Daily vs Intermittent Iron Therapy in Pregnancy

The Centers for Disease Control and Prevention estimates that as many as 8 million American
women of childbearing age are iron deficient. In a typical singleton gestation, the maternal
need for iron averages close to 1000 mg. Of this 300 mg is for the fetus and placenta; 500 mg
for maternal hemoglobin mass expansion; and 200 mg that is normally shed through the gut,
urine, and skin. The total amount of 1000 mg considerably exceeds the iron stores of most
women and results in iron-deficiency anemia unless iron supplementation is given.

Correction of anemia and restitution of iron stores can be accomplished with simple iron
compounds-ferrous sulfate, fumarate or gluconate. Oral iron is an effective treatment for
iron deficiency anemia and is inexpensive, safe and widely available.

In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous
sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of
195 mg elemental iron. However, recent absorption studies concluded that maximal absorption
of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. This study
was done in non pregnant iron-deficient women. Greater doses do not result in more iron
absorption and are associated with more side effects. The findings of this study have been
implemented by many into various areas of medicine.

Daily oral supplementation in pregnant women has been a long-standing, cost-effective
recommended intervention both in the public health and clinical fields. However, adherence to
daily iron and folic acid supplementation still faces challenges. Data from national surveys
from 46 countries (2003 to 2009) indicate that about 52% to 75% of mothers receive any iron
tablets during pregnancy, and the duration of supplementation is usually short.

According to a study by Khalafallah, the side effects or oral iron therapy including
gastrointestinal disturbances characterized by colicky pain, nausea, vomiting, diarrhea, and
constipation occur in about 50% of a patient taking iron preparations, and the investigators
estimate that their patients have similar complaints and intolerances.

Many pregnant women taking oral iron, especially at doses greater than 30 mg daily of
elemental iron daily, have gastrointestinal side effects, which cause them to discontinue the
iron therapy. Taking iron supplementation on an intermittent basis may help to reduce
gastrointestinal side effects and improve iron stores.

In the United States, the oral iron preparation of ferrous sulfate is often used to replete
iron-deficient women. To the investigators' knowledge, studies have not been performed to
evaluate daily vs. oral intermittent oral iron therapy in the United States, which has a
different nutritional status and access to health care than other countries.

This study will randomize patients to the standard therapy: taking iron ferrous sulfate 325
mg (daily) by mouth once a day by mouth or intermittent therapy of taking ferrous sulfate 325
mg three- four times a week on alternating days. Hematological markers (hemoglobin,
hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor), will be
assessed prior to treatment and after treatment is completed.

Inclusion Criteria:

1. Pregnant women who are not underweight (BMI < 18.5 kg/m2)

2. Reproductive-aged women 18-50

3. Singleton Pregnancy.

4. Patients undergoing third trimester blood work from 26-28 weeks.

5. Women who have had previously normal first-trimester blood work (hemoglobin,
hematocrit, MCV) without any evidence of existing anemia.

6. Pregnant women with anemia designated with hemoglobin concentration less than 11 g/dL
or hematocrit less than 33%

7. No pre-existing iron deficiency anemia or not already on iron supplementation.

Exclusion Criteria:

1. Women with medical problems known to affect iron metabolism or homeostasis

2. Women with existing thalassemias or anemias.

3. Women with abnormal bloodwork indicating anemia earlier in the pregnancy.

4. Women are already taking iron supplementation during the pregnancy for treatment of
iron deficiency anemia.

5. Chronic illness is influencing iron absorption.

6. Underlying malabsorption disease.

7. History of bariatric surgery.

8. Severe anemia with maternal hemoglobin levels less than 6 g/dL

9. Preterm Labor, PPROM, signs of infection.