THE EFFECT OF LEVOTHYROXINE TREATMENT ON MATERNAL AND PERINATAL OUTCOMES IN PREGNANT WOMEN WITH SUBCLINICAL HYPOTHYROIDISM: A 5-YEAR RETROSPECTIVE STUDY AT A TERTIARY CARE HOSPITAL IN TURKEY

Abstract

Subclinical hypothyroidism is characterized by elevated thyroid stimulating hormone (TSH) levels with normal free thyroxine (fT4) levels. The aim of this study was to compare obstetric and neonatal outcomes in pregnant women with and without treatment for subclinical hypothyroidism. In this study, maternal and perinatal outcomes were evaluated in a total of 270 pregnant women who were diagnosed with subclinical hypothyroidism as a result of screening performed in three trimesters of pregnancy between 2015 and 2020 and followed up in our clinic, 149 of whom received levothyroxine treatment and 121 of whom did not receive treatment. Further, different cutoff values for TSH were compared. The rates of neonatal intensive care unit (NICU) requirement were not different according to the levothyroxine use status of the patients (p=0.73, p>0.05). Miscarriage rates did not differ according to levothyroxine use (p=0,87, p>0,05). TSH, T4 and antithyroid peroxidase levels did not differ according to the maternal use of levothyroxine (p>0,05). Birth weight, gestational week at birth, 1- and 5-minute APGAR scores, neonatal TSH and T4 levels did not differ according to the maternal use of levothyroxine (p>0,05). Among the adverse maternal and perinatal outcomes, the need for NICU admission and the rates of placental abruption, fetal distress, preterm premature rupture of membranes, preeclampsia, preterm labor, and small for gestational age were not significantly different among the TSH cutoff groups (p>0,05). The rate of premature rupture of membranes was higher in the group with TSH levels ≥2.5 mIU/L (p=0.04). Choosing 2.5 mIU/L as the cutoff value for TSH levels allows early diagnosis of subclinical hypothyroidism with a higher rate in pregnant Turkish women and proactive therapeutic management. Our study provides limited evidence for the success of levothyroxine therapy for adverse obstetric and neonatal outcomes.

Keywords

• Adverse pregnancy-fetal outcomes
• Levothyroxine
• Pregnancy
• Screening
• Subclinical hypothyroidism
• Thyroid hormone replacement

Thanks

Financing has not been used. The authors declare that they have no conflict of interest. Patients signed informed consent for the publication of their data. All procedures comply with the ethical standards of the national research committee and the 1964 Declaration of Helsinki, its later amendments, or comparable ethical standards.

References

1. [1] Krassas, G. E., Poppe, K., and Glinoer, D. (2010). Thyroid function and human reproductive health. Endocrine reviews, 31(5), 702–755.
2. [2] Alexander, E. K., Pearce, E. N., Brent, G. A., Brown, R. S., Chen, H., Dosiou, C., Grobman, W. A., Laurberg, P., Lazarus, J. H., Mandel, S. J., Peeters, R. P., and Sullivan, S. (2017). 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid : official journal of the American Thyroid Association, 27(3), 315–389.
3. [3] Practice Bulletin No. 148: Thyroid disease in pregnancy. (2015). Obstetrics and gynecology, 125(4), 996–1005.
4. [4] Tiroid hastalıkları tanı ve tedavi kılavuzu. (2017). Türkiye Endokrinoloji ve Metabolizma Derneği. Türkiye Klinikleri Yayın Seri. ISBN: 978- 975-9118-66-2;157.
5. [5] De Groot, L., Abalovich, M., Alexander, E. K., Amino, N., Barbour, L., Cobin, R. H., Eastman, C. J., Lazarus, J. H., Luton, D., Mandel, S. J., Mestman, J., Rovet, J., and Sullivan, S. (2012). Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism, 97(8), 2543–2565.
6. [6] Lazarus, J., Brown, R. S., Daumerie, C., Hubalewska-Dydejczyk, A., Negro, R., and Vaidya, B. (2014). 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. European thyroid journal, 3(2), 76–94.
7. [7] Stagnaro-Green A. (2011). Overt hyperthyroidism and hypothyroidism during pregnancy. Clinical obstetrics and gynecology, 54(3), 478–487.
8. [8] Oglak, S. C., and Obut, M. (2021). Subclinical hypothyroidism of unexplained infertility patients does not affect intrauterine insemination success: A case-control study. Annals of Medical Research, 28(7), 1346–1350.

9. [9] Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., Woeber, K. A., and American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults (2012). Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 18(6), 988–1028.
10. [10] Rugge, J. B., Bougatsos, C., and Chou, R. (2015). Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Annals of internal medicine, 162(1), 35–45.
11. [11] Karcaaltincaba, D., Ozek, M. A., Ocal, N., Calis, P., Inan, M. A., and Bayram, M. (2020). Prevalences of subclinical and overt hypothyroidism with universal screening in early pregnancy. Archives of gynecology and obstetrics, 301(3), 681–686.
12. [12] ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. (2019). Obstetrics and gynecology, 133(1), 1.
13. [13] Ölmez, F., Oğlak, S. C., and Can, E. (2022). The Implication of Aquaporin-9 in the Pathogenesis of Preterm Premature Rupture of Membranes. Zeitschrift fur Geburtshilfe und Neonatologie, 226(4), 233–239.
14. [14] Oğlak, S. C., Yavuz, A., Olmez, F., Gedik Özköse, Z., and Süzen Çaypınar, S. (2022). The reduced serum concentrations of β-arrestin-1 and β-arrestin-2 in pregnancies complicated with gestational diabetes mellitus. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 35(25), 10017–10024.
15. [15] Oğlak, S. C., Ölmez, F., and Tunç, Ş. (2022). Evaluation of Antepartum Factors for Predicting the Risk of Emergency Cesarean Delivery in Pregnancies Complicated With Placenta Previa. The Ochsner journal, 22(2), 146–153.
16. [16] Casey, B. M., Thom, E. A., Peaceman, A. M., Varner, M. W., Sorokin, Y., Hirtz, D. G., Reddy, U. M., Wapner, R. J., Thorp, J. M., Jr, Saade, G., Tita, A. T., Rouse, D. J., Sibai, B., Iams, J. D., Mercer, B. M., Tolosa, J., Caritis, S. N., VanDorsten, J. P., and Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network (2017). Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. The New England journal of medicine, 376(9), 815–825.
17. [17] Hollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., and Braverman, L. E. (2002). Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). The Journal of clinical endocrinology and metabolism, 87(2), 489–499.
18. [18] Stagnaro-Green, A., Roman, S. H., Cobin, R. H., el-Harazy, E., Alvarez-Marfany, M., and Davies, T. F. (1990). Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA, 264(11), 1422–1425.
19. [19] Casey, B. M., Dashe, J. S., Wells, C. E., McIntire, D. D., Byrd, W., Leveno, K. J., and Cunningham, F. G. (2005). Subclinical hypothyroidism and pregnancy outcomes. Obstetrics and gynecology, 105(2), 239–245.
20. [20] Jaeschke, R., Guyatt, G., Gerstein, H., Patterson, C., Molloy, W., Cook, D., Harper, S., Griffith, L., and Carbotte, R. (1996). Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?. Journal of general internal medicine, 11(12), 744–749.
21. [21] Mooradian A. D. (2011). Subclinical hypothyroidism in the elderly: to treat or not to treat?. American journal of therapeutics, 18(6), 477–486.
22. [22] Mir, F., Chiti, H., and Mazloomzadeh, S. (2022). Short-Term Adverse Pregnancy Outcomes in Women with Subclinical Hypothyroidism: A Comparative Approach of Iranian and American Guidelines. Journal of thyroid research, 2022, 9315250.
23. [23] Simten, G. E., and Cingillioğlu, B. (2022). Effects of subclinical hypothyroidism on maternal and obstetric outcomes during pregnancy. The European Research Journal, 8, 247–255.
24. [24] Luo, J., and Yuan, J. (2022). Effects of Levothyroxine Therapy on Pregnancy and Neonatal Outcomes in Subclinical Hypothyroidism. International journal of general medicine, 15, 6811–6820.
25. [25] Dash, S. C., Sahoo, N., Rout, U., Mishra, S. P., Swain, J., and Mazumder, A. G. (2022). Outcomes With Levothyroxine Treatment in Early Pregnancy With Subclinical Hypothyroidism. Cureus, 14(5), e24984.
26. [26] Geng, X., Chen, Y., Wang, W., Ma, J., Wu, W., Li, N., and Sun, C. (2022). Systematic review and meta-analysis of the efficacy and pregnancy outcomes of levothyroxine sodium tablet administration in pregnant women complicated with hypothyroidism. Annals of palliative medicine, 11(4), 1441–1452.
27. [27] Yamamoto, J. M., Benham, J. L., Nerenberg, K. A., and Donovan, L. E. (2018). 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, 8(9), e022837.
28. [28] Jiao, X. F., Zhang, M., Chen, J., Wei, Q., Zeng, L., and Liu, D. (2022). The impact of levothyroxine therapy on the pregnancy, neonatal and childhood outcomes of subclinical hypothyroidism during pregnancy: An updated systematic review, meta-analysis and trial sequential analysis. Frontiers in endocrinology, 13, 964084.
29. [29] Qian, X., Sun, Y., and Xu, X. (2022). Effect of Levothyroxine Sodium Tablets on Pregnancy Outcome and Offspring Development Quotient of SCH during Pregnancy. Journal of healthcare engineering, 2022, 9001881.