206 PTEROYLGLUTAMIC ACID 



in the pathogenesis of megaloblastic anemia of pregnancy. Ungley states 

 that "Several of our patients had excellent diets . . ."^"^ His further argu- 

 ment that "In others, the diet, although not good, was at least no worse 

 than that of other women who did not develop anaemia" cannot be given 

 much weight, since such an observation is common to all clinical nutritional 

 deficiency states. Certainly, in most of the reported instances of this condi- 

 tion pre-existing dietary inadequacy has been noted and malnutrition has 

 characterized every case within the writer's experience. Such nutritional 

 abnormalities may well include deficiencies other than PGA itself, such as 

 amino acids and ascorbic acid which play a role in PGA and CF metabohsm. 

 On the other hand, contributing factors, such as the increased demands of 

 gestation, possible digestive disturbances, and alterations in the output of 

 sex hormones, as suggested by Ungley,^^^ may play a part in the actual 

 development of severe macrocytic anemia. 



Diminished secretion of intrinsic factor during gestation was proposed 

 as a cause of macrocytic anemia of pregnancy, on the basis of clinical ex- 

 periments by Strauss and Castle. ^^^ In the light of present knowledge, such 

 an explanation involves a defect in the absorption and utiUzation of vitamin 

 Bi2 . The same result might, as suggested by these authors, follow a low 

 dietary intake of extrinsic factor (B12). However, before the isolation of 

 PGA and B12 , numerous observers reported the ineffectiveness of purified 

 liver extract injections in the treatment of pregnancy macrocytic anemia, 

 followed by good results obtained from yeast, whole liver, or crude liver 

 extracts. The earlier therapeutic observations were summarized and ana- 

 lyzed critically by Watson and Castle. ^^^ Since PGA and B12 became avail- 

 able, it has been universal experience that the former constitutes effective 

 and complete therapy for this type of anemia,^^*- ^^^ whereas vitamin B12 is 

 essentially valueless and may even be detrimental. ^■'°""'' 



Patients with macrocytic anemia of pregnancy may exhibit striking 

 clinical and hematological manifestations in addition to anemia. In a case 

 observed by the author,^^" spiking fever, glossitis, vulvovaginitis, and 

 diarrhea were conspicuous. During a period of vitamin B12 administration, 



166 C. C. Ungley, Brit. J. Nutrition 6, 299 (1952). 



1" M. B. Strauss and W. B. Castle, Am. J. Med. Set. 185, 539 (1933). 



168 J. Watson and W. B. Castle, Proc. Soc. Exptl. Biol. Med. 58, 84 (1945). 



169 L. S. P. Davidson, R. H. Girdwood, and J. R. Clark, Brit. Med. J. I, 819 (1948). 

 17" F. H. Bethell, M. C. Meyers, and R. B. Neligh, /. Lab. Clin. Med. 33, 1477 (1948). 

 "1 L. A. Day, B. E. Hall, and G. L. Pease, Proc. Staff Meetings Mayo Clinic 24, 149 



(1949). 

 1" V. Ginsberg, J. Watson, and H. Lichtman, J. Lab. Clin. Med. 36, 238 (1950). 

 1" R. H. Furman, W. B. Daniels, L. L. Hefner, E. Jones, and W. J. Darby, Am. 



Practitioner and Dig. Treatment 1, 146 (1950). 

 1" C. C. Ungley and R. B. Thompson, Brit. Med. J. I, 919 (1950). 



