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Levothyroxine fails to improve live-birth rates in women with thyroid peroxidase antibodies

By Jane Lewis
The use of levothyroxine in euthyroid women with thyroid peroxidase antibodies does not result in a higher rate of live births, reports new research in The New England Journal of Medicine.

Previous studies have shown a strong association between the presence of thyroid peroxidase antibodies (aTPO positive) and an increased risk of miscarriage and preterm birth, even when thyroid function was normal, wrote the authors of the study. However, trials investigating whether the use of levothyroxine could reduce the incidence of such adverse outcomes have yielded mixed results.

‘This is a good study and important in the field,’ commented Professor Duncan Topliss, Director, Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne. ‘The issue of positive antithyroid antibodies and effect on pregnancy outcomes is unclear and this research makes an important contribution.’

In the UK multicentre, randomised, placebo-controlled trial, women who were aTPO positive and had a history of miscarriage or infertility were randomly assigned to receive either 50mcg once daily of levothyroxine (n=476) or placebo (n=476), from before conception to the end of pregnancy. Results showed no significant difference between the two groups, either in livebirth rates after at least 34 weeks of gestation or other pregnancy or neonatal outcomes, including miscarriage and preterm birth.

The authors cited the trial’s size and its inclusion of multiple centres and multiple clinical populations as strengths, while acknowledging that the fixed dose of levothyroxine used may be a limitation.

According to Professor Topliss, significant among earlier studies casting doubt over the use of levothyroxine was a US national assess­ment (Maraka, et al, BMJ 2017; 356: i6865) that found apparent benefit of levothyroxine therapy in women with thyroid stimulating hormone levels of 4.1mU/L or greater, but an adverse association of levothyroxine on preterm delivery, gestational diabetes and pre­eclampsia.

‘The current study provides strong data that levothyroxine given to euthyroid but aTPO­ positive women is of no benefit on subsequent pregnancy outcome, and should not be recommended,’ he said. ‘Given the findings of Maraka et al, there may be adverse effects of levothyroxine therapy, so only if there is a clear outweighing benefit should it be offered.’
N Engl J Med 2019; 380: 1316-1325.