Recent Developments in Long-term Effects of Mild Hypothyroidism During Pregnancy on Offspring Intelligence

doi:10.12114/j.issn.1007-9572.2020.00.163

Abstract

Abstract: There are substantial available data showing impaired child intelligence resulting from overt maternal hypothyroidism during pregnancy.This review addresses the effect of mild maternal hypothyroidism on long-term development of intelligence of children.It is concluded that mild maternal hypothyroidism may affect children's mental development.However，the mechanisms that cause this change and how to eliminate these risk factors remain unclear and a large number of clinical and basic experiments are still required to provide evidence for treatment.

Key words: Pregnancy complications, Hypothyroidism, Duration of pregnancy, Hypothyroxemia, Offspring intelligence

摘要： 妊娠期母体患有明显的甲状腺功能减退时会对子代的远期智力造成不良影响。本文主要对妊娠期母体轻度甲状腺功能减退对子代远期智力的影响进行综述，得出母体轻度甲状腺功能减退可能影响子代的智力发育，但是对于引起这种变化的具体机制以及如何消除这类危险因素，目前还没有确切的方案，仍需大量临床试验和基础实验提供治疗依据。

关键词: 妊娠并发症, 甲状腺功能减退症, 妊娠期, 低甲状腺素血症, 子代智力

GAO Xue,LONG Yan,LIN Li. Recent Developments in Long-term Effects of Mild Hypothyroidism During Pregnancy on Offspring Intelligence　[J]. Chinese General Practice, 2020, 23(15): 1838-1842. DOI: 10.12114/j.issn.1007-9572.2020.00.163.
高雪,龙燕,蔺莉. 妊娠期轻度甲状腺功能减退对子代远期智力的影响研究进展[J]. 中国全科医学, 2020, 23(15): 1838-1842. DOI: 10.12114/j.issn.1007-9572.2020.00.163.

References

［1］HADDOW J E，PALOMAKI G E，ALLAN W C，et al．Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child［J］．N Engl J Med，1999，341（8）：549-555．DOI：10.1056/NEJM199908193410801.
［2］ALEXANDER E K，PEARCE E N，BRENT G A，et al．2017 guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum［J］．Thyroid，2017，27（3）：315-389．DOI：10.1089/thy.2016.0457.
［3］KRONENBERG H M，MELMED S，POLONSKY K S.威廉姆斯内分泌学［M］．向红丁，译.北京：人民军医出版社，2011.
［4］THORPE-BEESTON J G，NICOLAIDES K H，FELTON C V，et al．Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus［J］．N Engl J Med，1991，324（8）：532-536．DOI：10.1056/NEJM199102213240805.
［5］VULSMA T，GONS M H，DE VIJLDER J J.Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis［J］．N Engl J Med，1989，321（1）：13-16．DOI：10.1056/NEJM198907063210103.
［6］LANDERS K，RICHARD K.Traversing barriers—how thyroid hormones pass placental，blood-brain and blood-cerebrospinal fluid barriers［J］．Mol Cell Endocrinol，2017，458：22-28．DOI：10.1016/j.mce.2017.01.041.
［7］GOTHIé J D，DEMENEIX B，REMAUD S.Comparative approaches to understanding thyroid hormone regulation of neurogenesis［J］．Mol Cell Endocrinol，2017，459：104-115．DOI：10.1016/j.mce.2017.05.020.
［8］DE ESCOBAR G M，OBREGóN M J，DEL REY F E．Maternal thyroid hormones early in pregnancy and fetal brain development［J］．Best Pract Res Clin Endocrinol Metab，2004，18（2）：225-248．DOI：10.1016/j.beem.2004.03.012.
［9］WILLIAMS G R.Neurodevelopmental and neurophysiological actions of thyroid hormone［J］．J Neuroendocrinol，2008，20（6）：784-794．DOI：10.1111/j.1365-2826.2008.01733.x.
［10］MOOG N K，ENTRINGER S，HEIM C，et al．Influence of maternal thyroid hormones during gestation on fetal brain development［J］．Neuroscience，2017，342：68-100．DOI：10.1016/j.neuroscience.2015.09.070.
［11］ZHANG Y Y，FAN Y X，YU X H，et al．Maternal subclinical hypothyroidism impairs neurodevelopment in rat offspring by inhibiting the CREB signaling pathway［J］．Mol Neurobiol，2015，52（1）：432-441．DOI：10.1007/s12035-014-8855-x.
［12］LIU D J，TENG W P，SHAN Z Y，et al．The effect of maternal subclinical hypothyroidism during pregnancy on brain development in rat offspring［J］．Thyroid，2010，20（8）：909-915．DOI：10.1089/thy.2009.0036.
［13］LI Y B，SHAN Z Y，TENG W P，et al．Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months［J］．Clin Endocrinol（Oxf），2010，72（6）：825-829．DOI：10.1111/j.1365-2265.2009.03743.x.
［14］P?KKIL? F，M?NNIST? T，HARTIKAINEN A L，et al．Maternal and child's thyroid function and child's intellect and scholastic performance［J］．Thyroid，2015，25（12）：1363-1374．DOI：10.1089/thy.2015.0197.
［15］WANG S，TENG W，GAO Y，et al．Early levothyroxine treatment on maternal subclinical hypothyroidism improves spatial learning of offspring in rats［J］．J Neuroendocrinol，2012，24（5）：841-848．DOI：10.1111/j.1365-2826.2011.02275.x.
［16］CASEY B M，THOM E A.Subclinical hypothyroidism or hypothyroxinemia in pregnancy［J］．N Engl J Med，2017，377（7）：701．DOI：10.1056/NEJMc1707415.
［17］POP V J，BROUWERS E P，VADER H L，et al．Maternal hypothyroxinaemia during early pregnancy and subsequent child development：a 3-year follow-up study［J］．Clin Endocrinol（Oxf），2003，59（3）：282-288．DOI：10.1046/j.1365-2265.2003.01822.x.
［18］OOSTENBROEK M H W，KERSTEN R H J，TROS B，et al．Maternal hypothyroxinaemia in early pregnancy and problem behavior in 5-year-old offspring［J］．Psychoneuroendocrino，2017，81：29-35．DOI：10.1016/j.psyneuen.2017.03.021.
［19］WANG Y，WANG Y，DONG J，et al．Developmental hypothyroxinemia and hypothyroidism reduce proliferation of cerebellar granule neuron precursors in rat offspring by downregulation of the sonic hedgehog signaling pathway［J］．Mol Neurobiol，2014，49（3）：1143-1152．DOI：10.1007/s12035-013-8587-3.
［20］AUSó E，LAVADO-AUTRIC R，CUEVAS E，et al．A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration［J］．Endocrinology，2004，145（9）：4037-4047．DOI：10.1210/en.2004-0274.
［21］LAVADO-AUTRIC R，AUSó E，GARCíA-VELASCO J V，et al．
Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny［J］．J Clin Invest，2003，111（7）：1073-1082．DOI：10.1172/JCI16262.
［22］CISTERNAS P，LOUVEAU A，BUENO S M，et al．Gestational hypothyroxinemia affects glutamatergic synaptic protein distribution and neuronal plasticity through neuron-astrocyte interplay［J］．Mol Neurobiol，2016，53（10）：7158-7169．DOI：10.1007/s12035-015-9609-0.
［23］KAWAHORI K，HASHIMOTO K，YUAN X M，et al．Mild maternal hypothyroxinemia during pregnancy induces persistent DNA hypermethylation in the hippocampal brain-derived neurotrophic factor gene in mouse offspring［J］．Thyroid，2018，28（3）：395-406．DOI：10.1089/thy.2017.0331.
［24］HALES C，TAYLOR P N，CHANNON S，et al．Controlled antenatal thyroid screening Ⅱ：effect of treating maternal suboptimal thyroid function on child cognition［J］．J Clin Endocrinol Metab，2018，103（4）：1583-1591．DOI：10.1210/jc.2017-02378.
［25］HOLLOWELL J G，STAEHLING N W，FLANDERS W D，et al．Serum TSH，T4，and thyroid antibodies in the United States population（1988 to 1994）：national health and nutrition examination survey（NHANESⅢ）［J］．J Clin Endocrinol Metab，2002，87（2）：489-499．DOI：10.1210/jcem.87.2.8182.
［26］DE LEO S，PEARCE E N.Autoimmune thyroid disease during pregnancy［J］．Lancet Diabetes Endocrinol，2018，6（7）：575-586．DOI：10.1016/S2213-8587（17）30402-3.
［27］夏艳，周跃华，宗旦棣，等．妊娠期母体甲状腺自身免疫与亚临床甲减对子代智力与运动发育影响的研究［J］．临床和实验医学杂志，2015，14（8）：670-672．DOI：10.3969/j.issn.1671-4695.2015.08.022.
XIA Y，ZHOU Y H，ZONG D D，et al．Impact of mental development in offspring by maternal thyroid autoimmunity and subclinical hypothyroidism in pregnancy［J］．Journal of Clinical and Experimental Medicine，2015，14（8）：670-672．DOI：10.3969/j.issn.1671-4695.2015.08.022.
［28］SVENSSON J，LINDBERG B，ERICSSON U B，et al．Thyroid autoantibodies in cord blood sera from children and adolescents with autoimmune thyroiditis［J］．Thyroid，2006，16（1）：79-83．DOI：10.1089/thy.2006.16.79.

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