Maternal screening for hypothyroidism and hypothroxinemia

An Update on Thyroid Development, at the 3rd Ferring Pharmaceuticals International Pediatric Endocrinology Symposium, on Friday looked at maternal hypothyroidism and maternal hypothyroxinemia and fetal brain development. Datamonitor's Joanne Birtwistle looks at the arguments for pre-conception screening and early maternal screening.

At the 3rd Ferring Pharmaceuticals International Pediatric Endocrinology Symposium Update on Thyroid and Development, Dr Marvin Mitchell, of the State Laboratory Institute and University of Massachusetts Medical School, presented on maternal hypothyroidism and child development.

Subclinical gestational hypothyroidism

Subclinical hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) with normal thyroxin (T4). Gestational hypothyroidism can lead to intrauterine death, abortion, premature delivery, and IQ loss. Data shows that the higher the TSH, the greater the risk that the child will have some loss of IQ points.

Dr Mitchell's studies, involving a total of 12,000 pregnant women living in Maine in the US, found that 38% of children from women with gestational hypothyroidism had an IQ that was 1 standard deviation (SD) below the control mean. This equated to 1/1000 births being at risk from brain damage.

Dr Mitchell asserts that there is sufficient evidence that all women should be screened as early in pregnancy as possible for untreated hypothyroidism, advisably at their first prenatal visit at six weeks.

He says that prevention through screening could be achieved at minimum cost by using the model of the newborn screening programs for congenital hypothyroidism. Most US states mandate a routine screening test on all newborns to detect hypothyroidism. He pointed out that with a screening cost of around $5 per child, (covering TSH, T4, and all processing and notification costs) the frequency of occurrence means that the average cost of detecting subclinical hypothyroidism would be $5,000 per affected child.

During post-presentation discussions, it was pointed out that, ideally, screening should be done for planned pregnancies (as many now are in Western societies) before conception. Indeed, first trimester screening is often done towards the end of the first trimester, not necessarily at six weeks, and by this point some damage to the fetal brain might already have occurred.

Maternal hypothyroxinemia

At the update, Dr Gabriella Morreale de Escobar, Emeritus Professor at the Institute for Biomedical Research Alberto Sols, joint Center of CSIC and Automation University, presented on the role of the maternal thyroid hormone on early brain development.

Dr Morreale de Escobar argues there is increasing evidence that it is not just TSH that is an important determinant of neuropsychological development and that early hypothyroxinemia (defined as T4 concentrations that are low for the stage of pregnancy, whether or not circulating TSH is increased) increases the risk of a child having a lower IQ and ADHD.

In the paper 'Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia?' a team of researchers led by Dr Morreale de Escobar argue that the conditions resulting in first trimester hypothyroxinemia pose an increased risk for poor neuropsychological development of the fetus. The paper states that hypothyroxinemia seems to be much more frequent in pregnant women than either clinical or subclinical hypothyroidism, especially where the iodine intake of the pregnant woman is inadequate to meet her increased needs for T4.

Mild to moderate iodine deficiency is the most widespread cause of maternal hypothyroxinemia in Western societies. As a result, advising women to take iodine supplements as soon as pregnancy begins or, indeed, before, could prevent many children being born with learning difficulties. This is because although maternal hypothyroxinemia is potentially damaging for neurodevelopment of the fetus throughout pregnancy, it is especially dangerous during its first half, when the mother is the only source of hormone for the developing brain. Dr Morreale de Escobar thinks that a mother's iodine dose should be doubled during pregnancy as a preventative measure.

The ideal solution, to prevent and minimize the risk of thyroid-related fetal brain damage during development, would be for dual screening of both subclinical hypothyroidism and hypothyroxinemia at the first available instance that the mother presents. This may be before conception in planned pregnancies or as early as possible in the first trimester. Alongside this women, and their doctors, need to be made more aware of the importance of iodine supplementation both before and during pregnancy, particularly where iodine fortification in food is not enforced, such as in the UK, and among women following vegan or vegetarian diets who may be at greater risk of deficiency.

Related Datamonitor Research

• Strategic Perspectives: CNS Disorders in Women - Premenstrual Syndrome/Premenstrual Dysphoric Disorder
• Pipeline Insight: Hormone Replacement Therapy - Wyeth positions to strike back?
• Pharmaceutical Marketing Online: Targeting a Female Audience

To order these reports contact peter.barfoot@bioportfolio.com or telephone +44 1300 321501 or +1 415 680 2472 and a representative will get back to you.

You can also order on line at: http://www.bioportfolio.com/cgi-bin/acatalog/search.html