Anaemia in pregnancy

Anaemia in pregnancy

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 115 g/L.

The National Institute for Health and Care Excellence (NICE) advises that women should be offered screening for anaemia at booking and at 28 weeks of gestation¹ . Anaemia is defined as an Hb level <110 g/L 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 <105 g/L. Postpartum the diagnostic level is 100 g/L² .

Causes of anaemia in pregnancy (aetiology)

Iron-deficiency anaemia accounts for the majority of 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. Physiological requirements for iron in pregnancy are three times higher than in non-pregnant menstruating women and iron requirement increases as pregnancy advances.

Less common causes

• Folic acid deficiency.

• Sickle cell disease.

• Haemoglobin sickle-C (HbSC).

• Beta thalassaemia (more common in patients from Southeast Asia, Southern Europe and Africa).

• Vitamin B12 deficiency.

• Chronic haemolysis (hereditary spherocytosis).

• Paroxysmal nocturnal haemoglobinuria.

• Leukaemia.

• Gastrointestinal bleeding.

• Coeliac disease.

• Parasitic diseases (eg, hookworm, schistosomiasis).

Epidemiology

Anaemia in pregnancy is a common problem. In the UK, prevalence is estimated to be 24.4% antenatally³ . Nearly a third of women are anaemic postpartum. Worldwide prevalence of anaemia in pregnancy is estimated to be around 38% (compared to 29% of non-pregnant women)⁴ .

Anaemia in pregnancy symptoms (presentation)

Anaemia in pregnancy may be asymptomatic. However, the following symptoms are most common:

• Fatigue

• Dyspnoea

• Dizziness

The patient may appear pale.

Investigations

• 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, this suggests possible B2-thalassaemia (estimate HbA2 and use Hb electrophoresis).

• Normal MCV (76-96 fl) with low Hb is typical of pregnancy.

• Ferritin is not required as a routine test. A two-week trial of oral iron with a subsequent improvement in Hb level confirms the diagnosis of iron deficiency ² . However, ferritin should be checked in women with haemoglobinopathy or where the cause is in doubt.
  

Management²

Routine iron replacement in pregnancy is not recommended in the UK¹ .

• Women with known haemoglobinopathy should have serum ferritin checked and be offered oral supplements if their ferritin level is low (<30 μg/L).

• Women not known to have a previous problem who have 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.

• Once women become iron-deficient in pregnancy it is not possible to ensure repletion through diet alone and oral supplementation is needed. Until further research determines the optimal dose of elemental oral iron, 40-80 mg (eg, as ferrous sulfate 200 mg daily) is suggested, checking Hb at 2-3 weeks to ensure an adequate response² .

• Referral to a haematologist should be considered if there are significant symptoms and/or severe anaemia (Hb<70 g/L) or late gestation (>34 weeks) or if there is failure to respond to a trial of oral iron.

• IV iron therapy is indicated when there is absolute non-compliance with, or intolerance of, oral iron therapy or proven malabsorption or when a rapid Hb response is required and systematic reviews have found that pregnant women receiving intravenous (IV) iron, compared with oral iron, achieved the target Hb more often, had an increased Hb after four weeks and had fewer side-effects⁵ .

• The most recent (2011) Cochrane review comments that although iron therapy restores indices to normal, data on outcomes are scarce and gastrointestinal side-effects are common⁶ .

Thalassaemias⁷

• 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.

• Women with thalassaemia should have specialist antenatal care, high-dose folate (5 mg per day), frequent ultrasound scans, regular Hb monitoring and transfusions.

See the separate Thalassaemia article for more detail.

Sickle cell anaemia⁸

There are approximately 110–200 pregnancies in women with sickle cell disease (SCD) per year in the UK. Pregnancy in women with SCD is associated with higher risk of mortality and morbidity.

• Genetic defect causes production of abnormal 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.

• Iron supplements are not needed unless serum iron and ferritin levels are reduced. If given routinely, iron supplementation causes iron overload leading to haemochromatosis.

• If Hb falls below 60 g/L, or there is a fall of 20 g/L from baseline, a transfusion is considered.

• 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 two hours and, if it falls ≥20 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 caution⁹ . Other measures tried in sickle crisis include steroids, fluid replacement therapy and oxygen but there is a lack of RCTs¹⁰ .

Complications of sickle cell anaemia in pregnancy

Data from a national study in the UK showed an increased risk of both sickle-related complications (acute pain, acute chest syndrome) and pregnancy-related complications (hypertension, venous thromboembolism and urinary tract infections)¹¹ . Women with SCD were more likely to require blood transfusion or admission to the critical care unit.

• 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 birth weight (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.

• Sickle cell crisis, stroke and pulmonary embolism are further complications which may occur.

• A US retrospective study has shown that pregnancy-related VTE in women with SCD appears to be 1·5-5 times greater than in the general population¹² .

• Frequent urinary tract infections are common and require prompt treatment.

• Pregnancy-associated hypertension is also thought to be more common.

See the separate Sickle Cell Disease and Sickle Cell Anaemia article for more detail.

Complications²

Women with anaemia in pregnancy have been shown to have a higher risk of:

• Maternal death.

• Fetal death.

• Premature delivery.

• Low birth-weight babies.

• Cardiac failure.

• Their babies having subsequent developmental problems.

• Poor work capacity/performance.

• Susceptibility to infection.

However, the threshold at which these complications arise remains unclear.

Prevention

A number of studies have looked at the value of widespread routine use of prenatal iron. Some have found a positive effect on birth weight and other outcomes¹³ . Others point to the potential adverse effects of iron supplementation in women with normal levels (placental insufficiency, haemochromatosis, side-effects, accidental poisoning of children in the household, cost, etc)² . The most recent Cochrane review found that supplementation reduces the risk of maternal anaemia and iron deficiency in pregnancy but the positive effect on other maternal and infant outcomes is less clear¹⁴ . Implementation of iron supplementation recommendations may produce heterogeneous results depending on the populations' background risk for low birthweight and anaemia, as well as the level of adherence to the intervention.