EASE-Iron: Efficacy and Adverse Side Effects of Two Forms of Iron in Pregnancy
Study Details
Study Description
Brief Summary
This two-arm, double-blind randomized clinical trial will recruit 208 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 and again at 37 weeks gestation to assess how different forms of iron impact body iron stores. Rectal swabs will also be taken at baseline and 37 weeks gestation to detect presence of harmful bacteria in the gut and quantify their abundance. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
To address our primary aim of determining the optimal form of iron in prenatal supplements, we seek to answer the following research questions:
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Does providing a more bioavailable form of iron (24 mg elemental iron as ferrous bisglycinate) effectively increase ferritin concentration in maternal venous blood and umbilical cord blood, as compared to the standard 24 mg elemental iron as ferrous fumarate?
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Does 12 weeks of 24 mg daily oral iron as ferrous fumarate increase biomarkers of potential harm (gut inflammation, gut pathogen abundance, adverse side effects) in pregnant individuals, as compared to 24 mg daily oral iron as ferrous bisglycinate?
Pregnant individuals 13-25 weeks gestation will be randomized to one of two trial arms to receive either 24 mg elemental iron as ferrous fumarate or 24 mg elemental iron as ferrous bisglycinate for a minimum of 12 weeks during pregnancy until delivery, with optional continuation until 4-weeks postpartum for breastmilk collection. All participants will also receive the standard form and dose of other critical micronutrients during pregnancy (e.g., folate, calcium) through the provision of a prenatal multivitamin (not containing iron).
Interested individuals may undergo the informed consent process anytime prior to 25 weeks gestation. Once an individual indicates that they are interested in participating in the trial, the individual will be assigned a unique study ID and a baseline visit will be scheduled.
The baseline visit will occur between 13-25 weeks gestation and will involve discontinuation of current iron/prenatal vitamin supplementation, review and signing the informed consent form (a scanned copy will be shared with the participant), randomization to an iron group, provision of study supplements, completion of a baseline questionnaire, measurement of weight and height, a small blood draw and collection of a rectal swab sample.
The intervention period is a minimum of 12 weeks (from baseline at 13-25 weeks to delivery). Participants will supplement daily with the iron and prenatal multivitamin supplements. Monthly follow-up surveys will be sent to participants via email to check-in and receive updates regarding any changes to medical history or medication use.
The endline visit will occur at approximately 37 weeks gestation and will involve collecting any remaining supplements (for capsule counts and assessment of adherence), a weight measurement, a small blood draw, collection of a rectal swab sample, and completion of a short endline questionnaire.
Optional continuation of study: After the endline visit, participants who are planning to breastfeed will have the option to continue supplementing with the study supplements until approximately 4 weeks postpartum, at which time they will provide a small breastmilk sample.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Ferrous fumarate 24 mg elemental iron/day |
Dietary Supplement: Ferrous fumarate
Participants will supplement with 24 mg elemental iron in the form of ferrous fumarate daily for a minimum of 12 weeks.
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| Experimental: Ferrous bisglycinate 24 mg elemental iron/day |
Dietary Supplement: Ferrous bisglycinate
Participants will supplement with 24 mg elemental iron in the form of ferrous bisglycinate daily for a minimum of 12 weeks.
|
Outcome Measures
Primary Outcome Measures
- Maternal ferritin concentration [Blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)]
µg/L; reflects body iron stores
- Umbilical cord ferritin concentration [Umbilical cord blood collected at time of delivery]
µg/L; proxy measure for newborn iron stores
Secondary Outcome Measures
- Maternal hemoglobin concentration [Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)]
g/L; obtained through a complete blood count
- Umbilical cord hemoglobin concentration [Umbilical cord blood collected at time of delivery]
g/L; measured using a HemoCue device
- Placental iron concentration [Placenta collected at time of delivery]
µg/g; reflects iron transfer to fetus
- Gut pathogen abundance [Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)]
Ct values; quantifies abundance of harmful bacteria in the gut
- Fecal calprotectin [Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)]
µg/g; reflects gut inflammation
- Adverse side effects [Endline (37 weeks gestation)]
Includes reported gastrointestinal side effects (e.g., constipation, diarrhea, nausea) and any other side effects experienced
- Markers of inflammation [Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation); umbilical cord blood sample collected at time of delivery]
Includes AGP (g/L) and CRP (mg/L), used in combination to adjust ferritin concentration
- Hepcidin concentration [Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation); umbilical cord blood sample collected at time of delivery]
nmol/L; hormone that influences iron regulation
- Breastmilk iron stores [Breastmilk sample collected at 4-weeks postpartum]
Includes measurement of breastmilk iron content (mg/mL) and lactoferrin (mg/mL)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Pregnant individual (singleton pregnancy)
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19-42 years of age
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Planning to deliver at BC Women's Hospital
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Living in the greater Vancouver area and willing to travel to the University of British Columbia for study visits
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13-25 weeks gestation
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Willing to participate and able to provide informed consent
Exclusion Criteria:
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Having a pre-existing medical condition known to impact iron status (e.g., inherited hemoglobin disorder (i.e., sickle cell, hemochromatosis, thalassemia or other structural hemoglobin variant), malabsorptive disorders (i.e., chronic pancreatitis, cystic fibrosis, celiac disease) and inflammatory bowel disease (i.e., Crohn's disease, ulcerative colitis), gastric bypass surgery, atrophic gastritis, advanced liver disease, kidney dialysis)
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Using medications known to interfere with iron metabolism or the gut pathogen equilibrium (e.g., chronic use of proton pump inhibitors, anti-inflammatory agents, non-steroidal anti-inflammatory drugs, antibiotics)
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Having a personal neural tube defect (NTD) history or a previous NTD pregnancy
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Receiving ongoing blood transfusions
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Currently smoking or having smoked in the past 3 months
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Pre-pregnancy body mass index (BMI) ≥30 kg/m^2
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Allergy to any study supplement ingredients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of British Columbia, Food, Nutrition and Health Building | Vancouver | British Columbia | Canada | V6T 1Z4 |
Sponsors and Collaborators
- University of British Columbia
Investigators
- Principal Investigator: Crystal Karakochuk, PhD, University of British Columbia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H23-00016