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NEJM Study Shows Children Born to Mothers with Untreated Thyroid Disease Have Lower I.Q.'s

Data Indicate Need for Routine Thyroid Screening During Pregnancy



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SCARBOROUGH, Maine, Aug. 18, 1999 -- Untreated thyroid disease during pregnancy may negatively impact a child's psychological development, resulting in a significantly lower I.Q. score and a decrease in motor skills, attention, language and reading abilities, according to data published in today's New England Journal of Medicine (NEJM). Results of the study show that women with untreated thyroid deficiency during pregnancy are nearly four times more likely to have children with lower I.Q. scores. Approximately 1 out of every 50 women have hypothyroidism (underactive thyroid) during pregnancy.

In the study, 19 percent of the children born to mothers whose thyroid deficiency was undetected scored 85 or less on the I.Q. testing, as compared to only 5 percent of those born to mothers without thyroid disease during pregnancy. On average, the I.Q. scores of the children whose mothers were untreated for thyroid deficiencies during pregnancy were 7 points lower than those of the children in the control group. A score of 107 was found to be average among the children in the control group. Scores of 85 or below typically signal that a child will have difficulty in school.

"The fact that the average I.Q. scores in children of the untreated hypothyroid women were lower is significant," said James E. Haddow, MD, lead study author, Vice President and Medical Director for the Foundation for Blood Research. "Even more important, however, is the high percentage of children whose score is below 85. The children whose scores are in this range may face life-long developmental challenges. It might be possible to prevent these problems through the early diagnosis and treatment of thyroid disease in their mothers."

The study, which was conducted by the Foundation for Blood Research with support from the National Institute of Child Health and Human Development, a division of the National Institutes of Health (NIH), is the largest population-based trial designed specifically to assess developmental problems in children born to mothers with hypothyroidism during pregnancy.

Study Design

The purpose of the study was to determine whether undetected or inadequately treated maternal thyroid deficiency during pregnancy is associated with lower I.Q. or other developmental problems in the children. Blood samples were stored from 25,216 women who received routine prenatal care in New England between 1987 and 1990. During their pregnancies, all of the mothers received appropriate medical care and all known cases of thyroid disease were treated.

In 1996 and 1997, all of the stored blood samples were tested for thyroid deficiency using the most sensitive blood test for thyroid disease, the thyroid stimulating hormone (TSH) test. From the overall study population, 62 mothers with thyroid disease were identified. Of the 62 women with hypothyroidism, 48 were not known to be thyroid deficient during their study pregnancy. The other 14 women were known to be hypothyroid, but treatment during pregnancy was not optimal. In order to establish a comparison, a control group of 124 children was selected from mothers in the study population whose thyroid function was normal during pregnancy.

Developmental Testing

All of the children (186) underwent a series of I.Q. tests relating to intelligence, attention, language, reading and visual-motor performance between the age of 7 and 9. The tests were selected according to the areas of development that are typically impacted by other in utero diseases, as well as pediatric (congenital) thyroid disease. The following tests were administered by one of two certified psychologists and supervised by the project's consulting psychologist: the Wechsler Intelligence Scale for Children -- Third Edition (WISC-III), the Peabody Individual Achievement Test-Revised, the Continuous Performance Test, the Test of Language Development -- Second Edition, the Development test of Visual Motor Integration and a pegboard test. Of these tests, the WISC-III is considered the gold-standard measure of intelligence, taking into account the aggregate of skills and concepts that reflect a child's mental ability.

Neither the staff involved with the testing nor the study children knew whether they were cases or controls.

Study Findings

The study found that the 62 case children whose mothers had thyroid deficiency during pregnancy performed less well on all of the tests. Their average WISC-III full-scale I.Q. averaged 4 points lower than that of the 124 children in the control group. Fifteen percent of the children had scores of 85 or less, compared with only 5 percent of the children in the control group. The children of the 48 women who were not treated for thyroid disease during the pregnancy had an average I.Q. score that was 7 points lower than the children in the control group, with 19 percent scoring 85 or less.

"Children who have an I.Q. less than 85 are likely to have difficulties in school, may be less likely to go to college and may be less successful in their careers and interpersonal relationships," said Susan Waisbren, Ph.D., associate professor of psychology in the Department of Psychiatry at the Harvard Medical School, the Children's Hospital, Boston.

At the end of the study, the women who did not know that they were hypothyroid during the pregnancy were re-contacted to determine whether their hypothyroidism was subsequently diagnosed. Sixty-four percent of the undiagnosed case women had confirmed hypothyroidism at the time of the follow-up. The average time to diagnosis was five years.

"Our findings indicate that routine screening for thyroid disease for women before or during pregnancy may be warranted," said Dr. Haddow. "In addition to the potential benefits to the child, the mothers themselves would benefit. Not only did it take an average of five years to diagnose hypothyroidism using traditional medical assessment, but also a few women were not diagnosed until 10 years later."

The Critical Role of the Thyroid Gland

The thyroid gland plays a vital role in the overall body function during all stages of life. Although relatively small, it produces a hormone that regulates the body's overall metabolism -- the rate at which the body produces energy from nutrients. If left untreated, thyroid disease can lead to an increased risk for heart disease, worsening osteoporosis and infertility. An estimated 13 million Americans have a thyroid problem, but more than half remain undiagnosed.

Thyroid hormones are particularly important during pregnancy and play a key role in fetal development. Until the fetal thyroid gland is developed at approximately 12 week's gestation, the maternal thyroid is solely responsible for delivering thyroid hormone, which is essential to fetal brain development, to the child. The placenta and amniotic fluid transfer small but crucial amounts of thyroid hormone from the mother to the baby.

Untreated hypothyroidism in women has been associated with early miscarriages and an increased risk of stillbirth. Women who have been diagnosed with thyroid disease prior to conception need to be monitored closely throughout their pregnancy in order to regulate properly the levels of thyroid in the blood. Typically, treatment needs to be increased by approximately 40 percent in order to normalize TSH levels in women who were previously diagnosed with hypothyroidism.

Thyroid disease can be diagnosed through a simple blood test called a TSH. Once diagnosed, hypothyroidism can be treated with a synthetic hormone replacement tablet, such as Synthroid(R) (levothyroxine sodium tablets, USP), taken once-a-day.

"Many women don't realize that thyroid function is important. If hypothyroidism is diagnosed prior to pregnancy, its treatment needs to be monitored closely and adjusted during the pregnancy as hormone levels fluctuate," noted Dr. Haddow. "Early detection and treatment of hypothyroidism is emerging as an important health issue for both the woman and her unborn child."

Foundation for Blood Research

The Foundation for Blood Research (FBR) is a nonprofit medical research and education institute composed of laboratory, public health, biostatistical and education experts. Its purpose is to find more effective ways to identify, manage and prevent human disease through clinical and laboratory investigation, epidemiology, outreach science education, computer-based analysis, public health program design and clinical testing. To learn more about the FBR, visit their website at http://www.fbr.org.

Funding for this study was provided by the National Institute of Child Health and Human Development, Knoll Pharmaceutical Company and the Thrasher Research Fund.

CONTACT: CONTACT: Louise Leavitt, or Kerry Beth Daly, both of Fleishman-Hillard, 212-453-2000, for Foundation for Blood Research

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