Infancy, Iron Absorption, Iron Requirements, Lactation, Pregnancy
Conditions
Brief summary
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.
Interventions
OTHERCO-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
OTHEROral 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
OTHERIntravenous 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
Sponsors
Columbia University
Jomo Kenyatta University of Agriculture and Technology
Msambweni County Referral Hospital
ETH Zurich
University of Oxford
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Iron absorbed, lossed and gained in the first trimester | Change in 57Fe tracer abundance between gestational age 6, 10 and 15 weeks | isotope dilution |
| Iron absorbed, lossed and gained in the second trimester | Change in 57Fe tracer abundance between gestational age 15, 20 and 25 weeks | isotope dilution |
| Iron absorbed, lossed and gained in the third trimester | Change in 57Fe tracer abundance between gestational age 25, 30 and 35 weeks | isotope dilution |
| Iron absorbed, lossed and gained throughout pregnancy | Change in 57Fe tracer abundance between gestational age 6, 10, 15, 20, 25, 30 and 35 weeks | isotope dilution |
| Iron absorbed, lossed and gained in lactating women | Change in 57Fe tracer abundance between 6, 14 and 24 weeks postpartum | isotope dilution |
| Iron absorbed, lossed and gained in infancy | Change in 57Fe tracer abundance between age 6, 14 and 24 weeks | isotope dilution |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Erythropoietin concentration (mU/ml) | gestational age 10 weeks | EPO |
| Erythroferrone concentration (ng/ml) | gestational age 10 weeks | ERFE |
| Hepcidin concentration (ng/ml) | gestational age 10 weeks | Hep |
| Serum ferritin concentration (ug/l) | gestational age 10 weeks | SF |
| Soluble transferrin receptor concentration (ul/l) | gestational age 10 weeks | sTfR |
| C-reactive protein concentration (mg/l) | gestational age 10 weeks | CRP |
| Fractional iron absorption (%) in the second trimester | gestational age 20 weeks | shift in iron isotopic ratios |
| Blood volume (l) | gestational age 10 weeks | — |
| Intestinal fatty acid binding protein | gestational age 10 weeks | I-FABP |
| Retinol binding protein | gestational age 10 weeks | RBP |
| soluble CD14 | gestational age 10 weeks | sCD14 |
| Insulin-like growth factor 1 | gestational age 10 weeks | IGF-1 |
| Fibroblast growth factor 21 | gestational age 10 weeks | FGF21 |
| alpha-glycoprotein concentration (mg/dl) | gestational age 10 weeks | AGP |
| Fractional iron absorption (%) in the third trimester | gestational age 30 weeks | shift in iron isotopic ratios |
| Erythrocyte iron incorporation (%) in the second trimester | gestational age 20 weeks | shift in iron isotopic ratios |
| Erythrocyte iron incorporation (%) in the third trimester | gestational age 30 weeks | shift in iron isotopic ratios |
| Hemoglobin concentration (g/dl) | gestational age 6 weeks | Hb |
| Mean corpuscular volume (fl) | gestational age 6 weeks | MCV |
Countries
Kenya
Contacts
Primary ContactNicole Stoffel, PhD
Backup ContactJoyce Wali, BSc
Outcome results
None listed