Maternal Hypothyroidism and Child Development

Klein, Robert Z.; Mitchell, Marvin L.

doi:10.1159/000023435

Cited by 31 publications

(17 citation statements)

References 11 publications

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“…Moreover, these children scored lower than controls on multiple aspects of cognitive functioning including auditory and visual attention, reading, visuomotor ability and word discrimination. The results suggest that fine and graphomotor skills and reading abilities are sensitive to TH insufficiency after 16 weeks' gestation, whereas visual attention abilities are sensitive to TH insufficiency before 16 weeks (32, 33).…”

Section: Maternal Hypothyroidismmentioning

confidence: 97%

Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental Findings

Zoeller

Rovet

2004

J Neuroendocrinology

536

369

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The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congential hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions.Clinical and experimental studies demonstrate thyroid hormone (TH) is essential for normal brain development. This was documented initially in children with congenital hypothyroidism (1-5), followed by animal studies focused on cerebellar development, which occurs largely postnatally (6-9). However, recent observations in humans (10-13) provide important new evidence that TH is also important in early (foetal) brain development, and that the timing and severity of TH insufficiency predicts the type and severity of the neurological deficits. Because these deficits presumably reflect the impact of a loss of TH on different aspects of brain development, this clinical research provides clues as to when and where TH exerts its actions in developing brain.Animal models of developmental TH insufficiency are beginning to provide mechanistic explanations for these observations in humans. The use of genetic models of TH insufficiency, of TH receptor deletion and mutation, and of cofactor deletion (14-17), are showing us how different brain regions may exhibit different sensitivity to TH during development. Moreover, these studies show that TH exerts different effects in different brain areas at different times during development. However, despite advances in our understanding of TH action, the specific developmental events affected by TH remain poorly understood. Several recent comprehensive reviews on TH actions in brain development have appeared (6,7,14). Thus, our go...

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Section: Maternal Hypothyroidismmentioning

confidence: 97%

Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental Findings

Zoeller

Rovet

2004

J Neuroendocrinology

536

369

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“…It is possible that the persistent elevation of maternal TPOaAbs, as detected in third-trimester specimens, is a proxy for subclinical hypothyroxinemia that was not identified or treated by the CPP clinicians despite their rigorous protocol. The association between subclinical hypothyroxinemia during pregnancy and impaired intellectual development in the offspring has been documented (23). Nonetheless, evidence is accumulating that even in euthyroid women, TPOaAbs compromise fetal development (24).…”

Section: Articlesmentioning

confidence: 99%

Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore Collaborative Perinatal Project

et al. 2012

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Background: Maternal thyroid autoantibodies during pregnancy have been implicated in neurodevelopmental delays, including early childhood cognitive deficits. We evaluated whether maternal autoantibodies to thyroid peroxidase (TPOaabs) during late pregnancy were associated with childhood intelligence quotient (IQ) scores in their offspring and how the children's TPOaab-associated sensorineural hearing loss (hL) might affect the result. Methods: We evaluated banked third-trimester sera corresponding to 1,733 children for whom childhood cognitive test scores and audiology data were available. The mothers and their children participated in the National Institutes of health (NIh)-sponsored collaborative Perinatal Project (cPP) that ran from 1959 to 1974. results: a modest, statistically significant, effect of TPOaabs on cognitive performance observed at 4 y of age lessened in both magnitude and P value by the age of 7 y. children with sensorineural hL (sNhL) had lower IQ scores at both ages. conclusion: Our data suggest that the reported effect of maternal TPOaabs on IQ may involve early developmental delays or transient effects rather than permanent deficits. Reports associating TPOaabs directly with IQ may reflect a portion with unexamined TPOaab-associated sNhL. Whether the TPOaab-associated sNhL is in the neurodevelopmental pathway of later cognitive delays or is independently associated with IQ requires investigation in other studies.

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“…Intellectual impairment occurs in humans when a congenitally hypothyroid infant develops in the context of low circulating TH levels, or when both the maternal and fetal supply of these hormones has been inadequate during pregnancy (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Although more rare than hypothyroidism, hyperthyroidism during infancy can also lead to significant structural and intellectual deficits.…”

Section: Th Effects On Cerebellar Functionmentioning

confidence: 99%

Thyroid hormone and cerebellar development

Anderson

2008

Cerebellum

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Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

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Maternal Hypothyroidism and Child Development

Cited by 31 publications

References 11 publications

Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental Findings

Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental Findings

Childhood IQ, hearing loss, and maternal thyroid autoimmunity in the Baltimore Collaborative Perinatal Project

Thyroid hormone and cerebellar development

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