Are IQs Low in Offspring of Euthyroid Women With Low T4?

Summary:

The purpose of the proposed study is to test the hypothesis that the key thyroid-related factor in early fetal brain development is T4 derived from the maternal circulation. According to this hypothesis, low circulating maternal levels of free T4 may adversely influence fetal brain development, even when the mother is clinically euthyroid (i.e. has normal TSH levels).

Specific Aims:

The proposed project aims to determine whether free T4 levels at or below the 3rd centile in euthyroid women during early pregnancy are associated with reduced neuropsychological development in their offspring. We will recruit a cohort of 5,000 pregnant women whose serum samples have been submitted for routine prenatal screening for Down syndrome and neural tube defects in the early second trimester of pregnancy. After the women provide consent, thyroid-stimulating hormone (TSH) measurements will be performed. The women defined as euthyroid by TSH measurement will comprise the study group. Free T4 measurements will be performed on their stored sera after delivery. Then, a nested case-control study design will be used. Inclusion criteria will include: liveborn, singleton infant delivered in Maine at 36 weeks or later, weighing at least 2,500 grams, and with no reported congenital anomalies. Multiple gestations will be excluded. Eligible women with free T4 measurements below the 3rd percentile (cases) will each be matched with a woman/infant pair with normal free T4 measurements (controls). Overall, 100 offspring in each category will undergo neurodevelopmental testing at age 2 years, using a test battery that will focus on language development and attainment of milestones and motor development. The study will have an 80% power to detect a 6 point difference in full scale IQ.

Study Timeline: