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2000
Volume 25, Issue 1
  • ISSN: 1871-529X
  • E-ISSN: 2212-4063

Abstract

Background

Gestational hypertension (GH) and preeclampsia (PE) are two important complications of pregnancy. Considering the U-shaped association between thyroid-stimulating hormone (TSH) and hypertensive disorders of pregnancy in some reports, we decided to investigate the effect of levothyroxine treatment on GH and PE in pregnant women with subclinical hypothyroidism (SCH) overt hypothyroidism (OH), and autoimmune thyroid diseases.

Methods

Google Scholar and databases, such as ProQuest, Medline, Cochrane Library, ScienceDirect, and Scopus were searched electronically for clinical trials and observational studies using the following search terms: ((“levothyroxine” OR “LT4” OR “thyroxine supplementation”) AND (“subclinical hypothyroidism” OR “SCH” OR “thyroid peroxidase antibodies” OR “autoimmune thyroid disease”) AND (“pregnancy outcomes” OR “preeclampsia” OR “gestational hypertension” OR “PIH”)). Further, we investigated the impact of levothyroxine on the incidence of GH and/or PE compared with control or placebo groups from April 4 to November 1, 2022.

Results

After treatment with levothyroxine, the odd ratios (ORs) of GH and PE in subclinical [OR = 1.03, 95% CI: (0.85, 1.25), I2 = 35.25%, =0.78, OR = 1.02, 95% CI: (0.66,1.58), I2 = 46.86%, =0.94, respectively] and overt hypothyroidism [OR=1.10, 95% CI: (0.70,1.71), I2=38.44%, =0.69, OR=1.32, 95% CI: (0.83, 2.09), I2=0.00%, =0.24, respectively] were not different from controls. Furthermore, this result was observed in studies that recruited women with SCH and OH [OR=1.12, 95% CI: (0.58, 2.14), I2=92.74%, =0.74, OR=0.51, 95% CI: (0.15, 1.72), I2=97.30%, =0.28, respectively]. Additionally, the odds ratios of GH and PE were statistically similar in women who were TPOAb-positive compared to those who were TPOAb-negative (OR=1.01,95% CI: (0.80, 1.28), (I2 =0.00%, =0.00). However, LT4 reduced the risk of GH in treated TPOAb+ women compared with untreated TPOAb+ (OR=0.43, 95% CI: (0.30, 0.62), I2=0.00%, =0.00).

Conclusion

Following LT4 therapy, the incidence rates of GH and PE in all forms of hypothyroidism showed no significant difference compared to the control group. However, the decrease in GH was noteworthy for TPOAb+ women using levothyroxine compared to those not using it.

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2025-09-04

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References

  1. KrassasG. KarrasS.N. PontikidesN. Thyroid diseases during pregnancy: A number of important issues.Hormones2015141596910.1007/BF03401381 25885104
     [Google Scholar]
  2. KorevaarT.I.M. PopV.J. ChakerL. GoddijnM. de RijkeY.B. BisschopP.H. BroerenM.A. JaddoeV.W.V. MediciM. VisserT.J. SteegersE.A.P. VrijkotteT.G. PeetersR.P. Dose dependency and a functional cutoff for TPO-antibody positivity during pregnancy.J. Clin. Endocrinol. Metab.2018103277878910.1210/jc.2017‑01560 29240902
     [Google Scholar]
  3. WangJ. GongX.H. PengT. WuJ.N. Association of thyroid function during pregnancy with the risk of pre-eclampsia and gestational diabetes mellitus.Endocrine Pract.202127881982510.1016/j.eprac.2021.03.014
     [Google Scholar]
  4. (a MardanianF. The association between serum TSH concentration whithin the normal range and nutritional status in euthyroid pregnant women at the first trimester of gestation.J. Res. Med. Sci.2021202126
     [Google Scholar]
  5. (b ChenX. WuC. WangZ. WuC. GuoY. ZhuX. HuY.P. ShiZ. SongQ. CuiX. SuJ. Iodine nutrition status and thyroid autoimmunity during pregnancy: a cross-sectional study of 4635 pregnant women.Nutrition journal.2022Jan 29; 21(1): 7.
     [Google Scholar]
  6. GhaderianS. RashidiH. EtessaminiaS. Levothyroxine dosage requirement during pregnancy.Drug Invent. Today2018106
     [Google Scholar]
  7. von DadelszenP. MageeL.A. Preventing deaths due to the hypertensive disorders of pregnancy.Best Pract. Res. Clin. Obstet. Gynaecol.2016368310210.1016/j.bpobgyn.2016.05.005 27531686
     [Google Scholar]
  8. DeviP.U. VanajaG. Maternal and perinatal outcome in antenatal women with hypothyroidism.Int. Arch. Integ. Med.2017412199207
     [Google Scholar]
  9. van den BoogaardE. VissenbergR. LandJ.A. van WelyM. van der PostJ.A.M. GoddijnM. BisschopP.H. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: A systematic review.Hum. Reprod. Update201117560561910.1093/humupd/dmr024 21622978
     [Google Scholar]
  10. TolozaF.J.K DerakhshanA. MännistöT. BliddalS. PopovaP.V. CartyD.M. ChenL. TaylorP. MossoL. OkenE. SuvantoE. ItohS. KishiR. BassolsJ. AuvinenJ. López-BermejoA. BrownS.J. BoucaiL. HisadaA. YoshinagaJ. ShilovaE. GrinevaE.N. VrijkotteT.G.M SunyerJ. Jiménez-ZabalaA. Riaño-GalanI. Lopez-EspinosaM.J. ProkopL.J. Singh OspinaN. BritoJ.P. Rodriguez-GutierrezR. AlexanderE.K. ChakerL. PearceE.N. PeetersR.P. Feldt-RasmussenU. GuxensM. ChatziL. DellesC. Roeters van LennepJ.E. PopV.J.M. LuX. WalshJ.P. NelsonS.M. KorevaarT.I.M. MarakaS. Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: A systematic review and individual-participant data meta-analysis.Lancet Diabetes Endocrinol202210424325210.1016/S2213‑8587(22)00007‑935255260
     [Google Scholar]
  11. LintulaA. Keski-NisulaL. SahlmanH. Hypothyroidism and the increased risk of preeclampsia – interpretative factors?Hypertens. Pregnancy202039441141710.1080/10641955.2020.1800030 32787605
     [Google Scholar]
  12. DingZ. LiuY. MarakaS. AbdelouahabN. HuangH.F. FraserW.D. FanJ. Pregnancy and neonatal outcomes with levothyroxine treatment in women with subclinical hypothyroidism based on new diagnostic criteria: A systematic review and meta-analysis.Front. Endocrinol.20211279742310.3389/fendo.2021.797423 34956101
     [Google Scholar]
  13. LiJ. ShenJ. QinL. Effects of levothyroxine on pregnancy outcomes in women with thyroid dysfunction: A meta-analysis of randomized controlled trials.Altern. Ther. Health Med.20172324958 28323629
     [Google Scholar]
  14. ShanZ. TengW. Thyroid hormone therapy of hypothyroidism in pregnancy.Endocrine2019661354210.1007/s12020‑019‑02044‑2 31617164
     [Google Scholar]
  15. MarakaS. Singh OspinaN.M. O’KeeffeD.T. Rodriguez-GutierrezR. Espinosa De YcazaA.E. WiC.I. JuhnY.J. CoddingtonC.C.III MontoriV.M. StanM.N. Effects of levothyroxine therapy on pregnancy outcomes in women with subclinical hypothyroidism.Thyroid201626798098610.1089/thy.2016.0014 27112035
     [Google Scholar]
  16. HanL. MaY. LiangZ. ChenD. Laboratory characteristics analysis of the efficacy of levothyroxine on subclinical hypothyroidism during pregnancy: A single-center retrospective study.Bioengineered20211214183419010.1080/21655979.2021.1955589 34288808
     [Google Scholar]
  17. CaseyB.M. ThomE.A. PeacemanA.M. VarnerM.W. SorokinY. HirtzD.G. ReddyU.M. WapnerR.J. ThorpJ.M.Jr SaadeG. TitaA.T.N. RouseD.J. SibaiB. IamsJ.D. MercerB.M. TolosaJ. CaritisS.N. VanDorstenJ.P. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy.N. Engl. J. Med.2017376981582510.1056/NEJMoa1606205 28249134
     [Google Scholar]
  18. MarakaS. MwangiR. McCoyR.G. YaoX. SangaralinghamL.R. Singh OspinaN.M. O’KeeffeD.T. De YcazaA.E.E. Rodriguez-GutierrezR. CoddingtonC.C.III StanM.N. BritoJ.P. MontoriV.M. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment.BMJ2017356i686510.1136/bmj.i6865 28122781
     [Google Scholar]
  19. ChenL.M. DuW.J. DaiJ. ZhangQ. SiG.X. YangH. YeE.L. ChenQ.S. YuL.C. ZhangC. LuX.M. Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: A single-center cohort study of a Chinese population.PLoS One2014910e10936410.1371/journal.pone.0109364 25353960
     [Google Scholar]
  20. JuR. LinL. LongY. ZhangJ. HuangJ. Clinical efficacy of therapeutic intervention for subclinical hypothyroidism during pregnancy.Genet. Mol. Res.20161544810.4238/gmr15049019 27886341
     [Google Scholar]
  21. YangJ. GuoH. DingS. TaoB. ZhangX. Effect of the treatment acceptance on the perinatal outcomes in women with subclinical hypothyroidism, positive thyroid gland peroxidase antibody in early pregnancy.Zhonghua Fu Chan Ke Za Zhi2015509652657 26675390
     [Google Scholar]
  22. LotfalizadehM. GhomianN. NezhadM. Prevalence and complications of hypothyroidism in pregnancy.Majallah-i Zanan, Mamai va Nazai-i Iran201720815
     [Google Scholar]
  23. MathuriyaG. PandayS. Levothyroxine replacement in subclinical hypothyroidism during pregnancy and its effect on fetomaternal outcome. Int. J. Clinic.Obstet. Gynaecol.20215417317710.33545/gynae.2021.v5.i4c.982
     [Google Scholar]
  24. ZhaoL. JiangG. TianX. ZhangX. ZhuT. ChenB. WangY. MaQ. Initiation timing effect of levothyroxine treatment on subclinical hypothyroidism in pregnancy.Gynecol. Endocrinol.2018341084584810.1080/09513590.2018.1451836 29560762
     [Google Scholar]
  25. AjmaniS.N. AggarwalD. BhatiaP. SharmaM. SarabhaiV. PaulM. Prevalence of overt and subclinical thyroid dysfunction among pregnant women and its effect on maternal and fetal outcome.J. Obstet. Gynaecol. India201464210511010.1007/s13224‑013‑0487‑y 24757337
     [Google Scholar]
  26. YeW. GuoY. ChenS. MaiH. FanL. Clinical observation of L-T4 treatment in subclinical hypothyroidism in pregnancy with autoantibody negative.Prog. Obstet. Gynecol.201928920922
     [Google Scholar]
  27. Cleary-GoldmanJ. MaloneF.D. Lambert-MesserlianG. SullivanL. CanickJ. PorterT.F. LuthyD. GrossS. BianchiD.W. D’AltonM.E. Maternal thyroid hypofunction and pregnancy outcome.Obstet. Gynecol.20081121859210.1097/AOG.0b013e3181788dd7 18591312
     [Google Scholar]
  28. YuY.H. FilionK.B. ReynierP. PlattR.W. YuO.H.Y. GrandiS.M. Use of levothyroxine among pregnant women with subclinical hypothyroidism in the United Kingdom: A population‐based assessment.Pharmacol. Res. Perspect.202195e0084810.1002/prp2.848 34390215
     [Google Scholar]
  29. BlumenthalN.J. EastmanC.J. Beneficial effects on pregnancy outcomes of thyroid hormone replacement for subclinical hypothyroidism.J. Thyroid Res.201720171710.1155/2017/4601365 28286688
     [Google Scholar]
  30. NegroR. SchwartzA. GismondiR. TinelliA. MangieriT. Stagnaro-GreenA. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy.J. Clin. Endocrinol. Metab.20109541699170710.1210/jc.2009‑2009 20130074
     [Google Scholar]
  31. TurunenS VääräsmäkiM MännistöT HartikainenAL Lahesmaa-KorpinenAM GisslerM SuvantoE Pregnancy and perinatal outcome among hypothyroid mothers: A population-based cohort study.Thyroid201929113514110.1089/thy.2018.031130417761
     [Google Scholar]
  32. SahuM. DasS. PanigrahiP.K. NandaS. A prospective study of routine screening of hypothyroidism in antenatal patients and their outcome with levothyroxine treatment.J. Clin. Diagn. Res.201711101077810.7860/JCDR/2017/26156.10778
     [Google Scholar]
  33. DasS. SahuM. PattanaikT. PanigrahiP.K. Association of thyroid status with pregnancy induced hypertension and impact of levothyroxine treatment.Annal. Int. Med. Dent. Res.201841712
     [Google Scholar]
  34. KiranZ. SheikhA. MalikS. MerajA. MasoodM. IsmailS. RashidM.O. ShaikhQ. MajeedN. SheikhL. IslamN. Maternal characteristics and outcomes affected by hypothyroidism during pregnancy (maternal hypothyroidism on pregnancy outcomes, MHPO-1).BMC Pregnancy Childbirth201919147610.1186/s12884‑019‑2596‑9 31805890
     [Google Scholar]
  35. LepoutreT. DebièveF. GrusonD. DaumerieC. Reduction of miscarriages through universal screening and treatment of thyroid autoimmune diseases.Gynecol. Obstet. Invest.201274426527310.1159/000343759 23147711
     [Google Scholar]
  36. NegroR. FormosoG. MangieriT. PezzarossaA. DazziD. HassanH. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications.J. Clin. Endocrinol. Metab.20069172587259110.1210/jc.2005‑1603 16621910
     [Google Scholar]
  37. JayaramanM. VermaA. HarikumarK.V.S. UgaleM. ModiK. Pregnancy outcomes with thyroxine replacement for subclinical hypothyroidism: Role of thyroid autoimmunity.Indian J. Endocrinol. Metab.201317229429710.4103/2230‑8210.109717 23776906
     [Google Scholar]
  38. VijayasreeM. Pregnancy and thyroid dysfunction: Need for universal screening - a pilot study.Bangladesh J. Med. Sci.2013131495210.3329/bjms.v13i1.14173
     [Google Scholar]
  39. CaseyB. 65: Thyroid peroxidase antibodies in women with subclinical hypothyroidism or hypothyroxinemia.Am. J. Obstet. Gynecol.20172161S4710.1016/j.ajog.2016.11.951
     [Google Scholar]
  40. NazarpourS. TehraniF. AmiriM. YarandiR. AziziF. Levothyroxine treatment and pregnancy outcomes in women with subclinical hypothyroidism: A systematic review and meta-analysis.Arch. Gynecol. Obstet.2019300480581910.1007/s00404‑019‑05245‑2 31399840
     [Google Scholar]
  41. HanY. WangJ. WangX. OuyangL. LiY. Relationship between subclinical hypothyroidism in pregnancy and hypertensive disorder of pregnancy: A systematic review and meta-analysis.Front. Endocrinol. (Lausanne)20221382371010.3389/fendo.2022.823710 35355565
     [Google Scholar]
  42. GengX. ChenY. WangW. MaJ. WuW. LiN. SunC. Systematic review and meta-analysis of the efficacy and pregnancy outcomes of levothyroxine sodium tablet administration in pregnant women complicated with hypothyroidism.Ann. Palliat. Med.20221141441145210.21037/apm‑22‑269 35523752
     [Google Scholar]
  43. KexinC. HongjuG. ShuxiaY. LirongC. Effect of levothyroxine for pregnancy outcomes due to subclinical hypothyroidism during pregnancy: A meta-analysis.Clinical Focus.2021369773
     [Google Scholar]
  44. AlexanderE.K. PearceE.N. BrentG.A. BrownR.S. ChenH. DosiouC. GrobmanW.A. LaurbergP. LazarusJ.H. MandelS.J. PeetersR.P. SullivanS. 2017 guidelines of the american thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum.Thyroid201727331538910.1089/thy.2016.0457 28056690
     [Google Scholar]
  45. DanziS. KleinI. Thyroid disease and the cardiovascular system.Endocrinol. Metab. Clin. North Am.201443251752810.1016/j.ecl.2014.02.005 24891175
     [Google Scholar]
  46. VasilopoulouE. LoubièreL.S. LashG.E. OhizuaO. McCabeC.J. FranklynJ.A. KilbyM.D. ChanS.Y. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.Hum. Reprod.20142961161117210.1093/humrep/deu046 24626803
     [Google Scholar]
  47. Adu-GyamfiE.A. WangY.X. DingY.B. The interplay between thyroid hormones and the placenta: A comprehensive review.Biol. Reprod.20201021817 31494673
     [Google Scholar]
  48. Di GirolamoR. LiberatiM. SilviC. D’AntonioF. Levothyroxine supplementation in euthyroid pregnant women with positive autoantibodies: A systematic review and meta-analysis.Front. Endocrinol.20221375906410.3389/fendo.2022.759064 35250850
     [Google Scholar]
  49. LauL. BenhamJ.L. LemieuxP. YamamotoJ. DonovanL.E. Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: A systematic review and meta-analysis of randomised controlled trials.BMJ Open2021112e04375110.1136/bmjopen‑2020‑043751 33622947
     [Google Scholar]
  50. PearceE.N. OkenE. GillmanM.W. LeeS.L. MagnaniB. PlatekD. BravermanL.E. Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use.Endocr. Pract.2008141333910.4158/EP.14.1.33 18238739
     [Google Scholar]
  51. BanerjeeS. Thyroid disorders in pregnancy.J. Assoc. Physicians India2011593234 21819002
     [Google Scholar]
  52. NazarpourS. Ramezani TehraniF. SimbarM. TohidiM. Alavi MajdH. AziziF. Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease.Eur. J. Endocrinol.2017176225326510.1530/EJE‑16‑0548 27879326
     [Google Scholar]
  53. WeetmanA.P. Immunity, thyroid function and pregnancy: molecular mechanisms.Nat. Rev. Endocrinol.20106631131810.1038/nrendo.2010.46 20421883
     [Google Scholar]
  54. SailakshmiM.; A, P. BrR. AkashS. Autoimmune thyroid disease in pregnancy.Int. J. Reprod. Contracept. Obstet. Gynecol.20143232132410.5455/2320‑1770.ijrcog20140606
     [Google Scholar]
  55. KarakostaP. AlegakisD. GeorgiouV. RoumeliotakiT. FthenouE. VassilakiM. BoumpasD. CastanasE. KogevinasM. ChatziL. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes.J. Clin. Endocrinol. Metab.201297124464447210.1210/jc.2012‑2540 23015651
     [Google Scholar]
  56. ZhangS.C. WangS.W. ZhaoX.D. ZhangJ.R. Obstetrical complications of thyroid peroxidase antibody positive during pregnancy and effects of intervention: a meta-analysis.Zhonghua Fu Chan Ke Za Zhi2016514250257 27116982
     [Google Scholar]
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Effect of Levothyroxine Therapy on Gestational Hypertension and Pre-eclampsia in Pregnant Women with Subclinical Hypothyroidism, Hypothyroidism, and Thyroid Autoimmunity: A Systematic Review and Meta-analysis
Cardiovasc Hematol Disord Drug Targets 25, 2 (2025); https://doi.org/10.2174/011871529X324722250207072454
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  • Article Type:     Review Article
Keyword(s): anti-thyroid autoantibodies; hypertension; Hypothyroidism; levothyroxine sodium; preeclampsia; pregnancy-induced

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