Levothyroxine Supplementation in Euthyroid Pregnant Women With Positive Autoantibodies: A Systematic Review and Meta-Analysis

Objectives: To explore the role of levothyroxine (LT4) supplementation in affecting the outcome of pregnant euthyroid women with thyroperoxidase (TPO) antibodies. Methods: MEDLINE, EMBASE, Google Scholar, and the Web of Science databases were searched. The primary outcome was pre-term birth (PTB), defined as live birth before 37 weeks of gestation; secondary outcomes were gestational hypertension, pre-eclampsia (PE), placental abruption, miscarriage, intra-uterine death (IUD), and admission to neonatal intensive care unit (NICU). All these outcomes were explored in euthyroid women with TPO antibodies receiving compared to those not receiving LT4 supplementation in pregnancy. Random-effect meta-analyses were used to analyze the data and results reported as pooled odds ratios (OR) with their 95% confidence intervals (CI). Results: The risk of PTB was lower in women with TPO antibodies receiving compared to those not receiving LT4 supplementation (OR of 0.60 (95% CI 0.4-0.9). However, this association came mainly from observational studies (OR: 0.29, 95% CI 0.1-0), while RCTs did not show any beneficial effect of LT4 supplementation in affecting such outcomes. Conversely, there was no difference in the risk of gestational hypertension, preeclampsia, placental abruption, miscarriage, and admission to NICU between the two groups. Conclusions: LT4 supplementation in TPO euthyroid women is not associated with a reduced risk of PTB in TPO-positive women with normal thyroid function.