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THYROID IN PREGNANCY
Does treating subclinical hypothyroidism in pregnancy with levothyroxine improve pregnancy outcomes?
BACKGROUND
Thyroid hormone plays an important role in development and growth of the baby during pregnancy. Low thyroid hormone levels (hypothyroidism) can increase risks of poor pregnancy outcomes, such as preterm birth or pregnancy loss/miscarriage. As such, overt hypothyroidism (high blood thyroid stimulating hormone (TSH) level with low free thyroxine (FT4) level) in pregnancy should always be treated with levothyroxine. However, despite multiple studies examining the subclinical hypothyroidism during pregnancy, it is still not clear whether subclinical hypothyroidism (slightly high TSH with normal FT4 levels) in pregnancy causes similar problems and whether treating subclinical hypothyroidism would improve these outcomes. It is clear that subclinical hypothyroidism is much more common during pregnancy than overt hypothyroidism.
The authors of this study evaluated findings of currently available trials to assess whether treating subclinical hypothyroidism in pregnancy with levothyroxine can improve poor pregnancy outcomes.
THE FULL ARTICLE TITLE
Sankoda A et al. Effects of levothyroxine treatment on fertility and pregnancy outcomes in subclinical hypothyroidism: a systematic review and meta-analysis of randomized controlled trials. Thyroid Epub 2024 Feb 18; doi: 10.1089/thy.2023.0546. PMID: 38368537
SUMMARY OF THE STUDY
In this study, the authors combined data from currently available clinical trials evaluating the effect of levothyroxine treatment, either started before pregnancy or during early pregnancy(within the 1st 20 weeks of pregnancy). Subclinical hypothyroidism was defined as a TSH >2.5mIU/L (high normal) with a normal FT4. Subgroup analyses were also done separating participants with TSH between 2.5-4mIU/L and those with a TSH >4.0mIU/L (clearly elevated). A total of 5 studies including a total of 763 patients were used for analysis of levothyroxine treatment starting before pregnancy, and 8 studies including a total of 2622 patients were used for analysis of levothyroxine treatment starting in early pregnancy.
This analysis showed that treating subclinical hypothyroidism with levothyroxine before pregnancy did not improve live birth, pregnancy, or miscarriage rates. However, the studies only included women undergoing infertility treatment. Only one of these studies had data for subgroup analysis, which showed treating with levothyroxine improved live birth rate in women with TSH >4.0mIU/L, but not in women with TSH between 2.5-4.0mIU/L.
Treating subclinical hypothyroidism with levothyroxine during early pregnancy also did not improve live birth, miscarriage, or preterm birth rates. However, subgroup analysis showed that levothyroxine may be helpful in certain situations. One study showed that treating pregnant women with history of multiple miscarriages and subclinical hypothyroidism decreased miscarriage rate by half. Treating pregnant women with TSH >4.0mIU/L decreased preterm birth rate by half, while preterm birth rate did not change in pregnant women with TSH between 2.5-4.0mIU/L.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors concluded that levothyroxine treatment for subclinical hypothyroidism before pregnancy or during early pregnancy before 20 weeks did not improve pregnancy rate or pregnancy outcomes. However, levothyroxine treatment did decrease miscarriage rate in women with multiple miscarriages and decreased preterm birth rate in women with TSH >4.0mIU/L. While we still do not have clear answers to a tricky question of whether to treat subclinical hypothyroidism in pregnancy, based on subgroup analyses, treating subclinical hypothyroidism may be beneficial in women with multiple miscarriages or with TSH >4mIU/L, the cutoff for abnormal TSH in pregnancy per the most recent 2017 American Thyroid Association guidelines.
— Sun Y. Lee, MD, MSc
ATA RESOURCES
Thyroid Disease in Pregnancy: https://www.thyroid.org/thyroid-disease-pregnancy/
ABBREVIATIONS & DEFINITIONS
Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.
Overt Hypothyroidism: clear hypothyroidism an increased TSH and a decreased T4 level. All patients with overt hypothyroidism are usually treated with thyroid hormone pills.
Subclinical Hypothyroidism: a mild form of hypothyroidism where the only abnormal hormone level is an increased TSH. There is controversy as to whether this should be treated or not.
TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.
Thyroxine (T4): the major hormone produced by the thyroid gland. T4 gets converted to the active hormone T3 in various tissues in the body.
Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tyrosint™ and generic preparations.
Miscarriage: this occurs when a baby dies in the first few months of a pregnancy, usually before 22 weeks of pregnancy.
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