Screening for Thalassemia

Thalassaemia is the most common genetic disorder in the world, with around 250 million people, 4.5 percent of the world population, affected by the fatal disease. As 2010, Malaysia registered 4,768 people as Thalassaemic which required regular blood transfusion. And 5% of its population are carrier.

Thalassemia is a group of inherited blood disorders that affect the body’s ability to produce hemoglobin and red blood cells. Patients have a lower than normal number of red blood cells in their bodies and low haemoglobin and affect oxygen carry capacity by red blood cell.

A person who has inherited one thalassaemia gene is said to have thalassaemia minor (thalassaemia trait).He or she is healthy and leads a normal life. Most people with thalassaemia minor do not know that they have it. However, the affected persons can pass on the abnormal gene to their children. Thalassaemia major is a severe form of anaemia. The affected person has inherited two thalassaemia genes, one from each parent. He or she may look normal at birth but within 1 – 2 years of life, will suffer from severe anaemia, which leads to poor growth and development as well as a shorter lifespan. The affected person will need blood transfusion every month to sustain life. At present, a bone marrow transplant is the only hope of possible cure for thalassaemia major.

Screening is needed to identify person who carry the affected gene and prevent severe forms of the disorder, namely haemoglobin (Hb) Barts hydrops fetalis and b-thalassaemia major (Cooley’s anaemia), to reduce morbidity and mortality among the thalassaemia patients, to reduce the prevalence of blood transfusion dependent thalassaemia cases and to create awareness regarding thalassaemia.

Prenatal screening in Malaysia

The purpose is to identify carriers of thalassaemia in order to assess the risk of an individual having an affected child and to provide information on the options available to avoid such eventuality. National screening programmes have resulted in reduction of affected births of beta-thalassaemia major and Hb Barts hydrops fetalis.

Prenatal diagnosis for thalassemia

Once the couple’s carrier status and genetic mutation are confirmed, they should be counselled that the chance of having a thalassaemia major fetus is one in four. The standard diagnostic method is chorionic villi sampling and DNA analysis between 11 and before 14 weeks of pregnancy. Amniocentesis is performed after 15weeks of gestation and the results may not be available early enough to allow for broader termination of pregnancy options.

Chorionic villi sampling (CVS)

CVS can be performed through the cervix (transcervical) or through the abdomen (transabdominal), depending on where the placenta is located. In both procedures, a small amount of placenta tissue is biopsied. There is a small risk of miscarriage after the procedure (0.5 – 1%). In addition there is a small risk of infection or bleeding.

Amniocentesis

Amniocentesis is performed by inserting a needle through the abdominal wall into the uterus under ultrasound guidance and withdrawing a small amount of fluid from the sac surrounding the foetus. There is a small risk of miscarriage after the procedure (0.5%). In addition there is a small risk of infection or leaking of amniotic fluid.

Thalassaemia in pregnancy

Majority of thalassemia diagnosis made before pregnancy. It is due to effective premarital and school screening program. Some women were diagnosed in pregnancy following anaemia work up. Pregnant women with thalassemia are at risk of miscarriage, pre eclampsia, a small for gestatinal age fetus, fetal growth restriction and needing for blood transfusion.

Not much complication is expected in those with minor thalassemia except for increase need for blood transfusion.

Those with thalassemia major or transfusion dependant are at greater risk of cardiomyopathy, endocrinopathy such as diabetes and thyroid disorder and osteophorosis. This is mainly contributed by iron overload.

Pre pregnancy care

It is important for women with thalassemia to have a pre-pregnancy assessment prior to pregnancy. Pre pregnancy care for women with thalassemia would include:

Antenatal care

Combine care

Pregnant women with thalassemia require regular antenatal care with the maternal and child clinic and combine care with the haematologist.

Treatment of anaemia

Anaemia in women with thalassemia minor and low ferritin level can be successfully managed with oral iron, however those with normal or high ferritin levels, suffices with folate intake.

Pregnant women who are transfusion dependent will require regular blood transfusions to meet their pre transfusion target in order to reduce maternal risks and prevent fetal growth restriction.

Iron chelating therapy in pregnancy

The need for chelating therapy is decided by the haematologist during the pre pregnancy assessment. Iron chelating therapy usually starts at around 20 weeks gestation and to be continued during her labour and post partum period.

Thrombosis prophylaxis

Women who are transfusion dependent and suffer from iron over load are at high risk to develop vein thrombosis. The risk is higher in those who had not had a splenectomy. Therefore, medical thromboprophylaxis with LMWH is needed these groups of patients during their pregnancy and post partum period.

Maternal monitoring

Women with thalassemia can be at risk in developing preeclamsia, diabetes or hypothyroidism. Regular antenatal assessment for pre eclampsia and MOGTT at 24 to 28weeks is indicated.

Fetal assessment

Detail fetal structural scan is offered especially in those women who received iron chelating therapy. It is usually done at around 18 to 22 weeks of gestation. Regular fetal growth assessment is started from 28 weeks gestation to identify fetal complication.

Delivery

Women with thalassemia are at greater risk to develop post partum haemorrhage, therefore, it is recommended that delivery to be conducted in tertiary hospital with adequate transfusion service. For those with uncomplicated pregnancy, delivery is usually planed at term. However earlier delivery indicated if maternal and fetal complications arise. At most, caesarean section is reserved for obstetric indications only. Breast feeding is not contraindicated and importance of effective contraception should be discussed prior to discharge.

Reference:

1. National Thalassaemia Screening Program , Malaysia
2. CPG: Management of Transfusion Dependent Thalassaemia      
3. CPG: Management of Thalassemia 
4. Thalassaemia in pregnancy, Best Practice & Research Clinical Obstetrics and Gynaecology 26 (2012) 37–51
5. Screening for thalassaemia in pregnant women a laboratory perspective ,Malaysian Journal of  Medicine and Health Sciences Volume 1 (2)
6. Management of Beta Thalassaemia in Pregnancy, Green-top Guideline No. 66, March 2014- RCOG