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F. Clarke Fraser, M.D., Ph.D.
JAMA. 1956;162(18):1651. doi:10.1001/jama.1956.02970350067024.
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To the Editor:—  I certainly agree with Dr. Ingalls (J.A.M.A.161:1047 [July 14] 1956) that "it is high time for orderly scientific methodologies to be used in the study of... congenital defects," but until the results of such studies are available for evaluation one cannot judge how far the findings of experimental teratology are applicable clinically. Dr. Ingalls has obtained evidence from experiments with mice that maternal hypoxia (or some related factor) can lead to developmental defects. From this he concludes that hypoxia is a "nonspecific stress." What exactly does he mean by "stress"? He goes on to say "Stress, of course, is to be defined more broadly than hypoxic stress" since other noxious agents such as x-rays, vitamin deficiencies, cortisone ( and, he might have mentioned, genes ) produce similar defects. Furthermore, he states, "a constellation of adverse maternal factors... anemia, hypothyroidism, organic heart disease, systemic hypertension, retroflexion, and tumor


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