Spyridoula Maraka, assistant professor of medicine1 2, Raphael Mwangi, statistical programmer analyst3, Rozalina G McCoy, assistant professor of medicine3 4, Xiaoxi Yao, research associate3 5, Lindsey R Sangaralingham, assistant professor of health services research3 6, Naykky M Singh Ospina, assistant professor of medicine2 7, Derek T O’Keeffe, assistant professor of medicine8 9, Ana E Espinosa De Ycaza, instructor in medicine9, Rene Rodriguez-Gutierrez, postdoctoral researcher2 10, Charles C Coddington III, professor of medicine11, Marius N Stan, assistant professor of medicine9, Juan P Brito, assistant professor of medicine2 9, Victor M Montori, professor of medicine

Abstract

Objective To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism.

Design Retrospective cohort study.

Setting Large US administrative database between 1 January 2010 and 31 December 2014.

Participants 5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L.

Exposure Thyroid hormone therapy.

Main outcome measure Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes.

Results Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P<0.01). Pregnancy loss was significantly less common among treated women (n=89; 10.6%) than among untreated women (n=614; 13.5%) (P<0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P<0.01).

Conclusion Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population.

BMJ