Natural history of perinatal coronary atherosclerosis due to maternal cigarette smoking and/or air pollution

Introduction. The knowledge on the natural history of atherosclerosis is mainly based on experimental studies in animals maintained on a high cholesterol diet. Aim of this study is to study the natural history of perinatal atherosclerosis due to maternal cigarette smoking and/or air pollution. Materials and Methods. Our study population included 22 stillborns and 49 infants who died suddenly and unexpectedly sine causa between the 32nd week of gestation and one year of age. The major epicardial coronary arteries (left main, left anterior descending branch, left circumflex, right posterior interventricular descending branch, right marginal branch) were excised transversely to their longitudinal axis in segments approximately 3-4 mm long. The segments were dehydrated, embedded in paraffin block and serially cut. The sections of each block were stained with Hematoxylin-eosin, trichromic Heidenhain (Azan) for histological examination, Alcian blue (at pH 0.5 and 2.5) for acid mucopolysaccharides analysis, Weigert for elastic fibers identification, and in selected cases submitted to specific immunohistochemical methods for lymphocyte, monocyte and smooth muscle cell typization. The cardiac conduction system was removed in two blocks, as devised in our guidelines, available on the web site http://users.unimi.it/~pathol/sids_e.html. Results. In 45% of the cases the mothers were smokers during pregnancy. This study showed a significant correlation between early atherosclerotic lesions and parental smoking. In fact, we observed a high incidence of preatherosclerotic lesions in the coronaries of fetuses of smoker mothers and of atherosclerotic plaques in infants of smoker parents. Precisely, in 55% of fetuses and in 67% of the infants, multifocal coronary atherosclerotic lesions of varying entity were detected. The alterations ranged from focal plaques with mild myointimal thickening to juvenile soft plaques in infants, reducing the arterial lumen. Conclusions. The atherogenic role of cigarette smoke derives almost exclusively from the results on the greatest incidence of the cardiovascular pathology in fetuses and infants of smoker mothers. The studies on the passive cigarette smoke effects already detectable in fetuses have allowed to describe the features of the initial atherosclerotic lesions and their progression in infancy if the maternal smoke persists. Since the fetus represents the ideal model for the evaluation of the maternal cigarette smoke effects, our data allow not only to determine the atherogenic role of the passive cigarette smoke, but also to re-examine the actual concepts on the nature of the atherosclerotic process.