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Kara Dent, West Midlands Perinatal Institute - March 2001

Sickle cell disease (SCD) is the most common haemoglobinopathy that we deal with in pregnancy. It was first described in the literature in a paper titled "Peculiar elongated and sickle shaped red blood corpuscles in a case of severe anaemia" (1). This is a lovely description of what happens to the haemoglobin molecule when deoxygenated and is characteristic of this autosomal recessive disorder.

There are different variations of this disease but the 3 more severe types are:

• Homozygous Sickle Cell disease (HbSS)
• Sickle Cell/HbC (HbSC)
• Sickle-cell Thalassemia

The minor variant is Sickle cell trait (HbAS) that affects around 1 in 12 adult African Americans (2). Anaemia is seen with this disorder in pregnancy but not the more severe complications of the above conditions. What is more significant for this group is if both parents carry the trait, putting the fetus at a 1 in 4 risk of developing SCD. This is relevant for prenatal diagnosis.

AETIOLOGY

Haemoglobin S occurs when there is a substitution of one amino acid by another: namely valine for glutamic acid. Valine is neutrally charged whereas glutamic acid has a negative charge. The latter allows hydrophobic binding when haemoglobin (Hb) is deoxygenated, causing the classic distortion of the molecule(3). This is remedied when Hb is oxygenated initially but not after recurrent episodes. Because of this, erythrocytes in SCD have a grossly reduced life span of only 17 days to the expected 120 days in the unaffected population (3). This explains why we see a chronic anaemia in these patients.

PREVALENCE

With around 5000 sickle cell sufferers in the UK, it is estimated that there are about 150 births per year(4). We are therefore talking about a restricted population and relying on figures based on pretty small studies. The Cochrane data, dealing with the question of whether this population should be electively transfused, or not, is based on only one study (5). This study is judged to be of poor methodology with only 72 women recruited and a data collection over 8 years. Other studies in the literature are retrospective and equally sized. The quoted statistics are a perinatal mortality rate of between 40 - 60 per 1000 deliveries (6) (4-6 times that of the normal population) with a maternal mortality rate of around 2% (7).

CLINICAL FEATURES

The normal physiology of pregnancy means an increase in oxygen consumption, blood viscosity and red cell mass. These increases put an extra demand on a woman suffering from sickle cell and increase the incidence of complications seen.

Painful crises are seen in around 35% of antenatal sicklers (7). These are vaso-occlusive attacks that result in pain from bones, chest and abdomen and require prompt treatment (namely: hydration, pain relief and analgesia.) They are episodes that can be brought on by factors such infection, acidosis, dehydration, hypertension, strenuous activity, drug overdose, hypothermia, blood loss, trauma and severe stress (8) - all to be avoided!

PRENATAL CARE:

Care of a woman with sickle cell disease in pregnancy should be via a team approach involving a haematologist and obstetrician working closely together. Seeing the couple prenatally provides an opportunity to counsel the couple about the risks for them associated with pregnancy. If the sickle status of the partner is unknown, he can be offered testing in order to predict the risk of the baby. If he should then test positive, a prenatal diagnosis is always an option - chorionic villous sampling (CVS) provides an early diagnosis at 11 to 13 weeks. Obviously it has its own risks.

Folic acid is advised throughout the pregnancy but, because these women are at risk of iron overload, they should not be routinely prescribed ferrous sulphate (7). They are reminded about diet and to be aware of the risk of infection, with early referral if they are in any doubt.

ANTENATAL CARE:

Because of the recognised association of sickle cell disease with IUGR, pre-eclampsia and premature labour (9), early signs of these are screened for throughout the pregnancy.

The question mark raised at the forum is how often should these women be screened? Do we need to send an MSU at every visit? Should we be requesting 2 weekly growth scans? Starting at what gestation? What about screening regularly for retinopathy and evidence of anaemia? Where is the evidence?

Current suggestions for the initial investigations include:

• Full medical history, specifically regarding prior crises
• Haemoglobin electrophoresis and red cell indices
• Reticulocyte count
• Liver function tests
• Hepatitis screening
• Blood group and antibody screen
• Rubella antibodies
• Syphilis serology
• Urinalysis

BLOOD TRANSFUSIONS:

The role of prophylactic blood transfusions is a controversial area in the management of these women. There are studies that show either a decrease in the incidence of painful crises (10) or no benefit at all (5,11,12). As mentioned before, there is only one RCT quoted in Cochrane on this. Whatever the effect on maternal morbidity, there is no evidence to show any advantage for perinatal outcome (5). The potential benefits for the pregnancy have to be offset against the disadvantages of transfusions.

NB.The problem with delayed haemolytic transfusion reactions is that these antibodies can be serologically undetectable and cause terrible problems for future cross matching (13).

Intrapartum care:

A caesarean section is only indicated for obstetric reasons. This is because it provides a higher risk for thromboembolism in an already at-risk population (14). Good pain relief in labour and adequate hydration are very important to reduce stress and sickling. Oxygen via a nasal prong or mask is advised to improve cardiac function(3),(5). As these infants are considered higher risk, especially if small for gestational age (SGA), continual monitoring is also suggested, as well as taking steps not to prolong the labour. For some units, assisted deliveries with an epidural are part of their standard protocol for these women (3).

Postpartum care:

• Early ambulation
• Anti-embolic stockings
• Appropriate hydration
• Aggressive treatment of suspected infection
• Breastfeeding with good hydration
• Neonatal testing (electrophoresis)
• Family planning advice

Conclusion:

Review of the literature on sickle cell disease in pregnancy shows a lack of evidence on which to base management. One of the main reasons for this is that the population being looked at is so small and large RCTs are therefore not possible. We know that those of African, Mediterranean and East Indian ancestry are at risk but should also be aware that with travel and inter-racial marriages, more may be at risk. Here in the West Midlands, it has been suggested that all women should be screened routinely in early pregnancy for sickle cell disease or trait.

What is important is to have clear protocols and management policies during pregnancy in place, dealing with the question of elective transfusions and delivery plans. An anaesthetist's collaboration at delivery can be invaluable and the antenatal care should be combined between the obstetric and haematological team. In this way, the patients' best interests should be served.

References:

1. Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anaemia. Arch intern Med. 1910;6:517,
2. Stein J. A screening protocol for a prenatal population at risk for inherited haemoglobin disorders: results of its application to a group of Southeast Asians and blacks. Am J Obstet Gynecol. 1984;150:333, Abstract
3. Rust OA. Pregnancy complicated by Sickle hemoglobinopathy. Clinical Obstetrics and Gynecology 1995;38(3):472-84, Abstract
4. Darbyshire P. Sickle cell diseases in the United Kingdom. The Practioner 1990;234(1492):722-6, Abstract
5. Koshy M. Prophylactic red cell transfusion in pregnant patients with sickle cell disease. A randomised co-operative study. N Engl J Med 1988;319:1447-52, Abstract
6. Howard RJ. Pregnancy in sickle cell disease in the UK: results of a multicentre survey of the effect of prophylactic blood transfusions on maternal and fetal outcome. Br J Obstet Gynaecol 1995;102:947-51, Abstract
7. Howard RJ. Management of sickling conditions in pregnancy. British Journal of Hospital Medicine 1996;56(1):7-10, Abstract
8. Martin J. Sickle cell crisis. In: Clark SL, Cotton DB, Hankins GDV, Phelan JP, eds. Critical care Obstetrics. 2nd ed. Cambridge, Massachusetts: Blackwell Scientific Publications, 1991:212
9. Koshy M. Sickle cell disease and pregnancy. Blood Reviews 1995;9:157-64, Abstract
10. Morrison JC. Prophylactic transfusions in pregnant patients with sickle cell disease. N Engl J Med 1989;320:1286-7, Abstract
11. Tuck S. Prophylactic blood transfusion in maternal sickle cell syndromes. Br J Obstet Gynaecol 1987;94:121-5, Abstract
12. Tuck S. Pregnancy in sickle cell disease in the UK. Br J Obstet Gynecol 1983;90:112-7, Abstract
13. Lauren A. Transfusion issues in a gravida with sickle cell disease. Obstetrics & Gynaecology. 1998;92(4):712, Abstract
14. ACOG technical bulletin. Haemoglobinopathies in pregnancy. International Journal of Gynecololgy & Obstetrics 1996;53:184-94