Khera K S
Teratog Carcinog Mutagen. 1987;7(3):287-95. doi: 10.1002/tcm.1770070309.
Evaluation of published human and animal teratology data revealed associations between maternal toxicity and congenital malformations and embryofetal death. This has been reported elsewhere in detail and is herein summarized. Regarding human data, intrauterine deaths were observed to occur in association with 1) maternal homeostatic changes due to phenylketonuria and diabetes and 2) maternal toxicity resulting from alcohol abuse, use of aminopterin, and, possibly, trimethadione. A pattern of malformations that was similar and thus suggestive of a common cause was noticed among malformations attributed to phenylketonuria, diabetes mellitus, aminopterin, alcohol, warfarin, phenytoin, phenobarbital, trimethadione, and valproic acid. On reviewing 234 studies of agents tested in hamsters, mice, rats and rabbits, a fairly strong association between maternal toxicity and embryo-fetal mortality was observed. Further, a consistent pattern of fetal malformations associated with maternotoxic effects was discovered in a survey of 476 studies of agents tested in these four species. In these reviews, it was postulated that maternal toxicity per se could possibly cause such fetal effects. For evaluating maternotoxic effects in experimental studies, the minimum maternal data required would be frequent measurements of maternal body weight and food consumption, signs of altered behavior, death, and gross lesions at necropsy.
对已发表的人类和动物致畸学数据的评估揭示了母体毒性与先天性畸形和胚胎-胎儿死亡之间的关联。这在其他地方已有详细报道，在此进行总结。关于人类数据，观察到宫内死亡与以下情况有关：1）由于苯丙酮尿症和糖尿病导致的母体体内稳态变化，以及2）因酗酒、使用氨甲蝶呤以及可能使用三甲双酮导致的母体毒性。在归因于苯丙酮尿症、糖尿病、氨甲蝶呤、酒精、华法林、苯妥英、苯巴比妥、三甲双酮和丙戊酸的畸形中，发现了一种相似的畸形模式，因此提示存在共同原因。在回顾对仓鼠、小鼠、大鼠和兔子进行测试的234项药物研究时，观察到母体毒性与胚胎-胎儿死亡率之间存在相当强的关联。此外，在对这四个物种进行测试的476项药物研究的调查中，发现了与母体毒性作用相关的一致的胎儿畸形模式。在这些综述中，推测母体毒性本身可能会导致此类胎儿效应。对于在实验研究中评估母体毒性作用，所需的最少母体数据将是频繁测量母体体重和食物摄入量、行为改变的迹象、死亡情况以及尸检时的大体病变。
