Foetal Malformations Due to Thalidomide

Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation

“…defects, respectively. Our findings confirm our model and correlates with the time-sensitive period of thalidomide action in human pregnancy (1)(2)(3)(4)(5). Application of CPS49 to HHst13-15 embryos (day 2) when the embryo is just beginning to be vascularized, with highly angiogenic, immature vessels, results in 100% embryonic lethality within 12 h (n ϭ 12/12) (Fig.…”

“…Here we show conclusively that loss of newly formed blood vessels is the primary cause of thalidomide teratogenesis, and developing limbs are particularly susceptible because of their relatively immature, highly angiogenic vessel network. We also demonstrate that these effects correlate to the increased fetal loss and developmental-time-sensitive action of thalidomide (2,3,(6)(7)(8).…”

“…It caused an increase in miscarriage and still birth rates and a 40% increase in infant mortality, and up to 10,000 children around the world were born with severe limb malformations, as well as other much less common congenital defects (1)(2)(3)(4)(5)(6)(7). Children with such defects are still being born today, particularly in Africa and South America, where thalidomide is now increasingly used in treating leprosy (8,9).…”

“…Children with such defects are still being born today, particularly in Africa and South America, where thalidomide is now increasingly used in treating leprosy (8,9). Over 80% of children born to mothers who took thalidomide had limb defects (2,3,5,6). These defects ranged from absence of the limb (amelia) or proximal limb elements (phocomelia) to loss of the thumb or digit tip and are induced in a small time-sensitive developmental window (2,3,(6)(7)(8).…”

“…Over 80% of children born to mothers who took thalidomide had limb defects (2,3,5,6). These defects ranged from absence of the limb (amelia) or proximal limb elements (phocomelia) to loss of the thumb or digit tip and are induced in a small time-sensitive developmental window (2,3,(6)(7)(8). The precise mechanism underlying thalidomide's teratogenic effects, its relative limb specificity, and the range of induced defects have not been established.…”