MICROCEPHALY

   Frombonne reported in 1999 that both macrocephaly and microcephaly were observed in autistic children.

   Macrocephaly (head circumference > 97th centile) was observed in 16.7% of autistic children, a significantly higher proportion than that expected. Macrocephaly was more frequent among older subjects.

   Microcephaly (head circumference < 3rd centile) was also significantly raised and found in 15.1% of the subjects (Frombonne et al, 1999).

   Infantile macrocephaly was associated with an increased risk of developing autism spectrum disorders (Bolton et al, 2001).

   It has been known for many years that this is due to lack of thyroid hormones during critical times of development. When iodine was supplemented at crucial times of development, the incidence of microcephaly was greatly reduced (Cao et al, 1994).

In 1994 Cao et al. reported:

• BACKGROUND. Endemic cretinism, caused by severe iodine deficiency during pregnancy, is the world's most common preventable cause of mental retardation. It can be prevented by iodine treatment before conception, but whether it can be prevented or ameliorated by treatment during pregnancy or after delivery is not known.
  METHODS. In a severely iodine-deficient area of the Xinjiang region of China, we systematically administered 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 women for two 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 children one to three years of age, who were studied when first seen, served as control subjects.
  RESULTS. The prevalence of moderate or severe neurologic abnormalities among the 120 infants whose mothers received iodine in the 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). The prevalence of microcephaly (defined as a head circumference more than 3 SD below U.S. norms) decreased from 27 percent in the untreated children to 11 percent in the treated children (P = 0.006), and the mean (+/- 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 neurologic 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 end 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.

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Bolton PF, Roobol M, Allsopp L, Pickles A - "Association between idiopathic infantile macrocephaly and autism spectrum disorders" Lancet 358(9283):726-7 (2001)
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=11551582&form=6&db=m&Dopt=r

Cao XY, Jiang XM, Dou ZH, Rakeman MA, Zhang ML, O'Donnell K, Ma T, Amette K, DeLong N, DeLong GR - "Timing of vulnerability of the brain to iodine deficiency in endemic cretinism"  N Engl J Med 331:1739-44 (1994) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7984194&form=6&db=m&Dopt=r

Frombonne E -”The epidemiology of autism: a review” Psych Med 29:769-786 (1999)