What is the best evidence-based oral iron supplement during pregnancy for mild iron deficiency (hypoferritinemia)?

From the Guidelines

For mild iron deficiency (low ferritin) during pregnancy, the best evidence-based oral iron supplement is 60 to 120 mg of elemental iron per day, as recommended by the American Family Physician in 2016 1. This dose can be achieved with ferrous sulfate 325 mg once or twice daily, providing 65-130 mg of elemental iron. It is essential to take the supplement between meals with vitamin C (like orange juice) to enhance absorption, but avoid taking with calcium, dairy, coffee, tea, or antacids which decrease absorption. Some key points to consider when taking oral iron supplements include:

• Starting with a lower dose and gradually increasing can help minimize side effects like constipation, nausea, and dark stools.
• If side effects are problematic, consider ferrous gluconate or ferrous fumarate which may be better tolerated, though they contain less elemental iron.
• Iron supplementation is crucial during pregnancy as iron requirements increase to support maternal blood volume expansion and fetal development.
• Treatment typically continues for 3-6 months or until ferritin levels normalize.
• If oral supplements aren't tolerated or effective, consult your healthcare provider about alternative formulations or intravenous iron therapy, as also suggested by the American Family Physician in 2016 1. The Centers for Disease Control and Prevention also recommended starting oral, low-dose supplements of iron at the first prenatal visit, but the dose of 30 mg/day is lower than the currently recommended dose of 60 to 120 mg of elemental iron per day 1.

From the FDA Drug Label

WARNINGS: Do not take within 2 hours of taking oral tetracycline antibiotics, since oral iron products tend to interfere with absorption of tetracycline. May cause gastrointestinal discomfort, nausea, constipation or diarrhea. If you are pregnant or nursing a baby, seek advice of a health professional before using this product. WARNINGS Do not take within 2 hours of taking oral tetracycline antibiotics, since oral iron products tend to interfere with absorption of tetracycline. May cause gastrointestinal discomfort, nausea, constipation or diarrhea. If you are pregnant or nursing a baby, seek advice of a health professional before using this product.

The best evidence-based oral iron supplement during pregnancy for mildly low ferritin is ferrous sulfate (PO) or ferrous gluconate (PO), as both are mentioned in the context of pregnancy and have similar warnings. However, the evidence provided does not directly compare the two or provide a clear recommendation for one over the other during pregnancy for mildly low ferritin levels.

• Key considerations:
  • Consult a health professional before using either product during pregnancy.
  • Be aware of potential gastrointestinal side effects.
  • Avoid taking within 2 hours of oral tetracycline antibiotics. 2 and 3

From the Research

Oral Iron Supplements for Mildly Low Ferritin During Pregnancy

• The best evidence-based oral iron supplement for mildly low ferritin during pregnancy is not explicitly stated in the provided studies, but some studies suggest that ferrous gluconate and ferrous bisglycinate may be effective options 4, 5, 6.
• A study from 1996 found that oral liquid ferrous gluconate was more effective and better tolerated than other solid or liquid formulations containing elementary iron in treating iron-deficiency anemia during or immediately after pregnancy 4.
• A systematic review and meta-analysis from 2023 found that ferrous bisglycinate supplementation resulted in higher hemoglobin concentrations and fewer reported gastrointestinal adverse events compared to other iron supplements in pregnant women 5.
• Another study from 2022 found that ferrous gluconate was more effective than ferrous sulfate in improving iron status and reducing the risk of iron deficiency anemia in toddlers, but the results may not be directly applicable to pregnant women 6.

Serum Ferritin Thresholds for Iron Deficiency Diagnosis

• A systematic review from 2017 found that the most commonly used thresholds for serum ferritin to diagnose iron deficiency were <12 and <15 ng/mL, but unified international thresholds are required for accurate assessments of the global disease burden and evaluation of intervention effectiveness 7.

Comparison of Iron Supplements

• A study from 2008 found that ferrous gluconate and ferrous sulfate had comparable efficacy in reducing iron deficiency in toddlers, but ferrous gluconate had a more beneficial effect on markers of iron status 8.
• The 2022 study mentioned earlier found that ferrous gluconate was more effective than ferrous sulfate in improving iron status and reducing the risk of iron deficiency anemia in toddlers 6.