Study on the Compensatory Mechanism of Iodine Nutrition and the Optimal Intake Level of Lactating Women

Nutritional Requirements Clinical Trial

Official title:

Study on the Compensatory Mechanism of Iodine Nutrition and the Optimal Intake Level of Lactating Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04492657
• Other study ID #: NSFC-8191001159
• Status: Recruiting
• Start date: January 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2020
• Source: Tianjin Medical University
• Contact: WanQi Zhang, doctorate
• Phone: 022-83336595
• Email: wqzhang[@]tmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Due to the lack of direct evidence of optimal iodine intake of Chinese children, pregnant and lactating women and infants were found during the recent revision of Chinese dietary reference intakes (DRIs) of iodine in 2013 by the applicant Pro. Zhang, and no systematical research about compensatory mechanism of iodine nutrition in lactating women was found yet. Previous study funded by United Nations International Children's Emergency Fund (UNICEF) cooperated with the international experts on iodine and key project of national natural science foundation of China under the guidance of Pro. Zhang, had obtained the safe intake range of iodine from children and pregnant women, more than 10 joint papers were published, which laid the foundation of population study and international cooperation.

Description:

Studies indicate lactating women and their infants are the most vulnerable population to the adverse effects of iodine deficiency and excess, and because of the complexity of the study of lactating mothers and infants and the difficulty of sample collection, it is proposed to overcome this problem with the help of the advanced dried blood spot technique and iodine balance study method from the panel of Iodine Global Network (IGN). Investigators intend to recruit 900 late pregnant women in Tianjin, Hebei and Shandong;then establishing a dynamic cohort of breastfeeding mother-infant to 6 months after delivery to investigate the physiological compensatory mechanism of iodine nutrition in lactating women with the combination of animal experiment; On the other hand, 180 exclusively breastfeeding mother and infants within postpartum 0-6 months, will be selected to participate the iodine balance study.

Optimized method of iodine balance experiment of infants by both foreign partner and Pro. Zhang's team will be adopted to obtain the first iodine balance value of Chinese lactating women and infants,providing the direct evidence for the revision of DRIs in lactating women and infants, and guide the lactating women proper iodine supplementation to meet the requirements of both mothers and infants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 40 Years

Eligibility

Inclusion Criteria:

• Women in their third trimester:?Aged 18-40, who have lived in the area for 1 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);

• Infants and young children:?0-6 months;?Breastfeeding;?Full term (38-42 weeks of gestation);?Normal birth weight (2500-4000g);?The thyroid-stimulating hormone (TSH) value of heel blood was normal;?Apgar score 8.

Exclusion Criteria:

• Women in their third trimester:?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;

• Infants and young children:?Have pathological jaundice, autoimmune disease, congenital heart disease and other diseases.

Related Conditions & MeSH terms

• Nutritional Requirements

Intervention

Other:
• no intervention
Natural exposure of iodine.

Locations

Country	Name	City	State
China	Institute of Nutrition and Health, Chinese Center for Disease Control and Prevention	Beijing
China	Shandong Institute of Endemic Disease Control and Prevention	Shandong
Switzerland	Swiss federal institute of Technology (ETH)	Zurich
United States	Boston University School of Medicine; Iodine Global Network (IGN)	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University

Countries where clinical trial is conducted

United States,  China,  Switzerland, 

References & Publications (48)

Aakre I, Bjøro T, Norheim I, Strand TA, Barikmo I, Henjum S. Excessive iodine intake and thyroid dysfunction among lactating Saharawi women. J Trace Elem Med Biol. 2015;31:279-84. doi: 10.1016/j.jtemb.2014.09.009. Epub 2014 Oct 6. — View Citation

Bizhanova A, Kopp P. Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology. 2009 Mar;150(3):1084-90. doi: 10.1210/en.2008-1437. Epub 2009 Feb 5. Review. — View Citation

Brough L, Thomson BM, Skeaff SA. Revisiting the Iodine Global Network's definition of iodine status by country. Br J Nutr. 2016 Jan 28;115(2):374-6. doi: 10.1017/S0007114515004389. Epub 2015 Dec 2. — View Citation

Calil-Silveira J, Serrano-Nascimento C, Kopp PA, Nunes MT. Iodide excess regulates its own efflux: a possible involvement of pendrin. Am J Physiol Cell Physiol. 2016 Apr 1;310(7):C576-82. doi: 10.1152/ajpcell.00210.2015. Epub 2016 Jan 20. — View Citation

Chan SS, Hams G, Wiley V, Wilcken B, McElduff A. Postpartum maternal iodine status and the relationship to neonatal thyroid function. Thyroid. 2003 Sep;13(9):873-6. — View Citation

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. — View Citation

Chen W, Sang Z, Tan L, Zhang S, Dong F, Chu Z, Wei W, Zhao N, Zhang G, Yao Z, Shen J, Zhang W. Neonatal thyroid function born to mothers living with long-term excessive iodine intake from drinking water. Clin Endocrinol (Oxf). 2015 Sep;83(3):399-404. doi: 10.1111/cen.12625. Epub 2014 Nov 5. — View Citation

Chen W, Wu Y, Lin L, Tan L, Shen J, Pearce EN, Guo X, Wang W, Bian J, Jiang W, Zhang W. 24-Hour Urine Samples Are More Reproducible Than Spot Urine Samples for Evaluation of Iodine Status in School-Age Children. J Nutr. 2016 Jan;146(1):142-6. doi: 10.3945/jn.115.215806. Epub 2015 Nov 25. — View Citation

Chen W, Zhang Q, Wu Y, Wang W, Wang X, Pearce EN, Tan L, Shen J, Zhang W. Shift of Reference Values for Thyroid Volume by Ultrasound in 8- to 13-Year-Olds with Sufficient Iodine Intake in China. Thyroid. 2019 Mar;29(3):405-411. doi: 10.1089/thy.2018.0412. — View Citation

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. — View Citation

Chen Y, Chen W, Du C, Fan L, Wang W, Gao M, Zhang Y, Cui T, Hao Y, Pearce EN, Wang C, Zhang W. Iodine Nutrition and Thyroid Function in Pregnant Women Exposed to Different Iodine Sources. Biol Trace Elem Res. 2019 Jul;190(1):52-59. doi: 10.1007/s12011-018-1530-8. Epub 2018 Oct 2. — View Citation

Chung HR, Shin CH, Yang SW, Choi CW, Kim BI. Subclinical hypothyroidism in Korean preterm infants associated with high levels of iodine in breast milk. J Clin Endocrinol Metab. 2009 Nov;94(11):4444-7. doi: 10.1210/jc.2009-0632. Epub 2009 Oct 6. — View Citation

De la Vieja A, Santisteban P. Role of iodide metabolism in physiology and cancer. Endocr Relat Cancer. 2018 Apr;25(4):R225-R245. doi: 10.1530/ERC-17-0515. Epub 2018 Feb 1. Review. — View Citation

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. — View Citation

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. — View Citation

Dworkin HJ, Jacquez JA, Beierwaltes WH. Relationship of iodine ingestion to iodine excretion in pregnancy. J Clin Endocrinol Metab. 1966 Dec;26(12):1329-42. — View Citation

Farebrother J, Zimmermann MB, Assey V, Castro MC, Cherkaoui M, Fingerhut R, Jia Q, Jukic T, Makokha A, San Luis TO, Wegmüller R, Andersson M. Thyroglobulin Is Markedly Elevated in 6- to 24-Month-Old Infants at Both Low and High Iodine Intakes and Suggests a Narrow Optimal Iodine Intake Range. Thyroid. 2019 Feb;29(2):268-277. doi: 10.1089/thy.2018.0321. — View Citation

Henjum S, Barikmo I, Strand TA, Oshaug A, Torheim LE. Iodine-induced goitre and high prevalence of anaemia among Saharawi refugee women. Public Health Nutr. 2012 Aug;15(8):1512-8. doi: 10.1017/S1368980011002886. Epub 2011 Nov 7. — View Citation

Henjum S, Kjellevold M, Ulak M, Chandyo RK, Shrestha PS, Frøyland L, Strydom EE, Dhansay MA, Strand TA. Iodine Concentration in Breastmilk and Urine among Lactating Women of Bhaktapur, Nepal. Nutrients. 2016 Apr 28;8(5). pii: E255. doi: 10.3390/nu8050255. — View Citation

Huynh D, Condo D, Gibson R, Muhlhausler B, Ryan P, Skeaff S, Makrides M, Zhou SJ. Iodine status of postpartum women and their infants in Australia after the introduction of mandatory iodine fortification. Br J Nutr. 2017 Jun;117(12):1656-1662. doi: 10.1017/S0007114517001775. — View Citation

Ingenbleek Y, Malvaux P. Iodine balance studies in protein-calorie malnutrition. Arch Dis Child. 1974 Apr;49(4):305-9. — View Citation

Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. — View Citation

Kleinau G, Biebermann H. Constitutive activities in the thyrotropin receptor: regulation and significance. Adv Pharmacol. 2014;70:81-119. doi: 10.1016/B978-0-12-417197-8.00003-1. Review. — View Citation

Knudsen N, Bülow I, Jørgensen T, Perrild H, Ovesen L, Laurberg P. Serum Tg--a sensitive marker of thyroid abnormalities and iodine deficiency in epidemiological studies. J Clin Endocrinol Metab. 2001 Aug;86(8):3599-603. — View Citation

Liu L, Wang D, Liu P, Meng F, Wen D, Jia Q, Liu J, Zhang X, Jiang P, Shen H. The relationship between iodine nutrition and thyroid disease in lactating women with different iodine intakes. Br J Nutr. 2015 Nov 14;114(9):1487-95. doi: 10.1017/S0007114515003128. Epub 2015 Sep 14. — View Citation

Mao IF, Ko YC, Chen ML. The stability of iodine in human sweat. Jpn J Physiol. 1990;40(5):693-700. — View Citation

Nazeri P, Dalili H, Mehrabi Y, Hedayati M, Mirmiran P, Azizi F. Breast Milk Iodine Concentration Rather than Maternal Urinary Iodine Is a Reliable Indicator for Monitoring Iodine Status of Breastfed Neonates. Biol Trace Elem Res. 2018 Sep;185(1):71-77. doi: 10.1007/s12011-018-1246-9. Epub 2018 Jan 25. — View Citation

Nazeri P, Zarghani NH, Mirmiran P, Hedayati M, Mehrabi Y, Azizi F. Iodine Status in Pregnant Women, Lactating Mothers, and Newborns in an Area with More Than Two Decades of Successful Iodine Nutrition. Biol Trace Elem Res. 2016 Jul;172(1):79-85. doi: 10.1007/s12011-015-0575-1. Epub 2015 Dec 2. — View Citation

Nicola JP, Reyna-Neyra A, Carrasco N, Masini-Repiso AM. Dietary iodide controls its own absorption through post-transcriptional regulation of the intestinal Na+/I- symporter. J Physiol. 2012 Dec 1;590(23):6013-26. doi: 10.1113/jphysiol.2012.241307. Epub 2012 Sep 24. — View Citation

Pan Z, Cui T, Chen W, Gao S, Pearce EN, Wang W, Chen Y, Guo W, Tan L, Shen J, Zhang W. Serum iodine concentration in pregnant women and its association with urinary iodine concentration and thyroid function. Clin Endocrinol (Oxf). 2019 May;90(5):711-718. doi: 10.1111/cen.13945. Epub 2019 Mar 7. — View Citation

Pearce EN, Andersson M, Zimmermann MB. Global iodine nutrition: Where do we stand in 2013? Thyroid. 2013 May;23(5):523-8. doi: 10.1089/thy.2013.0128. Epub 2013 Apr 18. Review. — View Citation

Perron B, Rodriguez AM, Leblanc G, Pourcher T. Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. J Endocrinol. 2001 Jul;170(1):185-96. — View Citation

Ryan J, Curran CE, Hennessy E, Newell J, Morris JC, Kerin MJ, Dwyer RM. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue. PLoS One. 2011 Jan 19;6(1):e16023. doi: 10.1371/journal.pone.0016023. — View Citation

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. — View Citation

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. — View Citation

Stinca S, Andersson M, Herter-Aeberli I, Chabaa L, Cherkaoui M, El Ansari N, Aboussad A, Weibel S, Zimmermann MB. Moderate-to-Severe Iodine Deficiency in the "First 1000 Days" Causes More Thyroid Hypofunction in Infants Than in Pregnant or Lactating Women. J Nutr. 2017 Apr;147(4):589-595. doi: 10.3945/jn.116.244665. Epub 2017 Feb 15. — View Citation

Suzuki K, Kimura H, Wu H, Kudo N, Kim WB, Suzuki S, Yoshida A, Caturegli P, Kohn LD. Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells. Biochem Biophys Res Commun. 2010 Mar 5;393(2):286-90. doi: 10.1016/j.bbrc.2010.01.123. Epub 2010 Feb 2. — View Citation

Swanson CA, Zimmermann MB, Skeaff S, Pearce EN, Dwyer JT, Trumbo PR, Zehaluk C, Andrews KW, Carriquiry A, Caldwell KL, Egan SK, Long SE, Bailey RL, Sullivan KM, Holden JM, Betz JM, Phinney KW, Brooks SP, Johnson CL, Haggans CJ. Summary of an NIH workshop to identify research needs to improve the monitoring of iodine status in the United States and to inform the DRI. J Nutr. 2012 Jun;142(6):1175S-85S. doi: 10.3945/jn.111.156448. Epub 2012 May 2. — View Citation

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. 2018 Dec 11:1-31. doi: 10.1017/S0007114518003653. [Epub ahead of print] — View Citation

Thomasz L, Oglio R, Salvarredi L, Perona M, Rossich L, Copelli S, Pisarev M, Juvenal G. Regulation of NADPH oxidase NOX4 by delta iodolactone (IL-d) in thyroid cancer cells. Mol Cell Endocrinol. 2018 Jul 15;470:115-126. doi: 10.1016/j.mce.2017.10.004. Epub 2017 Oct 7. — View Citation

Van Sande J, Dequanter D, Lothaire P, Massart C, Dumont JE, Erneux C. Thyrotropin stimulates the generation of inositol 1,4,5-trisphosphate in human thyroid cells. J Clin Endocrinol Metab. 2006 Mar;91(3):1099-107. Epub 2005 Dec 29. — View Citation

Wang W, Sun Y, Zhang M, Zhang Y, Chen W, Tan L, Shen J, Zhao Z, Lan S, Zhang W. Breast milk and infant iodine status during the first 12 weeks of lactation in Tianjin City, China. Asia Pac J Clin Nutr. 2018;27(2):393-398. doi: 10.6133/apjcn.062017.03. — View Citation

Yan YQ, Dong ZL, Dong L, Wang FR, Yang XM, Jin XY, Lin LX, Sun YN, Chen ZP. Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals. Clin Endocrinol (Oxf). 2011 Feb;74(2):262-9. doi: 10.1111/j.1365-2265.2010.03910.x. — View Citation

Yu X, Shen H, Liu L, Lin L, Gao M, Wang S. Changes of sodium iodide symporter regulated by IGF-I and TGF-ß1 in mammary gland cells from lactating mice at different iodine levels. Biol Trace Elem Res. 2012 Apr;146(1):73-8. doi: 10.1007/s12011-011-9227-2. Epub 2011 Oct 13. — View Citation

Zhang Y, Du C, Wang W, Chen W, Shao P, Wang C, Leng J, Shen J, Tan L, Zhang W. Effect of maternal and neonatal factors on neonatal thyroid stimulating hormone: Results from a population-based prospective cohort study in China. J Trace Elem Med Biol. 2018 Sep;49:151-156. doi: 10.1016/j.jtemb.2018.05.008. Epub 2018 May 25. — View Citation

Zimmermann MB, Aeberli I, Andersson M, Assey V, Yorg JA, Jooste P, Jukic T, Kartono D, Kusic Z, Pretell E, San Luis TO Jr, Untoro J, Timmer A. Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 µg/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab. 2013 Mar;98(3):1271-80. doi: 10.1210/jc.2012-3952. Epub 2013 Jan 23. — View Citation

Zimmermann MB, de Benoist B, Corigliano S, Jooste PL, Molinari L, Moosa K, Pretell EA, Al-Dallal ZS, Wei Y, Zu-Pei C, Torresani T. Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. J Clin Endocrinol Metab. 2006 Dec;91(12):4881-7. Epub 2006 Sep 12. — View Citation

Zimmermann MB, Moretti D, Chaouki N, Torresani T. Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt. Am J Clin Nutr. 2003 Jun;77(6):1453-8. — View Citation

* Note: There are 48 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disposable random urine	µg/L	baseline
Primary	Venous blood	µg/L	baseline
Primary	Water iodine intake	µg/day	baseline
Primary	Salt iodine concentration	µg/day	baseline
Primary	Colostrum	µg/L	1 week
Primary	Mother and child urine randomly at one time	µg/L	1 week
Primary	Neonatal heel blood	µg/L	1 week
Primary	Thyroglobulin(TG)	ug/L	1 week
Primary	Thyroid-stimulating hormone	mIU/L	1 week
Primary	Infant disposable random urine	µg/L	4 weeks
Primary	Infant disposable random urine	µg/L	24 weeks
Primary	Infant disposable random urine	µg/L	12 weeks
Primary	24 h urine	µg/L	4 weeks
Primary	24 h urine	µg/L	12 weeks
Primary	24 h urine	µg/L	24 weeks
Primary	Urinary iodine excretion	µg/day	4 weeks
Primary	Urinary iodine excretion	µg/day	12 weeks
Primary	Urinary iodine excretion	µg/day	24 weeks
Primary	Milk output	µg/day	4 weeks
Primary	Milk output	µg/day	12 weeks
Primary	Milk output	µg/day	24 weeks
Primary	Milk iodine excretion	µg/day	4 weeks
Primary	Milk iodine excretion	µg/day	12 weeks
Primary	Milk iodine excretion	µg/day	24 weeks
Primary	Average iodine intake	µg/day	4 weeks
Primary	Average iodine intake	µg/day	12 weeks
Primary	Average iodine intake	µg/day	24 weeks
Primary	Thyroid volume	cm³	1 week
Primary	Thyroid volume	cm³	4 weeks
Primary	Thyroid volume	cm³	12 weeks
Primary	Thyroid volume	cm³	24 weeks
Primary	Thyroid nodule	cm³	1 week
Primary	Thyroid nodule	cm³	4 weeks
Primary	Thyroid nodule	cm³	12 weeks
Primary	Thyroid nodule	cm³	24 weeks
Primary	Dried blood spot(DBS)	µg/L	3 days
Primary	Dried blood spot(DBS)	µg/L	12 weeks
Primary	Diet iodine intake	µg/day	1 week
Primary	Fecal iodine excretion	µg/day	1 week

External Links

•   UNICEF. Global map of iodized salt coverage, http://www.ign.org/cm_data/UNICEF_map.jpg [M]. State of the World's Children, 2017. UNICEF. 2017.