Hepcidin and Iron Metabolism in Pregnancy Correla

Authors: Magdalena Chełchowska Jadwiga Ambroszkiewicz Joanna Gajewska Ewa JabłońskaGłąb Tomasz M Maciejewski Mariusz Ołtarzewski

Publish Date: 2016/01/20

Volume: 173, Issue: 1, Pages: 14-20

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Abstract

To estimate the effect of tobacco smoking on iron homeostasis and the possible association between hepcidin and the neonatal birth weight and length concentrations of serum hepcidin and selected iron markers were measured in 81 healthy pregnant women 41 smokers and 40 nonsmokers The smoking mothers had significantly lower concentrations of serum hepcidin p  0001 iron p  0001 and hemoglobin p  005 but higher erythropoietin p  005 levels compared with nonsmoking pregnant women Logistic regression analysis showed the highest negative impact of the number of cigarettes smoked per day β = −046 p  001 and positive impact of ferritin level β = 047 p  0001 on serum hepcidin concentration The birth weight and the body length of smoking mothers’ infants were significantly lower than in tobacco abstinent group p  0001 In multiple regression analysis birth body weight β = 056 p  0001 and length β = 050 p  0001 were significantly related to maternal hepcidin values Tobacco smoking affected hepcidin level in serum of pregnant women in a dosedependent manner Low concentrations of iron and hemoglobin in maternal serum coexisting with high level of erythropoietin suggest that smoking could lead to subclinical iron deficiency and chronic hypoxia not only in mothers but also in fetus Low serum hepcidin concentration in smoking pregnant women might be associated with lower fetal birth weight and lengthIron deficiency during pregnancy continues to be a common clinical problem and is one of the most prevalent nutritional deficits both in the industrial and developing countries Iron requirements increase significantly near 10fold over gestation therefore pregnant women are particularly at risk of developing iron deficiency anemia The prevalence of anemia is dependent on nutritional status and use of sufficient prenatal supplements and ranges from 14 to 52  women who are not taking prenatal supplements to 0–25  among pregnant women receiving regular multivitamin containing iron and folic acid preparation 1 2 3 4 5In the last decade much attention was paid to research on new markers involved in the regulation of iron homeostasis 4 6 Hepcidin a 25aminoacids peptide hormone Hep25 has recently emerged as a key regulator of iron homeostasis Apart from main synthesis in the liver hepcidin messenger RNA mRNA is also expressed in the lung heart brain and placenta tissue Hepcidin regulates intestinal absorption macrophage release and the placental passage of iron This hormone inhibits the cellular efflux of iron by binding to and inducing the degradation of ferroportin the only known cellular iron exporter 7 The role of hepcidin in the regulation of iron metabolism in pregnancy and its effects on the fetus and consequently on the newborn is not fully understood Rising iron requirements in subsequent trimesters of pregnancy in both the mother and the fetus induces an increase in maternal dietary iron absorption and increase iron flux to the fetus via placenta 1 2 In uteroplacenta unit hepcidin causing degradation of syncytiotrophoblast ferroportin regulates iron release into the fetal circulation 8 9 Hepcidin expression is induced by iron overload and inflammation and is suppressed by anemia erythropoietic activity and hypoxia 10 11 Iron deficiency in pregnant women is assumed to be enhanced by cigarette smoking 12 13 Despite the fact that in the last years a decrease in the number of active smokers has been observed and knowledge of the adverse health effect of smoking during pregnancy is quite common 25–30  pregnant women in Poland continue smoking 14 15 Tobacco smoking is associated in doserelated manner with stimulation of erythropoiesis due to increased maternal and fetal iron requirements probably through a hypoxic effect 16 17 18 It is suggested that accompanying smoking hypoxia can suppress hepcidin mRNA expression and reduces hepcidin concentration in pregnant women as well as in newbornsThe aim of the study was to estimate the effect of tobacco smoking on serum hepcidin and selected iron parameters in pregnant women We evaluated relationships between hepcidin and other indicators of iron status Furthermore we investigated the possible association between serum hepcidin concentration and the neonatal birth weight and lengthTwo groups of women were taken from a prospective observational study for adverse effects of tobacco smoking in pregnant women visiting the Department of Obstetrics and Gynecology Institute of Mother and Child Warsaw Poland between January 2013 and March 2015 The study was conducted according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the Institute of Mother and Child All pregnant volunteers were made aware of the study objectives and informed written consent was obtained for analysis of biological samples and linking results to the data collected from questionnairesThe base study population wherein the present study was nested constituted 296 singleton pregnancies In the study group 41 cases were included which had hospital visits in the third trimester of pregnancy 32–36 weeks and continued smoking during pregnancy minimum five cigarettes per day and minimum 2 years before conception The control group consisted of 40 nonsmoking healthy pregnant women similar to age and gestational age Gestational age was estimated by the last menstrual period and confirmed or corrected by ultrasonographic measurements of the crownrump length dated in the first trimester The groups included only women with a single physiological pregnancy who before pregnancy had normal menstrual cycles were in good health at time of examination and declared good living conditions The exclusion criteria for the study were maternal diseases preeclampsia hypertension diabetes mellitus active hepatitis renal and cardiovascular diseases and inflammatory conditions multiple pregnancy birth defects detected during pregnancy alcohol drinking and assisted reproduction Women exposed to secondhand smoke smoking spouse or other family members coworkers were excluded from the tobacco abstinent group The classification of groups was confirmed by measurement of serum cotinine the major metabolite of nicotine in pregnant women A cutoff value of ≥137 μg/L was used to separate smokers from nonsmokers in accordance with others studies 19 All subjects in our study reported taking standard vitamins with iron and folate during pregnancy average 400–800 μg of folate 15–60 mg of ferrous fumarate dailyMaternal peripheral blood samples 5 mL were taken at the time of recruitment 30–34 weeks of gestation In order to obtain serum the blood was centrifuge at 2500×g at 4 °C for 10 min and was stored in small portions at −25 °C for subsequent biochemical analysis

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