Table 1.
Prospective randomized clinical studies of levothyroxine treatment and selenium supplementation in euthyroid pregnant women with thyroid autoimmunity.
| Trial | Study groups/type of pregnancy | Type of antithyroid antibody | Intervention | Main results |
|---|---|---|---|---|
| Levothyroxine treatment | ||||
| Negro et al. 2005, Italy (84) |
Treated group n = 36 Placebo group n = 36 |
TPOAb | LT4 instituted before ART at a dose of 1 µg/kg/day and maintained throughout pregnancy |
Significant reduction in miscarriage rates in LT4 group vs. placebo: 33% vs. 52%, p = 0.028 |
| Type of pregnancy: ART | ||||
| Negro et al. 2006, Italy (85) |
Treated group n = 57 Untreated group n = 58 |
TPOAb | LT4 started at a mean 10 weeks of gestation TSH <1.0 mIU/L-LT4 dose of 0.5 µg/kg/day TSH between 1.0 and 2.0 mIU/L-LT4 dose of 0.75 µg/kg/day TSH >2.0 mIU/L or TPOAb >1,500 kIU/L-LT4 dose of 1 µg/kg/day |
Significant decrease in the rates of miscarriage and preterm birth in LT4 group vs. controls: 3.5% vs. 13.8%, p < 0.05 and 7% vs. 22.4%, p < 0.05 |
| Type of pregnancy: spontaneous | ||||
| Negro et al. 2016, Italy (86) |
Treated group n = 198 Untreated group n = 195 |
TPOAb | LT4 instituted at the first trimester of pregnancy TSH between 0.5 and 1.5 mIU/L-LT4 dose of 0.5 µg/kg/day TSH between 1.5 and 2.5 mIU/L-LT4 dose of 1 µg/kg/day |
LT4 intervention with no significant impact on the rates of: miscarriage: 11.6% vs. 14.9%, p = 0.11 and preterm birth: 6.9% vs.10.8%, p = 0.27 |
| Type of pregnancy: spontaneous | ||||
| Wang et al. 2017, China (87) |
Treated group n = 300 Untreated group n = 300 |
TPOAb | Starting dose at preconception period: TSH <2.5 mIU/ ml- LT4 dose of 25 µg/day TSH ≥2.5 mIU/ml- LT4 dose of 50 µg/day During pregnancy, the LT4 dose was titrated to maintain the TSH level within 0.1–2.5 mIU/L in the first trimester, 0.2–3.0 mIU/L in the second trimester, and 0.3–3.0 mIU/L in the third trimester |
No difference between LT4 group and controls in the rates of: live birth: 31.7% vs. 32.3% pregnancy: 35.7% vs. 37.7% miscarriage: 10.3% vs. 10.6% |
| Type of pregnancy: ART | ||||
| Nazarpour et al. 2017, Iran (88) |
Treated group n = 18a Untreated group n = 24a |
TPOAb | LT4 instituted at a mean of 11 weeks of gestation TSH <1.0 mIU/L- LT4 dose of 0.5 µg/kg/day TSH between 1.0 and 2.0 mIU/L– LT4 dose of 0.75 µg/kg/day TSH >2.0 mIU/L or TPOAb >1,500 kIU/L- LT4 dose of 1 µg/kg/day |
No difference between LT4 and control groups in the rates of preterm birth: 11.1% vs. 16.7%, p = 0.69 |
| Type of pregnancy: spontaneous | ||||
| Dhillon-Smith et al. 2019, United Kingdom (89) |
Treated group n = 476 Placebo group n = 476 Women with history of miscarriage and/or infertility |
TPOAb | LT4 instituted before conception at a fixed dose of 50 µg/day and maintained throughout pregnancy | No difference between LT4 and placebo groups in the rates of: live birth 37.4% vs. 37.9% pregnancy 56.6% vs. 58.3% miscarriage 28.2% vs. 29.6% |
| Type of pregnancy: spontaneous or ART | ||||
| Van Dijk et al. 2022, Netherlands (90) |
Treated group n = 94 Placebo group n = 93 Women with recurrent pregnancy loss |
TPOAb | LT4 instituted before conception and continued at the same dose throughout pregnancy TSH <1.0 mIU/L- LT4 dose of 0.5 µg/kg/day TSH between 1.0 and 2.5 mIU/L- LT4 dose of 0.75 µg/kg/day TSH>2.5 mIU/L- LT4 dose of 1 µg/kg/day |
LT4 treatment compared with placebo, did not result in higher live birth rates: 50% vs. 48% |
| Type of pregnancy: spontaneous or ART | ||||
| Selenium supplementation | ||||
| Negro et al. 2007, Italy (91) |
Treated group n = 77 Placebo group n = 74 |
TPOAb | Selenomethionine 200 µg/day or placebo from 12 weeks of gestation until delivery and 12 months postpartum |
In the Se-treated group, the incidence of postpartum thyroiditis and permanent hypothyroidism after delivery were significantly lower compared with placebo group. Se therapy decreased the TPOAb concentration in postpartum period but did not influence TSH and fT4 during pregnancy and maternal/fetal complications 19.4% in Se group and 21.6% in placebo group required LT4 treatment during pregnancy |
| Type of pregnancy: spontaneous | ||||
| Mao et al. 2016, United Kingdom (92) |
Treated group n = 10 Placebo group n = 15 |
TPOAb/TgAb | Selenium-enriched yeast 60 µg/day or placebo from 12 weeks of gestation until delivery |
Among TPOAb/TgAb-positive pregnant women, TSH and fT4 dropped significantly lower in the Se-treated group than in the placebo group. Se did not influence the TPOAb concentration |
| Type of pregnancy: spontaneous | ||||
| Mantovani et al. 2019, Italy (93) |
Treated group n = 21 Placebo group n = 24 |
TPOAb/TgAb | Selenomethionine 83 µg/day or placebo from 10 weeks of gestation until delivery and 6 months postpartum |
There was no effect of Se on TPOAb and TgAb during pregnancy in comparison to placebo group After delivery, a significant reduction of TPOAb and TgAb was noted in the Se group, while antibody titers rebounded in the placebo group No differences were found in thyroid function, volume, echogenicity, quality of life, maternal/fetal complications between Se, and placebo groups 56.5% in Se group and 70% in the placebo group required LT4 treatment during pregnancy |
| Type of pregnancy: spontaneous | ||||
a only a subgroup of women with euthyroidism defined as TSH< 4.0 is presented; LT4, levothyroxine; ART, assisted reproductive technology; TPOAb, thyroperoxidase antibody; TgAb, thyroglobulin antibody; TSH, thyroid stimulating hormone; Se, selenium.