ESPEYB16 3. Thyroid Thyroid and Pregnancy (2 abstracts)
3.5. Levothyroxine in women with thyroid peroxidase antibodies before conception
Dhillon-Smith RK , Middleton LJ , Sunner KK , Cheed V , Baker K , Farrell-Carver S , Bender-Atik R , Agrawal R , Bhatia K , Edi-Osagie E , Ghobara T , Gupta P , Jurkovic D , Khalaf Y , MacLean M , McCabe C , Mulbagal K , Nunes N , Overton C , Quenby S , Rai R , Raine-Fenning N , Robinson L , Ross J , Sizer A , Small R , Tan A , Underwood M , Kilby MD , Boelaert K , Daniels J , Thangaratinam S , Chan SY & Coomarasamy A
To read the full abstract: N Engl J Med. 2019;380:1316–1325.
This large multicenter randomized double-blind placebo-controlled trial, in euthyroid women with thyroid peroxidase antibodies and a history of miscarriage or infertility, found no effect of levothyroxine substitution from before conception to the end of pregnancy on likelihood of live birth.
In 2011, Thangaratinam (co-author of this study) et al. reported a strong association between thyroid peroxidase antibodies with miscarriage and preterm birth, as discussed in the Yearbook 2012 thyroid chapter [1]. The study rationale was further supported by a few small trials indicating apparent benefits of levothyroxine substitution on higher live birth rates in TPO antibody positive women. However, the evidence was insufficient for the 2017 American Thyroid Association guidelines to recommend levothyroxine substitution in these women [2].
The presented data from this large randomized controlled trial, which screened almost 20,000 women for eligibility and included 470 women each in the control and the treatment arm, provide robust evidence for no advantage of levothyroxine treatment of TPO antibody positive women for the primary end point of number of live births. These results are important for counseling of women positive for TPO antibodies concerning miscarriage risk and suggest that non-thyroid hormone mechanisms are involved in TPO antibody associated miscarriages.
References: 1. Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616. PMID: 21558126.
2. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27:315–389. PMID: 28056690.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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