People with sickle cell disease (SCD) who are of childbearing age have many choices regarding family planning. Counseling includes discussion of contraception, complications of pregnancy outcomes, and the importance of maintaining good health habits, including taking folic acid and iron, if needed. Patients should also receive genetic counseling and their partners should be offered testing to determine the presence of a hemoglobinopathy. Both should then be counseled about their chances for having an infant with sickle cell disease.
|Preeclampsia (14%)||Miscarriages (6%)|
|Eclampsia (1%)||Stillbirth (1%)|
|Pyelonephritis (<1%)||Small for gestational age, <10th percentile (21%)|
|Placenta previa (1%)||Premature, <37 weeks at birth (27%)|
|Rupture of membranes (6%)|
|Premature labor (9%)|
|*Acute anemic event (3%)|
|Maternal mortality (0.45%)|
|*defined as decrease in hemoglobin levels
by 30% of baseline
Data are based on study of 445 pregnancies in 297 women (predominantly in women with Hb SS) recorded between 1979 and 1986 in 19 centers participating in the Cooperative Study of Sickle Cell Disease (ref. 1).
In a large multicenter observational study (1), hypertension was the most common complication during pregnancy for women with SCD (see table). One-fifth of the pregnancies produced preterm deliveries and infants that were small for gestational age. No increase in the frequency of pain crises occurred during pregnancy. Ninety-nine percent of the pregnancies carried to 28 weeks gestation produced live deliveries. This study debunked a widely held and unsubstantiated belief that pregnancy is contraindicated for women with SCD. However, prenatal care for women with SCD should be managed by a multi-disciplinary team that includes an obstetrician, nutritionist, primary care physician and hematologist. The team must decide who will be responsible for each aspect of the patient's care. Close monitoring combined with prompt diagnosis and aggressive treatment of complications during the prenatal and neonatal period by a multidisciplinary team will produce better outcomes.
New technologies in preventing or curing sickle cell disease: A few centers are developing a technique known as preimplantation selection (5). In this procedure, eggs from the mother are fertilized in vitro and those that do not contain markers for sickle cell disease are implanted into the mother's uterus. This variation of the commonly available in vitro fertilization technique (IVF) requires great expertise in manipulating the fertilized cells. Other members of the team must be expert in the analysis of minute amounts of DNA, the genetic material that determines whether the child will have sickle cell disease. The need for leading experts in two medical and scientific areas severely limits the availability of this approach to preventing sickle cell disease in the children of couples at risk.
Cord blood transplant is a more widely available option for couples with a child who is severely affected by sickle cell disease (6). Cord blood from subsequent newborns who have normal hemoglobin or sickle cell trait can be used as a source of hematopoietic stem cells. A bone marrow transplantation can cure the child with sickle cell disease. The probability that cord blood from a later sibling will be an HLA match is, of course, only 25%. Although the risks are lower, cord blood transplantation nonetheless runs the risk of significant complications in the recipient including graft-versus-host disease. For some children, however, transplantation is literally a new lease on life. Providers should inform eligible couples of the option early in the pregnancy to allow training and coordination of the obstetrics team by the cord blood donation program. The Chidlren's Hospital of Oakland Research Institute trains the obstetricians, collects and stores the cord blood stem cells without charge for couples with children affected by sickle cell disease or thalassemia.
The correlation of placenta previa with prior uterine surgery makes a history of previous cesarean section or uterine curettage key items in the prenatal evaluation. Adequate nutritional assessment and avoidance of factors that precipitate painful events should emphasized with each visit. The patient's pre-pregnant weight, height, and optimal weight gain in pregnancy should be recorded. Physical exam should also include determination of splenic size.
The initial comprehensive laboratory studies should include a complete blood count with a reticulocyte index, hemoglobin electrophoresis, serum iron, total iron binding capacity (TIBC), ferritin levels, liver function tests, measurement of antibodies to hepatitis A, B, and C, as well as HIV, urine examination and culture, electrolytes, blood urea nitrogen (BUN), creatinine, blood type and group, and red cell antibody screen. Rubella antibody titre, tuberculin skin test, pap smear, cervical smear, and gonococcus culture and screening for sexually transmitted diseases as well as bacterial vaginosis should also be performed.
A baseline hemoglobin concentration of 6-8 g/dL is typical for patients with sickle cell disease along with a high reticulocyte count and sickle cells on the peripheral smear. Microcytosis often reflects associated thalassemia and/or iron deficiency. Women who are doubly heterozygous for hemoglobin SC or sickle ß(+)-thalassemia often have higher hemoglobin levels that range between 9-12 g/dL. A low reticulocyte count can reflect inflammation, infection, or deficiencies of folate or iron which can suppress the bone marrow response. The rate of hemolysis can be gauged by the bilirubin levels, LDH values and reticulocyte count.
Abnormal liver function tests can reflect chronic hepatitis, acute cholecystitis, cholelithiasis or other causes of liver toxicity. Screening for red cell antigens that commonly cause alloimmunization (Rh C and E as well as Kell antigens) will allow the blood bank to provide phenotypically matched units if transfusions are needed.
Hepatitis vaccine should be administered when appropriate for hepatitis B negative patients. If asymptomatic bacteruria is found, the patient should receive antibiotics in order to prevent urinary tract infection and pyelonephritis.
Return visits are recommended two weeks after the initial visit. Low risk patients are scheduled for monthly visits until the 2nd trimester when they should be seen every two weeks and in the 3rd trimester every week. Maternal serum should be obtained between 15 and 18 weeks to assess alpha fetoprotein levels to determine risk of neural tube defect. The concentration of human chorionic gonadotrophin and estriol should also be measured in order to assess the risk of trisomy 21 or 18 in the fetus.
Uterine growth is usually assessed by measuring fundal height. Ultrasound should be performed for specific obstetric indications. Examination of the cervix, clinically or by vaginal ultrasound, is done in the 2nd and 3rd trimester to determine risk for pre-term labor.
The blood pressures in non-pregnant individuals with SCD tend to be in a lower range than that of women without hemoglobinopathy (90/50 to 110/70). Pregnant women with SCD should be observed closely if blood pressure rises above 125/75, or if the systolic BP increases by 30mm Hg, or the diastolic by 15mm Hg, in association with edema and proteinuria in the second trimester. Preeclampsia, which requires frequent monitoring, can be treated with bed-rest at home or in hospital, if needed. If preeclampsia is worsening, delivery of the fetus may be required if the gestational age is greater than 32 weeks. Expedited delivery is recommended for uncontrolled hypertension.
Women generally should be screened for diabetes at 26 weeks gestation with a 50 gram oral glucose challenge. If the blood glucose remains over 140mg/dL after one hour, further evaluation is necessary.
Women should receive leukoreduced packed red blood cells that have been phenotyped for major and minor antigens as discussed above. If the primary goal of transfusions is to reduce the percent of hemoglobin S and the hemoglobin level is high, one approach is to remove 500 ml of whole blood and transfuse 2 units of packed red blood cells. This procedure can be done manually or by automated methods to obtain a post transfusion hemoglobin level ranging between 10 and 11 g/dL and to reduce the percentage of hemoglobin S to 30-40% of the total hemoglobin concentration.
Acute Chest Syndrome
This complication usually presents with fever, cough, pleuritic chest pain, pulmonary infiltrates, leukocytosis and occasionally severe hypoxemia. The pregnant patient should be evaluated and treated in the same fashion as the nonpregnant patient.
Counseling is also an important component of postpartum care. Results
of the screen for sickle cell disease in the infant should be made available
to the mother and father as well as to the pediatrician. Contraception
and plans for future pregnancies should also be discussed. If a woman is
considering not undergoing future pregnancies, she can receive preliminary
counseling about tubal ligation for permanent birth control. Couples who
contemplate future pregnancies should be informed of the option of cord blood storage. Cord blood from a child with sickle cell trait or normal
hemoglobin can be banked against the risk of a future sibling afflicted
with sickle cell disease. Therefore, cord blood storage should be considered
by couples at risk for children with sickle cell disease even if they have
not had an affected child.