Fetal Iron Research Articles

Erythrocyte ferritin in human neonates: maternofetal iron kinetics revisited.

Serum and erythrocyte ferritin concentrations were measured in 369 healthy term neonates and their mothers, with a view to understanding maternofetal iron kinetics. Erythrocyte ferritin concentrations in the neonates were on average 100 times higher than maternal values, while those of serum ferritin were about 10 times higher. Maternal and fetal iron status were correlated in the overall study population. Serum and erythrocyte ferritin values were also correlated with each other in both the mothers and neonates. To study the influence of iron status on these conditions, we formed three groups of mother-child pairs of equal size, based on maternal iron status (serum ferritin). The correlations found in the overall population were not always present in each subgroup. In the infants born to mothers with adequate tissue iron reserves (serum ferritin > 12 micrograms/I), a statistical link was found between serum and erythrocyte ferritin levels. When the mothers had optimal iron status (serum ferritin > or = 22 micrograms/I), there was a correlation between the neonatal and maternal erythrocyte ferritin levels. No such links were found when the mothers had low tissue iron stores (serum ferritin < 12 mg/I). These data point to special iron kinetics during fetal life and the influence of maternal iron status.

Liver and brain iron deficiency in newborn infants with bilateral renal agenesis (Potter's syndrome).

Significant changes in fetal iron status potentially occur in pregnancies in which reduced fetal nutrient delivery is severe enough to result in intrauterine growth retardation (IUGR), particularly if chronic fetal hypoxia is also present and increases fetal iron demand for hemoglobin synthesis. Neonates rarely die following IUGR secondary to maternal preeclampsia, but bilateral renal agenesis, which is also characterized by reduced maternal-fetal blood flow, late gestation placental failure, and IUGR, is uniformly fatal. We measured neonatal liver iron concentration, as an assessment of fetal storage iron status, and heart and brain iron concentrations, as assessments of nonheme tissue iron status, in 11 infants who died in the neonatal period of bilateral renal agenesis, and compared them with values for gestational age-matched control infants whose gestation was not complicated by fetal growth retardation or hypoxia. Stainable nonheme iron in the hepatocytes was significantly reduced in all and completely absent in 8 of the 11 cases of renal agenesis (P < .001 compared with control). The mean +/- SEM liver iron concentration of the bilateral renal agenesis group (999 +/- 218 micrograms/g dry tissue weight) was 26% of the control value (3894 +/- 548 micrograms/g dry tissue weight; P < .001). Brain iron concentration was also lower in the group with bilateral renal agenesis (109 +/- 17 vs. 161 +/- 19; P = .015) and was correlated with liver iron concentration (r = .47; P = .03). Heart iron concentrations were similar in the two groups. Nine of the subjects with bilateral renal agenesis had placental weights below the fifth percentile for gestational age. The bilateral renal agenesis group had a lower mean birth weight (P < .001) and had a higher prevalence of fetal growth retardation (55% vs. 0%; P < .001). We conclude that infants with bilateral renal agenesis are at risk for severe iron deficiency of storage and nonstorage tissues. Liveborn infants with nonfatal fetal conditions characterized by significant restriction of maternal-fetal blood flow may also be at significant risk for postnatal iron deficiency.

The hematologic and plasma iron responses to severe fetal hemorrhage in the ovine fetus

OBJECTIVE: We previously reported that the ovine fetus does not significantly increase its red blood cell production rate after a 40% loss of blood in spite of a transient elevation in plasma erythropoietin concentration. In this study we hypothesized that, in response to a more severe loss of blood, the ovine fetus would undergo a sustained rise in plasma erythropoietin concentration and an augmentation in its red blood cell mass expansion rate. STUDY DESIGN: Twelve chronically catheterized fetal sheep (six control and six hemorrhaged) were studied beginning at 126 ± 1 (SE) days' gestation. Fetal blood volume, plasma volume, red blood cell mass, reticulocyte count, plasma erythropoietin level, and plasma iron level were measured for 10 consecutive days. On days 1, 2, and 3 the hemorrhaged fetuses had an average of 102 ± 4 ml per day of blood removed at a rate of 1 ml/min for a total of 305 ± 10 ml of blood removed. Statistical analysis was by one- and three-factor analysis of variance. RESULTS: Control animals had a progressive increase in blood volume, plasma volume, and red blood cell mass throughout the 10-day protocol. Reticulocyte counts and plasma iron and erythropoietin levels did not change. In fetuses at 24 hours after the third hemorrhage blood volume averaged 9.3% below ( p = 0.03) and plasma volume averaged 16.4% above ( p = 0.04) that in the control animals. Thereafter blood and plasma volumes expanded at rates similar to controls. Erythropoietin increased ( p < 0.001) but returned to prehemorrhage values by day 7. Posthemorrhage expansion of the red blood cell mass in the hemorrhaged animals was 1.9 times controls (6.8% ± 0.9%/day vs 3.5% ± 0.5%/day, p = 0.003). Fetal reticulocyte counts remained elevated throughout the posthemorrhage observation period ( p < 0.001). The fetal plasma iron concentration decreased ( p < 0.0001) and remained depressed. The recovery of red blood cell mass and the 10-day mean plasma iron concentration were highly correlated ( p = 0.01, r = 0.91). CONCLUSION: The ovine fetus significantly increases its release of red blood cells in response to a severe hemorrhage. Further, the ability of the fetus to restore its red blood cell mass appears to be dependent on the plasma iron concentration. (A M J O BSTET G YNECOL 1996;174:55-61.)

Positive correlation between fetal plasma iron and red cell mass restoration in anemic fetuses

Positive correlation between fetal plasma iron and red cell mass restoration in anemic fetuses

Placental transferrin receptor in diabetic pregnancies with increased fetal iron demand.

Augmented fetal hemoglobin synthesis during diabetic pregnancy increases fetal iron demand. To study the effect of increased fetal iron demand on placental transferrin receptor (TR), we utilized a monoclonal antibody to localize placental TR immunoreactivity and 125I-labeled transferrin to study TR binding characteristics in 10 placentas from poorly controlled diabetic mothers with increased fetal iron demand and 10 placentas from nondiabetic mothers. The infants born to the diabetics had higher cord serum C-peptide, erythropoietin, and hemoglobin concentrations, indicating fetal hyperinsulinemia and hypoxia, with augmented erythropoiesis and iron demand. TR immunoreactivity was localized to the syncytiotrophoblast in both groups, was greater in the diabetic group, and was inversely correlated with fetal storage iron (r = -0.75; P < 0.001). Scatchard analysis of 125I transferrin binding data confirmed greater receptor number (Bmax 17.9 +/- 2.2 vs. 12.6 +/- 1.3 pM/mg protein, P = 0.05), but reduced binding affinity [dissociation constant (Kd) 7.6 +/- 0.9 vs. 5.4 +/- 0.4 nM/l, P = 0.03] in the diabetic group. The TR staining intensity, Bmax, and Kd were each correlated with cord C-peptide, suggesting either a primary or secondary role for fetal hyperinsulinemia in TR expression. This study provides in vivo evidence that fetal factors, such as iron demand or hyperinsulinemia, influence regulation of placental TR in humans. The increase in placental syncytiotrophoblastic TR expression associated with reduced cord serum ferritin concentration suggests that the fetus utilizes both increased placental iron transport and mobilization of fetal iron stores to support augmented fetal erythropoiesis.

Iron concentration and distribution in the newborn liver

Recent observations on a correlation between fetal serum ferritin and gestational age, consistent with an increase in fetal iron stores during pregnancy, led us to study liver iron content in 22 human stillborns, newborns and infants of different gestational and postnatal age. At autopsy, a longitudinal liver slice was subdivided into ten blocks. Each sample was analyzed for iron content by atomic absorption spectroscopy. The mean iron concentration in the studied livers was 21.6 microM/g dry tissue (d.t.). A striking interindividual variability in iron content was observed: the hepatic concentration of the metal ranged from 3.3 to 64.4 microM/g d.t. No correlation was found between the hepatic iron concentration and gestational age or other clinical parameters of the patients studied. Moreover, the total storage iron of the liver did not appear to be correlated with the gestational age. The analysis of iron concentration in ten blocks in each liver revealed an irregular distribution of the metal. Lobar differences were observed, with a tendency of the left lobe to accumulate more iron than the right one. Furthermore, striking differences in iron content were found between adjacent liver samples, ranging in one instance from 4.5 up to 109.0 microM/g of dry tissue. Perls' stain for iron was positive in 7 out of the 22 livers examined, showing an irregular acinar distribution, with preferential periportal localization. Our data show that the newborn liver can be considered an interesting model for the study of iron storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships between Maternal and Fetal Liver Copper, Iron, Manganese, and Zinc Concentrations and Fetal Development in California Holstein Dairy Cows

Associations between maternal trace element deficiencies and abortion have been made for many mammalian species. Objectives of this study were to estimate and correlate maternal and fetal hepatic Cu, Fe, Mn, and Zn concentrations through gestation. Additionally, aborted fetuses, stratified by cause of abortion (infectious or noninfectious), were compared to size-matched nonaborted fetuses to examine for magnitude and direction of change in hepatic trace element status. Dam and fetal liver were removed at slaughter from 103 Holstein dairy cows judged grossly normal by ante- and postmortem examination. Liver samples were collected from fetuses submitted by veterinarians for routine diagnosis of abortion (n = 80). Hepatic Cu, Fe, Mn, and Zn concentrations were determined by flame spectrophotometry. Comparisons of groups, estimations of correlations, and derived prediction equations were made by least-squares methods. Maternal liver Cu, Fe, Mn, and Zn concentrations did not vary during gestation. Compared with the dam, fetal liver Fe and Zn concentrations were higher (P < 0.05), fetal Cu concentrations were similar (P > 0.05), and fetal liver Mn concentrations were lower (P < 0.05). As fetal size increased, fetal liver Cu and Zn concentrations increased (P < 0.05), fetal liver Fe concentration decreased (P < 0.05), and fetal liver Mn did not change (P > 0.05). Aborted fetuses had lower liver Cu, Mn, and Zn concentrations than did nonaborted fetuses (P < 0.05). Liver Fe concentration was lower in aborted fetuses than in nonaborted fetuses in the second trimester only (P < 0.05). Consistently lower liver Cu, Fe, Mn, and Zn concentrations in aborted fetuses suggest a nonspecific change in trace element status, which implies an effect of abortion, not a cause of abortion.

Restoration of fetal red blood cells and plasma proteins after a moderately severe hemorrhage in the ovine fetus

We hypothesized that the fetus, in response to a moderately severe hemorrhage, would restore its plasma volume and red blood cells so that plasma volume would be returned to normal within 24 hours and red blood cell mass would be restored in 5 to 7 days. Time-dated pregnant sheep (five control and six hemorrhage, gestational age 124 +/- 1 [SE] days) were subjected to a 10-day protocol. Fetal blood volume, plasma volume, red blood cell mass, and plasma protein mass were measured on protocol days 1, 3, 4, 6, 8, and 10. Fetal plasma erythropoietin and plasma iron concentrations were measured daily. On protocol day 3 the hemorrhage animals underwent a 120 ml fetal hemorrhage over 2 hours. Statistical analysis was by three-factor analysis of variance. Control animals had a progressive increase in blood volume, plasma volume, plasma protein mass, and red blood cell mass throughout the 10-day protocol. The 2-hour hemorrhage removed 39.8% +/- 1.2% of the prehemorrhage blood volume. During the 7-day posthemorrhage recovery period fetal blood volume and red blood cell mass in the animals that were hemorrhaged expanded in parallel to, but remained below, that of the control animals. There was no difference in the expansion of fetal plasma volume or plasma protein mass between the two groups. After hemorrhage there was a nonsignificant increase in the fetal reticulocyte index in the animals undergoing hemorrhage. In response to the hemorrhage, erythropoietin levels increased and remained marginally elevated, whereas plasma iron levels decreased in the hemorrhaged animals relative to controls during the 7-day recovery period. The normal expansion of plasma volume and plasma protein mass that occurs with fetal growth was not altered by a large fetal blood loss. However, in spite of a transient increase in plasma erythropoietin levels the fetuses undergoing hemorrhage did not restore their red blood cell mass or blood volume. These observations suggest that the ovine fetus is able to withstand a significant loss of red blood cells, but fetal transfusion may be needed to restore fetal red blood cell mass after a moderate-to-severe fetal hemorrhage.

Relationship between iron status in pregnant women and their newborn babies. Investigation in a Spanish population.

We studied 157 pregnant women living in Merida, Spain, during their third trimester of pregnancy and their newborns at birth, analyzing the mother's and the umbilical cord's blood for hemoglobin, hematocrit, mean corpuscular hemoglobin concentration (MCHC), serum iron and serum ferritin. We observed statistically correlations between hemoglobin and hematocrit values of the mother with erythrocyte count, hemoglobin and hematocrit values of her child and between serum iron of mother and child. The blood levels in the umbilical cord did not decrease until the ferritin value of the mother was < 12 micrograms/l. Under these conditions the ferritin levels in the umbilical cord blood (80.4 micrograms/l) were significantly lower than in those newborn infants whose mother had adequate ferritin levels (123 micrograms/l). We deduce that maternal iron status seems to condition, at least partially, fetal iron status, specially when the mother has some deficiencies. We did not find a lower birth weight in children of anemic mothers. Actually, we found an inverse correlation between maternal hemoglobin values and infant birth weight (r = -0.1731, p < 0.05). It is possible that the demands on the mother are increased in the case of a newborn infant of greater size.

Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers

Infants of diabetic mothers frequently have polycythemia, elevated serum erythropoietin concentrations, and decreased serum iron and ferritin concentrations, likely representing a redistribution of fetal iron into erythrocytes to support augmented fetal hemoglobin synthesis. We hypothesized that fetal liver, heart, and brain iron concentrations are also reduced in these infants. After obtaining autopsy tissue from infants who had died before 7 days of age, we measured liver, heart, and brain iron concentrations using atomic absorption spectrophotometry. Seven infants of diabetic mothers and seven gestational age-matched control infants were studied. All infants of diabetic mothers had pancreatic islet cell hyperplasia, indicating fetal hyperglycemia and hyperinsulinemia. Liver iron concentrations in the infants of diabetic mothers were 6.6% of control values (489.0 +/- 154.4 vs 7379.7 +/- 1473.8 micrograms/gm dry tissue weight (mean +/- SEM); p less than 0.001), heart iron concentrations were 43.9% of control values (124.7 +/- 20.5 vs 284.1 +/- 34.8 micrograms/gm dry tissue weight; p less than 0.002), and brain iron concentrations were 60.6% of control values (106.1 +/- 13.7 vs 175.2 +/- 10.7 micrograms/gm dry tissue weight; p less than 0.003). Heart and brain iron concentrations were directly correlated with liver iron concentrations (r = 0.80 for both; p less than 0.001) and indicated that hepatic iron was greater than 75% depleted before heart and brain iron reduction. We conclude that severely affected infants of diabetic mothers have reduced liver, heart, and brain iron concentrations. The role of tissue iron deficiency in the genesis of the abnormal clinical findings in these infants deserves further consideration.

Fetal iron and cytochrome c status after intrauterine hypoxemia and erythropoietin administration.

Chronic fetal hypoxemia stimulates erythropoiesis and may result in a redistribution of fetal iron from plasma into erythrocytes. We studied the response of fetal plasma erythropoietin (Ep) to hypoxemia, the role of Ep in stimulating erythropoiesis in utero, and the effect of augmented erythropoiesis on fetal plasma Ep and iron and tissue cytochrome c concentrations in 19 chronically instrumented late-gestation fetal sheep. The fetuses were stimulated to produce 28 erythropoietic responses after exposure to 1) acute hypoxemia (1-5 days), 2) chronic hypoxemia (greater than 7 days), and/or 3) administration of 1,500 U recombinant human Ep concurrently during normoxemia. Plasma Ep peaked less than 12 h after the onset of hypoxemia or Ep bolus. Plasma iron decreased 24-48 h later and returned to baseline 48-96 h after normalization of Ep levels to baseline. The plasma iron response was directly related to the erythropoietin stimulus (r = 0.79, P less than 0.001) and inversely related to liver iron concentration at death (r = -0.84, P less than 0.001). Nine fetuses with depleted liver iron concentrations at autopsy had significantly lower heart and skeletal muscle iron concentrations compared with animals with 10% of control liver iron remaining. Skeletal muscle and heart iron and cytochrome c concentrations were significantly correlated. Ep has a potent biological effect on fetal erythropoiesis and iron metabolism. Augmented fetal erythropoiesis, mediated by Ep, results in decreased plasma iron, hepatic storage iron, and skeletal and cardiac muscle iron and cytochrome c. The model potentially explains the iron abnormalities found in newborn infants after fetal hypoxia.

Maternal and fetal iron measurements in a hemochromatotic pregnancy

The findings in the cord blood sample of an infant from a treated hemochromatotic mother of a raised transferrin saturation (88%) and a raised ferritin concentration (250.2 micrograms/L) together with elevated maternal values (66% and 91.6 micrograms/L, respectively) yet a normal total placental iron content (26.9 mg) suggested that in common with gastrointestinal mucosal cells and reticuloendothelial cells in hemochromatosis, the placental cell may exhibit an abnormality of iron storage and transport.

Abnormal iron distribution in infants of diabetic mothers: Spectrum and maternal antecedents

Because chronic hypoxemia causes a redistribution of iron from serum and storage pools into an expanding erythrocyte mass, and because infants of diabetic mothers are often hypoxemic in utero and have a high prevalence of polycythemia at birth, we studied iron distribution in 43 term infants of diabetic mothers. Twenty-four infants were at an appropriate size for gestational age; 19 were large for gestational age. At birth, 28 infants (65%) had abnormal serum iron profiles; eight had decreased ferritin concentrations only (stage 1), nine had decreased ferritin and increased total iron-binding capacity values (stage 2), and 11 had these serum findings plus elevated free erythrocyte protoporphyrin concentrations (stage 3). The hypoglycemic infants who were large for gestational age (n = 14) had a higher prevalence of abnormal iron profiles than euglycemic infants who were appropriate in size for gestational age (n = 20; 93% vs 50%; p = 0.009). Progressively abnormal iron profiles were associated with higher glycosylated fetal hemoglobin values, greater degrees of macrosomia, increased hemoglobin and erythropoietin concentrations, and increased erythrocyte/storage iron ratios. Erythropoietin concentrations were inversely linearly correlated with serum iron values (n = 32, r = -0.54; p = 0.003). The combined erythrocyte and storage iron pools were significantly lower in infants with abnormal iron values whose mothers were diabetic, particularly in infants of women with confirmed diabetic vasculopathy. We speculate that these findings are likely due to (1) increased fetal iron utilization during compensatory hemoglobin synthesis in response to chronic hypoxemia and (2) reduced iron transfer during late gestation complicated by diabetes.

An ovine model of maternal iron poisoning in pregnancy

An ovine model of maternal iron poisoning in pregnancy was used to examine the placental transport of deferoxamine and ferrioxamine and to follow maternal and fetal serum iron concentrations when maternal serum iron levels exceeded total iron-binding capacity. Ewes in the third stage of gestation underwent hysterotomy and delivery of the fetal head through an abdominal incision while under ketamine and halothane anesthesia. The fetal external jugular vein was catheterized for sampling of venous blood while the fetus remained in utero. Administration of deferoxamine mesylate or ferrioxamine mesylate IV to ewes was not accompanied by measurable deferoxamine or ferrioxamine in fetal blood. In a final experiment, four gravid ewes in a control group received 2 mg/kg maternal body wt iron IV over 60 minutes. An experimental group comprising another four ewes received similar doses of iron but then received 50 mg/kg deferoxamine mesylate IV over 15 minutes. Control and deferoxamine ewes reached similar peak maternal serum iron concentrations (2,479 +/- 266 and 2,121 +/- 343 micrograms/dL, respectively). The markedly elevated maternal serum iron concentrations were not accompanied by meaningful elevations in fetal serum iron levels over baseline values. Maternal deferoxamine infusion resulted in a more rapid fall in maternal serum iron concentrations but had no effect on fetal serum iron levels. The ovine fetus appears to be protected from elevated maternal serum iron concentrations in the last trimester of pregnancy. It could not be demonstrated that meaningful quantities of deferoxamine or ferrioxamine cross the placenta in the last trimester.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal Ferritin Values and Foetal Iron Stores

Acta PaediatricaVolume 79, Issue 4 p. 467-467 Maternal Ferritin Values and Foetal Iron Stores M. B. Krawinkel, Corresponding Author M. B. KrawinkelDr Michael B. Krawinkel, Universitätskinderklinik, Schwanenweg 20, D-2300 Kiel 1, FRGSearch for more papers by this authorM. Bethge, M. BethgeSearch for more papers by this authorA. O. El Karib, A. O. El KaribSearch for more papers by this authorH. M. Ahmet, H. M. AhmetSearch for more papers by this authorO. A. Mirghani, O. A. MirghaniSearch for more papers by this author M. B. Krawinkel, Corresponding Author M. B. KrawinkelDr Michael B. Krawinkel, Universitätskinderklinik, Schwanenweg 20, D-2300 Kiel 1, FRGSearch for more papers by this authorM. Bethge, M. BethgeSearch for more papers by this authorA. O. El Karib, A. O. El KaribSearch for more papers by this authorH. M. Ahmet, H. M. AhmetSearch for more papers by this authorO. A. Mirghani, O. A. MirghaniSearch for more papers by this author First published: April 1990 https://doi.org/10.1111/j.1651-2227.1990.tb11495.xCitations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume79, Issue4April 1990Pages 467-467 RelatedInformation

Clinical pharmacokinetics of iron preparations.

The principle of iron conservation is the basis of iron metabolism; the normal basal loss of iron from the body is about 1 mg daily in a 70 kg man and 0.8 mg in a 55 kg woman. Iron is lost mainly by the menstrual and gastrointestinal routes. The total iron requirement during pregnancy is 800 mg; in the last month the requirement may amount to 7 to 8 mg/day. Supplementary iron is recommended for many menstruating women, and during the latter part of pregnancy. Correct fetal iron metabolism is ensured by proper maternal iron status, although there are contradictory opinions and findings about the relationship between maternal and fetal iron metabolism. Preterm infants fed on breast milk have a negative iron balance, and require an iron intake of about 0.6 mg/kg/day, and 3.4 mg/1 g haemoglobin, to compensate for intestinal and venesection iron losses, respectively. The absorption of supplementary iron by the preterm infant is a linear function of intake. Preterm infants do not require iron supplements when given repeated blood transfusions. During lactation the total iron losses of the mother are 1 mg/day, and thus no supplementary iron is needed if the iron metabolism has been in balance during the pregnancy. Serum ferritin concentration decreases continuously when iron stores in the body are reduced, and totally empty iron stores are the only known reasons for low serum ferritin concentration. Despite depleted iron stores, serum ferritin concentration can be normal or higher than normal in protein-energy malnutrition, up to 3 months after major surgery, in acute liver damage, in some patients with prolonged hyperglycaemia due to diabetes mellitus, in acute lobar pneumonia, active pulmonary tuberculosis and rheumatoid arthritis on gold therapy, in sepsis secondary to marrow hypoplasia induced by chemotherapy, in heavy drinkers and for a few days after myocardial infarction. In haemochromatosis, iron is deposited in liver (producing fibrosis), pancreas, endocrine glands and heart. The rise in the level of iron in the body is due to increased absorption and/or increased intake. This pathology may occur in transfusions, in alcoholism (especially when alcoholic beverages are contaminated with iron and the diet is low-protein), in several liver diseases, in congenital transferrin deficiency and in idiopathic disease. Patients susceptible to haemochromatosis should receive a low-iron diet. Serum ferritin determination may be helpful in early identification of susceptible members of a family with idiopathic familial haemochromatosis, but transferrin saturation is not a good indicator of either iron depletion or iron overload.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of maternal anaemia and iron depletion on foetal iron stores, birthweight and gestation.

Effect of maternal anaemia and iron depletion on foetal iron stores, birthweight and gestation.

Review article: Regulatory aspects of placental iron transfer — A comparative study

Abstract Receptor-mediated endocytosis is generally assumed to be the process by which the haemochrial placenta takes up iron from transferrin. The involvement of an additional non-endocytic process cannot, however, be excluded. It appears from a study of iron transport mechanisms and of the maturation of the transfer process that placental ferritin is involved in the transfer of iron from mother to fetus. The metabolic relationship between the ferritin pool and the placental transfer pool remains to be elucidated. There is no evidence for short-term regulation of placental transfer capacity in response to changes in the maternal iron supply or to changes in the trophoblastic iron content. This cannot yet be said of fetal feedback control of placental iron uptake because the experiments performed so far do not permit conclusions on this point. The capacity for iron uptake and transfer seems to increase in accordance with the ontogenetically determined placental growth pattern. This does not exclude long-range adaptive modifications of the transfer capacity in response to early maternal or fetal disturbances. The results obtained from studying placental maturation suggest that a possible long-term regulatory interaction between growing placenta and fetus may occur. Clinical evidence so far is inconclusive. The relatively moderate reductions in the fetal iron stores which are generally associated with severe iron-deficient pregnancies might be seen as an argument in favour of long-term placental control. The marked impact of pregnancy on maternal iron metabolism in rodents, as compared to other mammals, is possibly met by means of direct placental control of mucosal iron uptake. In primates, mucosal iron uptake during pregnancy seems to be governed by factors related to systemic iron deficiency only.

Maternal and fetal iron accumulation in Zn-deficient and salicylate-treated rats

Nonhemoglobin Fe (non Hb-Fe) content in fetal serum and liver is much higher than in maternal serum and liver. After feeding a Zn-deficient diet to pregnant rats from d 0 to 21, non Hb-Fe content in maternal and fetal serum and liver was increased. After oral application of salicylic acid (300 mg/kg) from d 16 to 20 to normally fed and Zn-deficient dams, non Hb-Fe content in maternal and particularly in fetal serum and liver was drastically increased. In the kidney, Fe was accumulated to a small amount resulting from Zn deficiency and salicylate treatment. Fe accumulation in the liver occurred in all cell fractions, particularly in microsomes. Fe accumulation was confirmed and extended histochemically by Prussian blue staining. It is assumed that salicylate increases intestinal Fe resorption and fetal transfer of Fe. It is discussed that salicylate nephrotoxicity and its enhancement by Zn deficiency is not caused by an Fe-dependent mechanism.

Iron and Zinc Concentrations and 59Fe Retention in Developing Fetuses of Zinc-Deficient Rats

Because disturbances in iron metabolism might contribute to the teratogenicity of zinc deficiency, we examined the effect of zinc deficiency on fetal iron accumulation and maternal and fetal retention of 59Fe. Pregnant rats were fed from mating a purified diet containing 0.5, 4.5 or 100 µg Zn/g. Laparotomies were performed on d 12, 16, 19 and 21 of gestation. Maternal blood and concepti were analyzed for zinc and iron. Additional groups of dams fed 0.5 or 100 µg Zn/g diet were gavaged on d 19 with a diet containing 59Fe. Six hours later maternal blood and tissues, fetuses and placentas were counted for 59Fe. Maternal plasma zinc, but not iron, concentration was affected by zinc deficiency on d 12. Embryo zinc concentration on d 12 increased with increasing maternal dietary zinc, whereas iron concentration was not different among groups. On d 16–21 plasma iron was higher in dams fed 0.5 µg Zn/g diet than in those fed 4.5 or 100 µg/g, whereas plasma zinc was lower in dams fed 0.5 or 4.5 µg Zn/g than in those fed 100 µg Zn/g diet. On d 19 zinc concentration in fetuses from dams fed 0.5 µg/g zinc was not different from that of those fed 4.5 µg/g zinc, and iron concentration was higher in the 0.5 µg Zn/g diet group. The increase in iron concentration in zinc-deficient fetuses thus occurs too late to be involved in major structural teratogenesis. Although whole blood concentration of 59Fe was not different in zinc-deficient and control dams, zinc-deficient dams had more 59Fe in the plasma fraction. Retention of 59Fe in maternal tissues and litters was not different in zinc-deficient and control groups, but 59Fe/g body weight in zinc-deficient fetuses was 170% of that in control rats. Analysis of zinc, iron and copper distribution by gel filtration chromatography showed that the increase in tissue iron was in the ferritin-hemosiderin peak in maternal and fetal liver and placenta.