Perinatal and Infant early atherosclerotic coronary lesions related to maternal smoking

Background: The observations reported in the literature regarding the fetal origin of coronary artery lesions are rare and controversial. Aim: To identify the features of early atherosclerotic coronary artery lesions in late fetal stillborns and infants and the possible atherogenic role of maternal cigarette smoking. Methods: We examined by autopsy 22 unexpected fetal deaths and 36 sudden infant death syndrome victims. In 28/58 of the cases mothers were smokers. Serially cut sections of major epicardial coronary arteries were stained with hematoxylin-eosin, Azan, Alcian blue and acetic orceine, and were immunotypified for CD68, CD34, α-SM-Actin, PCNA, c-fos, and apoptosis. Results: In 10/12 of fetuses and in 15/16 of infants of smoking mothers, multifocal coronary lesions of varying entity were detected. Only in 5 cases (2/10 fetus and 3/20 infants) arterial lesions were observed in infants with non-smoker mothers (p<0.0001). Alterations ranged from focal areas with mild myointimal thickening in prenatal life to early soft parietal plaques in infants. Smooth muscle cells (SMCs) showed loss of polarity, infiltrating subendothelium, mostly with rupture of the internal elastic lamina. No neoangiogenesis was observed. These early lesions, presented c-fos gene activation in the SMCs of the tunica media, and in some of these, positivity of the SMCs for apoptosis was also observed; suggesting that c-fos gene over-expression could might promote a proliferative process, as testified by the PCNA positivity. Conclusion: Early intimal alterations of the coronary arteries are already detectable in the prenatal and infancy period and are significantly associated with maternal cigarette smoking.