Risk Factors of Gestational Isolated Hypothyroxinemia and Its Effect on Maternal and Infant Outcomes

doi:10.12280/gjfckx.20210678

Abstract

Abstract:

Gestational isolated hypothyroxinemia, also known as gestational hypothyroxinemia, refers to pregnant women with negative thyroid autoantibodies, normal thyroid stimulating hormone (TSH) level but lower free thyroxine (FT₄) level than the lower limit of specific reference range during pregnancy. At present, the etiology of gestational isolated hypothyroxinemia is unclear. Whether it will increase the risk of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), preterm birth and other adverse outcomes of pregnancy remains controversial. Whether gestational isolated hypothyroxinemia affects the intelligence and nervous system development of offspring is still controversial. Therefore, one of the methods to solve the dispute is to carry out a multicenter research and longer follow-up visit to pregnant women with gestational isolated hypothyroxinemia and their offspring.

Key words: Pregnancy, Thyroxine, Triiodothyronine, Pregnancy complications, Pregnancy outcome, Developmental disabilities, Root cause analysis

LI Bao-juan, LIU Hui-kun, DONG Wei. Risk Factors of Gestational Isolated Hypothyroxinemia and Its Effect on Maternal and Infant Outcomes[J]. Journal of International Obstetrics and Gynecology, 2022, 49(1): 71-76.

References 39

[1]	Wang Y, Wang Y, Dong J, et al. Developmental hypothyroxinaemia and hypothyroidism limit dendritic growth of cerebellar Purkinje cells in rat offspring: involvement of microtubule-associated protein 2 (MAP2) and stathmin[J]. Neuropathol Appl Neurobiol, 2014, 40(4):398-415. doi: 10.1111/nan.12074. doi: 10.1111/nan.12074
[2]	Yang X, Yu Y, Zhang C, et al. The Association Between Isolated Maternal Hypothyroxinemia in Early Pregnancy and Preterm Birth[J]. Thyroid, 2020, 30(12):1724-1731. doi: 10.1089/thy.2019.0818. doi: 10.1089/thy.2019.0818
[3]	《妊娠和产后甲状腺疾病诊治指南》编撰委员会, 中华医学会内分泌学分会, 中华医学会围产医学分会. 妊娠和产后甲状腺疾病诊治指南(第2版)[J]. 中华内分泌代谢杂志, 2019, 35(8):636-665. doi: 10.3760/cma.j.issn.1000-6699.2019.08.003. doi: 10.3760/cma.j.issn.1000-6699.2019.08.003
[4]	López-Muñoz E, Mateos-Sánchez L, Mejía-Terrazas GE, et al. Hypothyroidism and isolated hypothyroxinemia in pregnancy, from physiology to the clinic[J]. Taiwan J Obstet Gynecol, 2019, 58(6):757-763. doi: 10.1016/j.tjog.2019.09.005. doi: S1028-4559(19)30210-4 pmid: 31759523
[5]	Censi S, Watutantrige-Fernando S, Groccia G, et al. The Effects of Iodine Supplementation in Pregnancy on Iodine Status, Thyroglobulin Levels and Thyroid Function Parameters: Results from a Randomized Controlled Clinical Trial in a Mild-to-Moderate Iodine Deficiency Area[J]. Nutrients, 2019, 11(11):2639. doi: 10.3390/nu11112639. doi: 10.3390/nu11112639
[6]	Delshad H, Raeisi A, Abdollahi Z, et al. Iodine supplementation for pregnant women: a cross-sectional national interventional study[J]. J Endocrinol Invest, 2021, 44(10):2307-2314. doi: 10.1007/s40618-021-01538-z. doi: 10.1007/s40618-021-01538-z
[7]	Refaat B, Azzeh F. Factors Associated with Thyroid Disorders and Iodine Adequacy in Pregnant Saudi Women[J]. Biol Trace Elem Res, 2021, 199(5):1715-1728. doi: 10.1007/s12011-020-02301-w. doi: 10.1007/s12011-020-02301-w
[8]	Shi X, Han C, Li C, et al. Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China[J]. J Clin Endocrinol Metab, 2015, 100(4):1630-1638. doi: 10.1210/jc.2014-3704. doi: 10.1210/jc.2014-3704
[9]	杨丽婉, 吴乃君, 陈笑嬉, 等. 妊娠早期孕妇尿碘水平与甲状腺功能的相关性研究[J]. 中国现代医学杂志, 2018, 28(3):83-86. doi: 10.3969/j.issn.1005-8982.2018.03.017. doi: 10.3969/j.issn.1005-8982.2018.03.017
[10]	Yu X, Shan Z, Li C, et al. Iron deficiency, an independent risk factor for isolated hypothyroxinemia in pregnant and nonpregnant women of childbearing age in China[J]. J Clin Endocrinol Metab, 2015, 100(4):1594-1601. doi: 10.1210/jc.2014-3887. doi: 10.1210/jc.2014-3887
[11]	Teng X, Shan Z, Li C, et al. Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China[J]. Thyroid, 2018, 28(8):968-975. doi: 10.1089/thy.2017.0491. doi: 10.1089/thy.2017.0491
[12]	Rosario PW, Oliveira LFF, Calsolari MR. Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study[J]. Arch Endocrinol Metab, 2018, 62(3):332-336. doi: 10.20945/2359-3997000000043. doi: 10.20945/2359-3997000000043
[13]	Zhao Y, Cao Z, Li H, et al. Air pollution exposure in association with maternal thyroid function during early pregnancy[J]. J Hazard Mater, 2019, 367:188-193. doi: 10.1016/j.jhazmat.2018.12.078. doi: S0304-3894(18)31226-3 pmid: 30594719
[14]	Ghassabian A, Pierotti L, Basterrechea M, et al. Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy[J]. JAMA Netw Open, 2019, 2(10):e1912902. doi: 10.1001/jamanetworkopen.2019.12902. doi: 10.1001/jamanetworkopen.2019.12902
[15]	Pearce EN, Oken E, Gillman MW, et al. Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use[J]. Endocr Pract, 2008, 14(1):33-39. doi: 10.4158/EP.14.1.33. doi: 10.4158/EP.14.1.33
[16]	Torres-Sánchez L, Gamboa R, Bassol-Mayagoitia S, et al. Para-occupational exposure to pesticides, PON1 polymorphisms and hypothyroxinemia during the first half of pregnancy in women living in a Mexican floricultural area[J]. Environ Health, 2019, 18(1):33. doi: 10.1186/s12940-019-0470-x. doi: 10.1186/s12940-019-0470-x
[17]	Han C, Li C, Mao J, et al. High Body Mass Index Is an Indicator of Maternal Hypothyroidism, Hypothyroxinemia, and Thyroid-Peroxidase Antibody Positivity during Early Pregnancy[J]. Biomed Res Int, 2015, 2015:351831. doi: 10.1155/2015/351831. doi: 10.1155/2015/351831
[18]	黄玉霞, 曹颖, 曾连英, 等. 妊娠期低甲状腺素血症与肥胖和代谢的相关性研究[J]. 中外医疗, 2020, 39(18):190-192. doi: 10.16662/j.cnki.1674-0742.2020.18.190. doi: 10.16662/j.cnki.1674-0742.2020.18.190
[19]	Gong X, Liu A, Li Y, et al. The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China[J]. J Endocrinol Invest, 2019, 42(5):599-607. doi: 10.1007/s40618-018-0960-7. doi: 10.1007/s40618-018-0960-7 pmid: 30334197
[20]	Korevaar TI, Steegers EA, de Rijke YB, et al. Placental Angiogenic Factors Are Associated With Maternal Thyroid Function and Modify hCG-Mediated FT₄ Stimulation[J]. J Clin Endocrinol Metab, 2015, 100(10):E1328-E1334. doi: 10.1210/jc.2015-2553. doi: 10.1210/jc.2015-2553
[21]	Tang L, Li P, Zhou H, et al. A longitudinal study of thyroid markers during pregnancy and the risk of gestational diabetes mellitus and post-partum glucose metabolism[J]. Diabetes Metab Res Rev, 2021, 37(4):e3441. doi: 10.1002/dmrr.3441. doi: 10.1002/dmrr.3441
[22]	李春莉, 余浪, 李秋红. 妊娠早期单纯低甲状腺素血症与妊娠期糖尿病相关性分析[J]. 中华内分泌代谢杂志, 2017, 33(3):194-197. doi: 10.3760/cma.j.issn.1000-6699.2017.03.004. doi: 10.3760/cma.j.issn.1000-6699.2017.03.004
[23]	谢俊豪, 李文文, 金百翰, 等. 甲状腺素水平对妊娠糖尿病及妊娠结局的影响[J]. 解放军医学杂志, 2020, 45(4):423-429. doi: 10.11855/j.issn.0577-7402.2020.04.13. doi: 10.11855/j.issn.0577-7402.2020.04.13
[24]	Su X, Zhao Y, Cao Z, et al. Association between isolated hypothyroxinaemia in early pregnancy and perinatal outcomes[J]. Endocr Connect, 2019, 8(4):435-441. doi: 10.1530/EC-19-0088. doi: 10.1530/EC-19-0088
[25]	谢俊豪, 李文文, 金百翰, 等. 妊娠期低甲状腺素血症的临床意义[J]. 医学研究杂志, 2020, 49(2):48-53. doi: 10.11969/j.issn.1673-548X.2020.02.012. doi: 10.11969/j.issn.1673-548X.2020.02.012
[26]	Korevaar TIM, Derakhshan A, Taylor PN, et al. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis[J]. JAMA, 2019, 322(7):632-641. doi: 10.1001/jama.2019.10931. doi: 10.1001/jama.2019.10931 pmid: 31429897
[27]	Chen L, Yang H, Ye E, et al. Insignificant Effect of Isolated Hypothyroxinemia on Pregnancy Outcomes During the First and Second Trimester of Pregnancy[J]. Front Endocrinol (Lausanne), 2020, 11:528146. doi: 10.3389/fendo.2020.528146. doi: 10.3389/fendo.2020.528146
[28]	Li X, Zuo J, Li YH, et al. Association between thyroid function and risk of gestational diabetes mellitus in assisted pregnancies: A retrospective cohort study[J]. Diabetes Res Clin Pract, 2021, 171:108590. doi: 10.1016/j.diabres.2020.108590. doi: 10.1016/j.diabres.2020.108590
[29]	Oostenbroek M, Kersten R, Tros B, et al. Maternal hypothyroxinaemia in early pregnancy and problem behavior in 5-year-old offspring[J]. Psychoneuroendocrinology, 2017, 81:29-35. doi: 10.1016/j.psyneuen.2017.03.021. doi: S0306-4530(16)31027-7 pmid: 28411411
[30]	龚珣. 妊娠期母体低T4血症后代注意缺陷多动障碍的研究[D]. 沈阳:中国医科大学, 2019.
[31]	Korevaar TIM. Both High and Low Maternal Thyroid Function Are Associated with Child Autistic Spectrum Disorders, While Only Hypothyroxinemia Is Associated with Child ADHD[J]. Clinical Thyroidology, 2018, 30(5):220-222. doi: 10.1089/ct.2018;30.220-222;30.220-222. doi: 10.1089/ct.2018;30.220-222;30.220-222
[32]	Levie D, Korevaar T, Bath SC, et al. Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data[J]. J Clin Endocrinol Metab, 2019, 104(12):5957-5967. doi: 10.1210/jc.2018-02559. doi: 10.1210/jc.2018-02559
[33]	Opazo MC, González PA, Flores BD, et al. Gestational Hypothyroxinemia Imprints a Switch in the Capacity of Astrocytes and Microglial Cells of the Offspring to React in Inflammation[J]. Mol Neurobiol, 2018, 55(5):4373-4387. doi: 10.1007/s12035-017-0627-y. doi: 10.1007/s12035-017-0627-y
[34]	Kawahori K, Hashimoto K, Yuan X, 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. doi: 10.1089/thy.2017.0331 pmid: 29415629
[35]	Grau G, Aguayo A, Vela A, et al. Normal intellectual development in children born from women with hypothyroxinemia during their pregnancy[J]. J Trace Elem Med Biol, 2015, 31:18-24. doi: 10.1016/j.jtemb.2015.02.004. doi: 10.1016/j.jtemb.2015.02.004
[36]	Casey BM, Thom EA, Peaceman AM, et al. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy[J]. N Engl J Med, 2017, 376(9):815-825. doi: 10.1056/NEJMoa1606205. doi: 10.1056/NEJMoa1606205
[37]	Alexander EK, Pearce EN, Brent GA, 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. doi: 10.1089/thy.2016.0457 pmid: 28056690
[38]	Lazarus J, Brown RS, Daumerie C, et al. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children[J]. Eur Thyroid J, 2014, 3(2):76-94. doi: 10.1159/000362597. doi: 10.1159/000362597 pmid: 25114871
[39]	Cao XY, Liu J, Zhang YJ, et al. Exposure of adult mice to perfluorobutanesulfonate impacts ovarian functions through hypothyroxinemia leading to down-regulation of Akt-mTOR signaling[J]. Chemosphere, 2020, 244:125497. doi: 10.1016/j.chemosphere.2019.125497. doi: 10.1016/j.chemosphere.2019.125497