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 (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%, 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]. Additionally, the odds ratios of GH and PE were statistically similar in women who were TPOAb-positive compared to those who were TPOAbnegative (OR=1.01,95% CI: (0.80, 1.28), (I² =0.00%, P =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%, P =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.