Maternal hypothyroidism tied to cognitive deficits in offspring

OB/GYN News, Nov 15, 2004 by Bruce Jancin

VANCOUVER, B.C. -- Children whose mothers were hypothyroid during pregnancy display selective cognitive deficits out to at least age 5 years, Joanne Rovet, Ph.D., said at the annual meeting of the American Thyroid Association.

The nature of these deficits correlates with the severity and gestational timing of the maternal thyroid deficiency, added Dr. Rovet, professor of pediatrics at the University of Toronto and senior scientist at the Hospital for Sick Children there.

The cognitive deficits are of such magnitude as to be clinically relevant. This is reflected in the finding that at age 5 years, the children were rated by teachers blinded as to their history as being significantly more disorganized than a group of controls.

Dr. Rovet reported on a prospective longitudinal study involving 53 offspring of mothers treated with L-thyroxine after being diagnosed as hypothyroid shortly before or at some point during pregnancy. The control group included 116 children born to mothers with normal thyroid function. Participants underwent assessment of intelligence and attention at 6, 12, and 18 months of age and comprehensive neuropsychological evaluation at age 5 years.

In infancy, the children of mothers hypothyroid during pregnancy displayed abnormal visual processing as well as deficits in attention, sensorimotor skills, and memory. The extent of these difficulties was positively correlated with maternal TSH level during the first and second trimesters.

At age 5, with data available on two-thirds of participants so far in this ongoing study, mean IQ was eight points lower in the children whose mothers were hypothyroid in pregnancy. The IQ score was inversely associated with third-trimester maternal TSH; the higher the mother's TSH late in pregnancy, the lower the child's IQ at age 5.

Subjects also scored significantly worse than controls on tests of working memory, attentiveness, and episodic and verbal associative learning. These scores, too, were negatively correlated with third-trimester maternal TSH.

The implication of this Canadian Institutes of Health Research-funded study is that it's important to identify and treat maternal hypothyroidism before pregnancy to avoid longstanding repercussions in the brains of the offspring, Dr. Rovet said.

Daniel Glinoer, M.D., noted that Dr. Rovet's findings are consistent with those of a published Dutch study in which 220 children underwent neurodevelopmental assessment at age 10 months. None of their mothers had overt clinical hypothyroidism during pregnancy. However, the 22 children of mothers having the lowest free T4 at 12 weeks' gestation scored significantly worse on the Psychomotor Developmental Index scale, compared with the others (Clin. Endocrinol. Oxf. 2003;59:282-8).

A low free T4 at 32 weeks' gestation, in contrast, had no adverse impact on the Dutch children's scores, underscoring the concept that the type of brain injury depends upon the gestational timing of the maternal thyroid hormone deficiency, explained Dr. Glinoer, professor of internal medicine at the Free University of Brussels.

In a separate presentation, Dr. Rovet focused specifically on the visual processing abnormalities that occur secondary to maternal thyroid disease.

Testing at age 6-8 months of 20 infants of women with hypothyroidism diagnosed before or during pregnancy, 7 infants whose mothers were diagnosed as hyperthyroid before or during pregnancy, and 15 infants whose mothers had normal thyroid function showed that the offspring of women with thyroid abnormalities had contrast sensitivity deficits.

BY BRUCE JANCIN

Denver Bureau