[CG] Management of iron deficiency during pregnancy and the puerperium

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Maternal anaemia is defined as:

  • Hb <110g/l        1st trimester
  • Hb <105g/l          2nd & 3rd trimesters

Maternal anaemia can result in maternal fatigue, increased risk of postpartum haemorrhage and is associated with an increased risk of stillbirth, preterm birth and neonatal low ferritin levels (1). Iron deficiency anaemia, the commonest cause of maternal anaemia can be treated easily by oral iron replacement.

 

Flow chart of investigation of anaemia in pregnancy

If Hb low (as above) check:

  • FBC (Hb & MCV)
  • Blood film
  • Reticulocytes
  • Serum ferritin

Consider commencing oral iron (as below) while awaiting results. (2) Check whether the woman is already taking iron tablets and confirm correct compliance.

Blood tests taken in the community should be followed up by the community midwife. Blood tests taken in the hospital should be followed up by the person requesting the test. Results of tests ordered through Trakcare will appear in the list of electronic results awaiting sign off. When results are signed off they should be actioned at the same time. A letter should be sent to the patient with a copy for the GP [Appendix 2] if treatment is required (see below).

Beware of congenital anaemias that are sometimes associated with a low MCV/MCH but do not respond to iron replacement. These conditions can be associated with iron overload and therefore iron replacement is relatively contraindicated. 

  • Thalassemia trait
  • Sickle cell disease (HbSS or HbSC)
  • Haemolytic anaemias (e.g. Hereditary spherocytosis)

Patients are likely to know they have these conditions.

Always test serum ferritin first to confirm iron deficiency and exclude iron overload, and discuss with a haematologist before giving iron to women with these conditions. 

If ferritin <30µg/l: commence oral replacement therapy. (2, 3, 4)   If taking iron already - confirm compliance and correct administration (as below).

What: Choice of iron tablet doesn’t matter e.g. ferrous fumarate / sulfate / gluconate

Dose: ONE tablet daily (Sytron 5ml daily)

When: in Morning (5)

How: On an empty stomach with water or fresh orange juice. (2,6, 7) Avoid tea / coffee for two hours afterwards as absorption of iron can be reduced. (8)  

Duration:  Throughout the remainder of pregnancy, continuing until 3 months postpartum. For postnatal women starting on iron replacement continue for at least 3 months.

Recent evidence shows once daily dosing is just as effective (7,9as twice or three times a day but has fewer side effects (increasing compliance). 7,90)  Alternate day dosing is possible for women unable to tolerate daily dosing.

If ferritin >30µg/l prior to iron treatment

  • Consider other causes of anaemia e.g. folate or Vitamin B12 deficiency. Check levels. If strong clinical suspicion of iron deficiency anaemia, consider checking transferrin (request “iron studies” on Trakcare)

Results of investigations performed for anaemia with Hb <105g/l

Ferritin

<30

<30

>30

>30

MCV (FBC)

Low

Normal

Normal / low

Normal

Transferrin

High/Normal/Low

High/Normal/Low

High

Normal / low

Cause

Iron deficiency anaemia

Iron deficiency anaemia

Iron deficiency anaemia is likely

Anaemia NOT likely due to iron deficiency – look for other causes 

Normal ranges:

Ferritin: >30µg/l for pregnancy

MCV - Mean Cell Volume (part of FBC result): 88-109 fl in pregnancy Transferrin:  2-4g/l

Monitor response

  • Check Hb and reticulocyte count 2-4 weeks after starting oral iron as treatment for iron deficiency anaemia. (2)
  • Blood tests may be delayed until the patient’s next appointment if treatment started before 20 weeks gestation unless Hb≤80g/l (early monitoring required).
  • Reticulocyte count will increase prior to rise in Hb and will indicate that red blood cell production is responding to therapy
  • If no response in reticulocyte count at 2 weeks, review the diagnosis / compliance.
  • Response will depend on the initial degree of iron deficiency, patient requirements e.g. multiple pregnancy, and compliance.

When to discuss with obstetric team (2)

  • Hb <70g/l
  • Significant symptoms of anaemia
  • Advanced gestation >34/40
  • Failure to respond after 2-3 weeks of correctly taken oral iron

If iron deficiency is confirmed and there is no response to oral iron replacement (non-compliant or known malabsorption), or oral iron cannot be tolerated despite once daily dosing (side effects: nausea, epigastric pain, constipation, diarrhoea)11, intravenous iron may be used (see Appendix 3). (11)

Check ferritin levels in the following women and give oral iron if ferritin <30µg/l (2)

Non-anaemic women at high risk of iron deficiency at booking

  • Previous anaemia
  • Para ≥ 3
  • Pregnancy interval < 1 year since delivery
  • Vegetarians / vegans
  • Teenagers
  • Recent history of bleeding
  • Multiple pregnancy

Non-anaemic women where an estimate of iron storage level is necessary

  • At high risk of bleeding
  • Women who would refuse blood transfusion
  • Women for whom it is difficult to obtain compatible blood

Anaemic women with

  • Known haemoglobinopathy
  • Prior to intravenous iron therapy [Appendix 3]

APPENDIX 1: Flow chart of investigation of anaemia in pregnancy

See above.

APPENDIX 2: Standard letter for women requiring oral iron therapy

Date:        

Dear 

A recent blood test has shown that you are anaemic (Hb          g/l), and /or your iron stores are low (Ferritin      µg/l). This is easily remedied by taking iron tablets. Please collect a prescription from your general practice reception.

I recommend:

What: 

Choice of iron tablet doesn’t matter e.g. ferrous fumarate / sulfate / gluconate.  Your GP can decide which one to prescribe. Sytron (liquid iron) is suitable if you can’t swallow tablets.

Dose

ONE tablet daily  (Sytron 5ml daily)

When:

in Morning 

How

On an empty stomach with water or fresh orange juice. Avoid tea / coffee for two hours afterwards as absorption of iron can be reduced.   

Duration:  For the rest of your pregnancy and for 3 months after delivery.

Yours sincerely,

Midwife / Doctor

c.c. Patient’s GP

APPENDIX 3: Intravenous iron (Ferrinject) therapy

Intravenous iron is much more expensive (drug & staff cost) than oral iron.

Most effective route of iron replacement is uncertain (12)    

Ferritin level MUST be checked prior to intravenous iron

Indications (13)

  • Non – compliance with oral iron therapy
  • Intolerance of oral iron
  • Known malabsorption condition
  • Late pregnancy >34/40 gestation if Hb < 80g/l & iron deficient
  • Postpartum in stable patient to avoid blood transfusion

Contraindications

  • History of anaphylaxis or allergy to intravenous iron
  • First trimester (possibly teratogenicity)
  • Acute / chronic infection
  • Chronic liver disease

Up to 25% patients develop side effects with intravenous iron

Risk of anaphylactoid reaction with i.v. iron between 1 in 100 – 1 in 1000

Risk of permanent skin staining with extra-vascularisation of intravenous iron

Postnatal use of iron

Intravenous iron can be used in a stable postpartum patient if she is not actively bleeding or requiring immediate increase in Hb.

Expect 30g/l increase in Hb in 14 days (14  

GGC guideline on “Blood transfusion in stable postpartum patients” (hyperlink) recommends:

Hb 90-100g/l – give oral iron

Hb ≤89g/l – if asymptomatic give iron (oral or i.v.); if symptomatic transfuse 1 unit packed red cells & reassess

 

See GGC guideline for Ferrinject administration: Ferinject                                                              

References
  1. Briley, A., Seed, P.T., Tydeman, G., et al. Reporting errors, incidence and risk factors for postpartum haemorrhage and progression to severe PPH: a prospective observational study. British Journal of Obstetrics and Gynaecology 2014;121: 876–888.
  2. Pavord S., Daru J., Prasannan N., et al. Uk Guidelines on the management of iron deficiency in pregnanacy. British Journal of Haematology 2019 doi: 10.1111/bjh.16221.
  3. van den Broek NR., Letsky EA., White SA., et al. Iron status in pregnant women: which measurements are valid? British Journal of Haematology 1998;103:817–824.
  4. Daru J., Allotey J., Pena-Rosas JP.,et al. Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review. Transfusion Medicine, 2017, 27, 167–174.
  5. Schaap, C.C., Hendriks, J.C., Kortman, G.A., et al (2013) Diurnal rhythm rather than dietary iron mediates daily hepcidin variations. Clinical Chemistry, 59, 527–535.
  6. Pena-Rosas, J.P., De-Regil, L.M., Malave, H.G., et al (2015) Intermittent oral iron supplementation during pregnancy. Cochrane Database of Systematic Reviews, Issue 10, Art. No. CD009997.
  7. Moretti D., Goede JS., Zeder C., et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. 2015; 126(17):1981-1989.
  8. Haider, B.A., Olofin, I., Wang, M., et al. Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. British Medical Journal 2013;346, f3443.
  9. Shinar S., Skornick-Rapaport A., & Masiovitz S. Iron supplementation in singleton pregnancy: is there a benefit to doubling the dose of elemental iron in iron-deficient pregnant women? A randomised controlled trial.  Journal of Perinatology 2017;37:782-786.
  10. Smith GA., Fisher SA., Doree C., et al Cochrane Database Systematic Reviews 2014; 7, CD009532.
  11. Tapiero H., Gate L., Tew KD. Iron: deficiencies and requirements. Biomedicine and Pharmacotherapy, 2001; 55: 324–332.
  12. Reveiz L, Gyte  GML, Cuervo  LG, et al. Treatments for iron‐deficiency anaemia in pregnancy. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD003094. DOI:10.1002/14651858.CD003094.pub3.
  13. Broche DE., Gay C., Armand-Branger S., et al. Severe anaemia in the immediate post-partum period. Clinical practice and value of intravenous iron. European Journal of Obstetrics & Gynecology and Reproductive Biology 2005; 123:S21-27

Last reviewed: 19 February 2021

Next review: 01 February 2024

Author(s): Dr Vicki Brace, Consultant Obstetrician, PRM & Dr Catherine Bagot, Consultant Haematologist, GRI

Version: 3

Approved By: Obstetric Guidelines Group