Effect of Total Dose Infusion of Iron Dextran on the Storage Iron Content of the Human Placenta

Abstract

The histochemical examination of a placenta obtained from a stillbirth, which occurred 3 days after the mother had received a total-dose infusion of iron dextran (at 32 weeks of gestation), revealed large amounts of hemosiderin in the trophoblast. This is in contrast to a study of iron-deficient patients, treated with total-dose infusion of iron dextran, which shows no resulting increase of stainable iron in the placenta. Further studies were made to assess in more detail the effect on placental iron of infusions of iron dextran given at different stages of pregnancy. In addition to histochemical examination of the placenta, the two forms of storage iron, hemosiderin and ferritin, were estimated respectively as the water-insoluble and water-soluble fractions of the non-heme iron. The results of these studies are given in the present report. Observations were made on placentas obtained in an uncontrolled manner at various intervals after total-dose infusion and after varying doses of iron dextran. The latter was infused over 6 hours in either 5 per cent dextrose or in normal saline. Control placentas were obtained from women delivered at full term who had not been anemic during pregnancy and had not received parenteral iron. The interval between the infusion and the onset of delivery varied greatly. One patient was delivered the same day, and several others went into labor within 10 days; but in most cases, the infusion was given more than 3 weeks before delivery. The most striking changes were in the placenta associated with the stillbirth, in which almost every villus contained large amounts of Prussian blue-positive material in the trophoblast or immediately beneath it (Fig. 1). No other placenta showed so much iron, but in those obtained at 4 days and at 6 days, there was still a large amount of similarly distributed Prussian blue material in the villi. In placentas obtained at 8 days or longer after the infusion, the findings were the same as in the controls, namely, occasional specks of Prussian blue-positive material found mainly in the stroma of the villi. There was virtually none in the trophoblast itself. In the study of water-insoluble non-heme iron (hemosiderin), a total of 35 duplicate analyses of homogenates were made, with a range of values from 6 to 108 mg of iron per 100 g dry weight (0.108 to 2.94 mmol). The largest difference between duplicates was 12 per cent, but in 30 cases the difference was less than 6 per cent. The mean of the duplicates was therefore taken. In 11 controls, the placental hemosiderin iron ranged from 4.2 to 12 mg per 100 g dry weight (0.076 to 0.216 mmol). In 26 specimens obtained after iron dextran infusion, the placental hemosiderin ranged from control levels up to 128 mg (2.30 mmol) per 100 g dry weight. The highest values were found in placentas obtained within 2 weeks of the infusion. Much lower concentrations occurred in placentas collected between 3 and 20 weeks after the infusion. The high concentrations found within 2 weeks of infusion were, however, quite variable. Two placentas were obtained 4 days after infusion, two at 6 days, and two at 12 days. There were large deficiencies in hemosiderin within each of these pairs. In two of the pairs, the differences could be related to differences in the dose of iron dextran, but the remaining pair came from a twin pregnancy and were therefore exposed to the same maternal blood level. All but two of the highest hemosiderin concentrations were associated with the largest doses of iron dextran, but they were also cases in which the placentas were obtained within 14 days of infusion. In cases with longer intervals between infusion and delivery (the majority), the placental iron concentrations did not vary with the dose of iron dextran. The water-soluble non-heme iron was determined in 17 treated cases. No estimation was made in any of the controls, but the results after treatment fell into two groups. In three of six cases with increased concentrations of hemosiderin iron, the ferratin iron was higher than in the remaining 14 cases. In most of the latter, the concentrations of hemosiderin iron were within the control range. In some patients, the maternal serum iron was measured at the time of delivery. The concentrations were high in most of these, due to the presence of circulating irondextran.