Selenium Supplementation in Pregnancy
Selenium Supplementation in Pregnancy
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.
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.
Inclusion Criteria:

 -  pregnant women with 10°± 2 weeks of gestation

 -  women in whom embryo transfer is expected within 60 days

 -  euthyroid women (0.4 μIU/ml < TSH < 2.5 μIU/ml), positive for TPOab and/or TgAb, not
 assuming LT4 replacement

 -  euthyroid women (0.4 μIU/ml < TSH < 2.5 μIU/ml), positive for TPOab and/or TgAb under
 LT4 replacement (to maintain TSH within the control range).

 -  women with TSH > 2.5 μIU/ml positive for TPOab and/or TgAb, not assuming LT4
 replacement (requiring the beginning of LT4 replacement)

 -  women with TSH > 2.5 μIU/ml positive for TPOab and/or TgAb, under LT4 replacement
 (requiring an adjustment of LT4 replacement)

 Exclusion Criteria:

 -  use of dietary supplements containing selenium in the previous 4 months;

 -  use of antidepressive/psychotic drugs, amiodarone, propanolol, lithium, cytokines;

 -  history of hyperthyroidism positive anti-thyrotropin ab;

 -  previous partial or total thyroidectomy;

 -  known fetal anomaly;

 -  known infections (PID, HIV, HCV) and mola hydatidoses;

 -  chronic renal failure;

 -  uncontrolled hypertension;

 -  uterine malformation;

 -  history of medical and metabolic complication such as heart disease or diabetes;

 -  previous embryo transfer failed within last 3 months;

 -  miscarriage within last 3 months;

 -  gestational diabetes in previous pregnancies.