Health and Nutrition Examination Survey (NHANES). Althoughlevels were sufficient some populations are at a level that needssupplementation. In North America all women who are planning apregnancy, are pregnant or breastfeeding, should take a daily oralsupplement that contains 150 μg of iodine (250 μg in pregnancy),optimally in the form of potassium iodide. Elsewhere, strategies varyaccording to regional dietary patterns and iodized salt availability.

doi:10.1016/j.ntt.2011.05.040

NBTS 29Thyroid Function and Clinical Hypothyroidism from aClinician's Perspective

Alex Stagnaro-GreenGeorge Washington University, Washington, DC, USA

Approximately 2.5% of all women who become pregnant havesubclinical hypothyroidism and another 0.5% of women have overthypothyroidism. Furthermore, euthyroid women with borderlinethyroid reserve pre-pregnancy, will frequently develop hypothyroid-ism during pregnancy as the maternal thyroid needs to increasehormonal production by 50%. Although well known that overthypothyroidism is associated with multiple adverse maternal andfetal effects research over the last twenty years has demonstrated thenegative impact of subclinical hypothyroidism. Specifically, subclinicalhypothyroidism has been associated with spontaneous miscarriage,pretermdeliveryanddecreased intelligencequotient in theunbornchild.A study published in 2010 performed in southern Italy demonstratedthat treatment of thyroid antibody positivewomenwho have TSH levelsabove 2.5 mIU/lwith levothyroxine decreased maternal/fetal complica-tions. The present talk will focus on the following issues: 1) changes inthyroid function tests during pregnancy, 2) the incidence of overt andsubclinical hypothyroidism during pregnancy, 3) the association ofmiscarriage, preterm delivery and decreased intelligence quotient withhypothyroidism, 4) intervention trials, both completed and ongoing,evaluating the impact of levothyroxine treatment of hypothyroidismduring pregnancy on the mother and fetus, and 5) the present status ofthe debate of universal screening for thyroid disease during pregnancy.

doi:10.1016/j.ntt.2011.05.041

NBTS 30Neurodevelopmental Consequences of Low-Level ThyroidHormone Disruption Induced by Environmental Contaminants

Mary GilbertUS EPA, Research Triangle Park, NC, USA

Inadequate levels of thyroid hormone during critical developmentalperiods lead to stunted growth, mental retardation, and neurological‘cretinism’. Animal models of developmental thyroid hormone defi-ciency mirror well the impact of severe insults to the thyroid system.However, it has become clear from studies in humans that evenmodestperturbations of the thyroid axis may not be benign. A number ofenvironmental contaminants reduce circulating levels of thyroidhormone, and do so by their interaction with a variety of target sites.The degree of thyroid hormone insufficiency induced by environmentalcontaminants is typically not severe, yet impact of modest fluctuationsin hormone has not been adequately addressed in animal models. Wehave investigated the dose-response relationships of thyroid hormonedisruption induced during pregnancy and lactation in rats exposed toa thyroid hormone synthesis inhibitor, propylthiouracil (PTU), dietary

iodine deficiency, and the environmental contaminant, ammoniumperchlorate. These treatments were delivered to produce graded levelsof hormone reduction and offspring were examined on a number ofcognitive endpoints, neuroanatomical, genomic, and neurophysiologicalparameters. We found that severe hormone depletion is not necessaryto alter brain development. Gene expression changes in cortex andhippocampus in PTU- and perchlorate-exposed pups were associatedwith mild alterations in serum hormones. Our work and othershas demonstrated cell fate specificity and neuronal migration are dis-rupted by PTU, a related synthesis inhibitor, methimazole, and iodinedeficiency. Electrophysiological impairments in hippocampal synaptictransmission in adult offspring were evident in all three models, andin our hands, were the most reliable in identifying brain dysfunction.Simple behavioral tasks (Morriswatermaze and fear conditioning) havenot proven very sensitive in identifying neurodevelopmental insults atlow levels of hormone insufficiency. In some cases, dam serumhormonelevels were more predictive of neurophysiological and moleculardeficits than hormones measured in pups. We conclude that long-termfunctional deficits accompany moderate levels of thyroid hormoneinsufficiency induced by a number ofmeans. It is likely that the negativeimpact of a xenobiotic-induced perturbation in thyroid hormone statuswill be exacerbated under conditions of iodine deficiency and this iscurrently under study. Does not reflect EPA policy.

doi:10.1016/j.ntt.2011.05.042

NBTS 31Neurobehavioral Effects of Hypothyroidism in Children fromAntenatal and Childhood Exposure

Joann RovetSick Childrens' Hospital, Toronto, Ontario, Canada

Thyroid hormone (TH) is essential for early brain development and ifinsufficient, will lead to significant brain abnormalities and neurobeha-vioral effects. In the human, demand for TH extends throughoutgestation but since the fetal thyroid system matures late and does notachieve full function until term, the fetus has to rely on themother for itssupply of TH. During the latter part of gestation, the fetal thyroid systemis maturing to assume full function at term. If either the maternal orchild's own thyroid supplies are inadequate due to maternal hypothyr-oidism (MH) or congenital hypothyroidism (CH), early brain develop-ment may be compromised and specific effects reflect timing of THinsufficiency. In this presentation, I will review recent studies of childneurodevelopment following MH or CH and will describe behavioralfindings from my lab on the specific sensory and cognitive sequelaeassociated with both conditions. For both groups, I will examine effectsby severity of each condition. In addition, I will describe preliminaryneuroimaging results showing how varying degrees of TH insufficiencyat specific times during gestation and/or early life affect later braindevelopment. I will present findings from structural and functional MRIstudies, with special emphasis on the hippocampus. I will conclude bydiscussing the real-world implications of these findings for everydayfunctioning in both populations.

doi:10.1016/j.ntt.2011.05.043

NBTS 32Prenatal Cocaine Exposure and Embryonic Cortical Development

Pradeep BhideMassachusetts General Hospital and Harvard Medical School, Boston,MA, USA

NBTS 2011 Abstracts 503