Iron Absorption and Requirements in Pregnancy and Lactation (PILLAR_II)

Assessment of Iron Absorption and Requirements During Pregnancy and Lactation in Kenyan Women

Iron requirements increase significantly during pregnancy. Current recommendations for iron intake in pregnant and lactating women (PLW) are mainly based on factorial estimates and extrapolated from non-PLW. High-quality quantitative data on iron requirements in PLW are lacking, particularly in Sub- Saharan Africa where anaemia and infections are common.

The primary objective of this study is to use the stable iron isotope technique to determine iron requirements and assess iron absorption and losses in PLW living in Kenya.

In this prospective observational study, we will enrol pregnant women in the first trimester (n = 250) from a previous study cohort (n=1000) who participated in an iron absorption study at least 12 months ago and received the stable iron (Fe) isotope 57Fe. This 57Fe has now distributed and equilibrated throughout the women's body iron. Once enrolled in the present study, following Kenyan guidelines, women will receive standard prenatal care, including routine daily iron and folate supplementation. We will collect venous blood samples in each trimester and at delivery, and during the first 6 months of lactation in the mothers and infants (heel prick samples). To directly assess dietary iron absorption, in a randomly selected subset of women (n=35), oral and intravenous stable iron isotope tracers (54Fe, 58Fe) will be administered in the 2nd and 3rd trimesters.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; Lactation; Iron Absorption; Iron Requirements; Infancy
• Intervention / Treatment: Other: CO-rebreathing; Other: Oral iron isotope administration (54Fe); Other: Intravenous iron isotope administration (58Fe)

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Nicole Stoffel, PhD; Phone Number: +41446328393; Email: nicole.stoffel@rdm.ox.ac.uk
• Study Contact Backup: Name: Joyce Wali, BSc; Phone Number: +254704862877; Email: stellawali507@gmail.com

Study Locations

• Kenya
  • Msambweni, Kenya
    • Recruiting
    • Msambweni Referral Hospital
    • Contact: Edith Mwasi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will recruit 250 pregnant women in the first trimester who previously participated in a stable iron isotope study (Clinical Trial ID: NCT05266703) and received 15 mg of the stable iron isotope 57Fe as an oral dose of ferrous sulphate at least 12 months before being enrolled in this trial.

Description

Inclusion Criteria:

• Providing consent to the informed consent form
• Participation in a previous stable isotope absorption study and having received an oral dose of 15 mg 57Fe at least 12 months prior to the date of inclusion in the study
• Positive pregnancy test and gestational age <10 weeks based on history of last menstrual period
• Permanent residence in the study area, and not expected to leave the study site for more than 4 weeks over the following 16 months
• Assessment of good health by professional staff at Msambweni Hospital

Exclusion Criteria:

• Pre-pregnancy body mass index >30 kg/m2
• Blood transfusion or intravenous iron treatment within 4 months of study start
• Major chronic infectious disease (e.g., tuberculosis, HIV+, hepatitis)
• Major chronic non-infectious disease (e.g., Type 1 or 2 diabetes, cancer)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
All participants; Women (n=250), are followed throughout their pregnancy. Mother-infant pairs are followed throughout the first 6-months postpartum. Women receive daily oral iron supplementation during pregnancy in accordance with local standards of care. Using the stable iron isotopes dilution methodology, concentration of the stable iron isotope tracer (57Fe) in circulation will be measured throughout pregnancy and up to 6 months postpartum in both, mother and infant.	Other: CO-rebreathing; In the CO-rebreathing method, a dedicated apparatus is used for inhaling and rebreathing a very small bolus of CO through a spirometer for ~2 min, which is absorbed through the lungs and binds to Hb, and then the increase of HbCO content of blood is measured 8 min after the CO inhalation. The increase of COHb in blood samples can then be used to precisely calculate Hb mass and blood volume
Randomly selected sub-group; To directly assess dietary iron absorption, in a randomly selected subset of women (n=35), oral and intravenous stable iron isotope tracers (54Fe, 58Fe) will be administered. Oral iron absorption and erythrocyte iron incorporation will be measured 14 days after tracer administration.	Other: CO-rebreathing; In the CO-rebreathing method, a dedicated apparatus is used for inhaling and rebreathing a very small bolus of CO through a spirometer for ~2 min, which is absorbed through the lungs and binds to Hb, and then the increase of HbCO content of blood is measured 8 min after the CO inhalation. The increase of COHb in blood samples can then be used to precisely calculate Hb mass and blood volume; Other: Oral iron isotope administration (54Fe); Participants randomly assigned to the sub-group, will receive 54Fe with a test meal in the second and third trimester for assessment of dietary iron absorption; Other: Intravenous iron isotope administration (58Fe); Participants randomly assigned to the sub-group, will receive intravenous 58Fe in the second and third trimester for assessment of erythrocyte iron incorporation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Iron absorbed, lossed and gained in the first trimester	isotope dilution	Change in 57Fe tracer abundance between gestational age 6, 10 and 15 weeks
Iron absorbed, lossed and gained in the second trimester	isotope dilution	Change in 57Fe tracer abundance between gestational age 15, 20 and 25 weeks
Iron absorbed, lossed and gained in the third trimester	isotope dilution	Change in 57Fe tracer abundance between gestational age 25, 30 and 35 weeks
Iron absorbed, lossed and gained throughout pregnancy	isotope dilution	Change in 57Fe tracer abundance between gestational age 6, 10, 15, 20, 25, 30 and 35 weeks
Iron absorbed, lossed and gained in lactating women	isotope dilution	Change in 57Fe tracer abundance between 6, 14 and 24 weeks postpartum
Iron absorbed, lossed and gained in infancy	isotope dilution	Change in 57Fe tracer abundance between age 6, 14 and 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional iron absorption (%) in the second trimester	shift in iron isotopic ratios	gestational age 20 weeks
Fractional iron absorption (%) in the third trimester	shift in iron isotopic ratios	gestational age 30 weeks
Erythrocyte iron incorporation (%) in the second trimester	shift in iron isotopic ratios	gestational age 20 weeks
Erythrocyte iron incorporation (%) in the third trimester	shift in iron isotopic ratios	gestational age 30 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 6 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 10 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 15 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 20 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 25 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 30 weeks
Hemoglobin concentration (g/dl)	Hb	gestational age 36 weeks
Hemoglobin concentration (g/dl)	mother	6 weeks postpartum
Hemoglobin concentration (g/dl)	infant	age 6 weeks
Hemoglobin concentration (g/dl)	mother	14 weeks postpartum
Hemoglobin concentration (g/dl)	infant	age 14 weeks
Hemoglobin concentration (g/dl)	mother	24 weeks postpartum
Hemoglobin concentration (g/dl)	infant	age 24 weeks
Mean corpuscular volume (fl)	MCV	gestational age 6 weeks
Mean corpuscular volume (fl)	MCV	gestational age 10 weeks
Mean corpuscular volume (fl)	MCV	gestational age 20 weeks
Mean corpuscular volume (fl)	MCV	gestational age 30 weeks
Mean corpuscular volume (fl)	mother	6 weeks postpartum
Mean corpuscular volume (fl)	infant	age 6 weeks
Mean corpuscular volume (fl)	mother	14 weeks postpartum
Mean corpuscular volume (fl)	infant	age 14 weeks
Mean corpuscular volume (fl)	mother	24 weeks postpartum
Mean corpuscular volume (fl)	infant	age 24 weeks
Erythropoietin concentration (mU/ml)	EPO	gestational age 10 weeks
Erythropoietin concentration (mU/ml)	EPO	gestational age 20 weeks
Erythropoietin concentration (mU/ml)	EPO	gestational age 30 weeks
Erythropoietin concentration (mU/ml)	EPO	6 weeks postpartum
Erythropoietin concentration (mU/ml)	EPO	14 weeks postpartum
Erythropoietin concentration (mU/ml)	EPO	24 weeks postpartum
Erythroferrone concentration (ng/ml)	ERFE	gestational age 10 weeks
Erythroferrone concentration (ng/ml)	ERFE	gestational age 20 weeks
Erythroferrone concentration (ng/ml)	ERFE	gestational age 30 weeks
Erythroferrone concentration (ng/ml)	ERFE	6 weeks postpartum
Erythroferrone concentration (ng/ml)	ERFE	14 weeks postpartum
Erythroferrone concentration (ng/ml)	ERFE	24 weeks postpartum
Hepcidin concentration (ng/ml)	Hep	gestational age 10 weeks
Hepcidin concentration (ng/ml)	Hep	gestational age 20 weeks
Hepcidin concentration (ng/ml)	Hep	gestational age 30 weeks
Hepcidin concentration (ng/ml)	Hep	6 weeks postpartum
Hepcidin concentration (ng/ml)	Hep	14 weeks postpartum
Hepcidin concentration (ng/ml)	Hep	24 weeks postpartum
Serum ferritin concentration (ug/l)	SF	gestational age 10 weeks
Serum ferritin concentration (ug/l)	SF	gestational age 20 weeks
Serum ferritin concentration (ug/l)	SF	gestational age 30 weeks
Serum ferritin concentration (ug/l)	mother	6 weeks postpartum
Serum ferritin concentration (ug/l)	infant	age 6 weeks
Serum ferritin concentration (ug/l)	mother	14 weeks postpartum
Serum ferritin concentration (ug/l)	infant	age 14 weeks
Serum ferritin concentration (ug/l)	mother	24 weeks postpartum
Serum ferritin concentration (ug/l)	infant	age 24 weeks
Soluble transferrin receptor concentration (ul/l)	sTfR	gestational age 10 weeks
Soluble transferrin receptor concentration (ul/l)	sTfR	gestational age 20 weeks
Soluble transferrin receptor concentration (ul/l)	sTfR	gestational age 30 weeks
Soluble transferrin receptor concentration (ul/l)	mother	6 weeks postpartum
Soluble transferrin receptor concentration (ul/l)	infant	age 6 weeks
Soluble transferrin receptor concentration (ul/l)	mother	14 weeks postpartum
Soluble transferrin receptor concentration (ul/l)	infant	age 14 weeks
Soluble transferrin receptor concentration (ul/l)	mother	24 weeks postpartum
Soluble transferrin receptor concentration (ul/l)	infant	age 24 weeks
C-reactive protein concentration (mg/l)	CRP	gestational age 10 weeks
C-reactive protein concentration (mg/l)	CRP	gestational age 20 weeks
C-reactive protein concentration (mg/l)	CRP	gestational age 30 weeks
C-reactive protein concentration (mg/l)	mother	6 weeks postpartum
C-reactive protein concentration (mg/l)	infant	age 6 weeks
C-reactive protein concentration (mg/l)	mother	14 weeks postpartum
C-reactive protein concentration (mg/l)	infant	age 14 weeks
C-reactive protein concentration (mg/l)	mother	24 weeks postpartum
C-reactive protein concentration (mg/l)	infant	age 24 weeks
alpha-glycoprotein concentration (mg/dl)	AGP	gestational age 10 weeks
alpha-glycoprotein concentration (mg/dl)	AGP	gestational age 20 weeks
alpha-glycoprotein concentration (mg/dl)	AGP	gestational age 30 weeks
alpha-glycoprotein concentration (mg/dl)	mother	6 weeks postpartum
alpha-glycoprotein concentration (mg/dl)	infant	age 6 weeks
alpha-glycoprotein concentration (mg/dl)	mother	14 weeks postpartum
alpha-glycoprotein concentration (mg/dl)	infant	age 14 weeks
alpha-glycoprotein concentration (mg/dl)	mother	24 weeks postpartum
alpha-glycoprotein concentration (mg/dl)	infant	age 24 weeks
Blood volume (l)		gestational age 10 weeks
Blood volume (l)	BV	gestational age 20 weeks
Blood volume (l)	BV	gestational age 30 weeks
Blood volume (l)	BV	6 weeks postpartum
Blood volume (l)	BV	14 weeks postpartum
Blood volume (l)	BV	24 weeks postpartum
Intestinal fatty acid binding protein	I-FABP	gestational age 10 weeks
Intestinal fatty acid binding protein	I-FABP	gestational age 20 weeks
Intestinal fatty acid binding protein	I-FABP	gestational age 30 weeks
Retinol binding protein	RBP	gestational age 10 weeks
Retinol binding protein	RBP	gestational age 20 weeks
Retinol binding protein	RBP	gestational age 30 weeks
soluble CD14	sCD14	gestational age 10 weeks
soluble CD14	sCD14	gestational age 20 weeks
soluble CD14	sCD14	gestational age 30 weeks
Insulin-like growth factor 1	IGF-1	gestational age 10 weeks
Insulin-like growth factor 1	IGF-1	gestational age 20 weeks
Insulin-like growth factor 1	IGF-1	gestational age 30 weeks
Fibroblast growth factor 21	FGF21	gestational age 10 weeks
Fibroblast growth factor 21	FGF21	gestational age 20 weeks
Fibroblast growth factor 21	FGF21	gestational age 30 weeks

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Columbia University; ETH Zurich; Jomo Kenyatta University of Agriculture and Technology; Msambweni County Referral Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 18, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Trace Elements; Micronutrients; Iron
• Other Study ID Numbers: PILLAR_II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No