Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers-The possible involvement of maternal methemoglobinemia

Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments.Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells.We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.In mammals, iron is a vital constituent of the oxygen-carrrier hemoglobin (Hb). Human Hb is a tetramer consisting of a pair of α-like globin chains and a pair of β-like chains. Each chain is bound to a prosthetic heme group, consisting of an iron atom in the ferrous state located at the center of a porphyrin ring; this structure has a high affinity for oxygen. Thus, Hb is best known for its oxygen-carrying capacity, which facilitates the transport of oxygen from the lungs to the tissues [1-3].There are numerous causes of hemoglobin-related diseases. A distinction can be made between genetically inherited diseases, such as thalassemias and sickle cell disease [4-6], and acquired disorders, such as methemoglobinemia [7-9], a rare condition characterized by the presence of a greater concentration than the normal physiological range of 1-2% methemoglobin in erythrocytes.Despite their different causes, these Hb disorders all arise from an oxidative denaturation of Hb. Oxidative injury can give rise to hemolysis with the consequent release into the circulation of Hb denatured products and of ferric iron (Fe3+), that is the ox