Iron Absorption and Transfer to the Fetus During Pregnancy in Normal Weight and Overweight/Obese Women and the Effects on Infants Iron Status

Study Overview
=================
Brief Summary
-----------------
Overweight and obesity causes low-grade systemic inflammation, which sharply increases risk for iron deficiency. Studies in our laboratory have shown that this is mainly the result of reduced dietary iron absorption because of increased hepcidin concentrations. During pregnancy, women have a large increase in iron needs because of the expansion of maternal blood volume and fetal needs. Iron deficiency anemia in infancy can impair cognitive development. Whether maternal adiposity impairs absorption and transfer of iron to the fetus, and thereby increases risk of iron deficiency in the mother and the infant is unclear.

Detailed Description
-----------------
In obese subjects, hepcidin concentrations are increased and iron absorption is believed to be reduced, leading to iron deficiency over time. How all this will influence iron supply of the fetus in obese pregnancy has not been well investigated to date. Even if maternal and fetal iron uptakes are regulated separately, it is unclear to what extent maternal subclinical inflammation might influence this process. A small study by Dao et al. indicated that maternal-fetal iron transfer was impaired in obese pregnant women, possibly due to hepcidin up-regulation. In this study, both maternal BMI as well as hepcidin were negatively correlated with cord blood iron status. Maternal hepcidin and c-reactive protein were significantly higher and cord blood iron was significantly lower in the obese compared to the normal weight. Hepcidin was shown to have an effect on iron transfer across the placenta in the study by Young et al.: the transfer was increased in women with undetectable hepcidin at delivery compared to those with higher levels. As of now, clear associations between maternal BMI or maternal hepcidin concentration and fetal iron status were not shown.

Official Title
-----------------
Maternal Iron Absorption and Utilization and Iron Transfer to the Fetus During Pregnancy in Normal Weight and Overweight/Obese Women and the Effects on Infant Iron Status

Conditions
-----------------
Overweight, Obesity, Pregnancy

Intervention / Treatment
-----------------
* Other: Stable iron isotope 57 (57Fe) labeled iron solution
* Other: Stable iron isotope 58 (58Fe) labeled iron solution


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women with either normal pre-pregnancy BMI (BMI 18.5 - 24.9kg/kg2) or with overweight or obesity (BMI > 27.5kg/m2) before pregnancy (assessed based on data reported by the women at their first visit at the hospital) 18 to 45 years old singleton pregnancy week of pregnancy 14±3 Exclusion Criteria: underlying malabsorption disease chronic illness, which influences iron absorption inflammatory status other than obesity medical problems known to affect iron homeostasis smoking during pregnancy no regular use of medication, which influences iron absorption

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isotopically labeled test meal week of pregnancy 20<br> | Other: Stable iron isotope 57 (57Fe) labeled iron solution<br>* test meal labeled with 12 mg 57Fe<br>|
| Experimental: Isotopically labeled test meal week of pregnancy 30<br> | Other: Stable iron isotope 58 (58Fe) labeled iron solution<br>* test meal labeled with 12 mg 58Fe<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional iron absorption | The fractional iron absorption from the first test meal will be calculated based on the shift of the iron isotopic ratios in the collected blood samples 14 days after administration of the isotopically labeled meal. | week 20 of pregnancy | 
| iron transfer from the mother to the fetus in cord blood/infant | To determine the amount of iron transferred from the mother to the fetus | delivery | 
| Fractional iron absorption | The fractional iron absorption from the second test meal will be calculated based on the shift of the iron isotopic ratios in the collected blood samples 14 days after administration of the isotopically labeled meal. | week 30 of pregnancy | 
| infants iron status | infants iron status | over the first six months of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma ferritin | Change in plasma ferritin | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in Hepcidin | Change in Hepcidin | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in transferrin receptor | Change in transferrin receptor | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in hemoglobin | Change in hemoglobin | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in c-reactive protein | Change in c-reactive protein | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in interleukin-6 | Change in interleukin-6 | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Chage in alpha-1-acid glycoprotein | Chage in alpha-1-acid glycoprotein | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in retinol binding protein | Change in retinol binding protein | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Change in riboflavin | Change in riboflavin | weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery | 
| Assessment of children's iron needs within their first 2 years of life using an isotope dilution technique | Assessment of children's iron needs within their first 2 years of life | Follow-up blood samples at 3, 6, 12, 18, 24 months after birth | 
| Assessment of recovery of mother's iron Status after pregnancy using an isotope dilution technique | Assessment of recovery of mother's iron Status after pregnancy | Follow-up blood samples at 3, 6, 12, 18, 24 months after delivery | 
| infants iron status | infants iron status | over the first 24 months of life | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Iron bioavailability, Hepcidin, Iron absorption