While identifying parents who are carriers for haemoglobin disorders before conception is preferable, discussing testing and the implications of carrier status early in pregnancy enables women and their partners to make informed choices.
Mutation of the genes that contain the information for cells to make haemoglobin can result in low or absent production of normal adult haemoglobin (thalassaemias) or changes in the structure of the haemoglobin protein (haemoglobin variants such as sickle cell disease).
When babies inherit mutated globin genes from both parents, they may be affected by or be a carrier for a haemoglobin disorder. It is very unlikely that the baby will be affected when only one parent is a carrier for a haemoglobin disorder, but the baby may be a carrier.
31.1.1 Prevalence of haemoglobin disorders
- Globally, over 330,000 affected infants are born each year (83% sickle cell disorders and 17% thalassaemias), around 7% of pregnant women are carriers of haemoglobin disorders and over 1% of couples are at risk .
- The risk of being a carrier for a haemoglobin disorder varies with ethnicity
- alpha thalassaemia is most prevalent among people of Chinese and South-East Asian origin but occurs in many other ethnic groups, including people from Southern European countries, the Middle East, the Indian subcontinent, Pakistan, Africa, the Pacific Islands and New Zealand (Maori)
- beta thalassaemia is prevalent among people from the Middle East, Southern Europe, Indian subcontinent, Central and South-East Asia and Africa
- sickle cell disease is seen in many populations including people from Africa, the Middle East, Southern Europe, India, Pakistan, South America and the Caribbean.
- In Australia
- alpha thalassaemia has been identified in some Aboriginal and Torres Strait Islander communities in the Northern Territory and northern Western Australia
- sickle cell disease has been most commonly seen in individuals of Southern European and Middle-Eastern origin (especially Lebanese and Turkish) but is becoming more prevalent with increasing immigration from sub-Saharan Africa and the Indian subcontinent.
31.1.2 Risks associated with haemoglobin disorders
- Thalassaemias vary in severity depending on the number of faulty globin genes . Symptoms range from mild anaemia to severe anaemia that requires blood transfusions lifelong. A baby with alpha thalassaemia, if born alive, does not usually survive for long after the birth (Bart’s hydrops fetalis).
- Sickle cell anaemia is characterised by chronic anaemia, bone and chest pain, organ damage, failure to thrive, repeated infections and painful swelling of the hands and feet .
31.2 Testing for haemoglobin disorders
In Australia, RANZCOG recommends that local policies for testing for haemoglobin disorders take into account the ethnic mix of women tested .
31.2.1 Discussing ethnicity
It is not possible to assume ethnicity from country of birth or surname. More information can be obtained by asking women where their parents, grandparents or great-grandparents were born RCT in the United Kingdom found that a questionnaire listing a range of ethnicities was more effective in ascertaining ancestry than a simple question about ethnic origins outside the United Kingdom .. An
The RANZCOG recommends that mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) be tested in all women . A small study found that MCV had a sensitivity of 92.9% and specificity of 83.9% for thalassaemia testing .
Testing using MCV and MCH will identify some but not all carriers of alpha and beta globin gene changes. It should be noted that some beta globin gene changes (eg sickle cell trait) result in normal red cell indices and detection relies on haemoglobin electrophoresis.
31.2.3 Harms and benefits of testing
Narrative reviews indicate testing of women at increased risk of being carriers for haemoglobin disorders can identify couples who are both carriers and have a 25% risk of having a pregnancy with a significant genetic disorder for which antenatal diagnosis is possible. No studies identified harms associated with testing. One study found that being well informed about haemoglobin disorders may reduce anxiety in women who are subsequently identified as carriers .
31.2.4 Timing of testing
Narrative reviews suggest that the ideal time for testing for haemoglobin disorders would be preconception. If this is not possible, testing should take place as early as possible in pregnancy. Studies have found that when testing was offered in primary care (eg as part of the pregnancy confirmation visit), women were tested at an earlier gestation .
31.2.5 Cost-effectiveness of testing
Studies have found that antenatal testing in populations with a high prevalence of haemoglobin disorders is cost effective. While testing at confirmation of pregnancy may require additional resources, it increases the number of women tested by 10 weeks gestation . Cost-effectiveness studies support testing of fathers after a woman has been identified as a carrier for a haemoglobin disorder rather than on confirmation of pregnancy .
As early as possible in pregnancy, routinely provide information about haemoglobin disorders and offer testing (full blood count).
Approved by NHMRC in June 2014; expires June 2019
Consider offering ferritin testing and haemoglobin electrophoresis as part of initial testing to women from high-risk population groups.
Approved by NHMRC in June 2014; expires June 2019
31.3 Further investigations
Further testing is recommended for women who (Gaff et al 2007):
- have a MCV ≤80 fL and/or MCH ≤27 pg
- have a family history of anaemia, thalassaemia or other abnormal haemoglobin variant and/or
- originate from high-risk population groups: Southern Europe, Middle East, Africa, China, South-East Asia, the Indian subcontinent, Pacific Islands, New Zealand (Maori), South America and some Aboriginal and Torres Strait Islander communities in northern Western Australia and the Northern Territory.
Relevant tests include:
- ferritin testing to exclude iron-deficiency anaemia
- electrophoresis or high pressure liquid chromatography, to identify haemoglobin variants (red cell indices can be normal in carriers for some haemoglobin disorders).
Further studies (eg DNA analysis) may be carried out for final clarification of the carrier state.
Diagnosis of an affected baby is generally by chorionic villus sampling, usually in the first trimester. A small study (n=777) found that ultrasound markers (middle cerebral artery peak systolic velocity plus fetal cardiothoracic ratio) had a low false positive rate in diagnosing alpha thalassaemia .
31.4 Discussing haemoglobin disorders
Providing women with sufficient information about haemoglobin disorders enables informed choices about testing. Discussion to inform a woman’s decision-making about testing for haemoglobin disorders should take place before testing and include:
- people can be carriers of haemoglobin disorders without being affected by the condition or may be only mildly affected
- people from some ethnic groups are more likely to be carriers of or affected by haemoglobin disorders
- if only one parent is a carrier, it is unlikely that the baby will be affected but he or she may be a carrier
- if both parents are carriers for a haemoglobin disorder, there is a chance that the baby will be affected by the condition
- there are implications for the health of an affected baby.
31.5 Practice summary: haemoglobin disorders
At the first antenatal visit.
- Aboriginal and Torres Strait Islander Health Practitioner
- Aboriginal and Torres Strait Islander Health Worker
- multicultural health worker.
- Discuss the reasons for testing for haemoglobin disorders
Explain that when both parents are carriers for a haemoglobin disorder, the baby may be affected (1 in 4 chance) with possible serious consequences.
- Offer testing to fathers
If a woman is identified as a carrier of a significant haemoglobin disorder, testing should be offered to the father. Other family members may also benefit from an offer of testing.
- Take a holistic approach
Arrange counselling for parents when both are identified as carriers of haemoglobin disorders.
- Document and follow-up
Ensure that women receive timely notice of the results of any tests carried out. Have a system in place so that women identified as carriers of haemoglobin disorders receive ongoing support.
CGE (2007) Fact sheet 34: Thalassaemias and sickle cell disease. Sydney: NSW Health Centre for Genetics Education.
- Brown K, Dormandy E, Reid E et al (2011) Impact on informed choice of offering antenatal sickle cell and thalassaemia screening in primary care: a randomized trial. J Med Screen 18(2): 65–75.
- Bryan S, Dormandy E, Roberts T et al (2011) Screening for sickle cell and thalassaemia in primary care: a cost-effectiveness study. Br J Gen Pract 61(591): e620–27.
- CGE (2007) Fact Sheet 34: Thalassaemias and Sickle Cell Disease. Sydney: NSW Health Centre for Genetics Education.
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