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.

Abstract

Background: Gestational hypertension (GH) and preeclampsia (PE) are two important complications of pregnancy. Considering the U-shaped association between thyroidstimulating 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 (SGH), 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%, P =0.78, OR = 1.02, 95% CI: (0.66,1.58), I² = 46.86%, P =0.94, respectively] and overt hypothyroidism [OR=1.10, 95% CI: (0.70,1.71), I² =38.44%, P =0.69, OR=1.32, 95% CI: (0.83, 2.09), I² =0.00%, P =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%, P =0.74, OR=0.51, 95% CI: (0.15, 1.72), I² =97.30%, P =0.28, respectively]. Also, these studies compared thyroperoxidase antibodies between TPOAb-positive participants with TPOAb-negative controls (OR=1.01, 95% CI: (0.80, 1.28), I² =0.00%, P =0.90). However, LT4 reduced the risk of GH in TPOAb+ women compared with untreated TPOAb+ (OR=0.43, 95% CI: (0.30, 0.62), I² =0.00%, P =0.00).

Conclusion: After LT4 therapy, the incidence rates of GH and PE in any form of hypothyroidism were not significantly different from controls. However, the reduction of GH in women with TPOAb+ who used levothyroxine needs further consideration.