Thalassaemia in pregnancy

Introduction

Thalassaemia is a heterogonous group of autosomal recessive haemolytic anaemias with a decreased synthesis of one or more globin chains. There are two main types classified according to the chain involved: alpha thalassaemia and beta thalassaemia.

Alpha thalassaemia

The alpha chains are produced by four alpha-globin genes, two (one each of HBA1 and HBA2) on each copy of chromosome 16. Alpha thalassaemia is caused by a decrease in the synthesis of these alpha chains; the severity of the condition depends on how many genes are affected (75).

The heterozygous form, alpha thalassaemia minor, may be asymp­tomatic, or the patient may have mild anaemia.

If three genes are mutated, the result will be a condition called haemoglobin H disease. Patients will have chronic anaemia and may require repeated blood transfusions.

The homozygous form, alpha thalassaemia major (Bart's Hb), where there is complete absence of the gene, is incompatible with life and results in a stillborn infant with severe hydrops fetalis.

Beta thalassaemia

There are two beta genes (HBB), one on each copy of chromosome 11. Beta thalassaemia is caused by a decrease in synthesis of these beta chains, and again, the severity depends on how many genes are affected (76).

The heterozygous form, beta thalassaemia minor, is asymptom­atic or the patient may have mild anaemia.

The homozygous form, beta thalassaemia major, is complicated by marked hypochromic microcytic anaemia from a few months after birth and the patient is blood transfusion dependent.

Beta thalassaemia intermedia, is a milder form, where a mu­tation causes moderate impairment of beta chain production.

Diagnosis

• Full blood count: patients present with a hypochromic microcytic anaemia with a mean corpuscular haemoglobin cut-off of 27 pg for thalassaemia carriers and 25 pg in the homozygous forms (77, 78).

• Iron studies: can be used to differentiate from iron deficiency anaemia—which also leads to a hypochromic microcytic anaemia.

• Haemoglobin electrophoresis: presence of haemoglobin H inclusion bodies is diagnostic of alpha thalassaemia. Haemoglobin A2 and haemoglobin F levels are elevated in beta thalassaemia carriers.

• Partner screening: this is important to enable genetic analysis and counselling about the risk of an affected child.

Diagnosis in the fetus

Once the couple's carrier status is confirmed, they should be in­formed that the risk of an affected child with thalassaemia major is one in four. The severity of disease in the fetus will depend on the type of thalassaemia in the parents:

• Non-invasive prenatal tests for beta thalassaemia (79):

^■ Free fetal DNA

^■ Preimplantation genetic diagnosis

• Invasive tests:

^■ Chorionic villous sampling

^■ Amniocentesis

• Ultrasound surveillance for alpha thalassaemia (Bart's):

^■ Fetuses affected with alpha thalassaemia will have major ab­normalities detected early on ultrasound; increased cardiothor- acic ratio, thickened placenta, abnormal middle cerebral artery Doppler and finally, hydrops fetalis in the second or third tri­mester (80).

Effect of thalassaemia on pregnancy

Maternal

• Pregnancy-induced hypertension and PET

• Gestational diabetes

• Anaemia

• Polyhydramnios

• Placental abruption

• Urinary tract infection

• Multiple pregnancy—there is a higher rate of multiple pregnancy, possibly due to the high rate of assisted reproduction (81)

• Cardiac failure

• Caesarean section

• Mirror syndrome—fluid retention and symptoms similar to PET; this occurs in women carrying a fetus with alpha thalassaemia and hydrops fetalis.

Fetal

• Miscarriage

• Intrauterine fetal growth restriction

• Preterm labour

• Stillbirth

• Increased neural tube defects (81).

Preconceptual care

Patients with thalassaemia may have cardiac, endocrine, and haem­atological comorbidities, it is therefore prudent to adopt a multidis­ciplinary approach in their care to optimize maternal and perinatal outcome:

• Echocardiogram: multiple transfusions may lead to iron load and cardiac failure in these patients, an echocardiogram must be per­formed to assess ventricular function.

• Liver function test.

• Optimise diabetes control and ascertain adequate thyroid replacement.

• Iron toxicity may lead to multiple endocrine disorders such as dia­betes and hypothyroidism.

• Screen for viral infections: there is a high risk of hepatitis B and C and HIV due to repeated blood transfusions.

• Review medications: discontinue iron chelation therapy, and pre­scribe a pregnancy safe antihypertensive if indicated.

• Folic acid, calcium, and vitamin D supplementation.

• Partner screening: this will enable adequate genetic counselling.

Antenatal care

Patients should be seen by obstetricians with experience in high- risk pregnancy, in conjunction with a fetal medicine specialist and multidisciplinary input from the relevant specialties. Management includes the following:

• Screening and treatment of anaemia: there is a high inci­dence of anaemia, use of oral iron should be individualised and women may need a blood transfusion for the first time in pregnancy.

• Glucose tolerance test.

• Blood pressure and urinalysis during each visit.

• Mid-stream urine sample during each visit.

• Serial ultrasounds for fetal growth and umbilical artery Doppler assessment.

• Vaginal delivery is recommended. A caesarean section should only be performed for obstetric reasons.

Postnatal care

• Postnatal thromboprophylaxis—high risk of thrombosis in alpha thalassaemia trait and beta thalassaemia intermedia and major.

• Breastfeeding is recommended.

• Resume iron chelation therapy if indicated.