INTRODUCTION — Although most pregnancies complicated by maternal sickle cell disease (SCD) are likely to result in livebirth, these pregnancies are at increased risk of obstetrical and fetal complications, as well as medical complications of SCD [1-4]. These risks are due, at least in part, to the metabolic demands, hypercoagulable state, and vascular stasis associated with pregnancy. Access to a multidisciplinary care team knowledgeable about sickle cell disease and high-risk obstetrics can significantly decrease morbidity and mortality.
Pregnancy-related issues in management of patients with SCD will be discussed here. General issues regarding clinical features, pathophysiology, diagnosis, and management of SCD are reviewed separately.
●(See "Overview of the clinical manifestations of sickle cell disease".)
●(See "Pathophysiology of sickle cell disease".)
●(See "Diagnosis of sickle cell disorders".)
●(See "Overview of the management and prognosis of sickle cell disease".)
PRE-PREGNANCY ISSUES — Given the risks of pregnancy for women with SCD and the fetus, preconceptional assessment and counseling, including referral to a genetic counselor, are recommended. The majority of women with SCD who become pregnant have not had adequate or effective preconception counseling, which should include information about the hemoglobin status of their partner, the likelihood of a newborn with SCD, the risk of pregnancy to their own health, and an awareness of available reproductive options [5,6].
Prepregnancy evaluation — The patient's clinical history of pain events and hospitalizations should be reviewed, and a detailed evaluation should be performed because of the increased prevalence of end-organ dysfunction (eg, sickle nephropathy) in adults with SCD. This evaluation generally includes:
●Confirmation of definitive diagnosis. (See "Diagnosis of sickle cell disorders".)
●Measurement of baseline blood pressure. Hypertension may be due to sickle nephropathy and is a risk factor for stroke and development of superimposed preeclampsia. (See "Sickle cell disease effects on the kidney" and "Preeclampsia: Clinical features and diagnosis" and "Overview of the clinical manifestations of sickle cell disease", section on 'Stroke and TIA'.)
●Retinal evaluation to detect early proliferative sickle retinopathy, which may worsen during pregnancy. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Retinopathy'.)
●Chemistry panel, urinalysis, and 24-hour protein excretion to determine baseline organ function, particularly sickle nephropathy. Knowledge of baseline parameters is important because both pregnancy and preeclampsia (which is common in SCD patients) may worsen renal function. (See "Sickle cell disease effects on the kidney".) The author obtains a baseline 24-hour urine collection to determine creatinine clearance and protein excretion, but the protein-to-creatinine ratio on a spot urine sample is also acceptable [7]. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)
●Hemoglobin/hematocrit and ferritin level. Women with SCD often have excessive iron stores, but a small proportion is iron deficient. Women with excessive iron stores should not receive prenatal vitamins with iron and should consider delaying pregnancy until they have been treated with iron chelators, which are contraindicated in pregnancy. (See "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Excessive iron stores'.)
●Baseline urine culture, because of the increased frequency of asymptomatic bacteriuria. Urinary tract infections are more common in sickle cell disease and more difficult to treat because of underlying renal papillary necrosis. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Asymptomatic bacteriuria'.)
●Baseline pulmonary function tests, including pulse oximetry, are recommended because of the increased risk of pulmonary embolism, acute chest syndrome, and bronchoreactive lung disease in pregnancy. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Pulmonary complications'.)
●Hepatitis B and C screening to assess risk of perinatal transmission. (See "Pregnancy in women with pre-existing chronic liver disease".)
●There are no formal guidelines to screen for pulmonary hypertension in pregnant women with SCD. Limited preliminary evidence justifies screening with an echocardiogram for pulmonary hypertension and early cardiac dysfunction, which are associated with increased mortality in pregnant women with SCD. Until additional evidence becomes available, we favor an individualized approach to determining the use of echocardiography. (See "Acquired heart disease and pregnancy" and "Overview of the clinical manifestations of sickle cell disease", section on 'Cardiac complications'.)
●Serologic red cell phenotyping and screening for red cell alloimmunization to identify patients with multiple red cell alloantibodies who may be difficult to match for transfusion and may be at risk for hemolytic disease of the fetus and newborn [8,9]. If the woman has alloantibodies to red cell antigens, her partner should be tested for the corresponding antigens. If the partner tests positive for the corresponding antigens, counseling concerning the risk of hemolytic disease of the newborn should be provided, and a plan for managing the pregnancy is made with a maternal-fetal specialist [10]. (See "Management of non-RhD red blood cell alloantibodies during pregnancy".)
●Testing partner for hemoglobinopathy [8,9]. The risk of SCD in offspring is 50 percent if the biologic father is heterozygous; the risk is 100 percent if he is homozygous. (See "Diagnosis of sickle cell disorders".)
Genetic counseling — Referral to a genetic counselor is useful to discuss the type and risk of inherited disease in offspring, and the variability of phenotype. This is also a good time to discuss the range of pregnancy options, as appropriate, including:
●Use of donor sperm from a male without hemoglobinopathy. This will ensure that the offspring will be heterozygous (ie, have sickle cell trait), which is essentially a benign carrier state. (See "Donor insemination" and "Sickle cell trait".)
●Preimplantation genetic diagnosis for selection of embryos without SCD. Preimplantation genetic diagnosis (PGD) of SCD is an option for couples whose goal is to only establish pregnancies in which the child is unaffected by SCD [11]. For PGD, the couple must conceive via in vitro fertilization (IVF). Preimplantation embryos are biopsied and only those unaffected by SCD are selected for transfer into the uterus. If HLA typing is also performed, unaffected embryos who are also HLA identical to an affected sibling can be selected to allow future stem cell transplantation of that sibling. PGD is expensive and may decrease the chance of achieving pregnancy and livebirth compared with natural conception, but there does not appear to be any long-term harm to offspring. (See "Preimplantation genetic testing".)
●Prenatal diagnosis, with the option of termination of an affected pregnancy (See 'Prenatal diagnosis' below.)
●A gestational carrier pregnancy allows the patient to avoid both the maternal and fetal risks associated with pregnancy complicated by SCD. A gestational carrier is a woman who agrees to carry a pregnancy for another woman (intended mother). The intended mother provides the egg and the intended father provides the sperm; egg donors or sperm donors without hemoglobinopathy can also be used. Conception is achieved via IVF, and the resulting embryo is transferred into the uterus of the gestational carrier. The gestational carrier has no genetic connection to the embryo. (See "Gestational carrier pregnancy".)
●In a traditional surrogate pregnancy, the surrogate, who does not have a hemoglobinopathy, undergoes intrauterine insemination (IUI) of sperm from the intended father (or a sperm donor). Therefore, the surrogate has a genetic, as well as a gestational, connection to the embryo. (See "Gestational carrier pregnancy".)
●Adoption is another option.
Management of medications and immunizations
●Immunization – Immunization status should be reviewed and updated, as needed, to comply with current guidelines. Polyvalent pneumococcal, Haemophilus influenza type B, and meningococcal vaccines are recommended for pregnant patients with SCD. Pregnancy should be avoided for at least four weeks after administration of a live vaccine. (See "Standard immunizations for nonpregnant adults" and "Immunizations during pregnancy".)
●Folic acid – Folic acid supplementation (0.4 to 0.8 mg/day) is recommended for all women of reproductive age to reduce the risk of neural tube defects in offspring. (See "Folic acid supplementation in pregnancy".)
There is consensus opinion among experts that the dose should be higher in women with SCD to accommodate this requirement, as well as routine pregnancy requirements and SCD requirements related to hemolysis. No dose finding studies have been performed. A dose of 4 or 5 mg/day has been recommended because it is likely to satisfy all of these needs [4,12]. This is higher than the dose found in prenatal vitamins (1 mg).
●Hydroxyurea – Many patients will be on hydroxyurea (hydroxycarbamide) therapy. Exposure to hydroxyurea, alone or in combination with other drugs, has been reported in fewer than 100 human pregnancies, including approximately 40 first trimester exposures [13]. An increase in major congenital defects was not observed in these limited human data but has been reported in animal studies. Given the relatively small number of exposed pregnancies and the observation that hydroxyurea produced malformations in animal studies, it is prudent to discontinue hydroxyurea three months before conception [4]. (See "Hydroxyurea use in sickle cell disease", section on 'Adverse effects'.)
●Iron chelators – Females on iron chelation therapy may continue this therapy until they conceive, but it should be discontinued at that time. In experimental animal studies, deferasirox did not increase the risk of congenital anomalies at doses lower than those used in humans, but deferoxamine was associated with congenital anomalies in some animal studies [13,14]. Data from exposure in humans are limited [15], especially for deferasirox, but no toxic or teratogenic effects have been reported. Individuals with excessive iron stores should consider delaying pregnancy until treatment has been completed. (See "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Excessive iron stores'.)
●ACE inhibitors and ARBs – Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are teratogenic and should not be used during pregnancy. Women using these drugs for treatment of hypertension should be switched to another drug, ideally at least one month before they attempt to conceive. Long-acting nifedipine, labetalol, and methyldopa are commonly used antihypertensive medications in pregnancy. Long-acting nifedipine is often favored for use in SCD. Short-acting nifedipine, while generally safe, may result in a sudden fall in blood pressure and is less commonly used. Labetalol, an alpha- and beta-adrenergic blocking agent, is also used in SCD. However, it is associated with maternal hepatotoxicity and therefore is not favored in patients with liver disease. Methyldopa may induce a positive Coombs test and occasionally a hemolytic anemia. Therefore, its use may complicate the interpretation of transfusion reactions in sickle cell patients on transfusion therapy.
Women using these drugs for prevention of progression of proteinuric or microalbuminuric kidney disease should be counseled about early detection of pregnancy. In this situation, they may continue to use these drugs but should discontinue the ACE inhibitor or ARB if their menstrual period is delayed by more than two days, at which time they should have a sensitive pregnancy test and consult with their physician. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy" and "Sickle cell disease effects on the kidney", section on 'Hypertension' and "Chronic hypertension in pregnancy: Prenatal and postpartum care".)
●Prophylactic penicillin – Prophylactic penicillin therapy may be continued during pregnancy. Penicillin has an excellent maternal-fetal safety profile for use in pregnancy. We do not routinely initiate penicillin prophylaxis because of pregnancy but continue it in patients who are already taking prophylaxis. In England, penicillin prophylaxis is recommended based on the hyposplenism associated with SCD [16], but evidence supporting this approach in pregnant women is not available.
●Analgesia – Pain can be managed using standard therapies.
•For mild pain, we use acetaminophen rather than nonsteroidal antiinflammatory drugs (NSAIDs), as NSAIDs may interfere with ovulation, thereby reducing the probability of conception.
•For moderate pain, we use hydrocodone with or without acetaminophen.
•For mild and moderate pain, nonmedicinal strategies (massage, warm heating pads, mind-body techniques) may hasten recovery and may be sufficient to manage pain in some cases.
•For severe pain, opioids are indicated. (See "Acute vaso-occlusive pain management in sickle cell disease".)
Management of pain during pregnancy is discussed below. (See 'Management of acute painful episodes' below.)
Counseling about medical, obstetrical, and infant outcomes — Several reviews and meta-analyses have consistently found increased risk of maternal deaths and obstetric and fetal complications in pregnant women with SCD when compared with controls [17,18]. These complications can be significantly decreased by early management of a multidisciplinary care team [19].
SCD course during pregnancy — There is consistent evidence that anemia and vaso-occlusive or acute painful episodes occur more often in pregnancy and are the most common maternal SCD complications associated with pregnancy, occurring in over 50 percent of pregnant women [20-27]. Painful episodes are more common with advancing pregnancy and postpartum [21]. The vast majority of the acute vaso-occlusive events (pain and acute chest syndrome) occur during the third trimester [28].
Mortality in women with SCD who became pregnant was evaluated in a systematic review and meta-analysis of cohort studies that included over 26,800 pregnancies in women with SCD, versus 26 million pregnancies in women without SCD [17]. The risk of maternal mortality in women with homozygous sickle hemoglobin was increased compared with controls (relative risk [RR] of death during pregnancy 5.98; 95% CI 1.94-18.44). The risk of death was lower in hemoglobin SC disease (one death in 279 pregnancies). High mortality rate was most pronounced in resource-poor settings (defined by gross national income) in this and other studies [18]. (See "Sickle cell disease in sub-Saharan Africa".)
In a prospective study from 2019 that looked specifically at low-resource settings in Ghana, the frequency of maternal death among women with SCD versus without SCD or trait was 1.3 percent (2/149) and 0.9 percent (1/117), respectively [29]. For women with SCD, this corresponds to a maternal mortality ratio of 100 maternal deaths per 1000 live births. By comparison, in 2017, the maternal mortality ratios for all of Ghana and for the United States were 3 and 0.2 per 1000 live births, respectively [30].
The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project of the US Agency for Healthcare Research and Quality, which included almost 18,000 deliveries with a discharge diagnosis of SCD and 17 million deliveries to women without SCD for the years 2000 to 2003 [3]. In this study, women with SCD accounted for 0.1 percent of the pregnancies but 1 percent of all maternal deaths. There were 10 deaths in the SCD group (mortality 72 deaths per 100,000 deliveries versus 12.7 deaths per 100,000 deliveries in women without SCD). Additional information on pregnancy outcomes was also reported. Compared with women without SCD, women with SCD were at increased risk of the following (odds ratios [ORs] in parentheses):
●Transfusion (OR 22.5; 95% CI 18.7-27.0)
●Systemic inflammatory response syndrome (SIRS; OR 12.6; 95% CI 2.1-13.6)
●Pneumonia (OR 9.8; 95% CI 8.0-12.0)
●Sepsis (OR 6.8; 95% CI 4.4-10.5)
●Asymptomatic bacteriuria (OR 6.8, 95% CI 3.1-14.9)
●Cerebral vein thrombosis (OR 4.9; 95% CI 2.2-10.9)
●Deep vein thrombosis (OR 2.5; 95% CI 1.5-4.1)
●Genitourinary tract infection (OR 2.3, 95% CI 1.9-2.7)
There was no statistical difference in rates of stroke (OR 2.0; 95% CI 0.6-6.9), pyelonephritis (OR 1.3; 95% CI 1.0-1.8), pulmonary embolus (OR 1.7; 95% CI 0.9-3.1), or myocardial infarction (OR 0). The findings in this report need to be interpreted cautiously because of limitations in the quality of the data, which were based on discharge codes and drawn exclusively from discharge record abstractions.
There are no studies this large comparing medical complication rates in pregnant women with SCD versus nonpregnant women with SCD. However, one well-designed study of 286 women with SCD concluded that rates of maternal morbidity from SCD were the same during pregnancy as during the nonpregnant state [1].
Pregnancy outcome — In addition to maternal outcomes described above (see 'SCD course during pregnancy' above), a pooled analysis of 16 available studies conducted through 2014 revealed the following increased risks in SCD pregnancies [18]:
●Fetal growth restriction (OR 2.79, 95% CI 1.85–4.21)
●Perinatal mortality (OR 3.76, 95% CI 2.34–6.06)
●Low birthweight (OR 2.00, 95% CI 1.42–2.83)
●Preeclampsia (OR 2.05, 95% CI 1.47–2.85)
●Maternal mortality (OR 10.91, 95% CI 1.83–65.11, p = 0.009)
●Eclampsia (OR 3.02, 95% CI 1.20–7.58)
Among pregnant women with SCD living in low- and middle-income countries, there is a significant increase in the likelihood of maternal death (OR 22.81, 95% CI 14.67–35.46, p <0.001) that is clearly amendable with improvement in multidisciplinary care. Further,
Other studies reveal women with SCD had a lower rate of postpartum hemorrhage (OR 0.5; 95% CI 0.3-0.6). There was no statistical difference in rates of gestational diabetes (OR 1.0; 95% CI 0.8-1.2) or intrauterine fetal death (OR 1.1; 95% CI 0.8-1.7). Similar pregnancy outcomes were reported in subsequently published meta-analyses [17,18], except maternal SCD was associated with higher odds of perinatal mortality (pooled OR 3.76, 95% CI 2.34-6.06) [18].
Medical and obstetrical complications would be expected to result in an increased risk of preterm birth less than 37 weeks. In a study from Grady Hospital in Atlanta, SCD patients were four times more likely than African-American HbAA patients to have a preterm delivery, and their mean gestational age at delivery was 34.1 weeks [31]. By comparison, in a study from Jamaica, the preterm birth rate was threefold higher among SCD patients but the mean gestational age at delivery for SCD and HbAA patients was 37.0 and 38.7 weeks, respectively [2].
Hospital discharge data do not capture miscarriage rates, as many of these women are managed in nonhospital settings. In a cohort study, women with SCD (n=52 women, 94 pregnancies) had an increased rate of miscarriage compared with non-SCD controls (n=68 women, 157 pregnancies) (miscarriage: 36 percent versus 10 percent, p<0.001).
The cesarean delivery rate tends to be higher in women with SCD. The increased rate is related to a higher frequency of pregnancy complications, and some centers have policies for a short trial of labor and early operative intervention at the first sign of a nonreassuring fetal heart rate tracing [32].
Birth outcome of affected infants — SCD of the fetus/neonate does not appear to influence birth outcome and neonatal course, when matched for gestational age and birthweight [33]. This is because sickling events do not occur until the production of fetal hemoglobin is replaced by the production of hemoglobin S, which usually occurs between 3 and 12 months of age [33,34]. However, life-threatening events, such as acute sequestration crisis, can occur in the first year of life [35]. (See "Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance".)
Effect of sickle disease genotype — Few studies have distinguished between the course of pregnancy for different SCD genotypes: hemoglobin (Hb) SS versus SC versus S-beta-thalassemia. The course of pregnancy in women with HbSC is generally more benign than in those with HbSS (eg, lower risk of acute pain, lower risk of critical care unit admission), but there is a spectrum of severity and severe complications are not rare among women with HbSC [20,36-38]. The risk of acute chest syndrome is similar for women with HbSS and those with HbSC [38].
Effect of sickle cell trait — In general, sickle cell trait has been investigated as a risk factor for several complications [39]. There is convincing evidence of its association with renal complications, including hematuria, hyposthenuria, and chronic kidney disease [40]. In addition, there is good evidence for sickle cell trait being a risk factor in deep vein thrombosis and pulmonary embolism [41].
However, it is unclear whether sickle cell trait is associated with an increased risk for pregnancy complications [39,42]. In a systematic review including nine studies, some studies showed a protective effect of sickle cell trait for preterm birth and stillbirth, and some showed an increased risk of anemia and bacteriuria [43]. Given the poor methodological quality of most of these studies, the results are difficult to interpret.
It is not clear whether women with sickle cell trait require any modification to routine pregnancy care because of their carrier status. Although a chart-based review comparing Black pregnant women with sickle cell trait to those without showed no increased risk of VTE in those with sickle cell trait, the study was underpowered to detect small differences [44]. In a nonpregnant population, others have observed an increased risk of VTE in African Americans with sickle cell trait compared with those with the wild-type genotype (see "Sickle cell trait", section on 'Vaso-occlusive phenomena') [41].
For this reason, we stress leg exercises, preventive anti-embolism stockings, and sequential compression devices for individuals with sickle cell trait requiring bedrest, as well as resumption of ambulation as early as possible. We follow the recommendations for heparin use for high risk populations [45]. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)
Because individuals with sickle cell trait are at risk for bacteruria and hematuria, we obtain a detailed history of any previous urinary abnormalities. If the history or initial urine screening tests are abnormal, we perform frequent surveillance testing. Screening and treatment are indicated because asymptomatic bacteriuria during pregnancy increases the risk of pyelonephritis and has been associated with adverse pregnancy outcomes, such as preterm birth and low birth weight infants. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)
It is important to test the woman's partner for hemoglobinopathy since their offspring would be a risk of homozygous hemoglobinopathy if both parents are carriers. (See "Prenatal screening and testing for hemoglobinopathy", section on 'Identifying at-risk parents'.)
MANAGEMENT DURING PREGNANCY
Prenatal care — Although complications are observed more frequently in women with HbSS than HbSC or HbS/beta-thalassemia, the level of care in pregnancy is the same for all of these disorders [4]. In addition to routine prenatal care, the following considerations apply to pregnant women with SCD. (See "Prenatal care: Initial assessment" and "Prenatal care: Second and third trimesters".)
●Access to a multidisciplinary care team knowledgeable about SCD and high-risk obstetrics can significantly decrease morbidity and mortality. It is useful to have a patient care plan available to all clinicians who may be responsible for the patient if she has a painful crisis. There should be appropriate protocols for transfusion indications, and early detection and management of SCD complications, including infection. Individualized pain care plans should provide narcotic doses, an algorithm for sending the patient to the emergency department, and instructions for the emergency department. Implementation of active management protocols for pregnancy in SCD decreased the mortality rate in Benin, Africa, from 27 percent to 1.8 percent [46].
●If some or all of the baseline evaluation was omitted pre-pregnancy, the missing assessments should be performed in early pregnancy. (See 'Prepregnancy evaluation' above.)
●We suggest monthly determination of hemoglobin level and chemistry panel. In our experience, these screening tests help with early identification of patients at greater risk for acute complications. While not prospectively evaluated, a similar approach has been adopted in the United Kingdom guidelines [4].
●Iron deficiency is not common in women with SCD, even those who are anemic, because chronic hemolysis and repeated blood transfusions often result in adequate or excessive iron stores. Therefore, iron supplementation is avoided unless iron deficiency is documented by a low serum ferritin level [47]. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Pregnancy'.)
●Folic acid supplementation should be continued during pregnancy (see 'Management of medications and immunizations' above). No dose finding studies have been performed. A dose of 5 mg/day has been recommended as likely to satisfy all of these needs [4]. This is higher than the dose found in prenatal vitamins (1 mg).
●Nausea and vomiting of pregnancy is common in all pregnant women. Control of symptoms, especially prevention of dehydration from anorexia or vomiting, may help to decrease the incidence of acute painful episodes [34]. (See "Nausea and vomiting of pregnancy: Treatment and outcome".)
●There are no convincing data to guide the frequency of screening for asymptomatic bacteriuria or the optimum approach to treatment. We suggest baseline and serial screening with urinalysis and culture [3]. For women with asymptomatic bacteriuria on initial urine culture, we prescribe a course of antibiotic therapy and retest monthly until delivery. If they have recurrent or persistent bacteriuria, we give suppressive therapy for the remainder of pregnancy. For women whose initial urine culture is negative, some clinicians screen each trimester, and others, including the author, rescreen monthly [16]. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Management'.)
●Close monitoring for development of preeclampsia is a standard part of prenatal care in all pregnancies.
Given the increased risk of preeclampsia, we administer low-dose aspirin from the beginning of the second trimester to 5 to 10 days before the expected date of delivery as long as aspirin is not contraindicated [48]. Guidelines for selecting women at moderate to high risk of developing preeclampsia who might benefit from low-dose aspirin therapy are reviewed separately. (See "Preeclampsia: Prevention", section on 'Candidates'.)
In patients with neurological signs and symptoms, it is important to distinguish preeclampsia/eclampsia from cerebrovascular disease related to SCD. (See "Acute ischemic and hemorrhagic stroke in sickle cell disease".)
●Since there is an increased risk of venous thromboembolism (VTE) in pregnancy, unless contraindicated, all hospitalizations should include VTE prophylaxis (see 'VTE prophylaxis during antepartum hospitalization' below). Since patients with SCD have an increased risk of pulmonary embolism (PE), VTE prophylaxis during the entire pregnancy may be appropriate for some high-risk patients (such as those with a history of PE) (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Patients who are pregnant'.)
●Given the possibility of placental ischemia [49,50], monitoring fetal growth with ultrasound and fetal well-being with nonstress tests or biophysical profile scoring is reasonable during the third trimester. There are no high quality data on which to base recommendations for the optimum method and frequency of screening for fetal growth restriction and fetal hypoxemia.
A guideline from the United Kingdom suggests ultrasound examinations at weeks 11 to 13 to establish the estimated date of delivery and screen for Down syndrome; weeks 18 to 20 to screen for congenital anomalies; and weeks 28, 32, and 36 to screen for fetal growth restriction [4]. (See "Fetal growth restriction: Screening and diagnosis" and "Overview of antepartum fetal assessment".)
If placental ischemia is suspected because of impaired fetal growth, preeclampsia, or abruption, management is the same as that for non-SCD pregnancies with these complications. (See "Preeclampsia: Antepartum management and timing of delivery" and "Acute placental abruption: Management and long-term prognosis" and "Fetal growth restriction: Evaluation".)
●Women with SCD have a high rate of alloimmunization, which should be assessed at the first prenatal visit. If negative initially, we usually repeat such testing at 24 to 28 weeks and again when the patient is admitted at the time of delivery.
Women with alloantibodies should be evaluated for risk of hemolytic disease of the fetus and newborn and managed accordingly. (See "Management of non-RhD red blood cell alloantibodies during pregnancy".)
In addition, the transfusion service should be notified so compatible blood is available for transfusion, if needed peripartum. Patients with sickle cell disease have an increased rate of alloimmunization due to differences in common antigens with the donors. This has resulted in the frequent use of limited red cell phenotypic matching for C, E, and Kell antigens. However, people of African descent have an additional increased risk of alloimmunization due to the high rate of Rh variants. Patients with Rh variants have incomplete antigens that will type positive for Rh when serologically tested, but the patient may develop Rh antibodies when exposed to the complete Rh antigen during transfusion or pregnancy. Molecular testing for Rh variants is expensive and its clinical applicability is being studied. In selected sickle cell patients who are at high risk for further alloimmunization and transfusion reactions during pregnancy, DNA testing for these Rh variants should be discussed with a transfusion medicine specialist and high-risk perinatal specialists [51-54]. (See "Management of non-RhD red blood cell alloantibodies during pregnancy" and "Transfusion in individuals with complex serologies on pretransfusion testing", section on 'Sickle cell disease' and "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Transfusion techniques'.)
The increased risk of alloimmunization in sickle cell disease does not change the standard recommendations for the use of anti-D immune globulin (eg, HyperRho S/D, RhoGAM) when appropriate. (See "RhD alloimmunization in pregnancy: Overview" and "RhD alloimmunization: Prevention in pregnant and postpartum patients".)
●Multiple gestation – In our experience, multiple gestation in women with SCD substantially increases the risk of preeclampsia, hypertension, vaso-occlusive episodes, and acute anemic events; therefore, these pregnancies require close attention.
In one report, most women with SCD who had multiple gestation experienced acute complications requiring hospitalization, including acute chest syndrome and cardiomyopathy [55]. These pregnancies require vigilant monitoring by a multidisciplinary team, with low-dose aspirin for prevention of preeclampsia; thromboprophylaxis; and consideration of prophylactic transfusion with phenotypically matched red cell units, especially for women with preexisting cardiac, renal, or pulmonary complications, and those with frequent episodes of acute vaso-occlusive pain or acute chest syndrome (see 'Prophylactic transfusion' below). These patients should be followed closely at a tertiary obstetrical center with involvement of a hematologist with expertise in managing SCD.
●Home-based prophylactic oxygen therapy – In SCD, oxygen demands may be increased due to several factors including anemia, sleep-disordered breathing, hypoxia, and/or asthma. Preliminary data from a retrospective study suggest that prophylactic nocturnal oxygen therapy may decrease transfusion requirements and complications, particularly in high-risk individuals [56]. In this study, oxygen was administered at 2 to 3 L/minute via an appropriately sized nose piece.
Prenatal diagnosis — Evaluation of the fetus for sickle hemoglobin, as well as other hemoglobinopathies, can be performed in at-risk pregnancies using invasive techniques, such as chorionic villus biopsy at 10 to 13 weeks of gestation or amniocentesis as early as 15 to 16 weeks. Fetal blood sampling can be performed after 20 weeks of gestation but is associated with a higher risk of fetal loss (1 to 2 percent) and has no advantage over other methods. (See "Prenatal screening and testing for hemoglobinopathy".)
Noninvasive detection of fetal SCD by evaluation of cell-free DNA in maternal plasma is under investigation. Clinical studies of this approach are promising, with a high sensitivity and specificity rate [57-59]. However, this testing is not commercially available.
A variety of personal factors influence parental decisions about termination of pregnancy when test results indicate an affected fetus. Early gestational age at the time of diagnosis also appears to affect this decision [60].
While pregnancy termination is usually well tolerated in SCD, the disease is a risk factor for increased severity of termination complications [61]. In our experience, these women have a very high incidence of acute painful episodes after pregnancy termination. Therefore, we suggest an inpatient procedure with intravenous hydration before and for 24 hours after the procedure. (See "Overview of pregnancy termination".)
Management of acute painful episodes — Dehydration, hypoxia, acidosis, infection, and cold may precipitate an acute pain event; therefore, these conditions should be avoided, if possible [4].
A 2009 Cochrane systematic review did not find any randomized trials addressing the efficacy and safety of treatment approaches for sickle cell pain events during pregnancy [62]. The standard approach to management consists of the following:
●Prompt evaluation for precipitating factors (eg, dehydration, hypoxia) and potential causes (particularly infection).
●Oral or intravenous fluid resuscitation.
●Aggressive pain control, similar to that used for women with SCD who are not pregnant [63]:
•Mild pain may be treated with acetaminophen.
•Use of nonsteroidal antiinflammatory drugs (NSAIDs) should be minimized, but a short course is reasonable given the lack of a clearly safer alternative. Whether NSAID use in the first trimester increases the risk of miscarriage, cardiac defects, or gastroschisis is unclear; epidemiologic studies have reported conflicting results [13].
NSAIDs are generally avoided after about 32 weeks of gestation because of an increased risk of premature narrowing or closure of the ductus arteriosus. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)
•Moderate pain may be treated with hydrocodone with or without acetaminophen.
•For mild and moderate pain, nonmedicinal strategies (message, warm heating pads, mind-body techniques) may be sufficient to manage the pain or hasten recovery.
•For severe pain, opioids are the therapy of choice.
•Epidural analgesia may be appropriate in some cases.
Additional information about evaluating pain and treating vaso-occlusive pain is presented separately. (See "Evaluation of acute pain in sickle cell disease" and "Acute vaso-occlusive pain management in sickle cell disease".)
Management of other complications of SCD — Management of other complications of SCD (eg, infection, acute chest syndrome) is generally similar to that in nonpregnant women. The risks of specific medications used to treat or prevent these complications in pregnant women can be checked by searching on the drug name in UpToDate and reading the pregnancy implications section of the drug information topic. The pregnancy risks need to be weighed against the risks of alternative medications or no treatment. (See "Evaluation and management of fever in children and adults with sickle cell disease" and "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)
We typically discontinue hydroxyurea prior to conception and do not restart it until the infant is weaned (no longer breastfeeding). Individuals who were receiving hydroxyurea prior to pregnancy may require transfusions. (See 'Transfusion therapy' below.)
Although the safety of radiation exposure during pregnancy is a common concern, a missed or delayed diagnosis of pulmonary embolism can pose a greater risk to the woman and her pregnancy than any hazard associated with ionizing radiation from diagnostic studies, such as chest x-ray, ventilation/perfusion (V/Q) lung scanning, computed tomographic pulmonary angiography (CTPA), or digital subtraction angiography. (See "Diagnostic imaging in pregnant and nursing patients" and "Diagnosis of pulmonary embolism in pregnancy", section on 'Imaging'.)
The standard differential diagnosis of SCD complications should be expanded to include pregnancy-related disorders. For example, neurological signs and symptoms (headache, visual changes, seizure) may be related to preeclampsia/eclampsia, and liver function abnormalities and hemolysis may be related to HELLP syndrome. (See "Preeclampsia: Clinical features and diagnosis" and "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)
Life-threatening events — The majority of deaths during pregnancy in SCD are sudden. Acute pulmonary failure, often associated with acute chest syndrome or pulmonary embolism, is commonly described [34,64,65]. These patients often have acute multi-organ failure. Neurologic events may be part of the multi-organ syndrome or present as independent ischemic episodes. Women with cardiomyopathy, pulmonary hypertension, or infection are particularly vulnerable to decompensation at delivery and in the first postpartum week.
These life-threatening events may be preceded by acute painful episodes, so it is important to effectively treat vaso-occlusive episodes and monitor for early signs of life-threatening events. Patients hospitalized with a painful event should receive intravenous fluids and oxygen therapy as needed to maintain intravascular volume and oxygenation. Early evidence of impaired pulmonary, hepatic, renal, or CNS function should be considered a signal of an impending life-threatening event; an investigation for the cause of the worsening function (such as acute chest syndrome, pulmonary embolism, cerebral ischemia, cardiomyopathy, pulmonary hypertension, HELLP) should be undertaken immediately. Transfusion therapy is often necessary before completion of the evaluation and the differential diagnosis to halt disease progression.
●(See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)
●(See "Acute ischemic and hemorrhagic stroke in sickle cell disease".)
●(See "Evaluation and management of fever in children and adults with sickle cell disease".)
●(See "Hepatic manifestations of sickle cell disease".)
●(See "Overview of the pulmonary complications of sickle cell disease".)
●(See "Acute and chronic bone complications of sickle cell disease".)
●(See "Sickle cell disease effects on the kidney".)
●(See "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)
●(See "Preeclampsia: Clinical features and diagnosis".)
Transfusion therapy — Transfusion therapy is commonly used during pregnancy to treat acute complications, in preparation for surgery, and in selected preventive transfusion programs.
Prophylactic transfusion — The use of prophylactic versus selective blood transfusions to reduce complications of pregnancy in patients with SCD is controversial, as available data are limited [66-71]. The 2020 American Society of Hematology guideline on transfusion in SCD suggests that regular transfusion be considered in women with a history of severe SCD-related complications, either prior to the current pregnancy or with previous pregnancies; in women with high-risk features such as other comorbidities or nephropathy; and in women who develop complications during pregnancy [71].
Examples of available data to guide decision-making include the following:
●In the seminal randomized trial including 72 pregnant patients with SCD, women treated with routine prophylactic transfusions had no difference in most medical, obstetrical, and neonatal outcomes compared with those who were treated only for medical/obstetrical emergencies [69]. The number of patients and events was small, so only large differences in these outcomes would achieve statistical significance. However, one significant benefit of routine prophylactic transfusion was observed: a reduction in incidence of acute painful episodes (5 of 36 patients [14 percent] versus 18 of 36 patients [50 percent], p<0.01).
●A 2015 meta-analysis that included 12 observational studies (1291 patients) found that prophylactic transfusions were associated with reduced maternal mortality (odds ratio [OR] 0.23; 95% CI 0.06-0.91), reduced painful episodes (OR 0.26; 95% CI 0.09-0.76) and reduced pulmonary complications (OR 0.25; 95% CI 0.09-0.72) [72]. These findings are limited given that the included studies had a moderate to high risk of bias and low event rates. Potential reductions in maternal mortality and adverse events must be weighed against the associated increases in cost, number of hospitalizations, and risk of alloimmunization.
Although not evaluated in randomized trials, some experts believe that use of prophylactic transfusion may be useful in the subgroup of pregnant women with SCD at highest risk of complications, such as those with previous perinatal mortality or severe anemia [4,67,68,73]. This is particularly important in the third trimester when the majority of acute vaso-occlusive complications occur [28]. These transfusions are performed on an outpatient basis every three to four weeks to keep hemoglobin ≥9 g/dL and <12.0 g/dL and percent hemoglobin S below 35 to 40 percent [26,34,66,69]. In the seminal trial described above, half the women received blood transfusion only if hemoglobin fell below 6 g/dL, and the other half received 2 units of blood every week for three weeks or until their hemoglobin level was 10 to 11 g/dL [69].
We follow a policy in which most patients with SCD (hemoglobin SS) receive transfusion therapy in the third trimester [66]. In high-risk patients with chronic organ dysfunction or significant history of acute chest syndrome and painful events, we initiate transfusion early in pregnancy. In patients with mild hemoglobin variants, or a benign clinical history, prophylactic transfusions are not utilized. In chronically ill patients with high baseline hemoglobin levels, exchange transfusions are indicated to maintain the hemoglobin A level greater than 30 to 50 percent. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Simple versus exchange transfusion'.)
We use leukocyte-depleted red blood cell units that are phenotypically-matched for at least the C, E, and Kell blood groups. Administration of intravenous furosemide may be needed to prevent fluid overload in patients with cardiac and/or pulmonary dysfunction [26,34,66,74,75]. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Transfusion techniques'.)
Transfusion for acute complications — Pregnant women with acute complications of SCD can benefit from transfusion [16,64]. Accepted indications for therapeutic transfusion therapy in individuals with SCD include acute stroke, acute chest syndrome, acute multi-organ failure, acute symptomatic anemia (eg, onset of heart failure, dyspnea, hypotension, marked fatigue [76]), reticulocytopenia (most commonly associated with Parvovirus B19 infection, but can occur with any infection), or following hepatic or splenic sequestration. Additional indications in pregnant/postpartum women include prior to cesarean delivery and preeclampsia that does not improve after delivery [77]. The general goal in patients with serious and/or life-threatening events is to raise the total hemoglobin to between 10 and 12 g/dL and to maintain the proportion of hemoglobin A at approximately 70 percent. Transfusion techniques are described separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Indications for transfusion' and "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Transfusion'.)
VTE prophylaxis during antepartum hospitalization — All patients with SCD admitted to the hospital with an acute medical illness (eg, pneumonia, vaso-occlusive pain episode) or obstetrical complication (eg, preterm rupture of membranes, preeclampsia) should receive venous thromboembolism (VTE) prophylaxis with a low molecular weight heparin (LMWH) or unfractionated heparin, unless they have a contraindication. However, antepartum anticoagulation may preclude or delay administration of neuraxial anesthesia for labor and delivery. This is discussed in more detail separately. (See "Overview of the management and prognosis of sickle cell disease", section on 'Thromboembolism prophylaxis' and "Use of anticoagulants during pregnancy and postpartum".)
Labor and vaginal delivery — There are no medical contraindications to vaginal delivery. No high quality studies have evaluated the optimum gestational age for delivery. In the absence of maternal or fetal complications, awaiting spontaneous labor is reasonable. Induction of labor and cesarean delivery are performed only for the usual obstetrical indications [4].
During labor and delivery, the parturient should be kept well oxygenated (O2 saturation ≥95 percent), warm, and hydrated to prevent sickling. We suggest continuous fetal heart rate monitoring since these pregnancies are at higher risk of complications (see 'Pregnancy outcome' above). Neuraxial anesthesia is useful to reduce maternal cardiac demands secondary to labor pain and anxiety. (See "Anesthesia for labor and delivery in high-risk heart disease: General considerations".)
Cesarean delivery — Optimally, cesarean delivery can be scheduled, but labor complications may necessitate an intrapartum urgent/emergent procedure. Preoperatively, the patient should be well-hydrated and oxygen saturation should be maintained at ≥95 percent. If there is time, simple transfusion to achieve hemoglobin 10 to 11 g/dL is reasonable in patients at increased risk of complications because of chronic lung disease, central nervous system disease, or multiorgan dysfunction. Regional anesthesia is generally safer and preferable to general anesthesia, but the choice is influenced by a variety of factors, such as the urgency of the procedure, maternal hemodynamic status, and physician and patient preference (see "Anesthesia for cesarean delivery"). Fluid balance is important because these patients are at risk for fluid retention from subclinical cardiomyopathy [78].
Cord blood — A cord blood specimen collected at the time of delivery is helpful for establishing the nature of the hemoglobinopathy present in the newborn and educating the parents about the possible need for specialized pediatric care. (See "Diagnosis of sickle cell disorders", section on 'Newborn screening' and "Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance".)
Umbilical cord blood also may be harvested for stem cells for future transplantation of a family member with SCD. This option should be discussed before pregnancy or in early pregnancy. (See "Collection and storage of umbilical cord blood for hematopoietic cell transplantation" and "Hematopoietic stem cell transplantation in sickle cell disease".)
POSTPARTUM MANAGEMENT
Postpartum care — Close maternal surveillance for infection and thromboembolism and initiation of measures to prevent these complications are important, especially in women who deliver by cesarean. Anorexia, nausea, urinary tract infection, wound infection, endometritis, and venous thromboembolism (VTE) are more common after cesarean than vaginal birth; the risk of VTE is estimated at >3 percent in women with a major risk factor for VTE (eg, SCD) who undergo cesarean [79].
The risk of fat and bone marrow embolism may increase during the postpartum period in women with SCD, including those with milder sickle variants [80].
Preventive measures for all postpartum women with SCD include:
●Antibiotic prophylaxis per local standards. In the United States, one dose of prophylactic antibiotics is administered prior to all cesarean deliveries. (see "Cesarean birth: Preoperative planning and patient preparation", section on 'Antibiotic prophylaxis') In the United Kingdom, broad-spectrum antibiotics (eg, amoxicillin and clavulanate, erythromycin) are recommended for labor and delivery and for five days post-delivery [4].
●Adequate fluid intake so the mother is well hydrated. This may necessitate intravenous fluid administration and anti-emetic therapy until oral intake is adequate.
●Adequate oxygenation (O2 saturation ≥95 percent). Supplemental oxygen should be given, as needed. Continuous positive airway pressure (CPAP) should be considered if chest signs and/or symptoms develop, or oxygen saturation falls below 92 percent [4].
Postpartum VTE prophylaxis — Early ambulation, avoidance of dehydration, and thromboembolism prophylaxis are recommended postpartum to reduce the risk of VTE.
●Cesarean delivery – Both the American College of Chest Physicians (ACCP) and the Royal College of Obstetricians and Gynaecologists (RCOG) recommend pharmacologic thromboprophylaxis (eg, with low molecular weight heparin [LMWH]) for women with SCD following cesarean delivery [79,81]. Mechanical thromboprophylaxis (thromboembolism stockings, pneumatic compression) is recommended for women who have contraindications to anticoagulation and is suggested in addition to anticoagulation for patients at highest risk of VTE because of multiple risk factors.
We individualize our approach to the duration of VTE prophylaxis after cesarean delivery. We administer LMWH for a minimum of 10 days to selected low-risk individuals such as those with a non-HbSS genotype who have a benign SCD course and no other risk factors for VTE. We generally administer LMWH for six weeks to patients with a HbSS genotype and/or a moderate to severe SCD history, older age, a history of pulmonary disease, an indwelling central venous catheter, a high platelet count, and/or a history of VTE or other VTE risk factors.
By comparison, the ACCP advises thromboprophylaxis while the patient is in the hospital, with continuation for up to six weeks postpartum for all post-cesarean delivery patients with significant ongoing risk factors for VTE but does not make a specific recommendation for duration of therapy in those with SCD [79]. The RCOG recommends anticoagulation for all patients with SCD for six weeks following cesarean delivery [81]. (See "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention", section on 'Postpartum'.)
●Vaginal delivery – Anticoagulation after vaginal delivery is more controversial because the risk of VTE is much lower than after cesarean delivery, although higher than during the antepartum period.
We administer pharmacologic thromboprophylaxis for five days after vaginal delivery but would continue anticoagulation in patients who remain hospitalized. The ACCP does not address post-vaginal delivery prophylaxis in patients with SCD [79]. The RCOG suggests LMWH prophylaxis for women with SCD following vaginal delivery while the patient is in hospital and for seven days post-discharge [81]. (See "Use of anticoagulants during pregnancy and postpartum", section on 'Postpartum and breastfeeding'.)
Resumption of medications for SCD — Following delivery, we re-start hydroxyurea at the steady state dose the patient was on prenatally, if she is not breastfeeding. In women who were on iron chelators pre-pregnancy, iron status should be re-evaluated postpartum. (See "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Monitoring iron stores'.)
Breastfeeding — Breastfeeding should be encouraged for its maternal and infant health benefits, except in mothers taking medications that are transferred into breast milk and considered potentially harmful to the infant (eg, hydroxyurea). The safety of medication use in breastfeeding mothers can be checked by searching on the drug name in UpToDate and reading the lactation section of the drug information topic, or by searching on the drug name in other resources, such as LactMed. (See "Maternal and economic benefits of breastfeeding" and "Infant benefits of breastfeeding" and "Breastfeeding: Parental education and support".)
Contraception — A 2012 systematic review including eight studies found no evidence that hormonal contraception use in women with SCD increased their risk of clinical complications [82]. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) consider all methods of combined (estrogen-progestin) and progestin-only hormonal contraception and the copper-releasing IUD safe and effective for women with SCD.
There is limited evidence that the use of depot medroxyprogesterone acetate (DMPA) reduces the frequency of acute painful episodes (OR 0.23; 95% CI 0.05-1.02; one randomized trial, 25 patients) [83].
Infant care — In addition to routine care, the neonate should be tested for hemoglobinopathy. Neonates with SCD do not have sickling events until the production of fetal hemoglobin is replaced by the production of hemoglobin S, which usually occurs between 3 to 12 months of age [33,34]. (See "Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance", section on 'Newborn screening follow-up'.)
For women who received chronic opioid therapy during pregnancy, the neonate should be monitored for opioid withdrawal syndrome. (See "Neonatal abstinence syndrome".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sickle cell disease and thalassemias".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Sickle cell disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Given the risks of pregnancy to women with sickle cell disease (SCD) and the fetus, preconceptional evaluation and counseling should be performed. This includes (see 'Pre-pregnancy issues' above):
•Evaluation of the patient's baseline status. (See 'Prepregnancy evaluation' above.)
•Testing the patient's partner for hemoglobinopathy to determine type and risk of inherited disease in offspring, followed by genetic counseling. (See 'Genetic counseling' above.)
•Discontinuing medications contraindicated in pregnancy (eg, hydroxyurea, iron chelation, angiotensin converting enzyme inhibitors and angiotensin II receptor blockers) and bringing immunizations up to date. (See 'Management of medications and immunizations' above.)
•Providing information on the course of SCD in pregnancy, the effect of SCD on pregnancy, and infant outcome. (See 'Counseling about medical, obstetrical, and infant outcomes' above.)
●SCD can be diagnosed preimplantation or prenatally. Prevention of an affected pregnancy is possible by a variety of assisted reproductive techniques. (See 'Genetic counseling' above and 'Prenatal diagnosis' above.)
●Severe anemia and vaso-occlusive or painful crises are more common in pregnancy. As in nonpregnant women, severe pain should be managed with opioids. (See 'Management of acute painful episodes' above.)
●Modifications of prenatal care for women with SCD include an increased dose of folic acid supplement (5 mg/day), checking ferritin level and only giving iron supplements or prenatal vitamins with iron if the patient is iron deficient, increased frequency of screening for asymptomatic bacteriuria, ultrasound screening for fetal growth restriction, and fetal assessment in the third trimester. (See 'Prenatal care' above.)
●Alloimmunization should be assessed at the first prenatal visit. If negative initially, we usually repeat such testing at 24 to 28 weeks and again at the time of delivery.
Women with alloantibodies should be evaluated for risk of hemolytic disease of the fetus and newborn and managed accordingly. In addition, the blood bank should be notified so that compatible blood is available for transfusion, if needed. (See 'Prenatal care' above.)
●Adequate hydration and oxygenation, keeping warm, and measures to reduce infection are important to reduce the risk of vaso-occlusion. The management of painful vaso-occlusive episodes is the same as that in nonpregnant women, except nonsteroidal antiinflammatory drugs (NSAIDs) are generally avoided after 30 weeks of gestation because of an increased risk of premature narrowing or closure of the ductus arteriosus. Opioids are the mainstay of therapy in pregnant and nonpregnant women. (See 'Management of acute painful episodes' above and 'VTE prophylaxis during antepartum hospitalization' above.)
●In SCD patients at high risk of complications, we suggest prophylactic transfusion therapy (Grade 2C). This is particularly important in the third trimester, when the majority of acute vaso-occlusive complications occur. Transfusion therapy should be individualized with involvement of a multidisciplinary team. Transfusion may be especially helpful in those with comorbidities and/or SCD complications prior to the current pregnancy, during the current pregnancy, or with previous pregnancies. Pregnant women with acute complications of SCD can also benefit from transfusion. (See 'Transfusion therapy' above.)
●There are no medical contraindications to vaginal delivery in SCD. In the absence of maternal or fetal complications, awaiting spontaneous labor is reasonable. Induction of labor and cesarean delivery are performed only for the usual obstetrical indications. (See 'Labor and vaginal delivery' above.)
●For women with SCD who undergo cesarean delivery, we suggest postpartum prophylactic anticoagulation (Grade 2B). We also suggest prophylactic anticoagulation after vaginal delivery (Grade 2C). We use low molecular weight heparin (LMWH). (See 'Postpartum VTE prophylaxis' above.)
●After cesarean delivery, the duration of postpartum therapy depends on patient-specific factors. We administer LMWH for a minimum of 10 days to selected low-risk individuals such as those with a non-HbSS genotype who have a benign SCD course and no other risk factors for venous thromboembolism (VTE). We generally administer LMWH for six weeks to patients with a HbSS genotype, moderate to severe SCD history, older age, a history of pulmonary disease, an indwelling central venous catheter, a high platelet count, and a history of VTE or other VTE risk factors. (See 'Postpartum VTE prophylaxis' above.)
After vaginal delivery, we administer pharmacologic thromboprophylaxis for five days but would continue anticoagulation in patients who remain hospitalized.
●Hormonal contraceptives and the copper-releasing intrauterine device (IUD) are safe and effective methods for women with SCD. (See 'Contraception' above.)
ACKNOWLEDGMENT — We are saddened by the death of Stanley L Schrier, MD, who passed away in August 2019. The editors at UpToDate gratefully acknowledge Dr. Schrier's role as Section Editor on this topic, his tenure as the founding Editor-in-Chief for UpToDate in Hematology, and his dedicated and longstanding involvement with the UpToDate program.
