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INTRODUCTION —

There are significant fetal and maternal complications in pregnancies experienced by mothers with sickle cell disease (SCD) . The increased metabolic demands, hypercoagulable state, and vascular stasis associated with pregnancy predispose to these complications. Although advances in medical and obstetrical care have led to an improvement in outcome, the complication rate remains significantly increased compared to normal pregnancies.

Prenatal diagnosis and management of pregnancy in patients with SCD will be discussed here. Other management issues in patients with SCD are discussed separately.

CLINICAL COURSE — The course of pregnancy is generally more benign in HbSC disease than in SCD :

* In one report a higher percentage of women with HbSC disease completed their pregnancies without complications (43 versus 21 percent) .

* In a cohort study, the rates of miscarriage and live deliveries in 95 pregnancies in patients with HbSC disease (12.5 and 85 percent, respectively) were similar to that of 157 pregnancies in AA controls (10.4 and 89 percent) and significantly better than rates noted in 94 pregnancies in patients with SCD (36 and 57 percent). However, the rates of painful crisis and acute chest syndrome were similar in the HbSC and SCD pregnancies .

PRENATAL DIAGNOSIS — Evaluation of the fetus for sickle cell hemoglobin, as well as other hemoglobinopathies, can be performed in the first or second trimester in at-risk pregnancies using a variety of techniques.

Fetal complications — Fetal complications are related to compromised placental blood flow and include the following :

* Spontaneous abortion
* Intrauterine growth restriction
* Increased rate of fetal death in utero
* Low birthweight
* Preterm delivery


In one series of 81 pregnancies complicated by SCD compared to 100 pregnancies from women without hemoglobinopathy, there was an increased incidence of preterm delivery and low birthweight, which was strongly correlated to the presence of preeclampsia . In two reports, 21 to 42 percent of infants born to women with SCD were small for gestational age , and the risk of spontaneous abortion was significantly increased (36 versus 10 percent in matched controls). Perinatal survival is over 90 percent in fetuses that reach the third trimester .

Mothers with sickle cell trait are at lower risk for complications related to the fetus , and appear to have a lower incidence of preterm delivery <32 weeks of gestation [13] , although an increased rate of preeclampsia has been described in some studies . (See "Clinical features, diagnosis, and long-term prognosis of preeclampsia").

In comparison, the hemoglobin phenotype of infants with sickle cell disease does not appear to influence birth outcome and neonatal course. This was illustrated in a study of 448 newborns with SCD and 118 with sickle cell trait. The rates of adverse birth outcomes and neonatal complications were similar to the rates in normal infants despite a greater risk of preterm birth and low birth weight .

In infants affected by sickle cell disease, there are no antenatal, perinatal, or immediate postpartum manifestations of the disease until the production of fetal hemoglobin is replaced by the production of hemoglobin S . This usually occurs when the infant is 6 to 12 months of age.

Maternal complications — Mothers with SCD experience increases in complications, including acute chest syndrome, pyelonephritis and endometritis, preeclampsia, thromboembolic events, preterm labor, premature rupture of the membranes, placental abruption, antepartum hospitalization, use of cesarean section, and postpartum infection . In one report, for example, antenatal complications occurred in 46 percent of pregnancies [4] . However, maternal mortality is comparable to nonpregnant women with SCD .

Bacteriuria and urinary tract infection occur with increased frequency in both sickle cell trait and SCD .

MANAGEMENT — Close maternal-fetal surveillance is warranted because of the increased risk of maternal and fetal complications . Maternal crises can be treated as in nonpregnant women, with some exceptions. Medications such as nonsteroidal antiinflammatory drugs, hydroxyurea, and 5-azacytidine, for example, can be teratogenic and are contraindicated during pregnancy. Urinary tract and pulmonary infections should be diagnosed promptly and treated with appropriate antibiotics.

During the first trimester, prevention of dehydration and control of nausea may help to decrease the incidence of painful crises .

The signs and symptoms of common pregnancy complications (eg, decreased fetal movement, vaginal bleeding, preterm contractions, abdominal pain, headache) should be reviewed with the patient at each visit. Antepartum fetal surveillance with nonstress tests and ultrasound monitoring of fetal growth and well-being are indicated during the last trimester, or earlier if maternal or fetal complications arise .

Waiting for the spontaneous onset of labor at term is appropriate; induction and cesarean section should be performed only for the usual obstetrical indications. During labor and delivery the woman should be well oxygenated and hydrated to prevent sickling and the fetus should be monitored continuously. Analgesia or regional anesthesia are useful to reduce maternal cardiac demands secondary to pain and anxiety.

Iron and folate supplementation — Iron stores are often markedly increased in these women due to chronic hemolysis and/or repeated blood transfusions. Accordingly, iron supplementation should not be given routinely and should only be given when iron studies (eg, serum iron, transferrin, and ferritin levels) indicate the presence of low iron stores.

All women should receive folate supplementation at a dose higher than that present in prenatal vitamin preparations (ie, 4 mg/day PO) .

Prophylactic transfusion — Although the routine use of prophylactic blood transfusions to reduce complications of pregnancy in patients with SCD has been recommended , this approach is controversial. A randomized, controlled trial in 72 patients found no significant difference in perinatal outcome between the offspring of mothers with SCD treated with prophylactic transfusions and those who were not [19] . However, prophylactic transfusion significantly reduced the incidence of painful crises. This advantage must be weighed against the associated increases in cost, number of hospitalizations, and risk of alloimmunization.

For these reasons, some recommend that transfusion therapy be reserved for patients with previous perinatal mortality, preeclampsia, acute chest syndrome, new onset neurologic event, severe anemia, or in preparation for surgical intervention .

Elective abortion — Most methods of abortion are well tolerated in women with SCD. While some experts feel that hypertonic saline injections are contraindicated for elective termination of pregnancy due to the risk of sickling-induced vaso-occlusion, this is controversial and many physicians do not agree with this conclusion.

In our experience, women with SCD have a very high incidence of acute painful episodes after therapeutic abortion. As a result, we recommend inpatient intravenous hydration with or without oxygen inhalation before and for the 24 hours after the procedure.

Postpartum care — Given that the mother is either homozygous for the sickle hemoglobin gene or is a double heterozygote (eg, heterozygous for sickle hemoglobin as well as either beta thalassemia or hemoglobin C), her infant will inherit some form of hemoglobinopathy. A cord blood specimen collected at delivery is helpful for establishing the nature of the hemoglobinopathy and educating the parents about the possible need for specialized pediatric care. (See "Diagnosis of sickle cell syndromes", section on Newborn screening and section on Comprehensive care).

Breast feeding is not contraindicated and should be encouraged, unless the woman is taking medications that are not advised for the infant. Close maternal surveillance for infection and thromboembolism is important, especially after an operative delivery.

CONTRACEPTION — Oral contraceptives do not appear to have unique adverse effects or to impair red cell deformability in women with SCD. As a result, modern low-dose combined oral contraceptives are preferred to barrier methods of contraception in women who are likely to have unintended pregnancies from inconsistent use of a diaphragm.

Alternative methods that are both safe and efficacious include Depo-Provera and contraceptive implants. There is limited information that the use of Depo-Provera may also reduce the incidence of sickle pain crises .


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