Committee on Practice Bulletins—Obstetrics ACOG Practice Bulletin Number 148: Thyroid disease in pregnancy, April 2015. Obstet Gynecol. 2015;125: 996–1005. Full text of ACOG Practice Bulletins is available to ACOG members at www.acog.org/Resources-And-Publications/Practice-Bulletins/Committee-on-...
Thyroid Disease in Pregnancy Uncontrolled thyrotoxicosis and hypothyroidism are associated with adverse pregnancy outcomes. Correspondingly, there is concern about the effect of overt (ie, symptomatic) maternal thyroid disease and even subclinical maternal thyroid disease on fetal development. In addition, medications that affect the maternal thyroid gland can cross the placenta and affect the fetal thyroid gland. This document reviews the thyroid-related pathophysiologic changes that occur during pregnancy and the effects of overt and subclinical maternal thyroid disease on maternal and fetal outcomes.
Used with permission. Copyright the American College of Obstetricians and Gynecologists.
What’s new in thyroid disease in pregnancy in 2015?
By Sarah J. Kilpatrick, MD, PhD
Dr. Kilpatrick is the Helping Hand Endowed Chair, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California. She is also on the editorial board of Contemporary OB/GYN.
Practice Bulletin 148 published in April of 2015 replaced Practice Bulletin 37 from 2002.1,2 Not surprisingly the basics of thyroid function and its alteration with thyroid disease (hypothyroidism and hyperthyroidism) have not changed in 13 years. Untreated overt hypothyroid or hyperthyroid disease is still harmful for a woman, her pregnancy, and/or her fetus. However, there are some interesting changes in the Practice Bulletin, most of which reflect the ongoing controversy about whether subclinical hypothyroid disease should be a concern in pregnancy, and there are some important affirmations.
Routine screening. The recommendation to not perform routine screening for thyroid disease in pregnancy not only has not changed, it has actually been moved from a Level C recommendation to a Level A recommendation. Remember, Level C recommendations are based on consensus and expert opinion only, whereas Level A recommendations are based on good and consistent scientific evidence. The change is based on 3 facts:
1. Reaffirmation that studies suggesting an association between subclinical hypothyroidism in pregnancy and impaired neurodevelopment in offspring are just that, an association;
2. Publication of new studies with mixed results about putative associations between subclinical hypothyroidism in pregnancy and other adverse outcomes (preterm delivery, preeclampsia, gestational diabetes)3-6; and most importantly
3. Publication of a large randomized trial that showed no difference in cognitive function in 3-year-old children of mothers randomized to screening and treatment versus no treatment for subclinical hypothyroid disease.7
So it is really time to stop screening until we have data that screening and treatment of women with subclinical hypothyroid disease results in improvement in maternal or neonatal outcomes!
More Level A Recommendations. There are better data available on several topics, moving more recommendations into level A. In 2002 there was only one Level A recommendation (levels of thyroid-stimulating hormone [TSH] or free thyroxine [measured directly as FT4 or calculated as the free thyroxine index or FTI] should be monitored to manage thyroid disease in pregnancy). In 2015 there are now 7 level A recommendations. The first recommendation is described above (do not do universal screening for thyroid disease in pregnancy). The remaining 6 are paraphrased below and none should be surprising:
1. TSH is the first-line screening test to assess thyroid status in pregnancy.
2. TSH and FT4 should be measured to diagnose thyroid disease in pregnancy.
3. Treat overt hypothyroid disease in pregnancy with adequate thyroid hormone to minimize risk of adverse outcomes.
4. TSH should be monitored in pregnant women who have overt hypothyroidism and the dosage of thyroid replacement adjusted accordingly.
5. Pregnant women with overt hyperthyroidism should be treated with thioamide to minimize risk adverse outcomes.
6. FT4 should be monitored in pregnant women with hyperthyroidism and thioamide dose adjusted accordingly.
TSH levels change in pregnancy. Table 1 in the 2002 Practice Bulletin shows no change in TSH in pregnancy.2 But we know that TSH levels decrease in the first trimester because hCG directly stimulates the TSH receptor, resulting in mild increased T4, which suppresses TSH. Many clinicians use a lower upper limit of normal in the first trimester compared with later in pregnancy. In the first trimester, TSH should be < 2.5 mIU/L compared with < 3.0 mIU/L after the first trimester. 8 Unfortunately, Table 1 in the 2015 Practice Bulletin does not include FTI, which is a very useful measure which can be used instead of free thyroxine, and does not change during pregnancy.
Subclinical hyperthyroidism. A new section has been included on subclinical hyperthyroidism, which is defined as an abnormally suppressed TSH accompanied by a normal FT4 level. Subclinical hyperthyroidism is present in approximately 1.5% of pregnant women.9 No adverse outcomes have been associated with this finding, and so, this is one more reason not to check thyroid function tests routinely.
Thyroid autoantibodies in pregnancy. A new section also has been included on thyroid autoantibodies in pregnancy and whether to screen for them. As you might expect, because data are insufficient to support any benefit of screening and treatment in pregnancy of euthyroid women, universal screening for thyroid autoantibodies in pregnancy is not recommended.
There are at least two notable recommendations that did not change but warrant mention because of their importance. Neonates of women with definitively treated Graves’ disease (status post thyroidectomy or treatment with I131 before pregnancy) have a higher risk of neonatal Graves disease compared with women with Graves disease currently on thioamide treatment during pregnancy. This is because the definitively treated women still have thyroid-stimulating antibodies that cross the placenta and could affect the fetus but they have no concurrent thioamide treatment, a drug that also crosses the placenta. Furthermore, we tend to forget these women had Graves disease because they are on thyroid replacement and, in our minds, they are labeled as having hypothyroidism.
The second affirmation is that routine measurements of thyroid function in women with hyperemesis gravidarum are still not recommended because it is well known that transient laboratory findings consistent with hyperthyroidism occur in the first trimester and are more common in women who have hyperemesis and that this transient gestational hyperthyroidism resolves and is not impacted by treatment.
Finally, the 2015 practice bulletin ends with a bit of a provocative “negative” performance measure: the percent of women without risk factors for thyroid disease during pregnancy who are nevertheless screened for thyroid disease. So, heed the above recommendation: Do not routinely screen women in pregnancy for thyroid disease.
1. American College of Obstetricians and Gynecologists. Practice Bulletin No. 148: Thyroid disease in pregnancy. Obstet Gynecol. 2015;125:996–1005.
2. American College of Obstetricians and Gynecologists Practice Bulletin No. 37: Thyroid disease in pregnancy. Obstet Gynecol. 2002;100:387–396.
3. Casey BM, Dashe JS, Spong CY, et al. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol. 2007;109:1129–1135.
4. Casey BM, Dashe JS, Wells CE, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105:239–245.
5. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol. 2008;112:85–92.
6. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol. 2012;119:983–988.
7. Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366:493–501.
8. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21:1081–1125.
9. Casey BM, Leveno KJ. Thyroid disease in pregnancy. Obstet Gynecol. 2006;108:1283–1292.