پیامد بارداری در زنان باردار مبتلا به کم کاری تیروئید (مقاله مروری)

نوع مقاله : مروری

نویسندگان

1 دانشجوی دکترای تخصصی بهداشت باروری، دانشکده پرستاری و مامایی، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

2 استاد گروه زنان و مامایی، مرکز تحقیقات اندوکرینولوژی تولید مثل، پژوهشکده غدد درون ریز، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.

3 دانشیار گروه مامایی و بهداشت باروری، دانشکده پرستاری و مامایی، دانشگاه علوم پزشکی شهید بهشتی تهران، تهران، ایران.

4 استاد گروه غدد و متابولیسم، پژوهشکده غدد درون ریز، دانشگاه علوم پزشکی شهید بهشتی تهران، تهران، ایران.

چکیده

مقدمه: کم کاری تیروئید، از شایع ترین اختلالات هورمونی دوران بارداری محسوب می شود و برآورد می شود که 3-2 درصد از زنان باردار به این عارضه مبتلا باشند. به علاوه 20-10 درصد از تمام زنان باردار یوتیروئید برای آنتی بادی های تیروئیدی مثبت هستند. برخی مطالعات نشان داده اند که این اختلالات خفیف تیروئید ممکن است در ارتباط با پیامد های بد مادری و جنینی باشد. مطالعه حاضر با هدف افزایش آگاهی و ارائه بررسی در مورد اثر نامطلوب کم کاری تیروئید بر نتایج بارداری انجام شد.
روش کار: این مرور نظام مند و آینده نگر با جستجو در پایگاه های Medline، EMBASE و کتابخانه Cochrane برای یافتن مقالات مرتبط انگلیسی با کلمات کلیدی مناسب انجام شد. در این بررسی از انواع مطالعات از قبیل کارآزمایی بالینی تصادفی شده، کوهورت (آینده نگر و گذشته نگر)، موردی شاهدی و گزارش موردی انجام شده در زمینه اختلالات تیروئیدی در بارداری و پیامد های بد آن ها استفاده شد. از بین 3480 مقالهبه دست آمده از جستجوهای الکترونیکی در شروع کار، 400 مقاله مرتبط وجود داشت که 130 مورد از مطالعات انجام شده در مورد کم کاری تیروئید آشکار، 203 مورد در کم کاری تحت بالینی تیروئید و 67 مورد در زمینه ایمنی تیروئید بود. از این مقالات، 47 مورد در جهت راستای اهداف مطالعه بودند که شامل 22 مورد در کم کاری تیروئید و 26 مورد در ایمنی تیروئید بودند.
یافته ها: کم کاری تیروئید آشکار دارای اثرات سوء متعدد بر نتایج بارداری است ولی در مورد اثرات کوتاه مدت و بلند مدت کم کاری تیروئید تحت بالینی و موارد آنتی بادی تیروئید مثبت، بحث وجود دارد. در مورد عوارض جنینی مادری در زنان باردار با عملکرد طبیعی تیروئید و آنتی بادی TPO مثبت نیز اختلاف نظر وجود دارد.
نتیجه‌گیری: اگرچه اثر بیماری های خود ایمنی تیروئید در بارداری به طور کلی پذیرفته شده است، اما اثرات کم کاری تیروئید تحت بالینی بدون افزایش آنتی بادی بر پیامدهای بارداری مورد بحث است. انجام مطالعات بیشتر برای شناسایی نتایج نامطلوب مادر و نوزاد در کم کاری تحت بالینی تیروئید مادر، ضروری به نظر می رسد.

کلیدواژه‌ها


عنوان مقاله [English]

Pregnancy outcomes in pregnant women with hypothyroidism (A review Article)

نویسندگان [English]

  • Sima Nazarpour 1
  • Fahimeh Ramezani Tehrani 2
  • Masoumeh Simbar 3
  • Freidoon Azizi 4
1 Ph.D student of Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2 Professor, Department of Obstetrics and Gynecology, Reproductive Endocrinology Research Center, Research Institute of Endocrinology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 Associate professor, Department of Reproductive and Midwifery, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Professor, Department of Endocrine and metabolism, Research Institute of Endocrinology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
چکیده [English]

Introduction: Hypothyroidism is considered as the most common thyroid disorder during pregnancy and about 2-3% of pregnant women suffer from this disorder. Furthermore, 10-20% of all pregnant women are positive for TPO antibodies and euthyroidism. Some studies have indicated that these slight thyroid dysfunctions could also be related to poor maternal and fetal outcomes. This study was performed with the aim to increase awareness and provide a review on adverse effect of hypothyroidism  on pregnancy outcomes.
Methods: In this review and prospective study, databases of Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. In this study, variety of studies including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports that were about thyroid dysfunctions and their adverse outcome in pregnancy were used.
Among 3480 articles foumd from the electronic searches in the beginning of the study, there were 400 related articles that 130 studies were related to overt hypothyroidism, 203 related to subclinical hypothyroidism and 67 related to thyroid safety. Of these articles, 47 cases were in line with the objectives of the study that included 22 studies about hypothyroidism and 26 about thyroid safety.
Results: Overt hypothyroidism has several adverse effects on pregnancy outcomes, but there is debate on short and long term effect of subclinical hypothyroidism, and thyroid antibody positivity. Also, there is no consensus on feto-maternal complication of pregnant women with normal function of thyroid and TPO antibody positive.
Conclusions: Although the impact of autoimmune thyroid disease on pregnancy outcomes is generally accepted, however the effect of subclinical hypothyroidism without increasing TPOAb on pregnancy outcomes is controversial. Further studies on maternal and neonatal outcomes in mother's subclinical thyroid dysfunction are needed.

کلیدواژه‌ها [English]

  • Anti-thyroid antibody
  • Hypothyroidism
  • pregnancy
  • TPO antibody
  1. Ramezani Tehrani F, Tohidi M, Rostami Dovom M, Azizi F. A Population Based Study on the Association of Thyroid Status with Components of the Metabolic Syndrome. Diabetes & Metabolism 2011; 2(156):2.
  2. Zadeh-Vakili A, Ramezani Tehrani F, Hashemi S, Amouzegar A, Azizi F. Relationship between Sex Hormone Binding Globulin, Thyroid Stimulating Hormone, Prolactin and Serum Androgens with Metabolic Syndrome Parameters in Iranian Women of Reproductive Age. Diabetes & Metabolism 2012; S 2:2.
  3. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum. Thyroid 2011; 21(10):1081-1125
  4. Rodien P, Coutant R, Vasseur C, Bourdelot A, Laboureau S, Rohmer V. Thyroid dysfunction and pregnancy. Rev Prat 2005; 55(2):174-9.
  5. Yamamoto T, Amino N, Tanizawa O, Ichihara K, Azukizawa M, Miyai K. Longitudinal study of serum thyroid hormones, chorionic gonadotrophin and thyrotrophin during and after normal pregnancy. Clin Endocrinol 1979;10(5):459-68.
  6. Glinoer D, D Nayer P, Bourdoux P, et al. Regulation of maternal thyroid function during pregnancy.J Clin Endocrinol Metab 1990; 71(2):276-87.
  7. Brent GA. Maternal thyroid function: interpretation of thyroid function tests in pregnancy.Clin Obstet Gynecol 1997; 40(1):3–15.
  8. Ramezani Tehrani F, Aghaee M, Asefzadeh S. The comparison of thyroid function tests in cord blood following cesarean section or vaginal delivery. International  Journal of Endocrinology and Metabolism 2003; 1(1):22-6.
  9. Cunningham F, Leveno KJ, Bloom SL, Hauth JC, Rouse Dj, Spong CY, et al. Williams Obstetrics. 23rd Edition. New York:McGrraw-Hill Companies; 2010.
  10. Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006; 91(7):2587-91.
  11. El Baba KA, Azar ST. Thyroid dysfunction in pregnancy. International journal of general medicine. 2012; 5:227-30.
  12. Lazarus JH. Thyroid function in pregnancy. British Medical Bulletin 2011; 97(1):137–48.
  13. Cignini p, Cafà EV, Giorlandino C, Capriglione S, Spata A, Dugo N. Thyroid physiology and common diseases in pregnancy: review of literature. Journal of Prenatal Medicine 2012; 6(4):64-71.             
  14. Casey BM, Leveno KJ. Thyroid disease in pregnancy. Obstet Gynecol. 2006; 108(5):1283–92.
  15. Negro R, Mestman JH. Thyroid disease in pregnancy. Best practice & research. Clinical endocrinology & metabolism 2011; 25(6):927-43.
  16. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005; 105(2):239–45.
  17. Vanderpump MPJ. The epidemiology of thyroid disease. British Medical Bulletin 2011; 99:39–51.
  18. Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol 2012; 119(2 Pt 1):315-20.
  19. Sahu MT, Das V, Mittal S, Agarwal A, Sahu M. Overt and subclinical thyroid dysfunction among Indian pregnant women and its effect on maternal and fetal outcome.  Archives of Gynecology andObstetrics 2010; 281(2):215–20.
  20. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol 2008; 112(1):85-92.
  21. Banerjee S. Thyroid Disorders in Pregnancy. Supplement to JAPI. January 2011; 59(Suppl):32-34.
  22. Vissenberg R, Goddijn M, Mol BW, van der Post JA, Fliers E, Bisschop PH.Thyroid dysfunction in pregnant women: clinical dilemmas. Ned Tijdschr Geneeskd 2012; 56(49):A5163.
  23. Abalovich  M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and Subclinical Hypothyroidism Complicating Pregnancy. Thyroid 2002 January;12(1):63-8.
  24. Idris I, Srinivasan R, Simm A, Page RC.  Maternal hypothyroidism in early and late gestation: effects on neonatal and obstetric outcome. Clin Endocrinol 2005; 63(5):560–5.
  25. Wolfberg AJ, Lee-Parritz A, Peller AJ, Lieberman ES. Obstetric and neonatal outcomes associated with maternal hypothyroid disease. J Matern Fetal Neonatal Med 2005;17(1):35-8.
  26. Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341(8):549–55.
  27. Glinoer D, Soto MF, Bourdoux P, Lejeune B, Delange F, Lemone M, Kinthaert J, Robijn C, Grun JP, de Nayer P. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab 1991; 73(2):421-7.
  28. Glinoer D, Riahi M, Grün JP, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab 1994; 79(1):197-204.
  29. Männistö T, Mendola P, Grewal J, Xie Y, Chen Z, Laughon SK. Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort. J Clin Endocrinol Metab 2013; 98(7):2725-33.
  30. Stagnaro-Green A, Chen X, Bogden JD, Davies TF, Scholl TO. The thyroid and pregnancy: a novel risk factor for very preterm delivery. Thyroid 2005; 15(4):351-7.
  31. Benhadi N, Wiersinga WM, Reitsma JB et al. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol 2009;160(6):985–91.
  32. Karakosta P, Alegakis D, Georgiou V, Roumeliotaki T, Fthenou E, Vassilaki M, et al. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab 2012; 97(12):4464-72.
  33. Stagnaro-Green A. Thyroid antibodies and miscarriage: where are we at a generation later?. Journal of Thyroid Research 2011.
  34. Negro R, Formoso G, Coppola L, Presicce G, Mangieri T, Pezzarossa A, et al. Euthyroid women with autoimmune disease undergoing assisted reproduction technologies: the role of autoimmunity and thyroid function. J Endocrinol Invest 2007; 30(1):3-8.
  35. 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.
  36. 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.
  37. 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.
  38. 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; 72:825–9.
  39. Ghorbani Behrooz H, Tohidi M, Mehrabi Y, Ghorbani Behrooz E, Tehranidoost M, Azizi F. Subclinical Hypothyroidism in Pregnancy: Intellectual Development of Offspring. Thyroid 2012; 21(10):1143-7.
  40. Liu H, Momotani N, Noh JY, Ishikawa N, Takebe K, Ito K. Maternal hypothyroidism during early pregnancy and intellectual development of the progeny. Arch Intern Med 1994; 154(7):785-92.
  41. Chevrier J, Harley KG, Kogut K, Holland N, Johnson C, Eskenazi B. Maternal Thyroid Function during the Second Half of Pregnancy and Child Neurodevelopment at 6, 12, 24, and 60Months of Age. Journal of Thyroid Research 2011.
  42. Downing S, Halpern L , Carswell J , Brown RS. Neuropsychological Development in Children of Mothers with Hypothyroidism Is Normal When Euthyroidism Is Achieved after Conception. Clinical thyroidology 2012; 24(7):1-4.
  43. Momotani N, Iwama S, Momotani K. Neurodevelopment in children born to hypothyroid mothers restored to normal thyroxine (T4) concentration by late pregnancy in Japan: no apparent influence of maternal T4 deficiency. J Clin Endocrinol Metab 2012; 97(4):1104-8.
  44. Van den Boogaard  E, Vissenberg R, Land JA, van Wely M, Van der Post JA, Goddijn M. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Human Reproduction Update 2011;17(5):605–19.
  45. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011; 21(10):1081–1125.
  46. Kahric-Janicic N, Soldin SJ, Soldin OP, West T, Gu J, Jonklaas J. Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy. Thyroid 2007;17(4):303-11.
  47. Bagis T, Gokcel A, Saygili ES. Autoimmune thyroid disease in pregnancy and the postpartum period: relationship to spontaneous abortion. Thyroid 2001;11(11):1049–53.
  48. Dendrinos S, Papasteriades C, Tarassi K, Christodoulakos G, Prasinos G, Creatsas G. Thyroid autoimmunity in patients with recurrent spontaneous miscarriages. Gynecol Endocrinol 2000; 14(4):270–74.
  49. NambiarV, Jagtap VS, Sarathi V, Lila A R, Kamalanathan S, Bandgar TR, et al. Prevalence and Impact of Thyroid Disorders on Maternal Outcome in Asian-Indian PregnantWomen. Journal of Thyroid Research 2011; 2011.
  50. Kutteh WH, Yetman DL, Carr AC, Beck LA, Scott RT Jr.  Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction. Fertil Steril 1999; 71(5):843-8.
  51. Bussen S, Steck T. Thyroid autoantibodies in euthyroid non-pregnant women with recurrent spontaneous abortions. Hum Reprod 1995; 10(11):2938-40.
  52. Pratt D, Novotny M, Kaberlein G, Dudkiewicz A, Gleicher N. Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.  American Journal of Obstetrics and Gynecology 1993; 168(3):837–84.
  53. Ashoor G, Maiz N, Rotas M, Jawdat F, Nicolaides KH. Maternal thyroid function at 11-13 weeks of gestation and spontaneous preterm delivery. Obstet Gynecol 2011; 117(2 Pt 1):293-98.
  54. Muller AF, Verhoeff A, Mantel MJ, Berghout A. Thyroid autoimmunity and abortion: a prospective study in women undergoing in vitro fertilization. Fertility and Sterility 1999; 71(1):30-4.
  55. Ghassabian A, Tiemeier H. Is measurement of maternal serum TSH sufficient screening in early pregnancy?. A case for more randomized trials.Clin Endocrinol (Oxf) 2012; 77(6):802-5.
  56. Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990; 264(11):1422-25.
  57. Singh A, Dantas ZN, Stone SC,  Asch RH. Presence of thyroid antibodies in early reproductive failure: biochemical versus clinical pregnancies. Fertility and Sterility 1995; 63(2):277-81.
  58. Iijima T, Tada H, Hidaka Y, Mitsuda N, Murata Y, Amino N. Effects of autoantibodies on the course of pregnancy and fetal growth. Obstetrics and Gynecology 1997; 90(3):364–69.
  59. Poppe K, Glinoer D, Tournaye H, Devroey P, van Steirteghem A, Kaufman L , et al. Assisted reproduction and thyroid autoimmunity: an unfortunate combination. J Clin Endocrinol Metab 2003; 88(9):4149-52.
  60. Marai I, Carp H, Shai S, Shabo R, Fishman G, Shoenfeld Y. Autoantibody panel screening in recurrent miscarriages. American Journal of Reproductive Immunology 2004; 51(3):235–40.
  61. Ghafoor F, Mansoor M, Malik T, Malik MS, Khan AU, Edwards R, et al. Role of thyroid peroxidase antibodies in the outcome of pregnancy. J Coll Physicians Surg Pak 2006; 16(7):468-71.
  62. Iravani AT, Saeedi MM, Pakravesh J, Hamidi S, Abbasi M. Thyroid autoimmunity and recurrent spontaneous abortion in Iran: a case-control study. Endocrine Practice 2008; 14(4): 458–64.
  63. Männistö T, Vääräsmäki M, Pouta A, Hartikainen AL, Ruokonen A, Surcel HM. Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies: a prospective populationbased cohort study. Journal of Clinical Endocrinology and Metabolism 2009; 94(3):772-9
  64. Soltanghoraee H, Arefi  S, Mohammadzadeh A,   Taheri A, Zeraati H, Hashemi SB, Akhondi MM. Thyroid autoantibodies in euthyroid women with recurrent abortions and infertility. Iranian Journal of Reproductive Medicine 2010;8(4):153-6.
  65. Haddow JE, Cleary-Goldman J, McClain MR, Palomaki GE, Neveux LM, Lambert-Messerlian G, et al. Thyroperoxidase and thyroglobulin antibodies in early pregnancy and preterm delivery. Obstet Gynecol 2010; 116(1):58-62.
  66. Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes. J Clin Endocrinol Metab 2011; 96(6):E920-24.