For the above reasons, and because gastrointestinal side effects of oral iron supplementation (constipation, nausea, and diarrhea) are negligible with doses less than 45–60 mg, supplementation with elemental iron (30 mg/day) is recommended for all pregnant women in the United States, regardless of indices.
Supplementation should be continued until three months postpartum in areas with high prevalence of anemia. A review of randomized clinical trials (most performed in Western countries) showed that routine supplementation in nonanemic women results in higher maternal Hb levels at term and one month postpartum, higher serum ferritin levels, lower rates of anemia at term (RR = 0.26) and of iron deficiency anemia in particular (RR = 0.33), and higher serum ferritin levels in the infants (Peña‐Rosas and Viteri 2009). However, no differences are noted in most clinical outcomes, such as preterm birth, preeclampsia, or need for transfusion, birthweight, small for gestational age, perinatal mortality or need for NICU admissions.
Treatment of iron deficiency anemia
Compared to routine supplementation in pregnancy, higher doses of iron are required for the treatment of maternal anemia (up to 200 mg/day). Oral iron therapy is most often utilized, with a list of the most commonly available formulations given in Table 11.2. Enteric‐coated forms should be avoided because they are poorly absorbed; absorption is increased by intake of iron on an empty stomach and with vitamin C or orange juice. Although several trials have been conducted to compare iron formulations, it is not possible to assess the efficacy of the treatments due to the use of different drugs, doses, and routes. Gut absorption decreases with increasing doses of iron; therefore it is best to divide the total daily dose into 2–3 doses.
Table 11.2 Oral preparations for therapy of iron deficiency anemia
Source: Based on ACOG Practice Bulletin No. 107, 2009.
| Type of iron | Elemental iron (mg) | Brand |
|---|---|---|
| Ferrous fumarate | 64–200 | Femiron, Feostat, Ferrets, Fumasorb, Hemocyte, Ircon, Nephro‐Fer, Vitron‐C |
| Ferrous sulfate | 40–65 | Chem‐Sol, Fe50, Feosol, Fergensol, Ferinsol, Ferogradumet, Ferosul, Ferratab, FerraTD, Ferrobob, Ferrospace, Ferrotime, Moliron, Slowfe, Yieronia |
| Ferrous gluconate | 38 | Fergon, Ferralet, Simron |
| Ferric | 50–150 | Ferrimin, Fe‐Tinic, Hytinic, Niferex, Nu‐iron |
A relationship exists between dose of oral iron and gastrointestinal side effects, with worsening of symptoms as dose increases, with such side effects leading to discontinuation of therapy in 50% of women. To encourage compliance, it is important to minimize side effects by increasing the dose gradually, with larger doses in the evening, and consideration for the use of an iron sulfate elixir which allows more gradual titration of dose. Stool softeners are often required to prevent constipation. Serum reticulocyte count should be elevated within 7–10 days of treatment initiation, with an improvement in hemoglobin levels less rapid – the hemoglobin deficit should be expected to halve in one month and normalize by 6–8 weeks after initiation of treatment. To replenish iron stores, oral therapy should be continued for three months after the anemia has been corrected.
Intravenous (IV) iron therapy is generally reserved for women who cannot or will not take oral iron preparations. Hemoglobin indices are equivalent after 40 days of treatment in women receiving IV iron therapy compared to those receiving oral therapy, but the rate of rise is more rapid in women receiving IV therapy. Randomized trials have not shown significant differences in need for maternal blood transfusion, neonatal birthweight, or neonatal anemia between the two forms of supplementation, and studies have demonstrated a preference for oral supplementation among most women. Therefore, IV therapy is indicated only in patients with severe anemia with intolerance to oral therapy or malabsorption. Iron dextran is associated with a greater risk of anaphylaxis and is not recommended in the light of other available formulations with a lower risk of allergic reaction. Intravenous preparations tested in pregnancy or puerperium are shown in Table 11.3.
Table 11.3 Intravenous preparations for therapy of iron deficiency anemia
Source: Based on ACOG Practice Bulletin No. 107, 2009.
| Type of intravenous iron | Commercial names | Dose |
|---|---|---|
| Iron dextran LMW | INFeD, Cosmofer | 1000 mg/60 min (diluted in 250–1000 mL of normal saline) |
| Ferric gluconate | Ferlecit | 125 mg/30 min (diluted in 100 mL of normal saline) |
| Iron sucrose | Venofer | 200 mg/60 min |
| Ferric carboxymaltose | Ferinject | 100 mg/15 min |
Erythropoietin is not indicated in the treatment of iron deficiency anemia unless the anemia is caused by chronic renal failure or other serious chronic medical conditions and is expensive with many associated side effects – its use should be reserved for treatment by a hematologist.
Blood transfusion is indicated only for anemia associated with hypovolemia from blood loss or in preparation for a cesarean delivery in the presence of severe anemia.
Suggested reading
1 Al R, Unlubilgin E, Kandemir O, et al. Intravenous versus oral iron for treatment of anemia in pregnancy: a randomized trial. Obstet Gynecol 2005; 106:1335–40.
2 American College of Obstetricians and Gynecologists. Neural tube defects. ACOG Practice Bulletin No. 44. Obstet Gynecol 2003; 102:203–13.
3 American College of Obstetricians and Gynecologists. Anemia in Pregnancy. ACOG Practice Bulletin No. 95. Obstet Gynecol 2008; 112:201–7.
4 Breymann C, Milman N, Mezzacasa A, et al. Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open‐label, randomized controlled trial (FER‐ASAP). J Perinat Med 2017; 45:443–53.
5 Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR 1998; 47:1–29.
6 Kadyrov M, Kosanke G, Kingdom J, et al. Increased fetoplacental angiogenesis during first trimester in anaemic women. Lancet 1998; 352:1747.
7 Klebanoff MA, Shiono PH, Selby JV, et al. Anemia and spontaneous preterm birth. Am J Obstet Gynecol 1991; 164:59.
8 Lieberman E, Ryan KJ, Monson RR, et al. Risk factors accounting for racial differences in the rate of premature birth. N Engl J Med 1987; 317:743.
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