Anaemia in Pregnancy

• Folic acid deficiency
• Sickle cell disease
• Haemoglobin SC
• Beta thalassaemia (more common in patients from South East Asia, Southern Europe and Africa)
• Vitamin B12 deficiency
• Chronic haemolysis (hereditary spherocytosis)
• Paroxysmal nocturnal haemoglobinuria
• Leukaemia
• GI bleeding

Incidence: this is a common problem.

Body of a healthy adult woman contains 3,500-4,500mg iron.

• 75% is in red blood cells as haemoglobin.
• 20% as ferritin in bone marrow and reticulo-endothelial system.
• 5% in muscles and enzyme systems.

Nearly all of iron in red blood cells is recycled as they are replaced every 100-120 days. Normal loss is 1mg iron from death of epithelial cells plus an average of 1mg daily from monthly menstrual loss.

• Average womans diet in developed world provides 12mg 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, very high level of infestation with hookworm, which causes considerable faecal blood loss.
• Recent evidence of occult coeliac disease in pregnancy and a strong association with anaemia.²

This is often asymptomatic. However the following are most common:

• Fatigue
• Dyspnoea

The patient may also appear pale.

• Hb ≤ 11.0g/dl
• MCV (mean cell volume): if ≤ 76fl then probable cause is iron deficiency, but if lower than concomitant with other signs of anaemia and RBC count raised, then suggests possible B2-thalassaemia (estimate HbA2 and use Hb electrophoresis).
• Normal MCV (76-96fl) with low Hb is typical of pregnancy.
• Serum ferritin 10-50g/dl needs monitoring and <10g/dl requires treatment.

A Cochrane review in 2000 found twenty trials. Iron supplementation raised or maintained the serum ferritin above 10 milligrams per litre. It resulted in a substantial reduction of women with a haemoglobin level below 10 or 10.5 g/dl in late pregnancy. Iron supplementation, however, had no detectable effect on any substantive measures of either maternal or fetal outcome.³One trial, with the largest number of participants of selective versus routine supplementation, showed an increased likelihood of caesarean section and post-partum blood transfusion, but a lower perinatal mortality rate (up to 7 days after birth).
There was little data from areas with high endemic levels of anaemia in pregnancy.

Iron deficiency

There is little evidence on the effects of treating iron deficiency anaemia in pregnancy due to the shortage of good quality trials.⁴

• Healthy patients on a normal mixed diet do not normally require iron supplements during first half of pregnancy.
• However, women on a restricted diet (e.g. vegetarians, vegans) and women in developing countries need iron supplementation.
• Iron supplementation during pregnancy is associated with significantly higher birthweight, independent of other pregnancy care factors, mother's nutritional status, smoke exposure, and a number of demographic and socioeconomic factors.⁶ Similar benefits were found in a RCT in the USA amongst women on low income.⁷

• Inherited blood disorders with reduced or absent production of alpha or beta chains of the globin content of haemoglobin.
• Women are carriers of thalassaemia, may be asymptomatic when not pregnant but more anaemic than usual during pregnancy.
• MCV ≤ 80fl 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 1st quarter of pregnancy and fetal cord blood sampling under ultrasound guidance in the 2nd quarter can be used to detect B2-thalassaemia major and termination of pregnancy offered.

• Genetic defect causes production of abnormal haemoglobin with a red blood cell life of ≤15 days.
  In a sickle cell crisis, RBC destruction causes severe haemolytic anaemia and bone pain. Commonest form is haemoglobin S but mainly affects people from East and West Africa. Where suspected, women should receive folate 15mg/day with frequent Hb counts.
• If Hb falls ≤ 6g/dl, need transfusion.
• Use of regular prophylactic transfusions reduced number of transfusions required, but was associated with more pain crises.⁸
• May give prophylactic antibiotics during childbirth and afterwards.
  If crisis occurs, give heparin, measure Hb every 2 hours and if falls ≥2g give exchange transfusion.

Complications

• Spontaneous abortion can occur in up to 25% of women affected by sickle cell anaemia with 15% approx perinatal mortality also often associated with pre-term delivery and low birth weight (30% ≤2500g).
• 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 requires prompt treatment.
• Pregnancy associated hypertension is also more common and may affect almost 1/3 of pregnancies.

Folate supplements of 1mg/day minimum should be given from confirmation of pregnancy although iron supplements are not needed unless serum iron and ferritin levels are reduced.
If given routinely, can reduce iron overload leading to haemochromatosis.

Women with anaemia have a mortality rate 3-5 times higher than normal and still birth rate 6 times normal.