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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.
To address our primary aim of determining the optimal form of iron in prenatal supplements, we seek to answer the following research questions:
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., folic acid, 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 provision of a stool collection kit for at-home stool collection.
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 follow-up visit will occur between 35-37 weeks gestation and will involve collecting any remaining supplements (for capsule counts and assessment of adherence), a weight measurement, a small blood draw, provision of at-home stool collection kit, and completion of a short follow-up questionnaire.
Optional continuation of study: After the follow-up visit, participants who are planning to breastfeed will have the option to continue supplementing with the study supplements and provide a prenatal colostrum sample and/or 4-week postpartum breastmilk sample.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ferrous fumarate | Active Comparator | 24 mg elemental iron/day |
|
| Ferrous bisglycinate | Experimental | 24 mg elemental iron/day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ferrous fumarate | Dietary Supplement | Participants will supplement with 24 mg elemental iron in the form of ferrous fumarate daily for a minimum of 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maternal ferritin concentration | µg/L; reflects body iron stores | Blood sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation) |
| Measure | Description | Time Frame |
|---|---|---|
| Maternal hemoglobin concentration | g/L; obtained through a complete blood count | Maternal blood sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation) |
| Umbilical cord ferritin concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Crystal Karakochuk, PhD | Contact | 604-822-0421 | crystal.karakochuk@ubc.ca | |
| Lulu Pei, MSc | Contact | 604-822-0421 | lulu.pei@ubc.ca |
| Name | Affiliation | Role |
|---|---|---|
| Crystal Karakochuk, PhD | University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BC Women's Hospital | Recruiting | Vancouver | British Columbia | V6H 3N1 | Canada |
Upon reasonable request, the Principal Investigator will share de-identified individual participant data.
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| ID | Term |
|---|---|
| D000090463 | Iron Deficiencies |
| ID | Term |
|---|---|
| D019189 | Iron Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C031621 | ferrous fumarate |
| C510030 | ferrous bisglycinate |
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| Ferrous bisglycinate | Dietary Supplement | Participants will supplement with 24 mg elemental iron in the form of ferrous bisglycinate daily for a minimum of 12 weeks. |
|
µg/L; proxy measure for newborn iron stores
| Umbilical cord blood collected at time of delivery |
| Umbilical cord hemoglobin concentration | g/L; measured using a HemoCue device | Umbilical cord blood collected at time of delivery |
| Placental iron concentration | µg/g; reflects iron transfer to fetus | Placenta collected at time of delivery |
| Gut microbial analysis | 16S rRNA gene sequencing and targeted real-time PCR (qPCR); gut microbiome composition | Stool sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation) |
| Adverse side effects | Includes reported gastrointestinal side effects (e.g., constipation, diarrhea, nausea) and any other side effects experienced | Follow-up (35-37 weeks gestation) |
| 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 follow-up (35-37 weeks gestation); umbilical cord blood sample collected at time of delivery |
| Hepcidin concentration | nmol/L; hormone that influences iron regulation | Maternal blood sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation); umbilical cord blood sample collected at time of delivery |
| Breastmilk iron stores | Includes measurement of breastmilk iron content (mg/mL) and lactoferrin (mg/mL) | Breastmilk sample collected at 4-weeks postpartum |
| University of British Columbia, Food, Nutrition and Health Building | Recruiting | Vancouver | British Columbia | V6T 1Z4 | Canada |
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