Intimal preatherosclerotic thickening of the coronary arteries in human fetuses of smoker mothers

BACKGROUND : Many studies have described the development of preatherosclerotic coronary artery lesions in infancy. The observations reported in the literature regarding the fetal origin of coronary artery lesions are rare and controversial. OBJECTIVES: To identify the features of preatherosclerotic coronary artery lesions in late fetal stillborns and the possible atherogenic role of maternal cigarette smoking. METHODS; We examined 22 stillborns (13 males and nine females), all of whom had died sine causa after the 32nd week of gestation. All underwent autopsy. Twelve of the mothers smoked over five cigarettes per day before and during the pregnancy. The four major epicardial coronary arteries were isolated along their whole length, embedded in paraffin and serially cut for histologic examination and immunohistochemical studies, particularly searching for the proliferating cell nuclear antigen and c-Fos expression. Alterations of chromosome 7 were also investigated by the fluorescence in situ hybridization technique. RESULTS: In over 50% of the fetuses, almost all from smoker mothers, multifocal structural alterations of coronary walls were evident. The smooth muscle cells (SMCs) presented loss of polarity, forming columns perpendicular to the axis of the media and infiltrating the subendothelial connective tissue. Increased amounts of mucoid ground substance were also observed in the subendothelial connective tissue. In all the cases with coronary alterations, study of the biological markers showed intense c-Fos positivity of the SMCs. CONCLUSIONS: Preatherosclerotic intimal alterations of the coronary arteries are already detectable in the prenatal period and are significantly associated with maternal cigarette smoking.