Intramuscular administration of iron dextran is inappropriate for treatment of moderate pregnancy anemia, both in intervention research on underprivileged women and in routine prenatal care provided by public health services

Abstract

Issues of biomedical ethics are major considerations in any investigation involving human subjects (2), even in the publication of research results (3). Biomedical ethics derives from a series of principles, among which the most important are those of beneficence, justice, nonmaleficence, and autonomy. An investigator from the prestigious Indian Medical Research Council participated in the research done by Sharma et al, and the study was reviewed (and approved) by the institutional review board of the host medical school. In the study by Sharma et al, the principle of beneficence was adhered to, because the subjects were all iron-deficient anemic women who had a need for additional iron and who received an iron-containing treatment. In terms of justice, there was no evidence in the study of discrimination or arbitrary exclusions of persons in need. However, serious problems arise regarding the principle of nonmaleficence, which derives from the Hippocratic principle of primum non nocere (first do no harm). As can be substantiated by the literature (4–6) and illustrated in the list of side effects given in Table 5 of the study, parenteral exposure to iron dextran imposes a series of serious risks to the health of the recipient. Among a sample of only 100 women in the intramuscular iron group, the documented frequency of local pain, skin staining, fever, and systemic symptoms—not to mention adverse reactions requiring hospitalization—is unacceptable. As cited by Sharma et al, 3 (0.14%) life-threatening, immediate reactions were observed in a previous study in which 2009 subjects received intravenous iron dextran injections (4). The same study also included 8 (0.38%) instances of severe delayed reactions including arthritis, myalgia, fever, and thrombophlebitis with pulmonary embolus that required observation and treatment for several days (4). There is no corresponding large-scale study on adverse and near-fatal events with intramuscular administration of iron dextran. Several case reports, however, showed that anaphylaxis may be encountered in such cases and may be fatal (eg, see reference 5). In the era before the availability of disposable syringes, a considerable percentage of intramuscular iron injections in Indian hospitals were associated with abscesses (6). Hence, there seems to be no comparability of risk between the 2 treatments in the study by Sharma et al; one treatment (parenteral administration of iron) is clearly more dangerous and life threatening than is the other (oral administration of iron). This brings us to the principle of autonomy, which dictates respect for individual free will based on informed choice. This takes on special dimensions when there is an inherent inequality of power between the investigators and the candidates for enrollment in a study (7). Given the impoverished and illiterate nature of the study’s target population from the slums of New Delhi, fully and completely “informing” these subjects of the nature, purpose, benefits, and risks of the proposed intramuscular exposure to iron dextran was virtually impossible. The investigators and their ethical committee obviously recognized ethical dilemmas because an initial proposal to enroll only women with severe anemia was considered and rejected. This proposal was disapproved because it was considered dangerous to leave such women at the mercy of oral iron treatment only; the gravity of the most severe anemia justifies the risk of parenteral iron administration. Exposing women with only moderate anemia to intramuscular iron treatment, however, was to err in the other direction.