Potential Preventive Effect of Selenium on Iodine-induced Thyroid Autoimmunity During Pregnancy

April 17, 2018 updated by: Ilze Konrade, Riga Stradins University

Safety and Efficacy of Iodine Supplementation During Pregnancy With and Without Selenium Co-administration: Randomized Controlled Trial

In 1994, the WHO and UNICEF Joint Committee on Health Policy recommended Universal Salt Iodization as a safe, cost-effective and sustainable strategy to ensure sufficient intake of iodine by all individuals. However, it is still absent in Latvia.

A recent countrywide study in 2013 shows iodine deficiency among pregnant women in Latvia: 81 % of pregnant women had UIC levels below the WHO recommended range of 150-250 mcg/g Cr.

Because mild to moderate iodine deficiency during pregnancy can adversely affect fetal brain development, WHO-UNICEF and ICCIDD advise an increase in the recommended daily dosage of iodine to 250 mcg/day for pregnant women and breastfeeding women and 150 mcg/day for women in the preconception period.

Data from a survey of the Latvian population indicate that approximately 100 mcg of iodine per day is consumed through foods and iodized salt. To meet the increased iodine requirement in pregnancy, pregnant women should take a supplement containing 150 mcg of iodine daily from the earliest time possible.

A sudden increase in iodine intake in an iodine-deficient population may increase thyroid autoimmunity. It is evident that thyroid disease has multiple adverse effects during pregnancy and in the developing fetus especially in women with elevated serum anti-thyroid antibody titers.

Studies have considered supplementing with selenium to reduce the risk of auto-immune thyroiditis/post-partum autoimmune thyroid disease. Of the 11 trials of selenium supplementation in patients with autoimmune thyroiditis, 7 have shown benefit with treatment for 6 months or longer.

Aim of study is to approve that 150 mcg of iodine daily improves iodine status in pregnant women and iodine 150 mcg in combination with selenium 100 mcg daily reduce risk of thyroid autoimmunity.

Hypothesis of study is that 150 mcg iodine daily during pregnancy improves iodine status. Iodine in combination with selenium is less associated with thyroid autoimmunity.

Study design: Pregnant women are randomized for either 150 mcg iodine intake daily or 150 mcg iodine combined with 100 mcg selenium daily. Interventional group is compared with controls without particular iodine supplementation.

Participants are asked to complete a questionnaire on dietary habits concerning iodine. Thyroid function (thyroid-stimulating hormone, free thyroxine) and thyroperoxidase antibodies (TPO-Ab) and urinary iodine are measured during first, second and third trimester of pregnancy and week 8 after delivery in both, intervention and control group.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

In 1994, the WHO and UNICEF Joint Committee on Health Policy recommended Universal Salt Iodization as a safe, cost-effective and sustainable strategy to ensure sufficient intake of iodine by all individuals. However, universal salt iodization is still absent in Latvia.

A recent countrywide study in 2013 shows iodine deficiency among pregnant women in Latvia. The median Cr-standardized UIC was 80.8 (interquartile range (IQR) 46.1-130.6) mcg/g Cr or 69.4 (IQR 53.9-92.6) mcg/L during pregnancy, and 81 % of pregnant women had UIC levels below the WHO recommended range of 150-250 mcg/g Cr.

Because mild to moderate iodine deficiency during pregnancy can adversely affect fetal brain development, WHO-UNICEF and ICCIDD advise an increase in the recommended daily dosage of iodine to 250 mcg/day for pregnant women and breastfeeding women and 150 mcg/day for women in the preconception period.

Data from a survey of the Latvian population indicate that approximately 100 mcg of iodine per day is consumed through foods and iodized salt. To meet the increased iodine requirement in pregnancy, pregnant women should take a supplement containing 150 mcg of iodine daily from the earliest time possible.

A sudden increase in iodine intake in an iodine-deficient population may increase thyroid autoimmunity. Studies have connected induction of disease processes with thyroglobulin (Tg) iodination, because hypo-iodinated Tg did not activate T cells; however, increasing the Tg iodine content to even normal levels in vitro led to antigenicity of the molecule. It is evident that thyroid disease has multiple adverse effects during pregnancy and the postpartum period, and in the developing fetus especially in women with elevated serum anti-thyroid antibody titers.

Previous studies have considered supplementing with selenium to reduce the risk of auto-immune thyroiditis/post-partum autoimmune thyroid disease. Potential mechanisms may be related to the selenoenzyme, GPx3, removing excess H2O2 produced in the thyrocyte for the iodination of tyrosine to give thyroid hormones, thereby preventing thyrocyte damage. Additionally, selenoprotein S (SEPS1) is involved in the control of the inflammatory response in the endoplasmic reticulum. Of the 11 trials of selenium supplementation in patients with autoimmune thyroiditis, 7 have shown benefit with treatment for 6 months or longer.

Aim of study is to approve that 150 mcg of iodine daily improves iodine status in pregnant women and iodine 150 mcg in combination with selenium 100 mcg daily reduce risk of thyroid autoimmunity.

Hypothesis of study is that 150 mcg iodine daily during pregnancy improves iodine status. Iodine in combination with selenium is less associated with thyroid autoimmunity.

Study design: Pregnant women are randomized for either 150 mcg iodine intake daily or 150 mcg iodine combined with 100 mcg selenium daily. Interventional group is compared with controls without particular iodine supplementation.

Participants are asked to complete a questionnaire on dietary habits concerning iodine intake at the moment they are recruited for study, at third trimester of pregnancy and week 8 after delivery.

Thyroid function (thyroid-stimulating hormone (TSH), free thyroxine (fT4) and thyroperoxidase antibodies (TPO-Ab) measures are assessed during first, second and third trimester of pregnancy and week 8 after delivery in both, intervention and control group. Blood samples are sent to the E. Gulbis Laboratory (Riga, Latvia), which operates according to EN ISO 15189:2008 standard. TSH, fT4 and TPO-Ab are measured by chemiluminescence immunoassay (Siemens, Malvern, PA, USA).

Urinary iodine, using the ammonium persulfate method, is also measured in first, second, third trimester of pregnancy and postpartum week 8 in intervention and control groups.

The urinary creatinine concentration is measured using the Jaffe method with the intention that iodine concentration adjusted for creatinine concentration (iodine/Cr) could be calculated. Creatinine standardized UIC is a more reliable method of iodine excretion than random spot UIC measurement since there is a great day-to-day variability in water intake.

Statistical analysis includes pairwise comparison of 1) median (interquartile range) urinary iodine concentration, median (IQR) or mean (SD) TSH, and median (IQR) or mean (SD) fT4; 2) proportion (95%CI) of women with UIC below 150 mcg, TSH above trimester-specific norm, and positive TPO antibodies among all three study groups at specific follow-up intervals. Mann-Whitney U test or two-sided t-test is used for comparing continuous variables, whereas chi2 test (or Fisher exact test) is used to compare proportions. If significant differences observed at baseline, the change in those parameters from visit to visit is calculated and compared. Logistic regression analysis is used to compare intervention groups with control group in order to adjust for differences in baseline characteristics.

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Latvia
      • Riga, Latvia
        • Recruiting
        • Riga Maternity hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • healthy women before 10 weeks of gestation
  • signed informed consent form

Exclusion Criteria:

  • pre-existing thyroid disease
  • pregnancy after assisted reproductive technologies
  • known hypersensitivity reaction to iodine or selenium, or other components of dietary supplement used in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Without additional iodine supplementation.
Experimental: Iodine
Receiving iodine.
Dietary supplement: Iodine
Receiving 150 μg iodine (as potassium iodide) daily
Experimental: Iodine + Selenium
Receiving iodine and selenium.
Dietary supplement: Iodine + Selenium
Receiving a combination of 150 μg iodine (as potassium iodide) and 100 μg selenium daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
UIC
Time Frame: At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)
Urinary iodine concentration
At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)
Change in anti-TPO Ab
Time Frame: At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)
Change in anti-thyroperoxidase antibodies
At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TSH
Time Frame: At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)
Thyroid stimulating hormone
At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)
fT4
Time Frame: At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)
Free thyroxine
At baseline - 9/10 weeks of gestation, second sample - 24 weeks of gestation (14 weeks from baseline), third sample - 34 weeks of gestation (24 weeks from the baseline) and fourth sample - 8 weeks postpartum- (38 weeks after the baseline sample)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Riga Stradins University

Collaborators

Latvian Institute of Organic Synthesis
Latvian Biomedical Research and Study Centre
Riga Maternity hospital

Investigators

  • Principal Investigator: Ilze Konrade, professor, Riga Stradiņš University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2018

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

January 1, 2019

Study Registration Dates

First Submitted

November 18, 2017

First Submitted That Met QC Criteria

December 13, 2017

First Posted (Actual)

December 19, 2017

Study Record Updates

Last Update Posted (Actual)

April 19, 2018

Last Update Submitted That Met QC Criteria

April 17, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RigaStradinsU_Iodine3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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