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In rodents, insufficient thyroid hormone (TH) gestationally has adverse effects on cerebral cortex development. Comparable studies of humans examining how TH insufficiency affects cortical morphology are limited to children with congenital hypothyroidism or offspring of hypothyroxinemic women; effects on cortex of children born to women with clinically diagnosed hypothyroidism are not known. We studied archived MRI scans from 22 children aged 10 to 12 years born to women treated for preexisting or de novo hypothyroidism within pregnancy (HYPO) and 24 similar age and sex controls from euthyroid women. FreeSurfer Image Analysis Suite software was used to measure cortical thickness (CT) and a vertex-based approach served to compare HYPO versus control groups and Severe versus Mild HYPO subgroups as well as to perform regression analyses examining effects of trimester-specific maternal TSH on CT. Results showed that relative to controls, HYPO had multiple regions of both cortical thinning and thickening, which differed for left and right hemispheres. In HYPO, thinning was confined to medial and mid-lateral regions of each hemisphere and thickening to superior regions (primarily frontal) of the left hemisphere and inferior regions (particularly occipital and temporal) of the right. The Severe HYPO subgroup showed more thinning than Mild in frontal and temporal regions and more thickening in bilateral posterior and frontal regions. Maternal TSH values predicted degree of thinning and thickening within multiple brain regions, with the pattern and direction of correlations differing by trimester. Notably, some correlations remained when cases born to women with severe hypothyroidism were removed from the analyses suggesting mild variations of maternal TH may permanently affect offspring cortex. We conclude that maternal hypothyroidism during pregnancy has long-lasting manifestations on the cortical morphology of their offspring with specific effects reflecting both severity and timing of maternal TH insufficiency.

Thyroid hormone (TH) is essential for normal development of the hippocampus, which is critical for memory and particularly for learning and recalling associations between visual and verbal stimuli. Adolescents with congenital hypothyroidism (CH), who lack TH in late gestation and early life, demonstrate weak verbal recall abilities, reduced hippocampal volumes, and abnormal hippocampal functioning for visually associated material. However, it is not known if their hippocampus functions abnormally when remembering verbal associations. Our objective was to assess hippocampal functioning in CH using functional magnetic resonance imaging (fMRI). Fourteen adolescents with CH and 14 typically developing controls (TDC) were studied. Participants studied pairs of words and then, during fMRI acquisition, made two types of recognition decisions: in one they judged whether the pairs were the same as when seen originally and in the other, whether individual words were seen before regardless of pairing. Hippocampal activation was greater for pairs than items in both groups, but this difference was only significant in TDC. When we directly compared the groups, the right anterior hippocampus was the primary region in which the TDC and CH groups differed for this pair memory effect. Results signify that adolescents with CH show abnormal hippocampal functioning during verbal memory processing.

Through its actions on regulatory genes that form, grow and sculpt the brain, thyroid hormone (TH) is essential for human brain development. Although much of what we know about these effects is based on research with rodents, recent studies of children exposed to TH insufficiencies during critical stages of early development provide preliminary evidence on how and when the human brain needs TH. This paper reviews some of the major studies from both the rodent research and research on offspring of women with hypothyroidism during pregnancy and children with congenital hypothyroidism (CH) who were assessed using neuropsychological tests and with advanced neuroimaging techniques. The final section will compare findings from children lacking TH due to maternal hypothyroidism and CH conditions, whose loss of TH at different times represents unique time windows for examining TH effects in the human brain.

Few studies have examined both episodic and semantic autobiographical memory (AM) performance during late childhood and early adolescence. Using the newly developed Children’s Autobiographical Interview (CAI), the present study examined the effects of age and sex on episodic and semantic AM and everyday memory in 182 children and adolescents. Results indicated that episodic and semantic AM both improved between 8 and 16 years of age; however, age-related changes were larger for episodic AM than for semantic AM. In addition, females were found to recall more episodic AM details, but not more semantic AM details, than males. Importantly, this sex difference in episodic AM recall was attenuated under conditions of high retrieval support (i.e., the use of probing questions). The ability to clearly visualize past events at the time of recollection was also related to children’s episodic AM recall performance, particularly the retrieval of perceptual details. Finally, similar age and sex effects were found between episodic AM and everyday memory ability (e.g., memory for everyday activities). More specifically, older participants and females exhibited better episodic AM and everyday memory performance than younger participants and males. Overall, the present study provides important new insight into both episodic and semantic AM performance, as well as the relation between episodic AM and everyday memory, during late childhood and early adolescence.

Many women of childbearing age are exposed to reproductive toxicants in the workplace. This article highlights the need for an evaluation of current occupational exposure guidelines for pregnant women working with hazardous agents that have the potential of being reproductive toxins. Limited information regarding reproductive risks associated with many chemicals in the workplace presents challenges in the establishment of standards that are ‘safe’ for vulnerable populations, such as the fetus. The management of these risks must take into consideration the limitations of available knowledge as well as individual risk factors that may amplify the likelihood of adverse outcomes. In 1981, Quebec adopted a policy that provides “precautionary leave” or reassignment of pregnant workers to other jobs if they are exposed to a factor suspected to compromise their health or that of their fetus during pregnancy. The advantages and disadvantages of this approach to managing reproductive hazards are discussed. The existence of a regulatory safety net at the level of the workplace for minimizing the impact of toxicant exposure on reproductive health outcomes is stressed. Management options that can be implemented early to provide added protection when a hazard cannot be reduced or eliminated are recommended.

Thyroid hormone is an essential hormone for growth, metabolism, and brain development. Children who lack thyroid hormone in utero or early life have poorer physical and neurological development. Some of the more common conditions leading to low pre- and postnatal thyroid hormone levels are congenital hypothyroidism, maternal thyroid disease during pregnancy, prematurity, and intrauterine exposure to substances such as maternal thyroid autoantibodies and environmental toxins (e.g., PCBs) (1). These groups are at varying risk of inadequate growth and neurodevelopment (2–4).

Screening newborns for congenital hypothyroidism (CH) has been effective in preventing the mental retardation that typically occurred when diagnosis was based on clinical symptomatology. This chapter provides an overview of the disease and its manifestations as well as a comparison of outcome in children with CH diagnosed clinically with those now being found via newborn screening. A detailed description of the author’s own longitudinal study of screened CH children is also presented with special emphasis on the factors predicting better outcome.

Sixty-nine children with congenital hypothyroidism detected through thyroid screening were compared with 39 unaffected siblings for cognitive and temperamental characteristics. Intelligence test results revealed: (1) IQs of hypothyroid children were normal but lower than siblings; (2) hypothyroid children were lower than siblings in gross motor and perceptual performance abilities; (3) athyrotic children had lower IQs than those with ectopic thyroids, goiter, or hypoplastic disease; (4) athyrotic, hypoplastic, and ectopic thyroid children had lower performance than verbal IQs, but there was no scale difference for those with goiter; (5) deficits differed according to test age; and (6) age of onset of treatment was not related to IQ or pattern of deficit. Temperament test findings revealed: (1) no increase in difficult or slow-to-warm-up children, (2) lower ratings were found for hypothyroid children than siblings on approach/withdrawal and persistence scales, and (3) higher rating was given for athyrotic children than those with goiter.