Selenium Supplementation in Pregnancy
Condition: Pregnancy; Infertility; Auto-immune Thyroiditis
MeSH terms: Infertility; Thyroiditis; Thyroiditis, Autoimmune; Hashimoto Disease
Study type: Interventional

Summary: 
      Serum levels of isolated anti-thyroperoxidase (TPOab) and anti-thyreoglobulin (Tgab)
      autoantibodies are strongly associated with an increased risk of miscarriage and premature
      deliveries in euthyroid pregnant women. Replacement of thyroxine (LT4) or other
      supplementations in euthyroid-Ab positivity during pregnancy has not been established. The
      development of a safe and effective intervention that modulates inappropriate inflammatory
      responses could be a very important component of prevention against adverse health outcomes
      during pregnancy.

      The anti-oxidant Selenium (Se) suppresses autoimmune destruction of thyrocytes and at daily
      dose of 200 mcg and 100 mcg decreases titers of serum TPOAb and TgAb also in Se-non-deficient
      patients with autoimmune thyroiditis (AIT).

      The use of Se in AIT has been shown to reduce the incidence of postpartum thyroiditis and
      hypothyroidism.

      Women with recurrent pregnancy loss had lower Se levels and Se deficiency has been implicated
      in the pathogenesis of AIT and in the impairment of T/B cell-mediated immunity.

      The purpose of the present study is performed to establish the effect of Se supplementation
      in euthyroid women with AIT (pregnant and in whom embryo transfer is expected within 60 days)
      on Ab trend, thyroid function and structure, implantation rates, pregnancy rates, pregnancy
      outcome and number of obstetrical, fetal and neonatal complications.
    

Detailed description: 
      Adverse outcomes, postpartum thyroid dysfunction and permanent hypothyroidism have been
      associated with isolated TPOab positivity in euthyroid pregnant women.

      In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a
      decreased activity of selenium-dependent glutathione peroxidase activity within thyroid
      cells. Selenium-dependent enzymes also have several modifying effects on the immune system.
      Therefore, even mild selenium deficiency may contribute to the development and maintenance of
      autoimmune thyroid diseases.

      Selenium substitution exerts anti-inflammatory and anti-oxidant activities. Se could
      represents an important supplementation in euthyroid women with AIT in order to improve
      thyroid function and structure and to prevent obstetrical adverse events related to
      autoimmune diseases and reactive oxygen species, such as recurrent miscarriage and
      pre-eclampsia.

      The aim of this study is to document the effects of Selenium Supplementation with and without
      L-thyroxine (LT4) in euthyroid women with AIT, during pregnancy.

      This protocol will evaluate the trend of TPOab and Tgab, selenium concentration, thyroid
      volume and echogenicity, nodule formation and number of adverse effects that affect the
      mother (during and after pregnancy), the fetus, the infant and the heath service, needing to
      elucidate the nature of the emerging associations.

      The study also aims to assess the impact of Selenium Supplementation on implantation rate and
      pregnancy rate in women with transfer planned within the next 60 days.

      This is designed as a phase IV study on treatment with a cohort size of pregnant women and
      women in whom embryo transfer is expected within 60 days with TSH value into the normal range
      (0.4-2.5 mUI/mL) and Tgab and/or TPOab positivity. We have performed two randomizations arms:
      Randomization arm A will include women LT4 replacement-free that will take Selenium or
      Placebo and Randomization arm B will include women already under LT4 replacement that will
      take Selenium or Placebo. Patients included in Randomization A will move into Randomization
      B, if TSH increases above 2.5 mUI/mL during pregnancy.

      Pregnant women with TSH > 2.5 mU/mL at time 0 will begin (or will adjust) LT4 replacement and
      will be included in Randomization arm B.

      Accounting for a 30% drop off, a total enrolment of 150 patients is planned. Patients will be
      randomized at time 0 (10°± 2 weeks of gestation). Follow-up visits will take place at weeks
      14 ± 2, 24 ± 2, 32 ± 2, 36 ± 2 weeks, and between months 3° and 6° after labour. An optional
      visit could be done 12 months after labor. Plasma and serum monitoring of thyroid hormones,
      Tgab, TPOab, Se concentration, Selenoproteins and cytokines, thyroid US, SF12 questionnaire
      will be made at all the follow-up visits. At visit 3 (24 ± 2 weeks) patients will optionally
      do the OGTT). Gestational, obstetrical, maternal, fetal, and infant anamnestic data will be
      taken, during the follow up visits and at labour.

      The long-term objective is to identify a safe and easily administered supplementation that
      improves:

        1. implantation and pregnancy rates in infertile women Tgab and/or TPOab positives

        2. maternal and fetal complication in pregnant euthyroid women Tgab and/or TPOab positives.
    

Intervention name(s): Selenium; Sugar Pill Placebo; Selenium + L-Thyroxine (LT4); Sugar Pill Placebo + L-Thyroxine (LT4)
Intervention type(s): Dietary Supplement; Other; Other; Other
Intervention description(s): 83 micrograms of selenium (in the form of selenium methionine) in tablet form taken orally daily for all the length of pregnancy and for 3-6th month after labour; Placebo supplements in the same capsule as selenium. 1 tablet daily for all the length of pregnancy and for 3-6th month after labour.; 83 micrograms of selenium (in the form of selenium methionine) in tablet form taken orally daily for all the length of pregnancy and for 3-6th month after labour
+ LT4 taken orally daily according to the dose required(in women already receiving it or needing of start it); Placebo supplements in the same capsule as selenium. 1 tablet daily for all the length of pregnancy and for 3-6th month after labour
+ LT4 taken orally daily according to the dose required(in women already receiving it or needing of start it)
Other intervention name(s): Intervention I (Se); Intervention II (Plb); Intervention III (Se+LT4); Intervention IV (Plb + LT4)
Intervention MeSH terms: Selenium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Selenium; Pregnancy; Auto-immune thyroiditis; Post-partum thyroiditis; Miscarriage; Pre-eclampsia; Implantation and Pregnancy rate; Infertility