Efficacy and Adverse Side Effects of Two Forms of Iron in Pregnancy

Pregnancy Clinical Trial

— EASE-Iron  

Official title:

Efficacy and Adverse Side Effects of Two Forms of Iron in Prenatal Micronutrient Supplements (EASE-Iron): A Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06014983
• Other study ID #: H23-00016
• Status: Recruiting
• Phase: N/A
• Start date: April 12, 2024
• Est. completion date: January 2026

Study information

• Verified date: April 2024
• Source: University of British Columbia
• Contact: Crystal Karakochuk, PhD
• Phone: 604-822-0421
• Email: crystal.karakochuk[@]ubc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

To address our primary aim of determining the optimal form of iron in prenatal supplements, we seek to answer the following research questions:

1. 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?

2. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 208
• Est. completion date: January 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 19 Years to 42 Years

Eligibility

Inclusion Criteria:

• Pregnant individual (singleton pregnancy)

• 19-42 years of age

• Planning to deliver at BC Women's Hospital

• Living in the greater Vancouver area and willing to travel to the University of British Columbia or BC Women's Hospital for study visits

• 13-25 weeks gestation

• Willing to participate and able to provide informed consent

Exclusion Criteria:

• 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)

• 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)

• Having a personal neural tube defect (NTD) history or a previous NTD pregnancy

• Receiving ongoing blood transfusions

• Currently smoking or having smoked in the past 3 months

• Pre-pregnancy body mass index (BMI) =30 kg/m^2

• Allergy to any study supplement ingredients

Related Conditions & MeSH terms

• Iron Deficiency
• Pregnancy

Intervention

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.
• Ferrous bisglycinate
Participants will supplement with 24 mg elemental iron in the form of ferrous bisglycinate daily for a minimum of 12 weeks.

Locations

Country	Name	City	State
Canada	BC Women's Hospital	Vancouver	British Columbia
Canada	University of British Columbia, Food, Nutrition and Health Building	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maternal ferritin concentration	µg/L; reflects body iron stores	Blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
Primary	Umbilical cord ferritin concentration	µg/L; proxy measure for newborn iron stores	Umbilical cord blood collected at time of delivery
Secondary	Maternal hemoglobin concentration	g/L; obtained through a complete blood count	Maternal blood sample collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
Secondary	Umbilical cord hemoglobin concentration	g/L; measured using a HemoCue device	Umbilical cord blood collected at time of delivery
Secondary	Placental iron concentration	µg/g; reflects iron transfer to fetus	Placenta collected at time of delivery
Secondary	Gut pathogen abundance	Ct values; quantifies abundance of harmful bacteria in the gut	Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
Secondary	Fecal calprotectin	µg/g; reflects gut inflammation	Flocked rectal swab collected at baseline (13-25 weeks gestation) and at endline (37 weeks gestation)
Secondary	Adverse side effects	Includes reported gastrointestinal side effects (e.g., constipation, diarrhea, nausea) and any other side effects experienced	Endline (37 weeks gestation)
Secondary	Markers of inflammation	Includes alpha-1 acid glycoprotein (AGP; g/L) and C-reactive protein (CRP; mg/L), used in combination to adjust ferritin 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
Secondary	Hepcidin concentration	nmol/L; hormone that influences iron regulation	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
Secondary	Breastmilk iron stores	Includes measurement of breastmilk iron content (mg/mL) and lactoferrin (mg/mL)	Breastmilk sample collected at 4-weeks postpartum