Abstract
During human pregnancy, iron requirements gradually increase, leading to higher amounts of erythropoietin (EPO) and reticulocytes, and changes in erythrocyte size and density. Women with pregestational obesity experience “obesity hypoferremia” during pregnancy, which alters iron homeostasis. In this study we aimed to describe the relationship between EPO and iron nutrition status during nonanemic pregnancy, and to explore whether obesity and inflammation influence erythropoiesis and red cell indices. We conducted a secondary analysis of a cohort followed throughout pregnancy. Participants were nonanemic women assigned to two study groups based on pregestational body mass index (pgBMI): adequate weight (AW, n = 53) or obesity (Ob, n = 40). All received a multivitamin supplement. At gestational ages (GA) 13, 21, 28 and 34, we measured hemoglobin and red cell indices with an ACT-5DIFF hematology counter, and reticulocyte percentage by manual cell counting. EPO, interleukin (IL–6) and markers of iron status, i.e., hepcidin, serum transferrin receptor (sTfr) and ferritin, were measured by ELISA. Bivariate correlations showed that EPO was positively associated with pgBMI, GA, sTfr and IL-6, but negatively associated with hepcidin, ferritin and hemoglobin, and unrelated to iron intake. Generalized linear models adjusted for confounding factors showed that EPO and erythrocyte concentrations were significantly higher in women in the Ob group, while mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and red cell distribution width (RDW) were lower; reticulocytes and mean corpuscular hemoglobin concentration (MCHC) were not different. Differences were not altered when controlling for inflammation (IL–6). These changes suggest that, in addition to altering iron metabolism, a larger maternal body size during pregnancy results in higher erythropoiesis without increasing hemoglobin, which is exhibited in the latter being distributed among more and smaller erythrocytes.
Highlights
IntroductionDuring the first-trimester, iron requirements decrease, since menstruation has ceased and early hemodynamic changes do not yet demand greater amounts of Nutrients 2020, 12, 975; doi:10.3390/nu12040975 www.mdpi.com/journal/nutrients
Maternal erythropoietin is associated with iron nutrition status
Maternal erythropoietin associated with iron nutrition is associated with higher
Summary
During the first-trimester, iron requirements decrease, since menstruation has ceased and early hemodynamic changes do not yet demand greater amounts of Nutrients 2020, 12, 975; doi:10.3390/nu12040975 www.mdpi.com/journal/nutrients. From the second trimester on, iron requirements steadily increase as maternal red blood cell mass expands, and placental and fetal growth accelerates [1,2]. To meet the increasing physiological iron needs and achieve a higher erythropoiesis rate, hormones such as hepcidin and erythropoietin play an important homeostatic role in maintaining hemoglobin concentrations. Hepcidin has been widely described for its pivotal role in regulating systemic iron availability through a negative feedback mechanism involving dietary iron absorption, as well as iron mobilization from reserves [3,4]. Erythropoietin, in turn, stimulates erythropoiesis, which is the proliferation, survival and differentiation of erythroid precursors within adult bone marrow [5]
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