Timing of Vulnerability of the Brain to Iodine Deficiency in Endemic Cretinism
Xue-Yi Cao, Xin-Min Jiang, Zhi-Hong Dou, Murdon Abdul Rakeman, Ming-Li Zhang, Karen O'Donnell, Tai Ma, Kareem Amette, Nancy DeLong, and G. Robert DeLong
Background Endemic cretinism, caused by severe iodine deficiencyduring pregnancy, is the world's most common preventable causeof mental retardation. It can be prevented by iodine treatmentbefore conception, but whether it can be prevented or amelioratedby treatment during pregnancy or after delivery is not known.
Methods In a severely iodine-deficient area of the Xinjiangregion of China, we systematically administered iodine to groupsof children from birth to three years of age (n=689) and womenat each trimester of pregnancy (n=295); we then followed thetreated children and the babies born to the treated women fortwo years. We used three independent measures of neural development: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 childrenone to three years of age, who were studied when first seen,served as control subjects.
Results The prevalence of moderate or severe neurologic abnormalitiesamong the 120 infants whose mothers received iodine in the firstor second trimester was 2 percent, as compared with 9 percentamong the 752 infants who received iodine during the third trimester(through the treatment of their mothers) or after birth (P=0.008).The prevalence of microcephaly (defined as a head circumferencemore than 3 SD below U.S. norms) decreased from 27 percent inthe untreated children to 11 percent in the treated children(P=0.006), and the mean ( ±SD) developmental quotientat two years of age increased (90 ±14, vs. 75 ±18in the untreated children; P<0.001). Treatment in the thirdtrimester of pregnancy or after delivery did not improve neurologicstatus, but head growth and developmental quotients improvedslightly. Treatment during the first trimester, which was technicallyproblematic, improved the neurologic outcome.
Conclusions Up to the end of the second trimester, iodine treatmentprotects the fetal brain from the effects of iodine deficiency.Treatment later in pregnancy or after delivery may improve braingrowth and developmental achievement slightly, but it does notimprove neurologic status.
Source Information
From the Xinjiang Anti-Epidemic and Health Station, Urumchi (C.X.-Y., D.Z.-H., M.A.R.); the Institute of Endemic Diseases Research, Urumchi (J.X.-M., Z.M.-L., K.A.); and Tianjin Medical College, Tianjin (M.T.) -- all in China; and Duke University Medical Center, Durham, N.C. (K.O., N.D., G.R.D.).
Address reprint requests to Dr. DeLong at the Division of Pediatric Neurology, Duke University Medical Center, Box 3936, Durham, NC 27710.
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