Obesity in Pregnancy: Iron Dysregulation in Mother and Fetus
Dates: 6/15/2015 - 12/15/2016
Co-Investigators: Mary Koenig, Lisa Tussings-Humphreys
Abstract: During pregnancy, an ample supply of iron is critical for placental growth, maternal blood volume adaptations and fetal growth and brain development. Thus, the effects of iron deficiency (ID) during pregnancy are profound and include maternal and infant mortality, preterm birth and irreversible cognitive defects in infants. In the United States (US), approximately 30% of reproductive-aged women are obese. Our team and others have reported that obesity in non-pregnant populations is associated with impaired dietary iron absorption and ID as a result of inflammation-induced overexpression of the iron-regulatory hormone hepcidin. Hepcidin promotes degradation of the ferroportin iron exporter, thereby reducing the efflux of iron from the gut, hepatocytes, reticuloendothelial macrophages and placenta.
Our preliminary data and two recent studies indicate that maternal obesity is associated with elevated maternal hepcidin, a likely downstream effect of systemic inflammation, and decreased infant iron status at birth compared to lean mother-infant dyads. This suggests that obesity impairs maternalfetal iron metabolism. Existing studies have not examined the precise mechanisms that explain the disruption to the flow of iron from mother to fetus, specifically, hepicidin-mediated disturbances to maternal dietary iron absorption and placental iron transfer. Thus, we propose to investigate the impact of maternal obesity on maternal dietary non-heme iron absorption and the placental transfer of the maternally-ingested non-heme iron through the use of naturally occurring stable iron isotopes. Our central hypothesis is that maternal obesity is associated with reduced maternal non-heme iron absorption and lower placental non-heme iron transfer due to an upregulation of maternal hepcidin.
We will recruit 25 obese (pre-pregnancy body mass index (BMI) > 30.0 kg/m2) and 25 lean (pre-pregnancy BMI 18.5-24.9 kg/m2) women with a singleton pregnancy from an urban medical center during the late second or early third trimester to be followed through labor and delivery. Women will ingest two stable- iron isotopes prepared as non-heme ferrous sulfate with and without a meal during the early third trimester of pregnancy. Two weeks later, a maternal venous blood sample will be collected to examine maternal absorption of the iron isotopes from red blood cell iron isotope ratios obtained via inductively coupled plasma mass spectrometry (ICP-MS). At labor and delivery, a cord blood sample will be collected to examine placental iron transfer of the maternally-ingested iron isotopes from cord blood iron isotope ratios obtained via ICP-MS. We will also explore the associations among maternal non-heme iron isotope absorption, placental iron isotope transfer, maternal and infant (via cord blood) hepcidin, iron status, systemic inflammation, and erythropoiesis. Identifying the precise biological mechanisms that link maternal obesity to lower infant iron status is essential and will provide the foundational knowledge necessary for determining appropriate therapies that will optimize iron bioavailability during pregnancy for obese women and their infants.