بررسی تأثیر درمان با لووتیروکسین در مادران مبتلا به اختلالات تیروئیدی بر تکامل روان‌شناختی کودکان، مرور سیستماتیک

نوع مقاله : مروری

نویسندگان

1 استادیار گروه مامایی، دانشکده پزشکی، دانشگاه آزاد اسلامی، واحد ورامین- پیشوا، تهران، ایران. مرکز تحقیقات اندوکرینولوژی تولید مثل، پژوهشکده غدد درون‌ریز، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

2 استاد گروه اندوکرینولوژی تولید مثل، مرکز تحقیقات اندوکرینولوژی تولید مثل، پژوهشکده غدد درون‌ریز، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

3 استاد گروه اندوکرینولوژی، مرکز تحقیقات اندوکرینولوژی، پژوهشکده علوم غدد درون‌ریز، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

چکیده

مقدمه: مطالعات متعددی ارتباط بین اختلالات تیروئید مادران در دوران بارداری و اختلالات عصبی در کودکان را مورد بررسی قرار داده‌اند و نقش قابل توجه هورمون‌های تیروئیدی مادر در تمام مراحل رشد سلول‌های مغزی کودکان غیرقابل انکار می‌باشد. علی‌رغم مطالعات انجام شده، هنوز در مورد اینکه آیا درمان با لووتیروکسین در نارسایی هورمون تیروئید مادر باعث بهبود نتایج تکامل عصبی در کودکان می‌شود، اطمینان کافی وجود ندارد.مطالعه مرور سیستماتیک حاضر با هدف بررسی اثر درمان با لووتیروکسین در زنان باردار مبتلا به اختلالات تیروئیدی بر تکامل عصبی کودکان انجام شد.
روش‌کار: در این مطالعه مرور سیستماتیک، پایگاه‌های PubMed، Web of Science، Wiley،Google Scholar، Science direct و Scopus databases از سال 2019-1950 برای یافتن مقالات مرتبط انگلیسی با کلمات ‌کلیدی مناسب مورد جستجو قرار گرفتند. در این بررسی از انواع مطالعات از قبیل کارآزمایی بالینی تصادفی شده، کوهورت، مورد شاهدی و گزارش موردی استفاده گردید. از بین 343 مقاله مرتبط در جستجوی اولیه، در نهایت 9 مطالعه واجد شرایط مورد ارزیابی قرار گرفتند.
یافته‌ها: از 9 مطالعه انجام شده در این زمینه، 7 مطالعه نشان دادند که تجویز لووتیروکسین به مادران مبتلا به اختلالات تیروئیدی، هیچ تأثیر معنی‌داری بر عملکرد شناختی کودکان و یا سایر شاخص‌های توسعه عصبی ندارد و تنها در یک مطالعه گزارش موردی و یک مطالعه با 13 نمونه مورد بررسی، درمان منجر به بهبود تکامل هوشی عصبی کودکان شده بود.
نتیجه‌گیری: درمان با لووتیروکسین در زنان باردار مبتلا به اختلالات تیروئید، تأثیری بر بهبود تکامل عصبی کودکان ندارد.

کلیدواژه‌ها

عنوان مقاله [English]

The effects of levothyroxine treatment in mothers with thyroid dysfunction on children's neurocognitive development: systematic review

نویسندگان [English]

  • Sima Nazarpour 1
  • Fahimeh Ramezani Tehrani 2
  • Fereidoun Azizi 3
1 Assistant Professor, Department of Midwifery, Faculty of Medicine, Islamic Azad University, Varamin-Pishva Branch, Tehran, Iran. Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Professor, Department of Reproductive Endocrinology, Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 Professor, Department of Endocrinology, Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
چکیده [English]

Introduction: Several studies have evaluated the association between maternal thyroid dysfunction during pregnancy and neurocognitive development in children. The important role of maternal thyroid hormones in all stages of the brain development in children is undeniable. Despite performed studies, there is still insufficient evidence on the beneficiary effect of the levothyroxine treatment in pregnant women with thyroid dysfunctions in terms of neurodevelopmental outcomes of children. This systematic review was performed with aim to evaluate the effects of treatment with levothyroxine in pregnant women with thyroid dysfunctions on neurocognitive development in children.
Methods: In this systematic review, databases of PubMed, Web of Science, Wiley, Google Scholar, Science Direct and Scopus were searched with appropriate keywords for the English related article from 1950 to 2019. This study used randomized clinical trials, cohort, case-control studies and case report. Among 343 related articles in initial search, 9 eligible studies were finally evaluated.
Results: From 9 studies in this field, seven studies showed that administration of levothyroxine in mothers with thyroid dysfunctions had no significant effect on children's cognitive function or other neurodevelopment indicators; only a case report and a study on 13 samples showed that treatment improved the children neurocognetive indicators.
Conclusions: Treatment with levothyroxine in pregnant women with thyroid dysfunctions has no significant effect on neurodevelopment of children.

کلیدواژه‌ها [English]

  • Hypothyroidism
  • Levothyroxine
  • Neurodevelopment
  • Offspring
  • Pregnancy
  • Thyroid dysfunction

مراجع

  1. Borhani HM, Pasand MH, Alipour F. The role of thyroid hormones in the central nervous system. Neurosc J Shefaye Khatam 2017; 5(4):87-97. (Persian).
  2. Bianco AC. Metabolic effects of thyroid hormones-beyond traditional prospects. Thyroid 2008; 18(2):99-100.
  3. Ahmed OM, El-Gareib A, El-Bakry A, El-Tawab SA, Ahmed R. Thyroid hormones states and brain development interactions. Int J Dev Neurosci 2008; 26(2):147-209.
  4. Morreale de Escobar G, Obregón MJ, Escobar del Rey F. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 2000; 85(11):3975-87.
  5. Vulsma T, Gons MH, de Vijlder JJ. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N Engl J Med 1989; 321(1):13-6.
  6. Krassas G, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010; 31(5):702-55.
  7. Sajedi F, Vameghi MP, Gorgani SH, Pour SS. Motor developmental delay in 7500 Iranian infants: prevalence and risk factors. Iran J Child Neurol 2009; 3(3):43-50.
  8. Nazarpour S, Ramezani Tehrani F, Simbar M, Tohidi M, Minooee S, Rahmati M, et al. Effects of levothyroxine on pregnant women with subclinical hypothyroidism, negative for thyroid peroxidase antibodies. J Clin Endocrinol Metab 2017; 103(3):926-35.
  9. Nazarpour S, Tehrani FR, Simbar M, Tohidi M, Majd HA, Azizi F. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. Eur J Endocrinol 2017; 176(2):253-65.
  10. Man EB, Brown J, Serunian S. Maternal hypothyroxinemia: psychoneurological deficits of progeny. Ann Clin Lab Sci 1991; 21(4):227-39.
  11. Man EB, Jones WS, Holden RH, Mellits ED. Thyroid function in human pregnancy: VIII. Retardation of progeny aged 7 years; relationships to maternal age and maternal thyroid function. Am J Obstet Gynecol 1971; 111(7):905-16.
  12. Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2007; 92(8 Suppl):S1-7.
  13. El Baba KA, Azar ST. Thyroid dysfunction in pregnancy. Int J Gen Med 2012; 5:227-30.
  14. Glinoer D, Riahi M, Grün J, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab 1994; 79(1):197-204.
  15. Glinoer D, Soto MF, Bourdoux P, Lejeune B, Delange F, Lemone M, et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab 1991; 73(2):421-7.
  16. Haddow JE, Garbe PL, Miller DT. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341(26):2016-7.
  17. Li Y, Shan Z, Teng W, Yu X, Li Y, Fan C, et al. Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25-30 months. Clin Endocrinol 2010; 72(6):825-9.
  18. Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, et al. Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol 1999; 50(2):149-55.
  19. Smit B, Kok J, Vulsma T, Briet J, Boer K, Wiersinga W. Neurologic development of the newborn and young child in relation to maternal thyroid function. Acta Paediatr 2000; 89(3):291-5.
  20. Williams F, Watson J, Ogston S, Hume R, Willatts P, Visser T, et al. Mild maternal thyroid dysfunction at delivery of infants born≤ 34 weeks and neurodevelopmental outcome at 5.5 years. J Clin Endocrinol Metab 2012; 97(6):1977-85.
  21. Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, et al. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med 2017; 376(9):815-25.
  22. Hershman JM. Levothyroxine therapy of subclinical hypothyroidism or hypothyroxinemia in pregnancy does not improve cognitive function in the offspring. Clin Thyroidol 2017; 29(4):132-5.
  23. Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012; 366(6):493-501.
  24. Pop VJ, de Vries E, van Baar AL, Waelkens J, De Rooy H, Horsten M, et al. Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development? J Clin Endocrinol Metab 1995; 80(12):3561-6.
  25. Ghassabian A, Bongers-Schokking JJ, De Rijke YB, Van Mil N, Jaddoe VW, de Muinck Keizer-Schrama SM, et al. Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children: the Generation R Study. Thyroid 2012; 22(2):178-86.
  26. Williams FL, Watson J, Ogston SA, Visser TJ, Hume R, Willatts P. Maternal and umbilical cord levels of T4, FT4, TSH, TPOAb, and TgAb in term infants and neurodevelopmental outcome at 5.5 years. J Clin Endocrinol Metab 2013; 98(2):829-38.
  27. Bath SC, Rayman MP. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012; 366(17):1640-1.
  28. Hales C, Taylor PN, Channon S, Paradice R, McEwan K, Zhang L, et al. Controlled antenatal thyroid screening II: effect of treating maternal sub-optimal thyroid function on child cognition. J Clin Endocrinol Metab 2018; 103(4):1583-91.
  29. Negro R, Stagnaro-Green A. Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ 2014; 349:g4929.
  30. Maraka S, Mwangi R, McCoy RG, Yao X, Sangaralingham LR, Singh Ospina NM, et al. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. BMJ 2017; 356:i6865.
  31. Maraka S, Singh Ospina NM, O'Keeffe DT, Rodriguez-Gutierrez R, Espinosa De Ycaza AE, Wi CI, et al. Effects of levothyroxine therapy on pregnancy outcomes in women with subclinical hypothyroidism. Thyroid 2016; 26(7):980-6.
  32. Korevaar TI, Muetzel R, Medici M, Chaker L, Jaddoe VW, de Rijke YB, et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol 2016; 4(1):35-43.
  33. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27(3):315-89.
  34. Medici M, Korevaar TI, Schalekamp-Timmermans S, Gaillard R, de Rijke YB, Visser WE, et al. Maternal early-pregnancy thyroid function is associated with subsequent hypertensive disorders of pregnancy: the generation R study. J Clin Endocrinol Metab 2014; 99(12):E2591-8.
  35. León G, Murcia M, Rebagliato M, Álvarez‐Pedrerol M, Castilla AM, Basterrechea M, et al. Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infanciay Medio Ambiente Cohort, Spain. Paediatr Perinat Epidemiol 2015; 29(2):113-22.
  36. Yamamoto JM, Benham JL, Nerenberg KA, Donovan LE. Impact of levothyroxine therapy on obstetric, neonatal and childhood outcomes in women with subclinical hypothyroidism diagnosed in pregnancy: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 2018; 8(9):e022837.
  37. Giacalone M, Zirilli A, Moleti M, Alibrandi A. Does the iodized salt therapy of pregnant mothers increase the children IQ? Empirical evidence of a statistical study based on permutation tests. Qual Quant 2018; 52(3):1423-35.
  38. Hales C, Taylor PN, Channon S, Paradice R, McEwan K, Zhang L, et al. Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function on child cognition. J Clin Endocrinol Metab 2018; 103(4):1583-91.
  39. Moleti M, Trimarchi F, Tortorella G, Candia Longo A, Giorgianni G, Sturniolo G, et al. Effects of maternal iodine nutrition and thyroid status on cognitive development in offspring: a pilot study. Thyroid 2016; 26(2):296-305.
  40. Downing S, Halpern L, Carswell J, Brown RS. Severe maternal hypothyroidism corrected prior to the third trimester is associated with normal cognitive outcome in the offspring. Thyroid 2012; 22(6):625-30.
  41. Kasatkina EP, Samsonova LN, Ivakhnenko VN, Ibragimova GV, Ryabykh AV, Naumenko LL, et al. Gestational hypothyroxinemia and cognitive function in offspring. Neurosc Behav Physiol 2006; 36(6):619-24.
  42. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25(9):603-5.
  43. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med 2010; 8(1):18.
  44. Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med 2018; 23(2):60-3.
  45. Dieb A, Salam R, Shaheen D, Shaeer E. Evaluation of foetal neurological behaviour in hypothyroid pregnant females–a pilot study. J Matern Fetal Neonat Med 2018; 32(16):2617-21.
  46. Ganaie MA, Charoo BA, Sofi RA, Ahmed A, Bhat JI. Maternal overt hypothyroidism and neurobehavioral outcome of neonates: a cohort study from an iodine-deficient area of Northern India. Indian Pediatr 2015; 52(10):864-6.
  47. Mitchell ML, Klein RZ. The sequelae of untreated maternal hypothyroidism. Eur J Endocrinol 2004; 151(Suppl 3):U45-8.
  48. Yuanbin L, Teng W, Shan Z, Zhang L, Zhao Y, Xiaohui Y, et al. Effect of maternal subclinical thyroid abnormalities on offspring's intellectual development. Chin J Endocrinol Metab 2008; 24(6):601-4.
  49. Murphy NC, Diviney MM, Donnelly JC, Cooley SM, Kirkham CH, Foran AM, et al. The effect of maternal subclinical hypothyroidism on IQ in 7‐to 8‐year‐old children: a case–control review. Aust N Z J Obstet Gynaecol 2015; 55(5):459-63.
  50. Päkkilä F, Männistö T, Hartikainen AL, Ruokonen A, Surcel HM, Bloigu A, et al. Maternal and child's thyroid function and child's intellect and scholastic performance. Thyroid 2015; 25(12):1363-74.
  51. Su PY, Huang K, Hao JH, Xu YQ, Yan SQ, Li T, et al. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J Clin Endocrinol Metab 2011; 96(10):3234-41.
  52. Chen LM, Chen QS, Jin GX, Si GX, Zhang Q, Ye EL, et al. Effect of gestational subclinical hypothyroidism on early neurodevelopment of offspring. J Perinatol 2015; 35(9):678-82.
  53. Liu Y, Chen H, Jing C, Li F. The association between maternal subclinical hypothyroidism and growth, development, and childhood intelligence: a meta-analysis. J Clin Res Pediatr Endocrinol 2018; 10(2):153-61.
  54. Pop VJ, Brouwers EP, Vader HL, Vulsma T, Van Baar AL, De Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3‐year follow‐up study. Clin Endocrinol 2003; 59(3):282-8.
  55. Vermiglio F, Lo Presti V, Moleti M, Sidoti M, Tortorella G, Scaffidi G, et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab 2004; 89(12):6054-60.
  56. Kooistra L, Crawford S, van Baar AL, Brouwers EP, Pop VJ. Neonatal effects of maternal hypothyroxinemia during early pregnancy. Pediatrics 2006; 117(1):161-7.
  57. Henrichs J, Bongers-Schokking JJ, Schenk JJ, Ghassabian A, Schmidt HG, Visser TJ, et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab 2010; 95(9):4227-34.
  58. Noten AM, Loomans EM, Vrijkotte TG, van de Ven PM, van Trotsenburg AP, Rotteveel J, et al. Maternal hypothyroxinaemia in early pregnancy and school performance in 5-year-old offspring. Eur J Endocrinol 2015; 173(5):563-71.
  59. Thompson W, Russell G, Baragwanath G, Matthews J, Vaidya B, Thompson‐Coon J. Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: a systematic review and meta‐analysis. Clin Endocrinol 2018; 88(4):575-84.
  60. Henrichs J, Ghassabian A, Peeters RP, Tiemeier H. Maternal hypothyroxinemia and effects on cognitive functioning in childhood: how and why? Clin Endocrinol 2013; 79(2):152-62.
  61. Patel J, Landers K, Li H, Mortimer R, Richard K. Thyroid hormones and fetal neurological development. J Endocrinol 2011; 209(1):1-8.
  62. Gilbert ME, Rovet J, Chen Z, Koibuchi N. Developmental thyroid hormone disruption: prevalence, environmental contaminants and neurodevelopmental consequences. Neurotoxicology 2012; 33(4):842-52.
  63. de Escobar GM, Obregón MJ, del Rey FE. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab 2004; 18(2):225-48.
  64. Calvo RM, Jauniaux E, Gulbis B, Asunción M, Gervy C, Contempré B, et al. Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. J Clin Endocrinol Metab 2002; 87(4):1768-77.
  65. Bernal J, Guadaño-Ferraz A, Morte B. Perspectives in the study of thyroid hormone action on brain development and function. Thyroid 2003; 13(11):1005-12.
  66. Román GC, Ghassabian A, Bongers‐Schokking JJ, Jaddoe VW, Hofman A, De Rijke YB, et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol 2013; 74(5):733-42.
  67. Behrooz HG, Tohidi M, Mehrabi Y, Behrooz EG, Tehranidoost M, Azizi F. Subclinical hypothyroidism in pregnancy: intellectual development of offspring. Thyroid 2011; 21(10):1143-7.
  68. Craig WY, Allan WC, Kloza EM, Pulkkinen AJ, Waisbren S, Spratt DI, et al. Mid-gestational maternal free thyroxine concentration and offspring neurocognitive development at age two years. J Clin Endocrinol Metab 2012; 97(1):E22-8.
  69. Rovelli R, Vigone MC, Giovanettoni C, Passoni A, Maina L, Corrias A, et al. Newborn of mothers affected by autoimmune thyroiditis: the importance of thyroid function monitoring in the first months of life. Ital J Pediatr 2010; 36(1):24.
  70. Chen Y, Xue F. The impact of gestational hypothyroxinemia on the cognitive and motor development of offspring. J Matern Fetal Neonatal Med 2018; 22:1-6.

مجله زنان، مامایی و نازایی ایران
دوره 22، شماره 8
آبان 1398
صفحه 62-73

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