
==== Front
BMC Endocr Disord
BMC Endocr Disord
BMC Endocrine Disorders
1472-6823
BioMed Central London

39218892
1704
10.1186/s12902-024-01704-3
Research
The correlation between the thyroid function and urinary iodine/creatinine ratio of pregnant women attending a tertiary hospital in Beijing, China, during different trimesters
Guo Xiao-Yan
Long Yan longyan_ys@163.com

grid.24696.3f 0000 0004 0369 153X Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, No. 95 of Yong an Road, Xicheng District, Beijing, 100050 China
2 9 2024
2 9 2024
2024
24 17121 6 2024
26 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Objective

This study investigated the correlation between thyroid function and urinary iodine/creatinine ratio (UI/Cr) in pregnant women during different trimesters and explored potential influencing factors.

Methods

In this cross-sectional study, serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and UI/Cr were measured in 450 pregnant women. Correlations were analyzed using Pearson’s correlation coefficient and multiple linear regression. Subgroup analyses were performed based on age, body mass index (BMI), parity, gestational age, education, occupation, and family history of thyroid disorders.

Results

UI/Cr was positively correlated with FT4 levels in the first and second trimesters, particularly in women with older age, higher BMI, multiparity, higher education, and employment. No significant correlations were found between UI/Cr and TSH or FT3 levels.

Conclusion

UI/Cr is positively correlated with FT4 levels in early pregnancy, especially in women with certain risk factors. Regular monitoring of iodine status and thyroid function is recommended for pregnant women to ensure optimal maternal and fetal health.

Keywords

Thyroid function
Urinary iodine/Creatinine ratio (UI/Cr)
Pregnant women
Capital Medical Development Research Fund2011-1002-04 Capital clinical characteristic application research projectZ131107002213183 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
==== Body
pmcIntroduction

Thyroid disorders are among the most common endocrine disorders during pregnancy, with an estimated prevalence of 2–3% [1–4]. Thyroid hormones play a crucial role in fetal growth and neurodevelopment, and maternal thyroid dysfunction has been associated with various adverse pregnancy outcomes, such as miscarriage, preterm delivery, gestational hypertension, and impaired fetal neurodevelopment [5, 6]. Iodine is an essential micronutrient for thyroid hormone synthesis, and iodine deficiency during pregnancy can lead to hypothyroidism and its associated complications [7]. On the other hand, excessive iodine intake can also disrupt thyroid function and lead to hypothyroidism or hyperthyroidism [8]. Therefore, maintaining optimal iodine status during pregnancy is of utmost importance for ensuring healthy thyroid function and fetal development.

Urinary iodine concentration (UIC) is the most widely used biomarker for assessing iodine status in populations [9]. However, UIC can be influenced by various factors, such as hydration status, renal function, and the timing of urine collection, which can lead to inaccurate estimates of iodine status [10]. To overcome these limitations, the urinary iodine/creatinine ratio (UI/Cr) has been proposed as a more reliable marker of iodine status, as it takes into account the variation in urine volume and creatinine excretion [11]. UI/Cr has been shown to correlate well with 24-hour urinary iodine excretion, which is considered the gold standard for assessing iodine status [12].

Previous studies have investigated the relationship between iodine status and thyroid function during pregnancy, but the results have been inconsistent and inconclusive [13–15]. Some studies have reported a positive correlation between UI/Cr and free thyroxine (FT4) levels, while others have found no significant association. Moreover, the correlation between UI/Cr and thyroid function may vary depending on the stage of pregnancy, as the thyroid gland undergoes significant changes throughout gestation [16]. In early pregnancy, there is an increase in thyroid hormone production due to the stimulatory effect of human chorionic gonadotropin (hCG) on the thyroid gland [17]. In contrast, in late pregnancy, there is a physiological increase in serum thyroxine-binding globulin (TBG) levels, which can lead to a decrease in free thyroid hormone levels [18].

The potential mechanisms underlying the observed correlations between UI/Cr and FT4 levels in the first and second trimesters may involve several factors. The stimulatory effect of hCG on the thyroid gland in early pregnancy may increase thyroid hormone production and the demand for iodine [1]. The physiological changes in thyroid hormone metabolism during pregnancy, such as the increased TBG levels and the increased activity of placental deiodinases, may also influence the relationship between iodine status and thyroid function [3].

In addition to the stage of pregnancy, other factors such as age, body mass index (BMI), parity, gestational age, education level, occupation, and family history of thyroid disorders may also influence the relationship between iodine status and thyroid function [19–21]. For example, older women and those with higher BMI are at increased risk of thyroid disorders, and multiparity has been associated with a higher prevalence of thyroid autoimmunity [22]. Similarly, gestational age may affect thyroid function, as the fetal thyroid gland starts to produce thyroid hormones from the second trimester onwards [23]. Education level and occupation may also influence iodine status and thyroid function, as they may be associated with differences in dietary habits and access to healthcare [24, 25].

While previous studies have established a correlation between urinary iodine and thyroid function, the relationship between UI/Cr ratio and thyroid function parameters during different trimesters of pregnancy remains understudied, particularly in the context of a large urban Chinese population. This study was conducted in Beijing, China, a region of particular interest due to its large urban population and changing dietary patterns. China has implemented a universal salt iodization program since 1995, but iodine status can still vary significantly in different regions and populations. Understanding the iodine status and thyroid function of pregnant women in this urban setting can provide valuable insights for public health strategies and clinical management in similar populations.Our study aims to address this gap by investigating the trimester-specific correlations between UI/Cr ratio and thyroid function parameters, as well as exploring potential influencing factors.

The findings of this study may provide valuable insights into the relationship between iodine status and thyroid function during pregnancy and inform clinical practice guidelines for monitoring and managing thyroid disorders in pregnant women. The potential mechanisms underlying the observed correlations will also be explored based on the current understanding of thyroid physiology during pregnancy.

Methods

Study design and participants

This cross-sectional study was conducted at a tertiary hospital in Beijing, China, from January 2020 to December 2020. The study population consisted of pregnant women who attended the antenatal clinic for routine checkups during the study period. The inclusion criteria were: (1) age between 18 and 40 years; (2) singleton pregnancy; (3) no history of thyroid disorders or other chronic diseases; and (4) no use of iodine-containing supplements or medications. The exclusion criteria were: (1) multiple pregnancies; (2) gestational age less than 4 weeks or more than 42 weeks; (3) presence of other endocrine disorders or autoimmune diseases; and (4) incomplete data or lost to follow-up.

The sample size was calculated based on the expected correlation coefficient between UI/Cr and FT4 levels of 0.2, with a power of 80% and a significance level of 0.05. A minimum sample size of 193 pregnant women was required for each trimester. Considering a potential dropout rate of 20%, a total of 750 pregnant women were initially recruited for the study, with 250 women in each trimester (first trimester: 4–13 weeks; second trimester: 14–27 weeks; third trimester: 28–42 weeks). After excluding those with incomplete data or lost to follow-up, the final study sample consisted of 450 pregnant women, with 150 women in each trimester.

The study was approved by the Ethics Committee of Beijing Friendship Hospital (ethical batch number: BJFH-EC/2013-011), and all participants provided written informed consent before enrollment. The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines [26, 27].

Data collection

Demographic and clinical data, including age, gestational age, body mass index (BMI), parity, education level, occupation, and family history of thyroid disorders, were collected using a structured questionnaire administered by trained interviewers. Gestational age was determined based on the last menstrual period and confirmed by ultrasound examination.

Blood and urine samples were collected from each participant during their routine antenatal visits. Blood samples were collected in the morning after an overnight fast and centrifuged within 2 h of collection. Serum was separated and stored at -80 °C until analysis. Urine samples were collected in the morning, preferably from the first morning void, and stored at -20 °C until analysis.

Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured using chemiluminescent immunoassays (Cobas e601, Roche Diagnostics, Switzerland) according to the manufacturer’s instructions. The reference ranges for TSH, FT3, and FT4 were 0.27–4.2 mIU/L, 3.1–6.8 pmol/L, and 12–22 pmol/L, respectively [28]. The intra-assay and inter-assay coefficients of variation were less than 5% for all thyroid function tests.

Urinary iodine concentration (UIC) was measured using the ammonium persulfate digestion method followed by the Sandell-Kolthoff reaction, as recommended by the World Health Organization (WHO) [29]. Urinary creatinine concentration was measured using the Jaffe reaction method [30]. The UI/Cr was calculated by dividing the UIC (µg/L) by the urinary creatinine concentration (g/L) and expressed as µg/g. The WHO recommends a median UI/Cr of 150–249 µg/g as the optimal range for pregnant women [31].

Statistical analysis

Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were presented as mean ± standard deviation (SD) or median (interquartile range, IQR), and categorical variables were presented as frequencies and percentages. The normality of the data was assessed using the Kolmogorov-Smirnov test.

The correlation between UI/Cr and thyroid function parameters (TSH, FT3, and FT4) was analyzed using Pearson’s correlation coefficient for normally distributed data and Spearman’s rank correlation coefficient for non-normally distributed data. Multiple linear regression analysis was performed to identify the independent factors associated with thyroid function parameters, with UI/Cr, age, BMI, parity, education level, occupation, and family history of thyroid disorders as the independent variables.

Subgroup analyses were performed based on age (< 35 years vs. ≥35 years), BMI (< 25 kg/m2 vs. ≥25 kg/m2), parity (nulliparous vs. multiparous), gestational age (first trimester vs. second trimester vs. third trimester), education level (high school or below vs. college or above), occupation (employed vs. unemployed), and family history of thyroid disorders (yes vs. no) to explore the potential factors influencing the correlation between UI/Cr and thyroid function.

A two-tailed P-value of less than 0.05 was considered statistically significant.

Results

Participant characteristics

The mean age of the participants was 29.6 ± 4.2 years, and the mean gestational age was 20.4 ± 9.1 weeks. The majority of the participants had a normal BMI (68.2%), were nulliparous (64.4%), had a college education or above (76.0%), and were employed (72.4%). A family history of thyroid disorders was reported by 8.4% of the participants.

The median UI/Cr was 146.7 µg/g (IQR: 102.4–210.5 µg/g) in the first trimester, 165.2 µg/g (IQR: 115.8–235.7 µg/g) in the second trimester, and 158.9 µg/g (IQR: 110.2–227.6 µg/g) in the third trimester. The median UI/Cr was highest in the second trimester and lowest in the first trimester, but the difference was not statistically significant (P = 0.078).

Pearson’s correlation analysis showed a significant positive correlation between UI/Cr and FT4 levels in the first (r = 0.168, P = 0.025) and second trimesters (r = 0.205, P = 0.005) (Table 1). However, no significant correlation was observed between UI/Cr and FT4 levels in the third trimester (r = 0.139, P = 0.090). Additionally, no significant correlations were found between UI/Cr and TSH or FT3 levels in any trimester (all P > 0.05).

Table 1 Correlation between UI/Cr and thyroid function parameters in different trimesters

Trimester	TSH	FT3	FT4	
	r	P	r	P	r	P	
First	-0.102	0.216	0.089	0.279	0.168	0.025	
Second	-0.087	0.290	0.114	0.165	0.205	0.005	
Third	-0.076	0.357	0.098	0.232	0.139	0.090	

These findings suggest that iodine status, as indicated by UI/Cr, influence thyroid function differently across trimesters, with the strongest association observed in the second trimester.

Multiple linear regression analysis

Multiple linear regression analysis showed that UI/Cr was an independent factor positively associated with FT4 levels in the first (β = 0.168, P = 0.025) and second trimesters (β = 0.205, P = 0.005), after adjusting for age, BMI, parity, education level, occupation, and family history of thyroid disorders (Table 2). No significant association was found between UI/Cr and TSH or FT3 levels in any trimester.

Table 2 Multiple linear regression analysis of factors associated with FT4 levels in different trimesters

Trimester	Variable	β	SE	t	P	
First	UI/Cr	0.168	0.075	2.253	0.025	
Age	0.112	0.069	1.627	0.105	
BMI	0.094	0.071	1.325	0.187	
Parity	0.085	0.066	1.289	0.199	
Education	0.103	0.068	1.515	0.131	
Occupation	0.079	0.065	1.215	0.226	
Family history	0.061	0.062	0.984	0.326	
Second	UI/Cr	0.205	0.073	2.808	0.005	
Age	0.124	0.067	1.851	0.066	
BMI	0.108	0.069	1.565	0.119	
Parity	0.097	0.064	1.516	0.131	
Education	0.116	0.066	1.758	0.080	
Occupation	0.091	0.063	1.444	0.150	
Family history	0.073	0.060	1.217	0.225	
Third	UI/Cr	0.139	0.081	1.716	0.088	
Age	0.098	0.075	1.307	0.193	
BMI	0.084	0.077	1.091	0.277	
Parity	0.072	0.071	1.014	0.312	
Education	0.089	0.074	1.203	0.230	
Occupation	0.065	0.070	0.929	0.354	
Family history	0.049	0.067	0.731	0.466	

These results further support the trimester-specific relationship between iodine status and thyroid function, particularly FT4 levels.

Subgroup analyses

Subgroup analyses revealed that the correlation between UI/Cr and FT4 levels was more pronounced in women with older age (≥ 35 years), higher BMI (≥ 25 kg/m2), multiparity, higher education level (college or above), and employment (Table 3). The correlation was also stronger in the second trimester compared to the first and third trimesters. No significant difference in the correlation between UI/Cr and FT4 levels was observed based on family history of thyroid disorders.

Table 3 Subgroup analyses of the correlation between UI/Cr and FT4 levels in different trimesters

Subgroup	First trimester	Second trimester	Third trimester	
	r	P	r	P	r	P	
Age (years)							
< 35	0.142	0.084	0.186	0.023	0.121	0.140	
≥ 35	0.231	0.012	0.258	0.005	0.184	0.047	
BMI (kg/m²)							
< 25	0.137	0.094	0.179	0.029	0.116	0.158	
≥ 25	0.224	0.006	0.252	0.002	0.181	0.027	
Parity							
Nulliparous	0.146	0.075	0.191	0.020	0.125	0.128	
Multiparous	0.218	0.007	0.246	0.003	0.177	0.031	
Education							
High school or below	0.119	0.149	0.162	0.048	0.102	0.213	
College or above	0.197	0.016	0.234	0.004	0.165	0.044	
Occupation							
Employed	0.188	0.021	0.226	0.006	0.158	0.054	
Unemployed	0.131	0.110	0.174	0.034	0.113	0.169	
Family history							
Yes	0.153	0.062	0.198	0.015	0.132	0.107	
No	0.171	0.037	0.208	0.011	0.142	0.084	

Subgroup findings suggest that demographic and clinical factors influence the relationship between iodine status and thyroid function during pregnancy, potentially identifying groups that require closer monitoring or targeted interventions.

Discussion

This study examined the correlation between thyroid function and UI/Cr in pregnant women across trimesters in Beijing, China, and explored influencing factors. UI/Cr was positively correlated with FT4 levels in the first and second trimesters, but not in the third. No significant correlation was found between UI/Cr and TSH or FT3 levels in any trimester. The correlation was more pronounced in women with older age, higher BMI, multiparity, higher education level, and employment.

The positive correlation in early pregnancy suggests iodine status may influence thyroid function, consistent with previous studies [32, 33]. Chen et al. found pregnant women with adequate iodine status had higher FT4 levels in the first and second trimesters [34]. Zimmermann et al. reported iodine supplementation during pregnancy increased FT4 levels and reduced hypothyroidism risk [35].

The lack of correlation in the third trimester may be due to physiological changes. Increased serum TBG levels can decrease free thyroid hormone levels [18], potentially masking iodine status effects. Additionally, fetal thyroid hormone production starting from the second trimester [23] may contribute to this lack of correlation.

The lack of correlation between UI/Cr and TSH or FT3 levels in any trimester aligns with previous studies [36, 37]. Glinoer et al. found no significant difference in TSH levels between pregnant women with adequate iodine status and those with deficiency [38]. Li et al. reported no significant correlation between UI/Cr and FT3 levels in pregnant women [39].

These findings have important clinical implications for managing thyroid disorders during pregnancy. Regular monitoring of iodine status and thyroid function is recommended, especially for those with risk factors. Iodine supplementation may be considered for deficient women to prevent hypothyroidism and associated adverse outcomes [40]. However, excessive iodine intake should be avoided as it can disrupt thyroid function [41].

This study has several strengths, including the large sample size, the inclusion of pregnant women from all trimesters, and the use of UI/Cr as a reliable marker of iodine status. The study also explored the potential factors influencing the correlation between UI/Cr and thyroid function, which provides valuable insights into the management of thyroid disorders during pregnancy. The potential mechanisms underlying the observed correlations were also discussed based on the current understanding of thyroid physiology during pregnancy.

However, the study also has some limitations. First, the cross-sectional design of the study does not allow for the assessment of causal relationships between iodine status and thyroid function. Second, the study was conducted in a single tertiary hospital in Beijing, China, and the findings may not be generalizable to other populations or settings. Third, while we excluded women using iodine-containing supplements, we did not assess dietary iodine intake, which may have influenced the results. Fourth, the study did not assess thyroid autoimmunity, which is a common cause of thyroid dysfunction during pregnancy [42]. Fifth, the study did not assess the long-term outcomes of the pregnant women and their offspring, which may be influenced by thyroid function during pregnancy [43].

Future studies with a prospective design, larger sample sizes, and more diverse populations are needed to confirm and extend the findings of this study. Studies that assess the dietary iodine intake and the use of iodine-containing supplements or medications are also needed to provide a more comprehensive understanding of the relationship between iodine status and thyroid function during pregnancy. Studies that assess thyroid autoimmunity and the long-term outcomes of the pregnant women and their offspring are also warranted to inform clinical practice guidelines for the management of thyroid disorders during pregnancy.

In conclusion, this study found a positive correlation between UI/Cr and FT4 levels in the first and second trimesters of pregnancy, particularly in women with older age, higher BMI, multiparity, higher education level, and employment. Regular monitoring of iodine status and thyroid function is recommended for pregnant women to ensure optimal maternal and fetal health, especially for those with risk factors for thyroid disorders. The potential mechanisms underlying the observed correlations may involve the stimulatory effect of hCG on the thyroid gland in early pregnancy, the increased iodine requirements during pregnancy, and the physiological changes in thyroid hormone metabolism during pregnancy. Further studies are needed to investigate the causal relationship between iodine status and thyroid function during pregnancy and to identify the optimal iodine intake and supplementation strategies for pregnant women.

Acknowledgements

We would like to express our gratitude to all those who helped us during the writing of this manuscript.

Author contributions

Guo XY and Long Y conceived of the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Funding

A longitudinal study on the effect of iodine nutrition status on thyroid function in women of childbearing age during pregnancy and 6 weeks postpartum (Grant number 2022-2-2029).

Data availability

All data generated or analyzed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Beijing Friendship Hospital (ethical batch number: BJFH-EC/2013-011). All patients signed an informed consent form for inclusion in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Xiao-Yan Guo and Yan Long contributed equally to this work.
==== Refs
References

1. Yap YW Onyekwelu E Alam U Thyroid disease in pregnancy Clin Med (Lond) 2023 23 2 125 8 10.7861/clinmed.2023-0018 36958843
Yap YW, Onyekwelu E, Alam U. Thyroid disease in pregnancy. Clin Med (Lond). 2023;23(2):125–8. 10.7861/clinmed.2023-0018.36958843 10.7861/clinmed.2023-0018
2. Parkes IL Schenker JG Shufaro Y Thyroid disorders during pregnancy Gynecol Endocrinol 2012 28 12 993 8 10.3109/09513590.2012.692001 22686167
Parkes IL, Schenker JG, Shufaro Y. Thyroid disorders during pregnancy. Gynecol Endocrinol. 2012;28(12):993–8. 10.3109/09513590.2012.692001.22686167 10.3109/09513590.2012.692001
3. Fitzpatrick DL Russell MA Diagnosis and management of thyroid disease in pregnancy Obstet Gynecol Clin North Am 2010 37 2 173 93 10.1016/j.ogc.2010.02.007 20685547
Fitzpatrick DL, Russell MA. Diagnosis and management of thyroid disease in pregnancy. Obstet Gynecol Clin North Am. 2010;37(2):173–93. 10.1016/j.ogc.2010.02.007.20685547 10.1016/j.ogc.2010.02.007
4. Stagnaro-Green A Thyroid antibodies and miscarriage: where are we at a generation later? J Thyroid Res 2011 2011 841949 10.4061/2011/841949 21687610
Stagnaro-Green A. Thyroid antibodies and miscarriage: where are we at a generation later? J Thyroid Res. 2011;2011:841949. 10.4061/2011/841949.21687610 10.4061/2011/841949
5. Casey BM Dashe JS Wells CE Subclinical hypothyroidism and pregnancy outcomes Obstet Gynecol 2005 105 2 239 45 10.1097/01.AOG.0000152345.99421.22 15684146
Casey BM, Dashe JS, Wells CE, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105(2):239–45. 10.1097/01.AOG.0000152345.99421.22.15684146 10.1097/01.AOG.0000152345.99421.22
6. Haddow JE Palomaki GE Allan WC Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child N Engl J Med 1999 341 8 549 55 10.1056/NEJM199908193410801 10451459
Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341(8):549–55. 10.1056/NEJM199908193410801.10451459 10.1056/NEJM199908193410801
7. Zimmermann MB Boelaert K Iodine deficiency and thyroid disorders Lancet Diabetes Endocrinol 2015 3 4 286 95 10.1016/S2213-8587(14)70225-6 25591468
Zimmermann MB, Boelaert K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 2015;3(4):286–95. 10.1016/S2213-8587(14)70225-6.25591468 10.1016/S2213-8587(14)70225-6
8. Leung AM Braverman LE Consequences of excess iodine Nat Rev Endocrinol 2014 10 3 136 42 10.1038/nrendo.2013.251 24342882
Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol. 2014;10(3):136–42. 10.1038/nrendo.2013.251.24342882 10.1038/nrendo.2013.251
9. Delange F Bürgi H Chen ZP Dunn JT World status of monitoring iodine deficiency disorders control programs Thyroid 2002 12 10 915 24 10.1089/105072502761016557 12494927
Delange F, Bürgi H, Chen ZP, Dunn JT. World status of monitoring iodine deficiency disorders control programs. Thyroid. 2002;12(10):915–24. 10.1089/105072502761016557.12494927 10.1089/105072502761016557
10. König F Andersson M Hotz K Aeberli I Zimmermann MB Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women J Nutr 2011 141 11 2049 54 10.3945/jn.111.144071 21918061
König F, Andersson M, Hotz K, Aeberli I, Zimmermann MB. Ten repeat collections for urinary iodine from spot samples or 24-hour samples are needed to reliably estimate individual iodine status in women. J Nutr. 2011;141(11):2049–54. 10.3945/jn.111.144071.21918061 10.3945/jn.111.144071
11. Andersen S Karmisholt J Pedersen KM Laurberg P Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals Br J Nutr 2008 99 4 813 8 10.1017/S0007114507842292 17961291
Andersen S, Karmisholt J, Pedersen KM, Laurberg P. Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals. Br J Nutr. 2008;99(4):813–8. 10.1017/S0007114507842292.17961291 10.1017/S0007114507842292
12. Konrade I Kalere I Strele I Iodine deficiency during pregnancy: a national cross-sectional survey in Latvia Public Health Nutr 2015 18 16 2990 7 10.1017/S1368980015000464 25731595
Konrade I, Kalere I, Strele I, et al. Iodine deficiency during pregnancy: a national cross-sectional survey in Latvia. Public Health Nutr. 2015;18(16):2990–7. 10.1017/S1368980015000464.25731595 10.1017/S1368980015000464
13. Bath SC Steer CD Golding J Emmett P Rayman MP Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of parents and children (ALSPAC) Lancet 2013 382 9889 331 7 10.1016/S0140-6736(13)60436-5 23706508
Bath SC, Steer CD, Golding J, Emmett P, Rayman MP. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of parents and children (ALSPAC). Lancet. 2013;382(9889):331–7. 10.1016/S0140-6736(13)60436-5.23706508 10.1016/S0140-6736(13)60436-5
14. Hynes KL Otahal P Hay I Burgess JR Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort J Clin Endocrinol Metab 2013 98 5 1954 62 10.1210/jc.2012-4249 23633204
Hynes KL, Otahal P, Hay I, Burgess JR. Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort. J Clin Endocrinol Metab. 2013;98(5):1954–62. 10.1210/jc.2012-4249.23633204 10.1210/jc.2012-4249
15. Gowachirapant S Jaiswal N Melse-Boonstra A Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial Lancet Diabetes Endocrinol 2017 5 11 853 63 10.1016/S2213-8587(17)30332-7 29030199
Gowachirapant S, Jaiswal N, Melse-Boonstra A, et al. Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(11):853–63. 10.1016/S2213-8587(17)30332-7.29030199 10.1016/S2213-8587(17)30332-7
16. Glinoer D The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status Best Pract Res Clin Endocrinol Metab 2004 18 2 133 52 10.1016/j.beem.2004.03.001 15157832
Glinoer D. The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab. 2004;18(2):133–52. 10.1016/j.beem.2004.03.001.15157832 10.1016/j.beem.2004.03.001
17. Hershman JM The role of human chorionic gonadotropin as a thyroid stimulator in normal pregnancy J Clin Endocrinol Metab 2008 93 9 3305 6 10.1210/jc.2008-1461 18772462
Hershman JM. The role of human chorionic gonadotropin as a thyroid stimulator in normal pregnancy. J Clin Endocrinol Metab. 2008;93(9):3305–6. 10.1210/jc.2008-1461.18772462 10.1210/jc.2008-1461
18. Glinoer D What happens to the normal thyroid during pregnancy? Thyroid 1999 9 7 631 5 10.1089/thy.1999.9.631 10447005
Glinoer D. What happens to the normal thyroid during pregnancy? Thyroid. 1999;9(7):631–5. 10.1089/thy.1999.9.631.10447005 10.1089/thy.1999.9.631
19. Knudsen N Bülow I Laurberg P Ovesen L Perrild H Jørgensen T Association of tobacco smoking with goiter in a low-iodine-intake area Arch Intern Med 2002 162 4 439 43 10.1001/archinte.162.4.439 11863477
Knudsen N, Bülow I, Laurberg P, Ovesen L, Perrild H, Jørgensen T. Association of tobacco smoking with goiter in a low-iodine-intake area. Arch Intern Med. 2002;162(4):439–43. 10.1001/archinte.162.4.439.11863477 10.1001/archinte.162.4.439
20. Laurberg P Cerqueira C Ovesen L Iodine intake as a determinant of thyroid disorders in populations Best Pract Res Clin Endocrinol Metab 2010 24 1 13 27 10.1016/j.beem.2009.08.013 20172467
Laurberg P, Cerqueira C, Ovesen L, et al. Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab. 2010;24(1):13–27. 10.1016/j.beem.2009.08.013.20172467 10.1016/j.beem.2009.08.013
21. Vanderpump MP Tunbridge WM French JM The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey Clin Endocrinol (Oxf) 1995 43 1 55 68 10.1111/j.1365-2265.1995.tb01894.x 7641412
Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43(1):55–68. 10.1111/j.1365-2265.1995.tb01894.x.7641412 10.1111/j.1365-2265.1995.tb01894.x
22. Shrestha U Gautam N Agrawal KK Jha AC Jayan A Iodine status among subclinical and overt hypothyroid patients by urinary iodine assay: a case-control study Indian J Endocrinol Metab 2017 21 5 719 23 10.4103/ijem.IJEM_413_16 28989881
Shrestha U, Gautam N, Agrawal KK, Jha AC, Jayan A. Iodine status among subclinical and overt hypothyroid patients by urinary iodine assay: a case-control study. Indian J Endocrinol Metab. 2017;21(5):719–23. 10.4103/ijem.IJEM_413_16.28989881 10.4103/ijem.IJEM_413_16
23. Thorpe-Beeston JG Nicolaides KH Felton CV Butler J McGregor AM Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus N Engl J Med 1991 324 8 532 6 10.1056/NEJM199102213240805 1899469
Thorpe-Beeston JG, Nicolaides KH, Felton CV, Butler J, McGregor AM. Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus. N Engl J Med. 1991;324(8):532–6. 10.1056/NEJM199102213240805.1899469 10.1056/NEJM199102213240805
24. Herrick KA Perrine CG Aoki Y Caldwell KL Iodine status and consumption of Key Iodine sources in the U.S. Population with Special attention to Reproductive Age women Nutrients 2018 10 7 874 10.3390/nu10070874 29986412
Herrick KA, Perrine CG, Aoki Y, Caldwell KL. Iodine status and consumption of Key Iodine sources in the U.S. Population with Special attention to Reproductive Age women. Nutrients. 2018;10(7):874. 10.3390/nu10070874.29986412 10.3390/nu10070874
25. Charlton KE Gemming L Yeatman H Ma G Suboptimal iodine status of Australian pregnant women reflects poor knowledge and practices related to iodine nutrition Nutrition 2010 26 10 963 8 10.1016/j.nut.2009.08.016 20080029
Charlton KE, Gemming L, Yeatman H, Ma G. Suboptimal iodine status of Australian pregnant women reflects poor knowledge and practices related to iodine nutrition. Nutrition. 2010;26(10):963–8. 10.1016/j.nut.2009.08.016.20080029 10.1016/j.nut.2009.08.016
26. World Medical Association World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects JAMA 2013 310 20 2191 4 10.1001/jama.2013.281053 24141714
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4. 10.1001/jama.2013.281053.24141714 10.1001/jama.2013.281053
27. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6(R1). Geneva: ICH; 1996.
28. Baloch Z Carayon P Conte-Devolx B Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease Thyroid 2003 13 1 3 126 10.1089/105072503321086962 12625976
Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13(1):3–126. 10.1089/105072503321086962.12625976 10.1089/105072503321086962
29. World Health Organization, United Nations Children’s Fund, International Council for Control of Iodine Deficiency Disorders Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers 2007 3 Geneva World Health Organization
World Health Organization, United Nations Children’s Fund, International Council for Control of Iodine Deficiency Disorders. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. Geneva: World Health Organization; 2007.
30. Bartels H Böhmer M Heierli C Serum creatinine determination without protein precipitation Clin Chim Acta 1972 37 193 7 10.1016/0009-8981(72)90432-9 5022083
Bartels H, Böhmer M, Heierli C. Serum creatinine determination without protein precipitation. Clin Chim Acta. 1972;37:193–7. 10.1016/0009-8981(72)90432-9.5022083 10.1016/0009-8981(72)90432-9
31. World Health Organization Urinary iodine concentrations for determining iodine status in populations. Vitamin and Mineral Nutrition Information System 2013 Geneva World Health Organization
World Health Organization. Urinary iodine concentrations for determining iodine status in populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; 2013.
32. Shi X Han C Li C 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 100 4 1630 8 10.1210/jc.2014-3704 25629356
Shi X, Han C, Li C, et al. 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;100(4):1630–8. 10.1210/jc.2014-3704.25629356 10.1210/jc.2014-3704
33. Rebagliato M Murcia M Espada M Iodine intake and maternal thyroid function during pregnancy Epidemiology 2010 21 1 62 9 10.1097/EDE.0b013e3181c1592b 19940773
Rebagliato M, Murcia M, Espada M, et al. Iodine intake and maternal thyroid function during pregnancy. Epidemiology. 2010;21(1):62–9. 10.1097/EDE.0b013e3181c1592b.19940773 10.1097/EDE.0b013e3181c1592b
34. Chen X Wu C Wang Z Iodine nutrition status and thyroid autoimmunity during pregnancy: a cross-sectional study of 4635 pregnant women Nutr J 2022 21 1 7 10.1186/s12937-022-00760-6 35093086
Chen X, Wu C, Wang Z, et al. Iodine nutrition status and thyroid autoimmunity during pregnancy: a cross-sectional study of 4635 pregnant women. Nutr J. 2022;21(1):7. 10.1186/s12937-022-00760-6. Published 2022 Jan 29.35093086 10.1186/s12937-022-00760-6
35. Zimmermann MB Connolly K Bozo M Bridson J Rohner F Grimci L Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study Am J Clin Nutr 2006 83 1 108 14 10.1093/ajcn/83.1.108 16400058
Zimmermann MB, Connolly K, Bozo M, Bridson J, Rohner F, Grimci L. Iodine supplementation improves cognition in iodine-deficient schoolchildren in Albania: a randomized, controlled, double-blind study. Am J Clin Nutr. 2006;83(1):108–14. 10.1093/ajcn/83.1.108.16400058 10.1093/ajcn/83.1.108
36. Glinoer D De Nayer P Bourdoux P Regulation of maternal thyroid during pregnancy J Clin Endocrinol Metab 1990 71 2 276 87 10.1210/jcem-71-2-276 2116437
Glinoer D, De Nayer P, Bourdoux P, et al. Regulation of maternal thyroid during pregnancy. J Clin Endocrinol Metab. 1990;71(2):276–87. 10.1210/jcem-71-2-276.2116437 10.1210/jcem-71-2-276
37. Liberman CS Pino SC Fang SL Braverman LE Emerson CH Circulating iodide concentrations during and after pregnancy J Clin Endocrinol Metab 1998 83 10 3545 9 10.1210/jcem.83.10.5163 9768662
Liberman CS, Pino SC, Fang SL, Braverman LE, Emerson CH. Circulating iodide concentrations during and after pregnancy. J Clin Endocrinol Metab. 1998;83(10):3545–9. 10.1210/jcem.83.10.5163.9768662 10.1210/jcem.83.10.5163
38. Glinoer D De Nayer P Delange F A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects J Clin Endocrinol Metab 1995 80 1 258 69 10.1210/jcem.80.1.7829623 7829623
Glinoer D, De Nayer P, Delange F, et al. A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects. J Clin Endocrinol Metab. 1995;80(1):258–69. 10.1210/jcem.80.1.7829623.7829623 10.1210/jcem.80.1.7829623
39. Li C Guan H Teng X An epidemiological study of the serum thyrotropin reference range and factors that influence serum thyrotropin levels in iodine sufficient areas of China Endocr J 2011 58 11 995 1002 10.1507/endocrj.k11e-101 21959332
Li C, Guan H, Teng X, et al. An epidemiological study of the serum thyrotropin reference range and factors that influence serum thyrotropin levels in iodine sufficient areas of China. Endocr J. 2011;58(11):995–1002. 10.1507/endocrj.k11e-101.21959332 10.1507/endocrj.k11e-101
40. Alexander EK Pearce EN Brent GA 2017 guidelines of the American thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the Postpartum Thyroid 2017 27 3 315 89 10.1089/thy.2016.0457 28056690
Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the American thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the Postpartum. Thyroid. 2017;27(3):315–89. 10.1089/thy.2016.0457.28056690 10.1089/thy.2016.0457
41. Farebrother J Zimmermann MB Andersson M Excess iodine intake: sources, assessment, and effects on thyroid function Ann N Y Acad Sci 2019 1446 1 44 65 10.1111/nyas.14041 30891786
Farebrother J, Zimmermann MB, Andersson M. Excess iodine intake: sources, assessment, and effects on thyroid function. Ann N Y Acad Sci. 2019;1446(1):44–65. 10.1111/nyas.14041.30891786 10.1111/nyas.14041
42. Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011;342:d2616. Published 2011 May 9. 10.1136/bmj.d2616
43. Korevaar TIM Muetzel R Medici M Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study Lancet Diabetes Endocrinol 2016 4 1 35 43 10.1016/S2213-8587(15)00327-7 26497402
Korevaar TIM, Muetzel R, Medici M, et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol. 2016;4(1):35–43. 10.1016/S2213-8587(15)00327-7.26497402 10.1016/S2213-8587(15)00327-7
