patient with a hemoglobin
perinatal risk.155 Patients with SCD and preeclampsia and/ level of 9 g/dL undergoing a primary cesarean delivery for
or fetal growth restriction should undergo delivery accord- breech presentation likely would not need a transfusion before
ing to specified guidelines.19,101 For patients with SCD a cesarean delivery. As is recommended for all pregnant pa-
complicated by multiple VOC, significant alloimmunization, tients with SCD admitted to the hospital, the blood bank should
or other SCD-specific complications, ideal delivery timing is be alerted so that matched blood can be available as needed.
unclear. Because of the lack of clear data in this area, the
timing of delivery for patients with complicated SCD should What are recommended components of
be individualized, weighing the maternal and perinatal risks postpartum care for sickle cell disease
with risks of prematurity. patients?
In addition to routine postpartum care, patients with SCD
What peripartum considerations are require additional postpartum considerations. Patients with
recommended for patients with sickle cell SCD have an increased risk of VTE. Intrapartum and post-
disease? partum, when patients with SCD are not ambulatory, sequen-
Preparation of patients with SCD for a safe delivery with tial compression devices should be applied, and early
adequate pain management should include multispecialty postpartum ambulation should be encouraged. Postoperative
collaboration. A consultation with an obstetrical anesthesia prophylactic anticoagulation should be considered after ce-
specialist is advised to discuss methods of analgesia and sarean delivery before hospital discharge, given the increased
anesthesia, particularly for patients who experience chronic VTE risk.160e162
pain. Patients with a history of transfusion should undergo Patients with SCD have an increased risk of postoperative
an antibody screen at least 2 days before anticipated de- ACS.157 It is best practice to keep an incentive spirometer at
livery if feasible, and obstetrical teams should determine the bedside of hospitalized patients with SCD to reduce the
blood preparation needs based on systems-level and risk of pulmonary complications.163,164
patient-level factors, including availability of products, cur- A pain management plan for patients with SCD is important.
rent hemoglobin level, and degree of sensitization, if any. Patients with SCD who undergo cesarean delivery have
The mode of delivery for patients with SCD is based on usual surgical pain that should be adequately treated and may
obstetrical indications; vaginal delivery is the preferred require higher doses of opioids because of opioid tolerance.
mode of delivery when possible. Avascular necrosis of the Opioid prescriptions for pain after cesarean delivery should be
femoral head does not preclude vaginal delivery.156 prescribed according to guidelines for the management of
pain in patients with SCD and the patient’s individualized pain
Should patients with sickle cell disease plan. Adjuncts to opioids for postoperative pain include
undergo prophylactic transfusion prior to a nonsteroidal anti-inflammatory medications, gabapentin, and
planned cesarean? regional blocks from anesthesiologists or pain management
“The TAPS (The Transfusion Alternatives Preoperatively in specialists.165,166
Sickle Cell Disease) Study” was an RCT that investigated the Finally, it is crucial to ensure a smooth transition from
effect of preoperative transfusions to reach a hemoglobin level obstetrician-gynecologist or MFM subspecialist care to pri-
of 10 g/dL and/or hemoglobin S level of <60% on perioperative mary care, including a referral to a hematologist or SCD
complications in patients with SCD scheduled to undergo low- specialist if the patient is not already established.167 If feasible,
or medium-risk surgeries.157 Postoperative ACS was signifi- patients should have a follow-up appointment with an SCD
cantly less likely in the transfused group. This led the authors to specialist scheduled upon discharge from the delivery-
recommend preoperative transfusions for eligible patients associated hospitalization. This may enhance access to life-
undergoing surgery. Based on this trial, and others,158,159 the saving disease-modifying therapy early in the postpartum
ASH SCD guideline on transfusion support “suggests preop- period.168 In addition, postdelivery counseling with an MFM
erative transfusion over no preoperative transfusion in patients specialist to review the course and outcome of the pregnancy
with SCD undergoing surgeries requiring general anesthesia and to set the stage for prepregnancy counseling before future
and lasting more than 1 hour” and remarks that “clinicians pregnancies is advised.
should aim for total hemoglobin levels of more than 9 g/dL
before surgery.”41 Robust data for pregnancy and cesarean Should pregnant patients with sickle cell
deliveries routinely performed under general anesthesia are not disease receive anticoagulation?
available, limiting the applicability of the TAPS findings and Patients with SCD have an increased risk of venous
ASH guidelines for use in helping patients with SCD prepare for thromboembolic events.26,160,161 Patients should be coun-
delivery. Therefore, in the absence of data, the decision of seled to present to their clinician with new-onset chest pain,
whether or not to transfuse before a cesarean delivery should cardiopulmonary complaints, or calf pain. Prophylactic
be individualized. For example, a patient with a history of ACS anticoagulation to reduce the risk of VTE should be
with a hemoglobin level of 7 g/dL and 3 previous cesarean considered for pregnant patients with SCD who are
deliveries would likely benefit from a planned RBC transfusion admitted to the hospital if decreased mobility is anticipated

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Summary of recommendations
Number Recommendation GRADE
1 We recommend that patients with SCD be managed by a multidisciplinary team that includes MFM, hematology Best practice
(ideally a hematologist specializing in SCD), genetics, pain management, and social work or behavioral health
(as appropriate) starting in early pregnancy.
2 We recommend that pregnant patients with SCD receive all routinely recommended antenatal vaccinations in addition 1A
to meningococcal and pneumococcal vaccinations if due.
3 We recommend prenatal vitamins without iron unless iron deficiency is confirmed and initiation of 4 mg of folic acid for 1B
patients with SCD.
4 We recommend fetal growth surveillance every 4 wk beginning in the 28th week of gestation. 1C
5 For patients with uncomplicated SCD and a normally grown fetus, we suggest weekly or twice-weekly antenatal testing 2B
beginning at 32e34 wk of gestation. For patients with complicated SCD (i.e., maternal hypertension, VOC, fetal growth
restriction, or other coexisting complication), we suggest initiating individualized antenatal testing at diagnosis or at a
gestational age when delivery would be considered if results are abnormal.
6 We recommend following evidence-based guidelines for the management of chronic and acute pain during pregnancy. Best practice
7 We suggest the use of prophylactic transfusions be individualized for high-risk patients with SCD in accordance with 2B
ASH guidelines and directed by a hematologist and MFM subspecialist in shared decision-making with the patient.
8 We recommend shared decision-making occur regarding the use of hydroxyurea in pregnancy, in conjunction with an 1C
SCD specialist and an MFM subspecialist, accounting for the timing of use and individual disease severity.
9 We recommend that reliable contraception be offered to patients with SCD to decrease the risk of an unintended pregnancy 1B
and associated maternal and perinatal risks.
MFM, maternal-fetal medicine; SCD, sickle cell disease; VOC, vaso-occlusive crisis.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

or if other risk factors develop. Patients with a previous or significant comorbidities that preclude the use of estrogen,
current VTE should be managed according to national including past or present thromboembolism, previous
guidelines.47,169 The risk of thrombosis increases as preg- stroke, or hypertension. For these reasons, progestin-only
nancy progresses with the highest risk in the postpartum methods, including long-acting reversible contraception
period (2.1%; 95% CI, 1.5e3.1) comparable with the per (LARC), are favored for patients with SCD.175 Offering LARC
pregnancy VTE risk encountered in pregnant patients with immediately after delivery may increase access to reliable
factor V heterozygote (0.5%e3.1%) and prothrombin gene contraception and is also recommended.176 In addition to
heterozygote (0.4%e2.6%) status.46,161,170 Therefore, contraceptive benefits, depot medroxyprogesterone ace-
provided there is no contraindication concerning one’s in- tate may reduce the risk of sickle pain crises and is another
dividual bleeding risk, postpartum prophylactic anti- option for these patients.177 We recommend that reliable
coagulation may be considered for the postpartum patient contraception be offered to patients with SCD to decrease the risk
with SCD to reduce the risk of VTE. of an unintended pregnancy and associated maternal and perinatal
risks (GRADE 1B). All conversations regarding contraception
What contraceptive choices should be should be individualized and employ principles of shared
offered to patients with sickle cell disease? decision-making and be sensitive to historical contraceptive
Recent studies of patients with SCD found that 56% of pa- coercion in this patient population.178
tients were not using any form of contraception171 and that
58% had an unintended pregnancy at least once.172 Pa- What lactation guidance should be provided
tients with SCD have an increased risk of maternal morbidity to pregnant and postpartum patients with
or death as a result of pregnancy.171 Reliable contraception sickle cell disease?
should be offered to decrease the risk of unintended preg- Similar to all patients, pregnant patients with SCD should be
nancy and associated maternal and perinatal risk. According provided education regarding maternal and neonatal ben-
to the CDC Medical Eligibility Criteria for Contraceptive Use, efits of breastfeeding and adequate support to optimize the
various forms of contraception are appropriate for people chance for breastfeeding success. Patients who dis-
with SCD.173 Combined hormonal contraception (CHC) is continued medications used for the management of
associated with an increased risk of VTE, and the presence SCD with knowledge of pregnancy should be provided
of SCD increases the risk of thrombotic events in the setting counseling in the second and/or third trimester of preg-
of CHC use.174 In addition, some individuals with SCD have nancy regarding the compatibility of their prepregnancy

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Society for Maternal-Fetal Medicine Grading System: Grading of Recommendations Assessment,

Development, and Evaluation (GRADE) recommendations226
GRADE of
recommendation Clarity of risk and benefit Quality of supporting evidence Implications
1A. Strong Benefits clearly outweigh risks and Consistent evidence from well- Strong recommendation that can
recommendation, burdens or vice versa. performed, RCTs or overwhelming apply to most patients in most
high-quality evidence of some other form. Further circumstances without reservation.
evidence research is unlikely to change Clinicians should follow a strong
confidence in the estimate of benefit recommendation unless a clear and
and risk. compelling rationale for an alternative
approach is present.
1B. Strong Benefits clearly outweigh risks and Evidence from RCTs with important Strong recommendation that applies
recommendation, burdens or vice versa. limitations (inconsistent results, to most patients. Clinicians should
moderate-quality methodologic flaws, indirect or follow a strong recommendation
evidence imprecise) or very strong evidence of unless a clear and compelling
some other research design. Further rationale for an alternative approach is
research (if performed) is likely to have present.
an effect on confidence in the
estimate of benefit and risk and may
change the estimate.
1C. Strong Benefits seem to outweigh risks and Evidence from observational studies, Strong recommendation that applies
recommendation, burdens or vice versa. unsystematic clinical experience, or to most patients. Some of the
low-quality RCTs with serious flaws. Any estimate evidence base supporting the
evidence of effect is uncertain. recommendation is, however, of low
quality.
2A. Weak Benefits closely balanced with risks Consistent evidence from well- Weak recommendation; best action
recommendation, and burdens. performed RCTs or overwhelming may differ depending on
high-quality evidence of some other form. Further circumstances or patients or societal
evidence research is unlikely to change values.
confidence in the estimate of benefit
and risk.
2B. Weak Benefits closely balanced with risks Evidence from RCTs with important Weak recommendation; alternative
recommendation, and burdens; some uncertainty in the limitations (inconsistent results, approaches likely to be better for
moderate-quality estimates of benefits, risks, and methodologic flaws, indirect or some patients under some
evidence burdens. imprecise) or very strong evidence of circumstances.
some other research design. Further
research (if performed) is likely to
influence confidence in the estimate
of benefit and risk and may change
the estimate.
2C. Weak Uncertainty in the estimates of Evidence from observational studies, Very weak recommendation, other
recommendation, benefits, risks, and burdens; benefits unsystematic clinical experience, or alternatives may be equally
low-quality may be closely balanced with risks RCTs with serious flaws. Any estimate reasonable.
evidence and burdens. of effect is uncertain.
Best practice Recommendation in which either (1)
there is an enormous amount of
indirect evidence that clearly justifies
a strong recommendation, direct
evidence would be challenging and an
inefficient use of time and resources,
to bring together and carefully
summarize, or (2) a recommendation
to the contrary would be unethical.
Adapted from Guyatt et al.227
GRADE, Grading of Recommendations Assessment, Development, and Evaluation; RCT, randomized controlled trial.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

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Guidelines
Organization Title Year of publication
81
ACIP General best practice guidelines for immunization 2023
ACIP Meningococcal vaccination86 2020
ACIP Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for 2012
adults with immunocompromising conditions87
ACOG ACOG Clinical Practice Guideline No. 4: screening and diagnosis of mental health conditions during pregnancy 2023
and postpartum113
ACOG ACOG Committee Opinion No. 495: vitamin D: screening and supplementation during pregnancy97 2011
13
ACOG ACOG Committee Opinion No. 691: carrier screening for genetic conditions 2017
ACOG ACOG Committee Opinion No. 713: antenatal corticosteroid therapy for fetal maturation110 2017
152
ACOG ACOG Committee Opinion No. 743: low-dose aspirin use during pregnancy 2018
102
ACOG ACOG Committee Opinion, No. 828: indications for outpatient antenatal fetal surveillance 2021
80
ACOG ACOG Practice Advisory: cell-free DNA to screen for single-gene disorders 2019
7
ACOG ACOG Practice Advisory: hemoglobinopathies in pregnancy 2022
ACOG ACOG Practice Bulletin No. 192: management of alloimmunization during pregnancy139 2018
47
ACOG ACOG Practice Bulletin No. 196: thromboembolism in pregnancy 2018
46
ACOG ACOG Practice Bulletin No. 197: inherited thrombophilias in pregnancy 2018
29
ACOG ACOG Practice Bulletin No. 212 Summary: pregnancy and heart disease 2019
19
ACOG ACOG Practice Bulletin, No 222: gestational hypertension and preeclampsia 2020
ACOG ACOG Practice Bulletin, No 227: fetal growth restriction100 2021
38
ASH Guidelines for sickle cell disease: cardiopulmonary and kidney disease 2019
18
ASH Guidelines for sickle cell disease: management of acute and chronic pain 2020
ASH Guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in 2020
children and adults39
ASH Guidelines for sickle cell disease: stem cell transplantation40 2021
41
ASH Guidelines for sickle cell disease: transfusion support 2020
ASH Guidelines for management of venous thromboembolism: venous thromboembolism in the context of 2018
pregnancy169
ASRM Combined hormonal contraception and the risk of venous thromboembolism: a guideline174 2017
ASRM Provision of fertility services for women at increased risk of complications during fertility treatment or 2022
pregnancy: an ethics committee opinion33
British Society for Management of sickle cell disease in pregnancy32 2021
Haematology
CDC CDC clinical practice guideline for prescribing opioids for pain124 2022
173
CDC U.S. medical eligibility criteria for contraceptive use 2016
119
National Institute Sickle cell disease: managing acute painful episodes in hospital 2012
for Health and
Care Excellence
SMFM SMFM Clinical Guideline #8: The fetus at risk of anemia-diagnosis and management140 2015
SMFM SMFM Consult Series #48: Immediate postpartum long-acting reversible contraception for women at high 2019
risk of medical complications175
SMFM SMFM Consult Series #52: Diagnosis and management of fetal growth restriction101 2020
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024. (continued)

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Guidelines (continued)
Organization Title Year of publication
154
Society of Guidelines for the management of hypertensive disorders of pregnancy 2014
Obstetric
Medicine of
Australia and New
Zealand
US Preventative Folic acid supplementation for the prevention of neural tube defects91 2017
Services Task
Force
The content of this document reflects the national and international guidelines related to the management of sickle cell disease in pregnancy.
ACIP, Advisory Committee on Immunization Practices; ACOG, American College of Obstetricians and Gynecologists; ASH, American Society of Hematology; ASRM, American Society for Reproductive
Medicine; CDC, Centers for Disease Control and Prevention; SMFM, Society for Maternal-Fetal Medicine.
Society for Maternal-Fetal Medicine. Sickle cell disease in pregnancy. Am J Obstet Gynecol 2024.

medications with lactation. Resources, such as LactMed,179 assume a significant risk of maternal morbidity and mor-
can provide contemporary, individualized information to tality. The combination of SCD, moyamoya, and preterm
enhance shared decision-making. Many medications, preeclampsia with severe features may be an indication for
including hydroxyurea, can be used safely during delivery before 34 weeks of gestation. In such cases, indi-
lactation.180e182 Preliminary data suggest that exclusive vidualized care planning should be undertaken with MFM
breastfeeding is associated with improved anthropometric and other involved specialists. Delaying delivery until ante-
indicators in children with SCD.183 natal corticosteroid administration should be individualized
on the basis of the degree of maternal hypertension,
Are there special considerations for the gestational age, and other comorbidities.
pregnant patient with sickle cell disease and
moyamoya disease? Are there any counseling or management
Moyamoya disease is a rare vascular disorder of the brain considerations for patients with isolated
resulting in compensatory vascular growth to bypass sickle cell trait?
blocked cerebral vessels that can develop in individuals with The presence of isolated SCT in pregnancy has an unclear
SCD.184e187 Symptoms of moyamoya disease include effect on perinatal outcomes. Although some studies have
headaches, seizures, visual disturbances, paralysis, weak- demonstrated increased rates of adverse outcomes, such
ness, paresthesia, and aphasia. If a patient with SCD pre- as stillbirth, preeclampsia, preterm delivery, and VTE among
sents with new-onset neurologic symptoms, consultation patients with isolated SCT, others have failed to demon-
with neurology and appropriate imaging studies are rec- strate an independent association between isolated SCT
ommended. Patients with moyamoya disease have an and any such outcomes.190e192 In 2020, the British Society
increased risk of hemorrhagic stroke, which may be for Haematology, noting the high worldwide prevalence of
aggravated by anticoagulation; therefore, anticoagulation is SCT, put out a call for further study.193 In the absence of
generally deferred.187,188 The combination of SCD, moya- high-quality data linking isolated SCT to adverse pregnancy
moya, and hypertensive disorders of pregnancy can lead to outcomes, prenatal care and genetic counseling regarding a
irreversible encephalopathy or death.189 Patients with potential risk to offspring should be provided if both parents
continuing pregnancies should be closely managed by a are carriers of SCT or a related hemoglobinopathy. An as-
multidisciplinary team. Acknowledging a lack of data, a BP sociation between SCT and urinary tract infections has been
goal of <130/80 mm Hg is reasonable for these patients to reported,194 although the benefits of increased screening in
reduce the risk of maternal stroke and death. In the setting of this population are not clear.195
a previous or current thromboembolism, a multidisciplinary
team should outline a plan of care acknowledging that How does racism impact patients with sickle
under-anticoagulation could lead to a life-threatening cell disease?
embolus and that over-anticoagulation could lead to a Any discussion of SCD must acknowledge the effects of
hemorrhagic stroke. Late preterm or early-term delivery may racism.30,31,196e198 Structural racism fuels several health
be considered in patients with SCD and moyamoya to disparities among populations affected by SCD, including
reduce the risk of preeclampsia, sudden labile BP spikes, inadequate healthcare coverage and access to care,199e201
and risk of hemorrhagic stroke and death. Patients with SCD lack of quality care because of inadequate provider knowl-
and moyamoya disease who develop severe preeclampsia edge of evidence-based guidelines,202e207 lack of sufficient

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specialty care,196 and lack of adequate research into 6. Centers for Disease Control and Prevention. Data & statistics on sickle
optimal prevention and treatment of morbidity and mortality cell disease. Available at: https://www.cdc.gov/ncbddd/sicklecell/data.
html. Accessed January 31, 2023.
associated with SCD vs other chronic illnesses.208 Optimi-
7. ACOG practice advisory: hemoglobinopathies in pregnancy. Available
zation of health outcomes for patients with SCD requires at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/
reducing the impact of structural racism at the national and articles/2022/08/hemoglobinopathies-in-pregnancy. Accessed January
institutional level.30 31, 2023.
In addition, interpersonal racism affects patients with SCD 8. Powars DR, Sandhu M, Niland-Weiss J, Johnson C, Bruce S,
Manning PR. Pregnancy in sickle cell disease. Obstet Gynecol 1986;67:
in the form of implicit bias and explicit discrimination. There
217–28.
are published reports of racial disparities in pain manage- 9. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet
ment209,210 and bias against Black patients,211,212 patients 2010;376:2018–31.
with chronic pain,213,214 women with pain,215e217 and, 10. Shah N, Beenhouwer D, Broder MS, et al. Development of a severity
specifically, patients with SCD.218,219 The intersection of classification system for sickle cell disease. Clinicoecon Outcomes Res
2020;12:625–33.
discrimination and chronic pain faced by patients with SCD
11. United States Preventive Services Task Force. Screening for sickle cell
may have a compounding effect on the overall burden of disease in newborns: recommendation statement. Am Fam Phys 2008;77:
SCD.220e222 In addition, discrimination contributes to the 1300–2.
undertreatment of pain in patients with SCD, who may be 12. Kutlar F. Diagnostic approach to hemoglobinopathies. Hemoglobin
unfairly labeled “difficult” or “drug-seeking” when request- 2007/01/01;31:243–50.
13. ACOG Committee Opinion No. 691: carrier screening for genetic
ing appropriate pain management.223e225 To minimize the
conditions. Obstet Gynecol 2017;129:e41–55.
effect of interpersonal racism on patients with SCD, 14. Yusuf HR, Atrash HK, Grosse SD, Parker CS, Grant AM. Emergency
healthcare providers must recognize and correct implicit department visits made by patients with sickle cell disease: a descriptive
biases, endeavoring to treat patients equitably, regardless study, 1999-2007. Am J Prev Med 2010;38(4Suppl):S536–41.
of race.30 15. Fingar KR, Owens PL, Reid LD, Mistry KB, Barrett ML. Characteristics
of inpatient hospital stays involving sickle cell disease, 2000-2016. In:
Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet].
Recommendations for future research on Rockville, MD: Agency for Healthcare Research and Quality; 2006. Sta-
sickle cell disease in pregnancy tistical Brief #251.
With rare exceptions, management recommendations 16. Serjeant GR, Ceulaer CD, Lethbridge R, Morris J, Singhal A,
throughout this document are largely based on observa- Thomas PW. The painful crisis of homozygous sickle cell disease: clinical
features. Br J Haematol 1994;87:586–91.
tional data. SCD research receives less federal and foun-
17. Kato GJ, Piel FB, Reid CD, et al. Sickle cell disease. Nat Rev Dis
dation funding per patient compared with other comparable Primers 2018;4:18010.
diseases,208 and rigorous data on the management of 18. Brandow AM, Carroll CP, Creary S, et al. American Society of Hema-
pregnant people with SCD are especially limited. We tology 2020 guidelines for sickle cell disease: management of acute and
encourage funding allocations that prioritize equity and aim chronic pain. Blood Adv 2020;4:2656–701.
19. Gestational hypertension and preeclampsia: ACOG Practice Bulletin,
to reduce this disparity, such as federal support for
Number 222. Obstet Gynecol 2020;135:e237–60.
comprehensive SCD centers. We advocate for the inclusion 20. Fitzhugh CD, Lauder N, Jonassaint JC, et al. Cardiopulmonary com-
of pregnant patients with SCD in ongoing research studies plications leading to premature deaths in adult patients with sickle cell
and for additional rigorous, prospective, randomized disease. Am J Hematol 2010;85:36–40.
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22. Elmariah H, Garrett ME, De Castro LM, et al. Factors associated with
outcomes for pregnant patients with SCD and their children
survival in a contemporary adult sickle cell disease cohort. Am J Hematol
requires addressing the effect of racism at the institutional 2014;89:530–5.
level through efforts, such as antiracism taskforces, 23. Kuo K, Caughey AB. Contemporary outcomes of sickle cell disease in
reporting systems for racist behavior, implicit bias training, pregnancy. Am J Obstet Gynecol 2016;215:505.e1–5.
and open dialogue with colleagues. n 24. Oteng-Ntim E, Meeks D, Seed PT, et al. Adverse maternal and peri-
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All authors and committee members have filed a disclosure of interests
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delineating personal, professional, business, or other relevant financial
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or nonfinancial interests in relation to this publication. Any substantial
212. James SA. The strangest of all encounters: racial and ethnic
conflicts of interest have been addressed through a process approved
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by the Society for Maternal-Fetal Medicine (SMFM) Board of Directors.
e00104416.
The SMFM has neither solicited nor accepted any commercial
213. Weinstein SM, Laux LF, Thornby JI, et al. Physicians’ attitudes toward
involvement in the specific content development of this publication.
pain and the use of opioid analgesics: results of a survey from the Texas
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214. FitzGerald C, Hurst S. Implicit bias in healthcare professionals: a This document has undergone an internal peer review through a
systematic review. BMC Med Ethics 2017;18:19. multilevel committee process within the SMFM. This review involves
215. Schäfer G, Prkachin KM, Kaseweter KA, Williams ACdC. Health care critique and feedback from the SMFM Publications and Document
providers’ judgments in chronic pain: the influence of gender and trust- Review Committees and final approval by the SMFM Executive Com-
worthiness. Pain 2016;157:1618–25. mittee. The SMFM accepts sole responsibility for the document con-
216. Tait RC, Chibnall JT. Racial/ethnic disparities in the assessment and tent. SMFM publications do not undergo editorial and peer review by
treatment of pain: psychosocial perspectives. Am Psychol 2014;69: the American Journal of Obstetrics & Gynecology. The SMFM Publi-
131–41. cations Committee reviews publications every 18 to 24 months and
217. Hoffmann DE, Tarzian AJ. The girl who cried pain: a bias against issues updates as needed. Further details regarding SMFM publica-
women in the treatment of pain. J Law Med Ethics 2001;29:13–27. tions can be found at www.smfm.org/publications.
218. DeLaune J, Close J, Murphy M. Addressing bias towards patients
with sickle cell disease. Lancet Haematol 2020;7:e508.
219. Bediako SM, Moffitt KR. Race and social attitudes about sickle cell The SMFM recognizes that obstetrical patients have diverse gender
disease. Ethn Health 2011;16:423–9. identities and is striving to use gender-inclusive language in all of its
220. Haywood C Jr, Diener-West M, Strouse J, et al. Perceived discrimi- publications. The SMFM will be using the terms “pregnant person” and
nation in health care is associated with a greater burden of pain in sickle cell “pregnant individual” instead of “pregnant woman” and will use the
disease. J Pain Symptom Manage 2014;48:934–43. singular pronoun “they.” When describing study populations used in
221. Mathur VA, Kiley KB, Haywood C Jr, et al. Multiple levels of suffering: research, the SMFM will use the gender terminology reported by the
discrimination in health-care settings is associated with enhanced labo- study investigators.
ratory pain sensitivity in sickle cell disease. Clin J Pain 2016;32:1076–85.
222. Kanter J, Gibson R, Lawrence RH, et al. Perceptions of US adoles- All questions or comments regarding the document should be referred
cents and adults with sickle cell disease on their quality of care. JAMA Netw to the SMFM Publications Committee at [email protected].
Open 2020;3:e206016.
223. Bergman EJ, Diamond NJ. Sickle cell disease and the ”difficult pa-
tient” conundrum. Am J Bioeth 2013;13:3–10. Reprints will not be available.

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