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

Sponsor

Swiss Federal Institute of Technology (Other)

Overall Status

Completed

CT.gov ID

NCT02747316

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Overweight Obesity Pregnancy	Other: Stable iron isotope 57 (57Fe) labeled iron solution Other: Stable iron isotope 58 (58Fe) labeled iron solution	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

83 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

Feb 1, 2016

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isotopically labeled test meal week of pregnancy 20	Other: Stable iron isotope 57 (57Fe) labeled iron solution test meal labeled with 12 mg 57Fe
Experimental: Isotopically labeled test meal week of pregnancy 30	Other: Stable iron isotope 58 (58Fe) labeled iron solution test meal labeled with 12 mg 58Fe

Arm

Intervention/Treatment

Experimental: Isotopically labeled test meal week of pregnancy 20

Other: Stable iron isotope 57 (57Fe) labeled iron solution

test meal labeled with 12 mg 57Fe

Experimental: Isotopically labeled test meal week of pregnancy 30

Other: Stable iron isotope 58 (58Fe) labeled iron solution

test meal labeled with 12 mg 58Fe

Outcome Measures

Primary Outcome Measures

Fractional iron absorption [week 20 of pregnancy]
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.
iron transfer from the mother to the fetus in cord blood/infant [delivery]
To determine the amount of iron transferred from the mother to the fetus
Fractional iron absorption [week 30 of pregnancy]
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.
infants iron status [over the first six months of life]
infants iron status

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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