Clinical Question: Does treatment with levothyroxine improve birth outcomes for pregnant euthyroid women who test positive for thyroid peroxidase antibodies?

Setting: Outpatient (primary care)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: White women receiving care in an academic obstetric clinic in Italy were screened for thyroid peroxidase (TPO) antibodies, free thyroxine (FT₄), and thyroidstimulating hormone (TSH) levels. Of the 1,074 women tested, 45 were excluded from the study because of overt hypothyroidism or hyperthyroidism; 984 completed the study. The 115 women who were positive for TPO antibodies and had normal FT₄ and TSH levels were randomized to treatment with levothyroxine or placebo. Treatment allocation was concealed and treatment began within one week of the initial visit for prenatal care. Medication dosing for women taking active treatment was calculated according to body weight and TSH level, and was a mean of 50 mcg. The participating women and the physicians providing obstetric care were blinded to treatment assignment.

Treated women had a significant reduction in spontaneous abortion (4 versus 14 percent; number needed to treat [NNT] = 10). Preterm births also were reduced in the treated group (7 versus 22 percent; NNT = 6; 95% confidence interval, 3 to 22).

Treated women had rates of spontaneous abortion and preterm birth similar to the 869 women who screened negative for TPO antibodies. In this population, in which 11 percent of women had a positive screen result, the number needed to screen to prevent one preterm birth would be 56, and the number needed to screen to prevent one miscarriage would be 93 (assuming that all women positive for TPO antibodies would have equally positive results with treatment).

This study may have been confounded by the women in the control group, who were younger on average than those in the treatment group; this may have influenced the rate of miscarriages. Also of note is that the study was conducted in Italy where iodization of salt is not compulsory. Iodine deficiency in this population may have reduced the functional reserve needed for the physiologic increase in thyroid hormone production during pregnancy.

Bottom Line: In this study, levothyroxine treatment of euthyroid women who tested positive for TPO antibodies significantly decreased spontaneous abortions and preterm births. Screening may be indicated for populations of pregnant women with a high incidence of autoimmune thyroid disease. Further studies in various populations are needed. (Level of evidence: 1b)