Clinical trial NCT06014983: Efficacy and Adverse Side Effects of Two Forms of Iron in Pregnancy
Official title: Efficacy and Adverse Side Effects of Two Forms of Iron in Prenatal Micronutrient Supplements (EASE-Iron): A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pregnancy
Iron Deficiency
Keywords: Iron
Pregnancy
Nutrition
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2023-08-28
Enrollment: 172
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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:

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 (adverse side effects, gut microbiome composition, gut inflammation) 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., 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.

Eligibility criteria: Inclusion Criteria:

* Pregnant individual (singleton pregnancy)
* 19-42 years of age
* 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

Primary outcomes:
measure: Maternal ferritin concentration
timeFrame: Blood sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation)
Secondary outcomes:
measure: Maternal hemoglobin concentration
timeFrame: Maternal blood sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation)
measure: Umbilical cord ferritin concentration
timeFrame: Umbilical cord blood collected at time of delivery
measure: Umbilical cord hemoglobin concentration
timeFrame: Umbilical cord blood collected at time of delivery
measure: Placental iron concentration
timeFrame: Placenta collected at time of delivery
measure: Gut microbial analysis
timeFrame: Stool sample collected at baseline (13-25 weeks gestation) and at follow-up (35-37 weeks gestation)
measure: Adverse side effects
timeFrame: Follow-up (35-37 weeks gestation)
measure: Markers of inflammation
timeFrame: 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
measure: Hepcidin concentration
timeFrame: 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
measure: Breastmilk iron stores
timeFrame: Breastmilk sample collected at 4-weeks postpartum
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Women's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia, Food, Nutrition and Health Building
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Crystal Karakochuk, PhD
role: PRINCIPAL_INVESTIGATOR
References: