Clinical trial NCT02747316: Iron Absorption and Transfer to the Fetus During Pregnancy in Normal Weight and Overweight/Obese Women and the Effects on Infants Iron Status
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight
Obesity
Pregnancy
Keywords: Iron bioavailability
Hepcidin
Iron absorption
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
First posted: 2016-04-21
Enrollment: 83
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Fractional iron absorption
timeFrame: week 20 of pregnancy
measure: iron transfer from the mother to the fetus in cord blood/infant
timeFrame: delivery
measure: Fractional iron absorption
timeFrame: week 30 of pregnancy
measure: infants iron status
timeFrame: over the first six months of life
Secondary outcomes:
measure: Change in plasma ferritin
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in Hepcidin
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in transferrin receptor
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in hemoglobin
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in c-reactive protein
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in interleukin-6
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Chage in alpha-1-acid glycoprotein
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in retinol binding protein
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Change in riboflavin
timeFrame: weeks of pregnancy 12, 18, 20, 28, 30, 36; 3 and 6 months after delivery
measure: Assessment of children's iron needs within their first 2 years of life using an isotope dilution technique
timeFrame: Follow-up blood samples at 3, 6, 12, 18, 24 months after birth
measure: Assessment of recovery of mother's iron Status after pregnancy using an isotope dilution technique
timeFrame: Follow-up blood samples at 3, 6, 12, 18, 24 months after delivery
measure: infants iron status
timeFrame: over the first 24 months of life
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Human Nutrition Laboratory ETH Zurich
Study officials:
References:
citation: Stoffel NU, Zimmermann MB, Cepeda-Lopez AC, Cervantes-Gracia K, Llanas-Cornejo D, Zeder C, Tuntipopipat S, Moungmaithong S, Densupsoontorn N, Quack Loetscher K, Gowachirapant S, Herter-Aeberli I. Maternal iron kinetics and maternal-fetal iron transfer in normal-weight and overweight pregnancy. Am J Clin Nutr. 2022 Apr 1;115(4):1166-1179. doi: 10.1093/ajcn/nqab406.