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NEW ORLEANS – Levothyroxine given before conception to women with normal thyroid function but with anti-thyroid peroxidase (TPO) antibodies did not reduce the rate of miscarriage in pregnant women, revealed a new study.
The findings were presented on March 23 at the ENDO 2019: Endocrine Society Annual Meeting by Rima K. Dhillon-Smith, MB, ChB, PhD, Lecturer Clinical Professor at the University of Birmingham, USA. United Kingdom, and published simultaneously in the New England Journal of Medicine.
Previous studies have shown an approximately four-fold higher risk of miscarriage in HIV-positive women for the anti-TPO antibody test, including those with recurrent miscarriage and infertility, and in unselected populations.
At the same time, studies on the use of levothyroxine in pregnancy, including badisted reproductive technologies, in women with anti-TPO antibodies and normal thyroid function, have shown mixed results. .
The present study is a randomized, double-blind, placebo-controlled trial involving nearly 1,000 euthyroid women with a history of miscarriage, but positive for thyroid peroxidase antibodies (TPO).
There was no difference in live birth rates between people who received 50 mg levothyroxine once a day or placebo before conception until the end of pregnancy. There was also no difference in secondary outcomes, including pregnancy loss, prematurity or neonatal outcomes.
"It's a bit disappointing in that there's no benefit, but it's really important because it tells us that we really should not be using thyroxine for these women and that we should not be giving them false hopes by telling them an advantage, "said Dhillon-Smith Medscape Medical News in an interview.
And, she noted in her presentation, the results also challenge the whole practice of testing thyroid antibodies in pregnant women with previous miscarriages or infertility.
"One of the prerequisites for a screening test is that you need a treatment or intervention that changes the results and that, for the time being, we do not have it." no, so are we just generating anxiety rather than helping them? "
Guest to comment, Loder L. Yanes Cardozo, professor and badistant professor of medicine at the Medical Center of the University of Mississippi in Jackson, said Medscape Medical News"It was an excellent study and it was a very large, randomized, very powerful clinical trial with many patients … Keep in mind that the target of treatment was [thyroid stimulating hormone]. They really did not intervene to reduce the anti-TPO antibody level, which is the one badociated with a miscarriage. "
Indeed, Michael T. McDermott, a physician and professor, professor of medicine and clinical pharmacy and director of the Department of Endocrinology and Diabetes at the University of Colorado, Aurora, explained that during a healthy pregnancy, women increased their thyroid hormone production by 30% to 50%. provide the fetus, and the presence of anti-TPO antibodies interferes with this production.
But if the mechanism involves the antibodies themselves, an effective intervention may be needed to target them. "We do not know the mechanism of miscarriages, so maybe we did not target the right thing," he said.
No difference in pregnancy outcome, plus suspicion of harm
In their article, Dhillon-Smith and colleagues note that the American Thyroid Association (ATA) guidelines of 2017 state that the administration of levothyroxine to euthyroid-positive women with TPO antibodies with a history of loss of pregnancy can be considered ", considering risk."
Indeed, "the working group on the guidelines drew attention to our ongoing trial," he added, namely the test on thyroid antibodies and levothyroxine (TABLET) .
The results of this study are now available. The trial was conducted among 952 women trying to conceive and who had a history of miscarriages or infertility, were biochemically euthyroid (TSH within precise baseline) and were positive for anti-TPO antibodies. . Of the 476 participants, 266 women randomized to levothyroxine and 274 randomized placebo women became pregnant.
The proportion of live births at 34 weeks or more was almost identical: 37.4% of the levothyroxine group versus 37.9% of the placebo group (P = 0.74).
The secondary outcomes in pregnant women also did not differ between levothyroxine and placebo groups, including the proportion of women who had a miscarriage (28.2% vs. 29.6%; P = 0.95) or live birth at less than 34 weeks (3.8% vs 3.6%; P = 1.02). And neonatal outcomes, such as birth weight or Apgar scores at 1 or 5 minutes, were similar between the two groups.
The proportion of women who withdrew from the study due to abnormal thyroid function tests did not differ between the levothyroxine and placebo groups (9.8% vs. 9.6%).
However, the proportion of pre-eclampsia (5% vs. 3%) and gestational diabetes (11% vs. 9%) was higher among those in the levothyroxine group, although the difference was not significant.
Cardozo noted that the results further corroborate the advice of not prescribing levothyroxine to these patients. "Although it was not significant, it is still a concern, there is no benefit, and it could be harmful."
McDermott said, "I'm not convinced of the harm, but we should not use it if it does not matter."
Where is the targeting of antibodies?
Dhillon – Smith acknowledged that the idea of targeting anti-TPO antibodies was in part based on the premise that miscarriages result from a widespread autoimmune imbalance. Some have suggested the use of immunoglobulin or intravenous steroids, while an ongoing trial is studying the use of selenium supplementation in autoimmune thyroiditis, but not during pregnancy.
McDermott noted that such an essay might be difficult to conduct in pregnant women. "Giving anything to pregnant women is difficult to get approved, even though selenium is an over-the-counter supplement, you can give it to non-pregnant women with positive anti-TPO antibodies." There is very little risk But during pregnancy, knowing the risk, giving preconception until they become pregnant may be less of an ethical issue. "
Meanwhile, Dhillon-Smith said one of his team's next steps would be to see if levothyroxine supplementation prior to conception could have a greater impact on the outcome of pregnancy in women with subclinical hypothyroidism.
In addition, "we must rethink the underlying cause and then think about how to change it."
The research was commissioned by the National Institute for Health Research in the United Kingdom. Dhillon-Smith, Cardozo and McDermott have not reported any relevant financial relationship.
ENDO 2019. Presented 23 March 2019. Summary OR11-1.
N Engl J Med. Posted online 23rd March 2019. Summary
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