Displacement of Iodine Balance Value During Pregnancy and the Mechanism of Breast Iodine Homeostasis During Lactation

Study on the Displacement of Iodine Balance Value During Pregnancy and the Mechanism of Breast Iodine Homeostasis During Lactation Under Different Iodine Exposure

In order to solve the bottleneck problems of"zero balance displacement"and"large variation of breastmilk"in the study of iodine EAR of pregnant women, lactating women and infants, firstly, this study intends to clarify the rate of metabolism and distribution of iodine during pregnancy by 125I tracer, SPECT/CT in vivo small animal imaging and γ counting study. Then, the iodine balance study in rats was conducted to verify the degree of "zero balance value displacement"caused by the difference of iodine absorption and store in different organs and tissues under different iodine exposure levels, so as to determine the iodine selection conditions of subjects in the population experiment. To determine the EAR of pregnant women by optimizing the population iodine balance experiment. Secondly, we proposed to study the regulatory mechanism of NIS and Pendrin in the mammary gland of lactating rats under different iodine nutrition levels to clarify the range of breastmilk iodine compensation. Mammary cell experiments intend to clarify the mutual regulations of iodine nutrition, oestrogen, and NIS and Pendrin. Based on the results of animal and cellular experiments, and the effect of genetic, oestrogen and iodine status were considered, a cross-sectional study of lactating women was conducted to determine the normal reference range of breastmilk iodine after screening out the people with abnormal indicators. This study will solve the bottleneck problems and difficulties in the iodine RNI research for pregnant women, lactating women and infants, found the iodine nutritional compensatory mechanism under special physiology, and provide the scientific basis for obtaining the accurate EAR basic data and the revision of iodine DRIs.

Study Overview

• Status: Not yet recruiting
• Conditions: Nutritional Requirements
• Intervention / Treatment: Other: dietary intervention

Detailed Description

In this study, the absorption, distribution, storage and excretion of 125I in rats were observed by small animal imaging technology in vivo, so as to clarify the characteristics of iodine metabolism under different iodine exposure, and provide a basis for optimizing the experimental cycle of iodine balance experiment. The iodine balance experiment of rats during pregnancy was carried out, the iodine storage in different organs was detected to explain the phenomenon of "zero point balance value shift", and the population with iodine nutrition background was determined as the experimental objects in the iodine balance experiment. The optimized iodine balance experiment was further verified in the population, and the iodine EAR of pregnant women was explored to provide reference data for formulating the recommended iodine intake of pregnant women in China in the future. The expression difference of NIS and Pendrin in lactating rats with different iodine nutritional status was used to determine the range of milk iodine compensation. To determine the synergistic and independent effects of iodine level and estrogen on the expression of NIS and Pendrin in lactating mammary gland cells cultured in primary culture. Through a cross-section study of lactating women, the correlation between milk iodine level and NIS, Pendrin gene mutation, iodine exposure level and estrogen was discussed, the phenomenon of "huge milk iodine variation" was explained, the normal reference range of milk iodine was defined, and the basis was laid for further determination of iodine AI and EAR of lactating mothers in 0-6 months. To clarify the steady-state mechanism of iodine metabolism in pregnancy-milk during special physiological periods with different iodine exposure levels, research ideas and related research results can also provide references for the determination of other nutrient requirements.

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

• Study Contact: Name: Wanqi Zhang, docotorate; Phone Number: 022-83336595; Email: wqzhang@tmu.edu.cn
• Study Contact Backup: Name: ying ye; Phone Number: 022-83336717; Email: yeying@tmu.edu.cn

Study Locations

• China
  • Lanzhou, China
    • Gansu Provincial Center for Disease Control and Prevention
    • Contact: ying ye; Phone Number: 022-83336717; Email: yeying@tmu.edu.cn
    • Contact: WanQi Zhang; Phone Number: 022-83336595; Email: wqzhang@tmu.edu.cn
    • Principal Investigator: Min Fu
    • Principal Investigator: Shaohan Li
  • Urumqi, China
    • Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention
    • Contact: ying ye; Phone Number: 022-83336717; Email: yeying@tmu.edu.cn
    • Contact: WanQi Zhang; Phone Number: 022-83336595; Email: wqzhang@tmu.edu.cn
    • Principal Investigator: Min Fu
    • Principal Investigator: Shaohan Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 40 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women in the third trimester (18-40 years old), lactating women (38-42 weeks of gestation), all from Tianjin, Xinjiang and Gansu.

Description

Inclusion Criteria:

Pregnant women:

• Aged 18-40, who have lived in the area for ≥5 year;
• Single pregnancy;
• Those who have no special dietary habits;

Lactating woman:

• Breastfeeding a child;
• Normal thyroid function during pregnancy;
• Term delivery (38-42 weeks of gestation);

Exclusion Criteria:

Pregnant women:

• Smoking or drinking;
• Iodized drugs or contrast agents have been used in the past year;
• A history of thyroid disease, autoimmune disease, endocrine disease, heart disease, chronic disease or family hereditary disease, etc

Lactating woman:

• A history of thyroid disease, autoimmune disease, endocrine disease, heart disease, chronic disease or family hereditary disease, etc;
• Iodized drugs or contrast agents have been used;

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urine iodine concentration	μg/L	pregnancy 1-40 weeks
Free thyroxine	pmol/L	pregnancy 1-40 weeks
Free triiodothyronine	pmol/L	pregnancy 1-40 weeks
Thyroglobulin(TG)	ug/L	pregnancy 1-40 weeks
Thyroid-stimulating hormone	mIU/L	pregnancy 1-40 weeks
Salt iodine concentration	μg/day	pregnancy 1-40 weeks
Urinary iodine excretion	μg/day	pregnancy 1-40 weeks
Fecal iodine excretion	μg/day	pregnancy 1-40 weeks
Dietary iodine intake	μg/day	pregnancy 1-40 weeks
Water iodine intake	ug/day	pregnancy 1-40 weeks
Thyroid peroxidase antibody	IU/mL	pregnancy 1-40 weeks
Thyroglobulin antibody	IU/mL	pregnancy 1-40 weeks
Milk iodine excretion	μg/day	Postpartum 0-6 months
Milk Iodine concentration	μg/L	Postpartum 0-6 months
Thyroid volume	cm³	Postpartum 0-6 months
Na+/I- symporter	mRNA	Postpartum 0-6 months
Pendrin	mRNA	Postpartum 0-6 months
estrogen	pmol/L	Postpartum 0-6 months
progesterone	pmol/L	Postpartum 0-6 months
oxytocin	ng/L	Postpartum 0-6 months
prolactin	pg/MI	Postpartum 0-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Milk output	μg/day	Postpartum 0-6 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University
• Investigators: Principal Investigator: Ling Zhang, Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention; Principal Investigator: Yanling Wang, Gansu Provincial Center for Disease Control and Prevention; Principal Investigator: Xiaomei Yao, Tianjin Medical University; Principal Investigator: Laixiang Lin, Tianjin Medical University; Principal Investigator: Zuoliang Dong, Tianjin Medical University; Principal Investigator: Yiming Shen, Tianjin Medical University; Principal Investigator: Chenchen Wang, Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention; Principal Investigator: Wenxing Guo, Tianjin Medical University; Principal Investigator: ZiYun Pan, Tianjin Medical University

Publications and helpful links

General Publications

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• Pearce EN, Lazarus JH, Moreno-Reyes R, Zimmermann MB. Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns. Am J Clin Nutr. 2016 Sep;104 Suppl 3(Suppl 3):918S-23S. doi: 10.3945/ajcn.115.110429. Epub 2016 Aug 17.
• Sang Z, Wang PP, Yao Z, Shen J, Halfyard B, Tan L, Zhao N, Wu Y, Gao S, Tan J, Liu J, Chen Z, Zhang W. Exploration of the safe upper level of iodine intake in euthyroid Chinese adults: a randomized double-blind trial. Am J Clin Nutr. 2012 Feb;95(2):367-73. doi: 10.3945/ajcn.111.028001. Epub 2011 Dec 28.
• Chen W, Li X, Wu Y, Bian J, Shen J, Jiang W, Tan L, Wang X, Wang W, Pearce EN, Zimmermann MB, Carriquiry AL, Zhang W. Associations between iodine intake, thyroid volume, and goiter rate in school-aged Chinese children from areas with high iodine drinking water concentrations. Am J Clin Nutr. 2017 Jan;105(1):228-233. doi: 10.3945/ajcn.116.139725. Epub 2016 Dec 7.
• Chen W, Zhang Y, Hao Y, Wang W, Tan L, Bian J, Pearce EN, Zimmermann MB, Shen J, Zhang W. Adverse effects on thyroid of Chinese children exposed to long-term iodine excess: optimal and safe Tolerable Upper Intake Levels of iodine for 7- to 14-y-old children. Am J Clin Nutr. 2018 May 1;107(5):780-788. doi: 10.1093/ajcn/nqy011.
• Sang Z, Wei W, Zhao N, Zhang G, Chen W, Liu H, Shen J, Liu J, Yan Y, Zhang W. Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women. J Clin Endocrinol Metab. 2012 Aug;97(8):E1363-9. doi: 10.1210/jc.2011-3438. Epub 2012 Jun 5.
• Shi X, Han C, Li C, Mao J, Wang W, Xie X, Li C, Xu B, Meng T, Du J, Zhang S, Gao Z, Zhang X, Fan C, Shan Z, Teng W. Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China. J Clin Endocrinol Metab. 2015 Apr;100(4):1630-8. doi: 10.1210/jc.2014-3704. Epub 2015 Jan 28.
• Yang L, Li M, Liu X, Wu M, Zhang J, Zhao L, Ding G, Yang X. Evaluation of Iodine Nutritional Status Among Pregnant Women in China. Thyroid. 2020 Mar;30(3):443-450. doi: 10.1089/thy.2019.0001.
• Tan L, Tian X, Wang W, Guo X, Sang Z, Li X, Zhang P, Sun Y, Tang C, Xu Z, Shen J, Zhang W. Exploration of the appropriate recommended nutrient intake of iodine in healthy Chinese women: an iodine balance experiment. Br J Nutr. 2019 Mar 14;121(5):519-528. doi: 10.1017/S0007114518003653. Epub 2018 Dec 11.
• Andersson M, Braegger CP. The Role of Iodine for Thyroid Function in Lactating Women and Infants. Endocr Rev. 2021 Nov 17:bnab029. doi: 10.1210/endrev/bnab029. Online ahead of print. Erratum In: Endocr Rev. 2022 Feb 02;: Endocr Rev. 2022 May 12;43(3):610.
• Stravik M, Gustin K, Barman M, Skroder H, Sandin A, Wold AE, Sandberg AS, Kippler M, Vahter M. Infant Iodine and Selenium Status in Relation to Maternal Status and Diet During Pregnancy and Lactation. Front Nutr. 2021 Dec 17;8:733602. doi: 10.3389/fnut.2021.733602. eCollection 2021.
• Zimmermann MB. The adverse effects of mild-to-moderate iodine deficiency during pregnancy and childhood: a review. Thyroid. 2007 Sep;17(9):829-35. doi: 10.1089/thy.2007.0108. Erratum In: Thyroid. 2008 Jan;18(1):97.
• Naess S, Markhus MW, Strand TA, Kjellevold M, Dahl L, Stokland AM, Nedrebo BG, Aakre I. Iodine Nutrition and Iodine Supplement Initiation in Association with Thyroid Function in Mildly-to-Moderately Iodine-Deficient Pregnant and Postpartum Women. J Nutr. 2021 Oct 1;151(10):3187-3196. doi: 10.1093/jn/nxab224.
• Zhang H, Wu M, Yang L, Wu J, Hu Y, Han J, Gu Y, Li X, Wang H, Ma L, Yang X. Evaluation of median urinary iodine concentration cut-off for defining iodine deficiency in pregnant women after a long term USI in China. Nutr Metab (Lond). 2019 Sep 9;16:62. doi: 10.1186/s12986-019-0381-4. eCollection 2019.
• Dold S, Zimmermann MB, Baumgartner J, Davaz T, Galetti V, Braegger C, Andersson M. A dose-response crossover iodine balance study to determine iodine requirements in early infancy. Am J Clin Nutr. 2016 Sep;104(3):620-8. doi: 10.3945/ajcn.116.134049. Epub 2016 Jul 27.
• Semba RD, Delange F. Iodine in human milk: perspectives for infant health. Nutr Rev. 2001 Aug;59(8 Pt 1):269-78. doi: 10.1111/j.1753-4887.2001.tb05512.x.
• Nazeri P, Mirmiran P, Shiva N, Mehrabi Y, Mojarrad M, Azizi F. Iodine nutrition status in lactating mothers residing in countries with mandatory and voluntary iodine fortification programs: an updated systematic review. Thyroid. 2015 Jun;25(6):611-20. doi: 10.1089/thy.2014.0491. Epub 2015 May 14.
• Chen Y, Gao M, Bai Y, Hao Y, Chen W, Cui T, Guo W, Pan Z, Lin L, Wang C, Shen J, Zhang W. Variation of iodine concentration in breast milk and urine in exclusively breastfeeding women and their infants during the first 24 wk after childbirth. Nutrition. 2020 Mar;71:110599. doi: 10.1016/j.nut.2019.110599. Epub 2019 Sep 23.
• Azizi F, Smyth P. Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf). 2009 May;70(5):803-9. doi: 10.1111/j.1365-2265.2008.03442.x. Epub 2008 Oct 6.
• Dold S, Zimmermann MB, Aboussad A, Cherkaoui M, Jia Q, Jukic T, Kusic Z, Quirino A, Sang Z, San Luis TO, Vandea E, Andersson M. Breast Milk Iodine Concentration Is a More Accurate Biomarker of Iodine Status Than Urinary Iodine Concentration in Exclusively Breastfeeding Women. J Nutr. 2017 Apr;147(4):528-537. doi: 10.3945/jn.116.242560. Epub 2017 Feb 22.
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• Mizokami T, Fukata S, Hishinuma A, Kogai T, Hamada K, Maruta T, Higashi K, Tajiri J. Iodide Transport Defect and Breast Milk Iodine. Eur Thyroid J. 2016 Jul;5(2):145-8. doi: 10.1159/000446496. Epub 2016 May 27.
• Al-Rasheed MM, Alzahrani AS, Macadam A, Overall A, Gard P, Dzimiri N. The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer. Gene. 2015 Nov 10;572(2):163-8. doi: 10.1016/j.gene.2015.07.009. Epub 2015 Jul 6.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 17, 2023
• Primary Completion (Anticipated): December 31, 2027
• Study Completion (Anticipated): December 31, 2027

Study Registration Dates

• First Submitted: February 2, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Estimate): February 16, 2023

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: nutrient; nutrition of special population; trace element iodine; zero balance displacement; large variation of breastmilk
• Other Study ID Numbers: NSFC-8223000919

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No