What is the safety of intravenous (IV) iron supplementation during pregnancy?

From the Guidelines

Intravenous (IV) iron therapy is generally considered safe during pregnancy, particularly in the second and third trimesters when oral iron supplementation is ineffective or not tolerated. The most recent and highest quality study, 1, provides expert consensus guidelines on the use of IV iron, including its safety and efficacy in pregnant women. Key points to consider when administering IV iron during pregnancy include:

• The preferred IV iron formulations during pregnancy include iron sucrose (Venofer), ferric carboxymaltose (Ferinject/Injectafer), and low molecular weight iron dextran (INFeD), with iron sucrose having the longest safety record in pregnancy.
• Typical dosing for iron sucrose is 200-300 mg per infusion given 1-3 times weekly until the calculated iron deficit is met.
• Ferric carboxymaltose can be administered in larger doses (up to 1000 mg per infusion), reducing the number of required visits.
• Treatment should be initiated when hemoglobin levels fall below 10.5 g/dL with confirmed iron deficiency, or when oral iron causes intolerable side effects or is ineffective.
• IV iron works by rapidly replenishing iron stores, allowing for increased red blood cell production and improved maternal and fetal outcomes.
• The risk of serious adverse reactions such as anaphylaxis is very low with modern IV iron preparations (less than 0.1%), and the benefits of treating maternal anemia typically outweigh these risks. However, IV iron should be administered in appropriate healthcare settings where any potential reactions can be promptly managed, as recommended by 1.

From the FDA Drug Label

Published studies on intravenous iron sucrose treatment after the first trimester of pregnancy have not shown adverse maternal or fetal outcomes Available reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects and miscarriage Animal reproduction studies of iron sucrose administered to rats and rabbits during the period of organogenesis at elemental iron doses equivalent to the maximum recommended human dose based on body surface area revealed no evidence of harm to the fetus Published data from randomized controlled studies and prospective observational studies on the use of Venofer in pregnant women have not reported an association of Venofer and adverse developmental outcomes

The safety of intravenous (IV) iron supplementation during pregnancy is generally considered acceptable after the first trimester, as no adverse maternal or fetal outcomes have been reported in published studies 2. However, insufficient data is available to assess the risk of major birth defects and miscarriage during the first trimester. Animal studies have also shown no evidence of harm to the fetus. It is essential to weigh the benefits of treating iron deficiency anemia against the potential risks, as untreated IDA can lead to adverse maternal and fetal outcomes, including:

• Post-partum anemia
• Preterm delivery
• Low birth weight Severe adverse reactions, including circulatory failure and anaphylactic reactions, can occur in pregnant women with parenteral iron products, which may cause fetal bradycardia.

From the Research

Safety of Intravenous Iron Supplementation

The safety of intravenous (IV) iron supplementation during pregnancy has been evaluated in several studies.

• IV iron preparations can be safely used for the treatment of iron deficiency anaemia (IDA) during pregnancy and the postpartum period 3.
• Intravenous ferric carboxymaltose (FCM) is associated with fewer adverse events than intravenous iron sucrose (IS) 4.
• IV iron sucrose treated IDA of pregnancy faster and more effectively than oral iron therapy, with no serious adverse drug reactions 5.
• Iron-containing drugs which have been studied in well-controlled clinical trials in pregnancy and postpartum, such as ferric carboxymaltose, must be preferred for safety reasons 6.
• Ferumoxytol, a superparamagnetic iron oxide, has been shown to be safe and effective for the treatment of iron deficiency and iron-deficiency anaemia of pregnancy, with no adverse events reported 7.

Adverse Events

The incidence of adverse events with IV iron supplementation during pregnancy is generally low.

• Intravenous FCM is associated with fewer adverse events than IS 4.
• Oral iron group had significant gastro-intestinal adverse effects compared to IV iron sucrose group 5.
• Anaphylactic reactions are extremely rare with non-dextrane products, but close surveillance during administration is recommended for all IV iron products 6.
• No adverse events were reported with the use of ferumoxytol for the treatment of iron deficiency and iron-deficiency anaemia of pregnancy 7.

Recommendations

The use of IV iron supplementation during pregnancy is recommended in certain situations.

• IV iron therapy is an alternative therapeutic option in patients who do not respond to oral iron therapy, have adverse reactions, do not comply with oral iron treatment, have a very low haemoglobin concentration, and require rapid iron repletion 3.
• IV iron therapy should be administered in the case of severe iron-deficiency anaemia, intolerance of oral iron, lack of response to oral iron, or in the case of a clinical need for rapid and efficient treatment of anaemia 6.
• Ferumoxytol represents an efficacious and safe method of administration of IV iron, which improves convenience for patients and practitioners, and is cost-saving due to fewer visits 7.