red blood cells


Definition and Epidemiology

red blood cells
  • WHO definition of anemia during pregnancy is a haemoglobin (Hb) level of less than 110 g/dl (in pre-March 2013 terminology, 11 g/dL) and post partum anemia as Hb less than 100 g/litre.

  • Iron deficiency, particularly during pregnancy, is the most common nutrient deficiency in the world, especially in developing and resource-poor countries. Even in developed countries, it is estimated that about 30-40% of pregnant women have iron deficiency anaemia.

  • British Committee for Standards in Haematology guidelines: Hb of less than 110 g/litre in the first and third trimesters, less than 105 g/litre in the second trimester and less than 100 g/litre in the postpartum period.

Physiological Changes

  • Low Hb concentrations are part of the normal physiological response to pregnancy due to a dilution effect.

  • Hb concentrations fall from early pregnancy to the lowest point at about 36 weeks gestation, when compared with a non-pregnant state. Maternal haematocrit follows a similar pattern.

  • Mean Hb and the haematocrit usually return to normal within 3 months in healthy women after a normal delivery.

  • Each normal prengnancy and delivery requires about 1 g of iron.

Iron Deficiency Anaemia (Microcytic Hypochromic)


  • One third to one half of all pregnant women who are not on iron supplements will have a haemoglobin of less than 110 g/litre. Those  on a healthy diet do not suffer serious clinical problems or develop symptoms. Women with multiple gestations or grand multiparas as well as thjose who smoke and/or have poor nutrition can develop symptomatic iron deficiency anaemia.

  • Other indications for checking serum ferritin levels in pregnant women not previously known to be anaemic include those with a high risk of iron depletion or poor stores such as previous anaemia, multiple pregnancies, parity >3. Short interpregnancy interval of < 1year, recent history of bleeding, teenage pregnancies.

  • Effective management is needed to prevent adverse outcomes during pregnancy, delivery and the postnatal period including increased susceptibility to infections and altered immune responses.

  • Maternal iron depletion also increases the risk of neonatal iron deficiency in the first 3 months of life, although the fetus is largely protected due to the up-regulation of placental transport proteins.

  • Some have suggested the use of routine iron supplementation for all pregnant women irrespective of their status. However, additional iron supplementation for women who have normal levels of iron may even be associated with increased blood viscosity, impaired placental circulation, therefore restricted fetal growth.

  • Routine iron supplementation for all pregnant women is not currently recommended except in those areas with a particularly large population of ‘at risk’ women with haemoglobinopathies.

Clinical Symptoms

Clinical symptoms and signs of severe iron deficiency anaemia in pregnancy include fatigue as the most common symptom as well as dyspnoea, palpitations, headaches, weakness, irritability and pallor.

Diagnosis and Management

  • A trial of oral iron should be the first line diagnostic test, as an increment seen at 2 weeks is a positive result for iron deficiency anaemia. The Hb concentration should rise by approximately 20 g/litre over 3-4 weeks.

  • Serum ferritin is the best indicator of iron deficiency. Serum iron, transferrin saturation and total iron binding capacity (TIBC) are less reliable indicators due to the wide fluctuation in levels from recent ingestion of iron, diurnal variation, infection etc.

  • Measurement of red cell zinc protoporphyrin (ZPP) levels, a rarely performed test, is more sensitive than serum ferritin levels, bearing an inverse relationship with the degree of iron availability.

  • Serum ferritin levels in women with adequate iron stores at conception initially rises, followed by a progressive fall by 32 weeks to about 50% pre-pregnancy levels due to haemodilution and utilization of iron. There is a small increase again in the third trimesters.

  • Women with known haemoglobinopathies should have their serum ferritin checked and offered oral supplements if the ferritin level is less than 30 micrograms/litre.

  • Women with established iron deficiency anaemia must be prescribed 100-200 mg of elemental iron/day (200 mg of either ferrous sulphate or fumarate contains 65 mg of elemental iron; 300 mg of ferrous gluconate has 35 mg of elemental iron) with advice regarding the correct administration to optimize absorption.

  • In those who are not anaemic yet, but are found to be iron deficient, a daily dose of 65 mg elemental iron may be offered. Hb and serum ferritin test must be repeated after 8 weeks, as these womenhave little iron stores to utilize should additional iron be required.

  • After restoration of the Hb to the normal range, it is important to advise that iron supplemtation can be continued for 3 months during pregnancy and at least until 6 weeks postpartum to replenish iron stores.

  • In those with severe anaemia, additional intrapartum precautions are needed and must be documented, including need for delivery in a hospital setting, blood group and save on admission, prompt establishment of IV access, active management of the third stage of labour and pre-planning in the event of postpartum haemorrhage.

Role of IV Parenteral Iron In Iron Deficiency Anaemia

  • Parenteral iron should be considered from the latter part of the second trimester onwards and during the postpartum period for women with refractory iron deficiency who are either totally non-compliantwith or intolerant of oral iron therapy or have proven malabsorption.
  • Contraindications for parenteral iron include a history of anaphylaxis , adverse reactions to a test dose of parenteral iron, the first trimester of pregnancy, active acute or chronic infection, chronic liver disease.
  • IV parenteral iron has little added advantage over oral iron therapy except the certainty od administration. Some studies have shown a more rapid rise of Hb and better replenishment of iron stores compared with oral therapy.

Blood Transfusion

  • This should be reserved for only those women who have developed severe anaemia (70g/litre at >36 weeks gestation), especially if associated with repeated APHs.

  • Although transfusion will ‘improve’ the Hb level, transfused red blood cells have a shorter lifespan and a reduced oxygen-carrying capacity,

  • Transfusion of blood has often been foundto trigger onset of uterine contractions, a factor to be borne in mind before a decision regarding transfusion is taken.

  • Blood transfusion should be reserved for those with continued bleeding or have a risk of further bleeding, imminent cardiac compromise or symptoms requiring immediate action.

Planning intrapartum management

  • If anaemia persists with H bevels 95 g/litre or less after 36-37 weeks gestation, even average blood loss in the third stage may not be adequately tolerated.

  • Active management of third stage with high dose oxytocin infusion for a minimum of 2-4 h in addition to the routine bolus of IM oxytocin.

Megaloblastic Anaemia: Folate Deficiency, Vitamin B12 Deficiency

  • Folate is a generic term for a naturally occurring family of B-group vitamins found in a variety of foods including green leafy vegetables, fruit, liver, yeast. Folic acid is the synthetic form of folate which is widely used in supplements and fortification.

  • Folate is vital for the growth of the fetus, placenta and maternal tissues. The fetus actively accumulates folates reserves.

  • The incidence of megaloblastic anaemia in pregnancy in the UK is estimated to be at least 0.2-5%, with most cases caused by folate deficiency rather than that of vitamin B12.

  • This quoted prevalence rate is based on serum folate levels and is likely to be a significant underestimate due to megaloblastic changes already present in the bone marrow, detectable only by bone marrow aspiration.

  • The prevalence of megaloblastic anaemia during pregnancy is influenced by nutritional and socio-economic status and therefore varies between different population groups.

  • The normal dietary folate intake in some countries is inadequate to supply the recommended amount required during pregnancy to prevent megaloblastic anaemia in one-quarter of all pregnant women.

  • In Europe, the recommended daily intake ranges from 200 to 400 micrograms of folate for adults. For a normal singleton pregnancy, it ranges from 300 to 600 micrograms/day and from 260 to 600 micrograms/day during lactation. The average daily intake in unsupplemented women in a UK study is 237 micrograms/day.

  • Metabolism during pregnancy is associated with a negative folate balance due to fetal requirements and increased folate breakdown. Megaloblastic anaemia occurs following 17-19 weeks of a negative folate balance, so is usually  encountered in late gestation.

  • Due to a combination of physiological haemodilution and a negative folate balance, there is normally a progressive fall in serum folate levels as pregnancy advances.

  • In a normal pregnancy, the serum folate concentration at term may be only 50% of non pregnancy values.


Diagnostic Tests

  • Serum folate levels in pregnancy are not particularly useful in the diagnosis of megaloblastic aneaemia associated with folate deficiency as postprandial and day-to-day variations are common.

  • There is also considerable overlap in the range of serum folate concentrations in pregnant women with normal haematopoiesis and those with megaloblastic anaemia.

  • Red cell folate is more reliable indicator of the folate status in pregnancy as it displays less short-term variation and is a better indicator of folate stores.


  • Without folate supplementation during pregnancy, one-third of women will have low folate levels  in the puerpurium and around 10% will develop macrocystic anemia. There are currently no DH recommendations in the UK for all women to take folate supplements throughout pregnancy.
  • It must be noted that pregnant women with severe iron deficiency may also have co-existing folate deficiency and simultaneous folate supplementation with that of iron must be borne in mind. If only iron supplementation is given, the resultant increase in red cell production may further deplete folate stores, resulting in severe megaloblastic anaemia.
  • Apart from the well-established link between maternal folate deficiency and fetal neural tube and cleft defects, an association has also been found with other adverse pregnancy outcomes such as abruption, recurrent miscarriage, fetal growth restriction, preterm delivery and low birth weight.

Refractory Anaemia Investiagations

  • In those with refractory anaemia, further investigations are required to establish aetiology, further investigations are required to establish aetiology and to guide management.

  • In such cases the following conditions need to be considered:

  • Any underlying renal disease – chronic UTIs, nephrotic syndrome, repeated pyelonephritis. Investigations: MSU, mmicrocopic haematuria, renal function tests and maternal renal scan as indicated.

  • Any underlying bowel disease (e.g. coeliacl disease, inflammatory bowel disease, malabsorbtion syndromes). Investigations may include stool samoles (x3) for evidence of parasites or melena, markers for coeliac disease


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