The Impact of Levothyroxine in Women with Positive Thyroid Antibodies on
Pregnancy Outcomes: A Systematic Review and Meta-Analysis of Randomized
Controlled Trials
Abstract
Background: Thyroid autoimmunity in pregnant women has been associated
with negative outcomes. Objective: To evaluate the effect of
levothyroxine therapy on pregnancy outcomes compared with placebo or no
treatment in women without overt hypothyroidism who are TPOAb and/or
TgAb-positive. Search Strategy: Ovid MEDLINE, EMBASE, CINAHL, Cochrane
Database of Systematic Reviews, and Cochrane Central Register of
Controlled Trials were searched from 1980 to April 17, 2019. Selection
Criteria: Pre-specified criteria for inclusion were: randomized trials
of levothyroxine versus control (placebo or no treatment) among women
with positive TPOAb or TgAb who were pregnant or considering conception.
Data Collection and Analysis: Pre-specified data elements were extracted
and where appropriate, meta-analyses were conducted. Main outcomes
include pregnancy achieved, miscarriage, preterm delivery and live
birth. Main Results: From 2,812 citations, 79 citations were identified
for full text review. Of these, six trials (total of 2,263 women) were
included for qualitative and quantitative analyses. Risk of bias was
deemed low for only one trial. There was no significant difference in
the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93,
1.13), miscarriage (RR 0.93; 95% CI 0.76, 1.14), preterm delivery (RR
0.66; 95% CI 0.39, 1.10), or live births (RR 1.01; 95% CI 0.89, 1.16)
in thyroid autoimmune women treated with levothyroxine compared to
controls. Conclusion: Among pregnant women or women planning conception,
with thyroid autoimmunity, there is a lack of evidence of benefit for
levothyroxine use. Recommendations to use levothyroxine in this setting
need to be reconsidered.