Although fertility is reduced in the woman with transfusion-dependent thalassemia disease, pregnancy may be possible for some. A handful of women have been reported in the medical literature, most having beta thalassemia intermedia, a few having beta thalassemia major. With the availability of assisted reproductive techniques, and as medical advances continue to increase quality of life and life expectancy of women with beta thalassemia, the numbers of successful pregnancies in these women will continue to grow. Given the mother's condition, there are important considerations during pregnancy for both maternal and fetal health. This section focuses on women with beta thalassemia, particularly those who are transfusion-dependent. However, some of the following considerations may also be important for women with alpha thalassemia, particularly those who have hemoglobin H-Constant Spring disease and require transfusions. The woman with transfusion-dependent thalassemia who is pregnant or considering becoming so should seek the advice of her medical team, including her hematologist, perinatologist, genetic counselor, and other specialists.

General Considerations

Medical care for individuals with beta thalassemia continues to improve with time, as do approaches toward assisted reproduction. As these trends continue, more and more women with this condition will be able to consider becoming pregnant. Issues regarding the health of the mother and the health of the fetus should be considered and discussed prior to conception. Other important considerations for some families have included the availability of a support system to aid in the care of an infant given its mother's medical needs. The expected longevity of the potential mother with thalassemia has also been an important consideration for some families in their decision to have children or not. This, too, has been related to the availability of social support for some families. Overall, given the support of family and a comprehensive medical team, growing numbers of women with thalassemia will continue to have healthy pregnancies and babies.

Pregnancy and Thalassemia: Health of the Mother

It is important to consider that the physiological stress of pregnancy can potentially exacerbate some of the symptoms of thalassemia in the expectant mother. The heart, liver, and endocrine system are particularly vulnerable in the pregnant woman with thalassemia disease. Evaluation of the functioning of each of these systems prior to and throughout pregnancy is important. Therefore, continued care by a hematologist is a necessity. The hematologist is integral to monitoring the transfusion regimen, which tends to increase in pregnancy, as well as the administration and dosages of iron chelating agents and other medications. A high-risk obstetrician, or perinatologist, is also needed to monitor the health of the expectant mother, as well as her fetus.

Iron chelation

Removing excess iron through the use of chelating medication is critical to the health and longevity of the woman with thalassemia. Increased transfusion requirements during pregnancy may increase the need for chelation therapy. However, the safety of desferrioxamine (Desferal) during pregnancy has not been established; it is unclear whether this medication poses any risk to the developing fetus. Depending in part on the quantity of liver iron stores, temporarily discontinuing the use of desferrioxamine may be considered during pregnancy. Some have suggested that pregnancy itself may serve as a chelator of iron, via the uptake of free iron by the developing fetus. Though data on Desferal use during pregnancy is minimal, CHO has experienced two successful pregnancies with a beta thalassemia major patient. As she was severely iron overloaded, she received high dose Desferal through a port throughout both pregnancies. Both infants have thus far experienced no deleterious effects as a result of chelation therapy. The pregnant woman with thalassemia should discuss with her physicians the benefits and possible risks of continuing or discontinuing desferrioxamine use during pregnancy.

Cardiac function and transfusion requirements

During pregnancy, the fluid component of the blood normally increases. This can increase the degree of anemia, which leads to the need for more frequent blood transfusions. Increased anemia can also result in the heart having to work harder to get adequate oxygen to all of the body's tissues. Increased blood volume can also put stress on the heart. In thalassemia, the heart may already be under stress from the damaging effects of iron overload. Therefore, it is important to have cardiac function checked prior to and throughout pregnancy. Regular attend-ance at scheduled transfusion appointments is also critical in order to reduce anemia and lessen the work that the heart must do.

Liver function

A liver biopsy may be indicated prior to pregnancy to assess the degree of iron overload. This information may be helpful in deciding whether or not to discontinue iron chelation. A liver biopsy can also help determine if there has been damage from iron deposition or previous hepatitis infection. Blood tests throughout pregnancy can also assess liver function.

Endocrine function

Individuals with thalassemia have an increased chance of developing insulin-dependent diabetes as a result of iron overload. The stress of pregnancy can worsen this condition, which can be detrimental to the health of the mother and developing baby. It is important to stabilize diabetes prior to becoming pregnant and to maintain adequate treatment throughout pregnancy. Thyroid function can also be impaired due to iron overload in the woman with thalassemia.

Splenic function

The spleen removes abnormal red blood cells from the circulation and performs important immune functions. Individuals who have thalassemia have unusually large numbers of abnormal red blood cells. The spleen becomes very active in removing these cells. This activity can enlarge the spleen making it more effective at removing even larger numbers or cells, causing a hemolytic anemia. During pregnancy, there is a greater need for hemoglobin both for normal growth and development of the fetus and due to the fact that the blood volume of the mother will increase dramatically. During this time, transfusion requirements in the pregnant woman is increased, particularly during the last trimester of pregnancy. If transfusion in adequate, the bone marrow will be suppressed and the work of the spleen can be decreased. Occasionally, this will lead to some decrease in spleen size and activity.

Nutritional needs

Pregnant women are routinely given prenatal vitamin supplements by their OB/GYN. Many of these supplements contain iron. Prenatal vitamins containing iron should be avoided by the pregnant woman with thalassemia, for whom iron overload is a concern.

Folate

Folate (folic acid) is important for cell growth and division. Therefore, during pregnancy the demand for folate increases. Folate supplementation is suggested for one month prior to conception and through the 8th week of gestation, at a minimum. This is thought to help prevent megaloblastic anemia (anemia marked by large, immature red blood cells) in women with thalassemia.

Vitamin C

Vitamin C (ascorbic acid) is administered during iron chelation (usually 100 to 250 mg with each session of chelation) to enhance the removal of iron. High doses of ascorbic acid can release a large amount of ionized iron and actually cause tissue damage, particularly in the heart. Ascorbic acid should be continued with chelation during pregnancy. Larger doses should be avoided.

The health of the mother with thalassemia is inter-related to the health of her developing baby. Therefore, the importance of comprehensive thalassemia care throughout pregnancy can not be over-emphasized. In addition, the perinatologist and genetic counselor are available to address issues related specifically to the health of the baby.

Fetal Risk for Thalassemia

For a woman with beta thalassemia disease or hemoglobin E/beta thalassemia disease, there may be a chance for her fetus to be at risk for inheriting thalassemia or another inherited blood disease, due to the inherited nature of these conditions. This depends on the hemoglobin type of the father of the baby. The fetus could be at risk if the father himself has thalassemia or sickle cell disease. More commonly, a risk to the fetus occurs when the father is a carrier of a beta globin trait. These traits could include beta thalassemia trait, hemoglobin E trait, sickle cell trait, or others. A genetic counselor can arrange testing for the father of the baby and explain the inheritance of hemoglobin types.

If a couple is found to be at risk for having a baby with thalassemia or another inherited blood disease, a genetic counselor can explain this risk, as well as testing options for the baby before birth. Tests are available as early as 10 weeks of pregnancy. These tests can often tell, with a high degree of accuracy, whether a baby has thalassemia. Because these tests are invasive, they are not risk-free. A genetic counselor can explain the risks and benefits associated with each of these tests. The choice to have or decline prenatal testing is a very personal one, which depends on the beliefs and values of the individual couple. A genetic counselor can help a couple identify their own issues, which might be important to the decision-making process both before and after prenatal testing.

Risks Related to Maternal Thalassemia

Some studies have reported that chronic maternal anemia can lead to a deficiency of oxygen circulation to the fetus. Such hypoxia can be associated with an increased chance for slowed fetal growth in utero, pregnancy loss, and preterm labor and delivery. Other studies in which maternal anemia was well managed did not report evidence of an increased risk for these complications. This emphasizes again the importance of continued thalassemia care throughout pregnancy.
Women with thalassemia tend to be smaller in stature than their brothers and sisters without thalassemia. The correspondingly small pelvic bones in some women with thalassemia may contribute to the increased chance for a cesarian delivery, which was noted to be the only obstetrical complication in these women.

While any woman can develop diabetes, women with thalassemia have a higher chance of this due to iron overload. Maternal diabetes, particularly the insulin-dependent type, is known to increase the risk for birth defects. The risk for prenatal and neonatal complications, including perinatal loss, is also increased with maternal diabetes. Good control of blood sugar levels, particularly in the early stages of pregnancy, and close follow-up by a perinatologist throughout pregnancy is known to help to reduce these risks.

Risks Related to Medications

Genetic counseling is an important resource for information about the adverse effects of maternal medications on the developing fetus. It is important for any pregnant woman to consult her physician before using any type of medication. Potential risks to the fetus depend on the type of medication, the dosage, and the period in pregnancy in which exposure takes place. Certain medications may also be present in breast milk and may pose a risk to the newborn baby. A genetic counselor or perinatologist can offer information about any particular woman's risk.

The woman with thalassemia may be on one or more medications, including iron chelating agents or anti-viral drugs to manage previous infections. Known or theoretical risks of each of these medications should be considered in determining whether they should be continued in pregnancy or if their doses should be adjusted. Desferal is the most commonly used medication among these women because of its important role in reducing iron overload and its consequences. The possibility of adverse effects is suggested by animal studies in which skeletal anomalies are noted at doses comparable to human dosages. Less than 40 cases among pregnant women have been published describing the outcome of pregnancy for women on chronic Desferal treatment. Among the women who continued their pregnancies, none took Desferal beyond the first trimester. There was no evidence among these infants to suggest adverse effects of Desferal. Some additional cases have been reported in which Desferal therapy was initiated late in pregnancy following iron overdose. At least one of these infants was reported to have iron deficiency attributable to maternal Desferal therapy. Overall, the number of reported cases in women is insufficient to establish the safety of Desferal in pregnancy. Regarding the safety during breast-feeding, Desferal is unlikely to have a harmful effect given its poor absorption across the adult gut. However, there is no available information regarding Desferal treatment during breast-feeding. Therefore, the expected benefits and risks of continuing therapy during pregnancy or breast-feeding for any individual woman should be discussed with her physician. This is true for any additional medications given to the pregnant woman with thalassemia.

Risks Related to Infectious Agents

Screening for infectious agents is an important part of prenatal care for any pregnant woman. Certain types of maternal infection may carry a risk of transmission to the fetus or have other adverse health effects on the fetus. These effects and the chance for fetal or perinatal infection depend on several factors: the type of agent, the severity of maternal infection, the amount of virus or other infectious agent present, the stage of pregnancy, and the mode of delivery. Information about a woman's specific risks can be obtained from a genetic counselor and/or a perinatologist. Although the safety of our nation's blood supply has increased dramatically over the last several years, blood transfusions continue to be a risk factor for acquiring certain infections. Women with thalassemia who are considering becoming pregnant should be screened for all forms of hepatitis and HIV infection prior to conception. If one of these infections is identified, specific information regarding the health risks and chance of transmission to the developing fetus is available. In some cases, preventative treatment or alternative options for delivery may be considered to help reduce the risk of transmission to the baby.


 

Alpha Thalassemia - Beta Thalassemia - Variant Hemoglobin