4o6 Fetal Hemorrhage and Vitamin E 



vascular changes. Since frank hemorrhage occvxrs most frequently in areas such 

 as the cerebral wall, where the tissues are relatively more compact than those 

 in which the vascular channels arc usually dilated and thrombosed, weakness 

 of the extravascular supporting tissues does not appear to be a factor. The 

 occurrence of demonstrable edema only in advanced stages of the disorder sug- 

 gests that altered permeability of the vascular wall is a secondary phenomenon. 

 Undoubtedly, the varying incidence and gross characteristics of the vascular 

 changes in different regions of the fetus constitute factors whose significance 

 cannot be fully appreciated at the present stage of these investigations. 



There is need for a reinvestigation of the early resorptive process in order 

 to determine whether there exist abnormalities of the vascular system com- 

 parable to those described above. Should such prove to be the case, the histo- 

 pathology of vitamin E deficiency in the female rat would have much in 

 common with spontaneous hemorrhage observed in vitamin E-deficient chick 

 embryos (Adamstone'^' '), together with the capillary thrombi in cerebellar and 

 cerebral vessels (Pappenheimer and Goettsch^) and the exudative diathesis 

 (Dam and Glavind") observed in young and adult chicks deprived of vitamin E. 

 It should be mentioned, however, that the present state of our knowledge does 

 not permit an explanation of the various histopathological manifestations 

 of vitamin E deficiency on the basis of either a structural or physiological de- 

 fect of the vascular wall or a suppression of hematopoiesis. These can be re- 

 garded only as a manifestation of underlying metabolic disturbances which, 

 when finally understood, will afford the real answer concerning the physiologi- 

 cal role and function of vitamin E. A more extensive discussion of these 

 vascular phenomena and their correlation with other lesions of vitamin E 

 deficiency in laboratory animals has been presented elsewhere.'" 



Summary and Conclusions 



Fetal death is of frequent occurrence in sterile vitamin E-deficient rats given 

 borderline doses of vitamin E and autopsied at the sixteenth day of pregnancy. 



Prior to exitus there appear abnormalities in the vascular system character- 

 ized by variable degrees of dilation and thrombosis of peripheral and deeper 

 vascular channels and by either localized or diffuse areas of hemorrhage which 

 are sometimes associated with edema, together with a paucity of blood in 

 other vessels of the fetus and in those of the fetal membranes. The fetus suc- 

 cumbs to generalized ischemia. Although suppressed hematopoiesis in the 

 liver and yolk sac, characteristic of earlier fetal death and resorption (Evans 

 and Burr^), cannot be excluded as a contributory factor, vascular injury is 

 regarded as the primary cause of late fetal death. 



These vascular changes, which can be directly correlated with the level of 

 vitamin E dosage and are not influenced by separate administration of vitamin 

 C or vitamin K, are undoubtedly pathognomonic for vitamin E deficiency and 

 resemble in many respects the capillary thrombi and exudative diathesis ob- 

 served in the vitamin E-deficient chick by other investigators. 



