Iron Supplements for Iron Deficiency in Pregnancy

(EASE-Iron Trial)

Recruiting at 1 trial location

Overseen By Lulu Pei, MSc

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Proton pump inhibitors, antibiotics

Disqualifiers: Sickle cell, Celiac, Smoking, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

172 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not use medications known to interfere with iron metabolism or gut health, such as proton pump inhibitors, anti-inflammatory agents, non-steroidal anti-inflammatory drugs, and antibiotics.

What data supports the effectiveness of the drug Ferrous bisglycinate for treating iron deficiency in pregnancy?

Research shows that Ferrous bisglycinate is effective in increasing iron levels in pregnant women with iron deficiency, with studies indicating it is as effective as other iron supplements like ferrous sulfate and ferrous fumarate, but with potentially fewer side effects. ^{1 2 3 4 5}

Is it safe to take iron supplements like ferrous bisglycinate during pregnancy?

Research shows that ferrous bisglycinate is generally safe for humans, with fewer stomach-related side effects compared to other iron supplements. Studies in pregnant women and animals indicate it is well-tolerated and effective in increasing iron levels without significant adverse effects. ^{1 2 4 6 7}

How does the drug Ferrous bisglycinate differ from other treatments for iron deficiency in pregnancy?

Ferrous bisglycinate is unique because it is more bioavailable (easier for the body to absorb) and causes fewer stomach-related side effects compared to traditional iron salts like ferrous fumarate. This makes it a more effective and tolerable option for pregnant women with iron deficiency. ^{1 2 3 8 9}

What is the purpose of this trial?

This two-arm, double-blind randomized clinical trial will recruit 172 generally healthy, low-risk pregnant individuals aged 19-42 years living in Vancouver, Canada. Participants will be randomized to receive one of two forms of iron (ferrous fumarate or ferrous bisglycinate) in addition to a prenatal multivitamin (without iron) daily during their pregnancy until delivery, with optional continuation until \~4 weeks postpartum for breastmilk sample collection. Blood samples will be taken at baseline (13-25 weeks gestation) and follow-up (35-37 weeks gestation) to assess how different forms of iron impact body iron stores. Stool samples will be obtained within 1 week of both baseline and follow-up visits to assess changes in gut microbiome composition. This research will inform more specific guidelines for optimal iron supplementation practices for the prevention and treatment of iron deficiency for both mother and baby.

Research Team

Crystal Karakochuk, PhD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for healthy pregnant individuals aged 19-42 in Vancouver, expecting one baby and planning to deliver at BC Women's Hospital. They should be 13-25 weeks into their pregnancy and able to visit the University of British Columbia. Exclusions include a BMI ≥30, smoking recently, certain pre-existing conditions affecting iron levels, or use of specific medications.

Inclusion Criteria

You are in your second trimester of pregnancy, between 13 and 25 weeks.

I am pregnant, between 19 and 42 years old, and expecting one baby.

I plan to give birth at BC Women's Hospital.

Exclusion Criteria

You have a history of neural tube defects or have had a previous pregnancy with a neural tube defect.

I have a health condition that affects my body's iron levels.

I am currently receiving blood transfusions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline visit includes informed consent, randomization, provision of study supplements, and collection of baseline data

1 day

1 visit (in-person)

Treatment

Participants receive daily iron and prenatal multivitamin supplements from baseline to delivery, with monthly follow-up surveys

12 weeks

Monthly virtual follow-ups

Follow-up

Follow-up visit includes collection of remaining supplements, weight measurement, blood draw, and stool collection

2 weeks

1 visit (in-person)

Optional Continuation

Participants who plan to breastfeed may continue supplementation and provide breastmilk samples postpartum

4 weeks postpartum

Treatment Details

Interventions

• Ferrous bisglycinate
• Ferrous fumarate

Trial Overview The study tests two types of iron supplements: Ferrous fumarate and Ferrous bisglycinate taken with prenatal vitamins during pregnancy until delivery. The goal is to compare how each supplement affects body iron stores and gut bacteria presence by analyzing blood samples and rectal swabs from start till around week 37.

Participant Groups

Group I: Ferrous bisglycinate Experimental Treatment 1 Intervention

24 mg elemental iron/day

Group II: Ferrous fumarate Active Control 1 Intervention

24 mg elemental iron/day

Ferrous bisglycinate is already approved in Canada, European Union, United States for the following indications:

Approved in Canada as Ferrous bisglycinate for:

• Prevention and treatment of iron deficiency in pregnancy

Approved in European Union as Ferrous bisglycinate for:

• Prevention and treatment of iron deficiency in pregnancy

Approved in United States as Ferrous bisglycinate for:

• Prevention and treatment of iron deficiency in pregnancy

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Findings from Research

In a study of 120 pregnant women with iron deficiency, supplementation with ferrous bisglycinate plus folinic acid showed significantly better iron absorption and hematological improvements compared to ferrous fumarate, despite a lower iron dosage.

The ferrous bisglycinate group reported fewer side effects, such as nausea and abdominal pain, indicating it may be a more tolerable option for managing iron deficiency during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial. Bumrungpert, A., Pavadhgul, P., Piromsawasdi, T., et al.[2023]

Ferrous bisglycinate supplementation for 4-20 weeks significantly increased hemoglobin concentrations in pregnant women compared to other iron supplements, with a standardized mean difference of 0.54 g/dL.

This novel iron supplement was also associated with fewer gastrointestinal adverse events, showing an incidence rate ratio of 0.36, indicating it may be a safer option for those at risk of iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Fischer, JAJ., Cherian, AM., Bone, JN., et al.[2023]

In a study of 80 pregnant women, ferrous bisglycinate (25 mg iron/day) was found to be as effective as ferrous sulfate (50 mg iron/day) in preventing iron deficiency and iron deficiency anemia during pregnancy.

Ferrous bisglycinate resulted in fewer gastrointestinal complaints compared to ferrous sulfate, making it a potentially safer option for iron supplementation in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial. Milman, N., Jønsson, L., Dyre, P., et al.[2019]

In a study of 150 pregnant women with iron deficiency anemia, both iron amino acid chelate (IAAC) and ferrous fumarate (FF) were effective in treating the condition over 12 weeks, but IAAC led to a significantly faster increase in hemoglobin levels.

IAAC was better tolerated than FF, with fewer reported side effects such as constipation and abdominal pain, making it a preferable option for treating iron deficiency anemia during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acid chelated iron versus an iron salt in the treatment of iron deficiency anemia with pregnancy: A randomized controlled study. Abdel Moety, GAF., Ali, AM., Fouad, R., et al.[2018]

In a study involving 100 pregnant women with iron deficiency anemia, both bovine lactoferrin and ferrous sulfate effectively increased hemoglobin and iron levels after 30 days of treatment, showing similar efficacy.

Bovine lactoferrin was associated with significantly fewer gastrointestinal side effects, such as abdominal pain and constipation, compared to ferrous sulfate, making it a potentially safer option for treating iron deficiency in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study. Nappi, C., Tommaselli, GA., Morra, I., et al.[2014]

Ferrous bisglycinate chelate (Ferrochel) is a highly stable and bioavailable form of iron that causes fewer side effects compared to traditional iron salts, making it a safer option for iron supplementation.

In a study with Sprague-Dawley rats, no adverse effects were observed at doses up to 500 mg/kg body weight/day, establishing this as the no-observed-adverse-effect level (NOAEL) for this compound.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of ferrous bisglycinate chelate. Jeppsen, RB., Borzelleca, JF.[2019]

Iron amino acid chelates, particularly ferrous bis-glycine chelate (FeBC), are effective in treating iron deficiency anemia and are better absorbed from various food sources compared to traditional ferrous sulfate.

Despite their efficacy, the use of FeBC in national fortification programs is limited by cost and potential changes in food taste, highlighting the need for further research on its bioavailability and comparison with other iron supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron amino acid chelates. Hertrampf, E., Olivares, M.[2013]

In a study involving 145 pregnant women, daily supplementation with 15 mg of iron from iron-bis-glycinate chelate (Ferrochel) was found to be significantly more effective than 40 mg of iron from ferrous sulfate in preventing iron deficiency, despite the lower dosage.

Only 30.8% of women taking Ferrochel experienced iron depletion compared to 54.5% of those taking ferrous sulfate, and taste issues led to non-compliance in 29.8% of the ferrous sulfate group, highlighting Ferrochel's better tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women. Szarfarc, SC., de Cassana, LM., Fujimori, E., et al.[2022]

In a study of 187 pregnant women with iron deficiency anemia, those treated with ferrous bis-glycinate experienced a significantly greater increase in hemoglobin levels (2.48 g/dL) compared to those receiving ferrous glycine sulfate (1.32 g/dL) after 8 weeks.

Ferrous bis-glycinate not only proved to be more effective, with 89.2% of women reaching hemoglobin levels above 11 g/dL, but also had a better safety profile, as the rate of adverse effects was significantly higher in the ferrous glycine sulfate group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial. Abbas, AM., Abdelbadee, SA., Alanwar, A., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial. [2019]

4. Ireland pubmed.ncbi.nlm.nih.gov

Amino acid chelated iron versus an iron salt in the treatment of iron deficiency anemia with pregnancy: A randomized controlled study. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of ferrous bisglycinate chelate. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Iron amino acid chelates. [2013]

8. Venezuela pubmed.ncbi.nlm.nih.gov

Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial. [2020]