TIMING OF VULNERABILITY OF THE BRAIN TO IODINE DEFICIENCY IN ENDEMIC CRETINISM

Background. Endemic cretinism, caused by severe iodine deficiency duri ng pregnancy, is the world's most common preventable cause of mental r etardation. It can be prevented by iodine treatment before conception, but whether it can be prevented or ameliorated by treatment during pr egnancy or after delivery is not known. Methods. In a severely iodine- deficient area of the Xinjiang region of China, we systematically admi nistered iodine to groups of children from birth to three years of age (n = 689) and women at each trimester of pregnancy (n = 295); we then followed the treated children and the babies born to the treated wome n for two years. We used three independent measures of neural developm ent: the results of the neurologic examination, the head circumference (which correlates with brain weight in the first postnatal year), and indexes of cognitive and motor development. Untreated children one to three years of age, who were studied when first seen, served as contr ol subjects. Results. The prevalence of moderate or severe neurologic abnormalities among the 120 infants whose mothers received iodine in t he first or second trimester was 2 percent, as compared with 9 percent among the 752 infants who received iodine during the third trimester (through the treatment of their mothers) or after birth (P = 0.008). T he prevalence of microcephaly (defined as a head circumference more th an 3 SD below U.S. norms) decreased from 27 percent in the untreated c hildren to 11 percent in the treated children (P = 0.006), and the mea n (+/-SD) developmental quotient at two years of age increased (90 +/- 14, vs. 75 +/- 18 in the untreated children; P < 0.001). Treatment in the third trimester of pregnancy or after delivery did not improve ne urologic status, but head growth and developmental quotients improved slightly. Treatment during the first trimester, which was technically problematic, improved the neurologic outcome. Conclusions. Up to the e nd of the second trimester, iodine treatment protects the fetal brain from the effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievement slightly, but it does not improve neurologic status.