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The normal physiological change of an increase in plasma volume causes haemodilution in a pregnant woman. Although the red cell mass increases, plasma volume increases disproportionately, resulting in a lowering of the haemoglobin (Hb) to approximately 11.5 g/dL.
The National Institute for Health and Clinical Excellence (NICE) advises that women should be offered screening for anaemia at booking and at 28 weeks of gestation. Anaemia is defined as an Hb level <11.0 g/dL at booking; haemodilution will result in further drops during pregnancy and subsequent reduction in oxygen-carrying capacity. In the second and third trimesters the diagnostic level for anaemia is an Hb level of <10.5 g/dL. Postpartum the diagnostic level is 10.0 g/dL.
Iron-deficiency anaemia accounts for 85% of all cases of anaemia that are identified and is characterised by low mean cell volume (MCV). It is usually caused by nutritional deficiency or low iron stores resulting from previous pregnancy or previous heavy menstrual blood loss.
Less common causes
- Folic acid deficiency.
- Sickle cell disease.
- Haemoglobin sickle-C (HbSC).
- Beta thalassaemia (more common in patients from South East Asia, Southern Europe and Africa).
- Vitamin B12 deficiency.
- Chronic haemolysis (hereditary spherocytosis).
- Paroxysmal nocturnal haemoglobinuria.
- Gastrointestinal bleeding.
- Occult coeliac disease in pregnancy (recent evidence suggests a strong association with anaemia).
Incidence: this is a common problem. It occurs in about a third of women in the third trimester.
The body of a healthy adult woman contains 3,500-4,500 mg iron.
- 75% is in red blood cells as haemoglobin (Hb).
- 20% is as ferritin in bone marrow and the reticulo-endothelial system.
- 5% is in muscles and enzyme systems.
Nearly all of the iron in red blood cells is recycled as they are replaced every 100-120 days. Normal loss in a nonpregnant woman is 1 mg iron daily from the death of epithelial cells plus an average of 1 mg loss for each day of menstruation.
- The average woman's diet in the developed world provides 12 mg iron daily, of which 14-20% is absorbed so a balance is maintained. However, in developing countries with a mainly vegetarian diet, iron levels are low because of the relative lack of iron in the diet and the ability of phytates in cereals to interfere with iron absorption. Also, in many countries, there is a very high level of infestation with hookworm, which causes considerable faecal blood loss.
This is often asymptomatic. However, the following are most common:
The patient may also appear pale.
- Haemoglobin (Hb).
- MCV: if ≤76 fl then the probable cause is iron deficiency but, if lower than concomitant with other signs of anaemia and a raised red blood cell count, then this suggests possible B2-thalassaemia (estimate HbA2 and use Hb electrophoresis).
- Normal MCV (76-96 fl) with low Hb is typical of pregnancy.
- Serum ferritin 10-50 μg/L needs monitoring and <10 μg/L requires treatment.
Routine iron replacement is not recommended in the UK.
- Women with known haemoglobinopathy should have serum ferritin checked and be offered oral supplements if their ferritin level is low
- Women with unknown haemoglobinopathy status with a normocytic or microcytic anaemia, should start a trial of oral iron and haemoglobinopathy screening should be offered.
- Non-anaemic women at increased risk of iron deficiency should have a serum ferritin checked early in pregnancy and be offered oral supplements if ferritin is low.
- Women with established iron deficiency anaemia should be given 100-200 mg elemental iron daily. They should be advised on correct administration to optimise absorption. Supplementation should continue for at least three months and should aim to restore iron stores.
- Cochrane comments that although iron therapy restores indices to normal, data on outcomes are scarce and gastrointestinal side-effects are common.
- Referral to secondary care should be considered if there are significant symptoms and/or severe anaemia (Hb<70 g/dL) or late gestation (>34 weeks) or if there is failure to respond to a trial of oral iron.
- Inherited blood disorders with reduced or absent production of alpha or beta chains of the globin content of haemoglobin (Hb).
- Women who are carriers of thalassaemia, may be asymptomatic when not pregnant but more anaemic than usual during pregnancy.
- MCV ≤80 fl requires investigation, with an HbA2 ≥3.5% being positive for B2-thalassaemia.
- In these cases, the father of the child should be tested and the couple offered genetic counselling.
- Chorionic villus sampling in the first quarter of pregnancy and fetal cord blood sampling under ultrasound guidance in the second quarter can be used to detect B2-thalassaemia major, and termination of pregnancy offered.
Sickle cell anaemia
- Genetic defect causes production of abnormal haemoglobin (Hb) with a red blood cell life of ≤15 days.
In a sickle cell crisis, red blood cell destruction causes severe haemolytic anaemia and bone pain. The most common form is haemoglobin S but this mainly affects people from East and West Africa. Where suspected, women should receive folate supplementation of 5 mg per day. FBC should be routinely checked at 20, 28 and 32 weeks.
- If Hb falls below 6 g/dL, a transfusion is needed.
- Use of regular prophylactic transfusions is not recommended.
- Give prophylactic antibiotics through pregnancy and afterwards.
If a crisis occurs, heparin should be given. Measure Hb every 2 hours and, if it falls ≥2 g, give exchange transfusion. One study reported significant adverse effects of transfusion in pregnancy patients with multiple red cell antibodies and advised using such treatment with caution. Other measures tried in sickle crisis include steroids, fluid replacement therapy and oxygen but there is a lack of RCTs.
Complications of sickle cell anaemia in pregnancy
- Spontaneous abortion can occur in up to 25% of women affected by sickle cell anaemia with 15% approximate perinatal mortality also often associated with preterm delivery and low birthweight (30% ≤2500 g).
- Stillbirth rates of 8-10% have been seen and thorough antenatal fetal testing is required to assess growth, including ultrasound of the umbilical artery for systolic/diastolic ratio. Frequent urinary tract infections are common and require prompt treatment.
- Pregnancy-associated hypertension is also more common and may affect almost one third of pregnancies.
Folate supplements of 5 mg per day should be given from confirmation of pregnancy. Iron supplements are not needed unless serum iron and ferritin levels are reduced.
If given routinely, iron supplementation causes iron overload leading to haemochromatosis.
Women with anaemia have a mortality rate 3-5 times higher than normal and a stillbirth rate 6 times higher than normal.
Further reading & references
- Antenatal care - uncomplicated pregnancy; NICE CKS. March 2011
- Blackwell S, Merck Manual 2008
- Antenatal care: routine care for the healthy pregnant woman; NICE Clinical Guideline (March 2008 - modified June 2010)
- UK Guidelines on the management of iron deficiency in pregnancy, British Committee for Standards in Haematology (July 2011)
- Hancock R, Koren G; Celiac disease during pregnancy. Can Fam Physician. 2004 Oct;50:1361-3.
- Reveiz L, Gyte GM, Cuervo LG, et al; Treatments for iron-deficiency anaemia in pregnancy. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD003094.
- Management of Sickle Cell Disease in Pregnancy, Royal College of Obstetricians and Gynaecologists (August 2011)
- Proudfit CL, Atta E, Doyle NM; Hemolytic transfusion reaction after preoperative prophylactic blood transfusion Obstet Gynecol. 2007 Aug;110(2 Pt 2):471-4.
- Marti-Carvajal AJ, Pena-Marti GE, Comunian-Carrasco G, et al; Interventions for treating painful sickle cell crisis during pregnancy. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD006786.
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Dr Hayley Willacy
Dr Hayley Willacy
Dr John Cox