Application and Comparison of Different Regression Models in Iodine Balance Experiment on Women of Childbearing Age and Pregnant Women.

The iodine balance experiment is a traditional approach to evaluate the physiological requirement for iodine, while the simple linear regression model (SLM) and the mixed effects model (MEM) are two primary methods used to analyze iodine balance experiments. In the present study, we aimed to compare the effects of these two regression models on the evaluation of iodine balance experiments to investigate appropriate valuation methods. By constructing SLM and MEM, zero iodine balance values (IBV) were determined, and the evaluation effects were compared. No changes were made to the experimental data for women of childbearing age, and cutoff values of 600 µg/day and 1000 µg/day, respectively, were chosen for further processing of the experimental data for pregnant women. Equation combinations 1-3 (EC1-3) were obtained by fitting SLM, and zero IBV were calculated as 110.26 µg/day, 333.06 µg/day, and 434.84 µg/day, respectively. EC4-6 were obtained by fitting MEM, and zero IBV were calculated as 110.44 µg/day, 335.79 µg/day, and 418.06 µg/day, respectively. The inclusion of inter-measurement variation as a random factor in the MEM yielded EC7-8, which reduced the test power of the iodine balance experiment on women of childbearing age. Our study suggested that when experimental conditions were tightly controlled, with fewer uncertainties or significant influences, computationally straightforward and well-understood SLM was preferred. If some uncertain factors might cause large changes in the experimental results, it was advised to use a more "conservative" MEM to calculate the zero IBV. ClinicalTrials.gov Identifier: Registered at Clinicaltrials.gov, NCT03279315 (17th September 2017, retrospectively registered), NCT03710148 (18th October 2018, retrospectively registered).

Iodine-specific food frequency questionnaire can evaluate iodine intakes of Chinese pregnant women.

Iodine is an essential trace element for the synthesis of thyroid hormones, which play an important role in growth and development, metabolism, and body organ function. There is no iodine-specific food frequency questionnaire (I-FFQ) for pregnant women in China. This study aimed to validate and optimize an I-FFQ. A total of 1802 pregnant women were included in this study. The iodine nutrition survey was performed using I-FFQ and 3-day estimated food diary (3DEFD). Seventy-one women of reproductive age repeated the I-FFQ twice to assess for FFQ reproducibility. Further optimization of the I-FFQ was accomplished by integrating iodine contributions to simplified questionnaire items. Correlation and Bland-Altman analyses were used to verify the consistency of I-FFQ with 3DEFD, as well as the stability and feasibility of I-FFQ optimization. The I-FFQ and 3DEFD had a strong correlation (R = 0.76, P < .001) and agreement (Kappa = 0.731, P < .001). A Bland-Altman plot showed that 5.1% of participants exceeded the limit of agreement. Nonpregnant women of reproductive age completed the I-FFQ twice, and the results had a strong correlation (R = 0.72, P < .001). A Bland-Altman analysis showed that 5.6% of individuals were located outside the limit of agreement. The consistency of I-FFQ before and after optimization was good (Kappa = 0.982, P < .001). Therefore, I-FFQ could be used as a valid tool to estimate iodine intake among Chinese pregnant women. The optimized I-FFQ could shorten survey time without affecting its accuracy.

The Relationship Between Iodine Excess and Thyroid Function During Pregnancy and Infantile Neurodevelopment at 18-24 Months.

BACKGROUND: Thyroid disease is a prevalent condition during pregnancy, and excessive iodine intake can lead to changes in thyroid function. However, research on the relationship between maternal iodine excess, thyroid hormones during pregnancy, and infantile neurodevelopment is limited. OBJECTIVES: This study aimed to explore the relationship between maternal iodine excess and thyroid hormones during pregnancy and infantile neurodevelopment. The objective was to provide evidence to support and enhance the prevention of neurodevelopmental retardation in infants. METHODS: From 2016 to 2018, a prospective study was conducted from pregnancy to 18-24 mo postpartum. Maternal urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), total serum iodine (TSI), and nonprotein-bound serum iodine during pregnancy were determined. The Gesell Development Scale was used to assess neurodevelopment of infants aged 18-24 mo. The iodine status of pregnant females was divided into following 4 groups on the basis of the distribution of maternal UIC: <100 µg/L (moderate deficiency), 100-149 µg/L (mild deficiency), 150-249 µg/L (sufficiency), and >250 µg/L (above requirement). RESULTS: Our study included 469 mother-infant pairs. Compared with the maternal UIC of 150-249 µg/L during pregnancy, risk of adaptive developmental delay was increased in infants with maternal UIC ≥250 µg/L (OR: 2.38; 95% CI: 1.06, 5.35). Pregnant females with TSI >90th quantiles were more likely to have offspring with language developmental delay than those with lower TSI in 10th-90th quantiles (OR: 3.06; 95% CI: 1.09, 8.58). Risk of fine motor developmental delay was increased in infants with maternal TSH ≥2.5 mIU/L during pregnancy (OR: 4.32; 95% CI: 1.43, 13.0). CONCLUSIONS: Maternal iodine nutritional status above requirement (UIC ≥250 µg/L or TSI >90th quantiles) during pregnancy negatively affects infantile neurodevelopment. Maternal TSH ≥2.5 mIU/L during pregnancy was an independent risk factor for infantile neurodevelopment. This trial was registered at clinicaltrials.gov as NCT03710148.

An Iodine Balance Study in Chinese School-age Children.

CONTEXT: Few iodine balance studies have been conducted in school-age children. OBJECTIVE: This study aimed to conduct an iodine balance study in school-age children. METHODS: We measured daily iodine intake, excretion, and retention for 3 consecutive days without any dietary interventions in school-age children. Linear mixed-effects models were used to fit the relationship between total iodine intake and iodine retention. RESULTS: 29 children aged 7-12 years (mean age 10.2 ± 1.4 years) with normal thyroid function and thyroid volume were recruited. The 0 balance value (iodine intake = iodine excretion, iodine retention = 0 µg/day) shifted with iodine intake in an iodine sufficient population. The 0 balance value for school-age children with an iodine intake of 235 (133, 401) µg/day is 164 µg/day. Children aged 7-12 years with iodine intake >400 µg/day were almost all in a positive iodine state. CONCLUSION: An iodine intake of 235 (133, 401) µg/day for children aged 7-10 years achieved a 0 balance value of 164 µg/day. Long-term iodine intake of >400 µg/day is not recommended.

Iodine Intakes of <150 µg/day or >550 µg/day are Not Recommended during Pregnancy: A Balance Study.

BACKGROUND: Adequate iodine intake during pregnancy is critical for maintaining maternal and fetal thyroid function and development. There are only limited data from iodine-balance studies to inform iodine requirements during pregnancy. OBJECTIVES: This is an iodine-balance study conducted to explore the associations among iodine intake, excretion, and retention to provide information regarding iodine requirements during pregnancy. METHODS: A 7-d iodine-balance experiment enrolled 93 healthy pregnant Chinese women from Hebei, Tanjin, and Shandong. Duplicates of all foods and beverages consumed were systematically collected and measured for iodine content. Iodine excretion was measured by collecting 24-h urine and feces samples. Simple linear regression models were used to assess relationships between total iodine intake and iodine retention, whereas mixed effect models were used to assess the relationship between daily iodine intake and iodine retention. RESULTS: The mean ± SD age of participating pregnant women was 29 ± 2 y at a median 22 (IQR: 13-30) wk of gestation. The mean 7-d iodine retention was 43.0 ± 1060 µg/7 d. A negative iodine balance was present in 56% of women whereas 44% had a positive balance. Pregnant women with iodine intakes <150 µg/d were in negative balance whereas those with intakes >550 µg/d were in positive balance. The daily iodine intake at zero balance was 343 µg/d, which was higher in women from Shandong (492 µg/d) than in those from Hebei and Tianjin (202 µg/d). CONCLUSIONS: Iodine intake at zero balance determined in pregnant women with adequate iodine nutrition is 202 µg/d, and the calculated recommended nutrient intake (RNI) is 280 µg/d. Iodine intakes of <150 µg/d and >550 µg/d are not recommended during pregnancy. This trial was registered at clinicaltrials.gov as NCT03710148.

Characteristics and predictors of breast milk iodine in exclusively breastfed infants: Results from a repeated-measures study of iodine metabolism.

Background: The iodine supply of exclusively breastfed infants entirely depends upon breast milk. Changes in breast milk iodine affect infants' iodine nutritional status. This study aimed to comprehensively assess the characteristics and predictors of breast milk iodine concentration (BMIC). Materials and methods: This 7-day iodine metabolism experiment was conducted in 25 exclusively breastfed mother-infant pairs. The duplicate portion method was used to measure the mother's daily iodine intake from foods and water, and maternal 24-h urine excretion was assessed. We recorded the number of breastfeeds per mother per day and collected breast milk samples before and after each feeding. Results: The median [quartile (Q)1-Q3 range] of BMIC was 115 (86.7, 172) µg/L. The BMIC before breastfeeding was generally higher than that after breastfeeding. Time-sequential analysis found that morning BMIC was most highly correlated with the prior day's iodine intake. Breast milk samples taken in the afternoon or after midnight are closer to the median level of BMIC throughout the day. The number of breast milk samples needed to estimate the iodine level with 95% CI within precision ranges of ± 20% was 83 for a population, 9 for an individual, and 2 for an individual's single day. Maternal total iodine intake (TII) and urine iodine were significantly associated with BMIC. 24-h urinary iodine excretion (24-h UIE) was found to be the best predictive indicator for the BMIC (ß = 0.71, 95% CI: 0.64, 0.79). Conclusion: BMIC is a constantly changing indicator and trended downward during each breastfeeding. Breast milk samples taken in the afternoon or after midnight are most representative. BMIC was significantly associated with recent iodine intake. Maternal 24-h UIE was the best predictor of BMIC.

Exploration of the optimal range of urinary iodine concentration in Chinese pregnant women in mildly iodine-deficient and -sufficient areas.

PURPOSE: There is some uncertainty about the optimal ranges for urinary iodine concentration (UIC) during pregnancy. This study aimed to explore associations between maternal UIC and thyroid function in iodine sufficient and mildly iodine deficient areas. METHODS: It was a cross-sectional study in which 1461 healthy pregnant women were enrolled to collect their blood and urine samples during their routine antenatal care in Tianjin and Wuqiang, China. Wuqiang was a mildly iodine-deficient region, while Tianjin was iodine sufficient. UIC, free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), serum iodine concentration (SIC) including total serum iodine concentration (tSIC) and non-protein bound serum iodine concentration (nbSIC) were assessed during the routine antenatal care visits. RESULTS: The median UIC in pregnant women was 174 (113, 249) µg/L in Tianjin and 111 (63, 167) µg/L in Wuqiang, respectively. Compared with Tianjin, UIC, FT3 and TSH were lower, and FT4, tSIC, nbSIC, rates of TPOAb and TgAb positivity and the thyroid dysfunction rate (TDR) were higher in Wuqiang (P < 0.001). FT3, FT4, tSIC and nbSIC increased during pregnancy in Tianjin with increasing UIC, while only FT3 and nbSIC increased in Wuqiang (P < 0.05). In Tianjin, the TDR increased with UIC and peaked at UIC ≥ 500 µg/L (P = 0.002), while in Wuqiang, the TDR showed a weak "U-shaped" relationship with UIC and the rate was lowest with UIC 100-149 µg/L. CONCLUSIONS: In iodine-deficient areas, there was a lower TDR in pregnant women with UIC 100-149 µg/L. We suspected that the optimal UIC criteria recommended by WHO may be a little high for pregnant women in mild-to-moderate iodine-deficient countries.

Evaluation of variation of saliva iodine and recommendations for sample size and sampling time: Implications for assessing iodine nutritional status.

BACKGROUND: Saliva iodine concentration (SIC) has been found to be a good indicator of iodine nutritional status. However, limited information is available regarding saliva iodine characteristics. AIMS: The study aimed to evaluate intra-day, intra-individual, and population SIC variation in order to provide information on optimal sample size and sampling time for assessing iodine nutritional status. METHODS: Twenty-nine healthy school-aged students were recruited. Iodine intake from diet and water, and iodine excretion through urine and feces were assessed over a three-day period. Saliva samples were collected six times a day. RESULTS: Diurnal variations were observed in SIC corresponding to iodine intake. The mean CV in SIC was lower than that for 24-hour urinary iodine concentration (24-h UIC) and 24-hour urinary iodine excretion (24-h UIE) not only at the individual level (42.73% vs. 47.71% and 49.69%) but also at the population level (71.29% vs. 100.43% and 72.49%). The number of saliva samples needed to estimate the iodine level with 95% CI within precision ranges of ±10%, ±20% was 55, 14 in an individual, and 180, 45 in a population. There was a good correlation between post-lunch SIC and total daily iodine intake. CONCLUSIONS: Saliva iodine has utility for evaluating the recent iodine nutrition of individuals and populations. The variation in SIC was lower than that for 24-h UIC and 24-h UIE. Saliva may be preferred over urine because of its ease of collection. Fourteen samples are needed to assess individual iodine status and forty-five saliva samples for assessment of population iodine status with reasonable precision. We recommend that saliva samples be collected after 14:00 in a day.

Saliva Iodine Concentration in Children and Its Association with Iodine Status and Thyroid Function.

CONTEXT: The effectiveness of saliva iodine concentration (SIC) in evaluating iodine status in children is not clear. OBJECTIVE: We aimed to explore associations between SIC and assessed indicators of iodine status and thyroid function. DESIGN: Cross-sectional study. SETTING: Primary schools in Shandong, China. PARTICIPANTS: Local children aged 8 to 13 years with no known thyroid disease were recruited to this study. MAIN OUTCOME MEASURES: Blood, saliva, and urine samples were collected to evaluate thyroid function and iodine status. RESULTS: SIC positively correlated with spot urinary iodine concentration (r = 0.29, P < 0.0001), 24-hour urinary iodine concentration (r = 0.35, P < 0.0001), and 24-hour urinary iodine excretion (r = 0.40, P < 0.0001). The prevalence of thyroid nodules (TN) and goiter showed an upward trend with SIC quantiles (P for trend < 0.05). Children with SIC <105 µg/L had a higher risk of insufficient iodine status (OR = 4.18; 95% CI, 2.67-6.56) compared with those with higher SIC. Those having SIC >273 µg/L were associated with greater risks of TN (OR = 2.70; 95% CI, 1.38-5.26) and excessive iodine status (OR = 18.56; 95% CI, 5.66-60.91) than those with lower SIC values. CONCLUSIONS: There is a good correlation between SIC and urinary iodine concentrations. It is of significant reference value for the diagnosis of iodine deficiency with SIC of less than 105 µg/L and for the diagnosis of iodine excess and TN with SIC of more than 273 µg/L. Given the sanitary nature and convenience of saliva iodine collection, SIC is highly recommended as a good biomarker of recent iodine status in school-aged children.

Trimester-Specific Thyroid Function in Pregnant Women with Different Iodine Statuses.

OBJECTIVES: To explore trimester-specific thyroid function changes under different iodine statuses throughout pregnancy. METHODS: A cross-sectional study was conducted to assess the pregnancy iodine status, and 2,378 healthy pregnant women covering all 3 trimesters were recruited. Urinary iodine concentration (UIC) was measured by collecting spot urine samples. Blood samples were collected to evaluate thyroid function. Thyroid B-ultrasonography was conducted to measure the thyroid volume (Tvol). RESULTS: The median UIC was 168 µg/L (111-263 µg/L). The UIC, free triiodothyronine (FT3), and free thyroxine (FT4) were significantly decreased as the pregnancy progressed (p < 0.001, p for trend <0.001), while Tvol increased (p < 0.001, p for trend <0.001). Thyrotropin (TSH) was significantly different between the 3 trimesters and showed an upward trend (p < 0.001), but the p for trend was not significant (p for trend = 0.88). After stratification by UIC, there were no significant differences in serum TSH, FT4, or FT3 level between UIC groups. Tvol was significantly higher in the UIC ≥500 µg/L group in the first trimester (ß: 2.41, 95% CI: 1.09-3.72, p <0.001), as well as in the 250 ≤ UIC < 500 µg/L group (ß: 1.65, 95% CI: 0.61-2.70, p < 0.001) and UIC ≥500 µg/L group (ß: 3.35, 95% CI: 1.96-4.74, p < 0.001) in the third trimester. CONCLUSIONS: No difference was observed in TSH, FT3, or FT4 among the different iodine status groups throughout pregnancy. Tvol increased as the pregnancy progressed, and it was especially higher in the UIC ≥500 µg/L group in the first and third trimesters.

Variation of iodine concentration in breast milk and urine in exclusively breastfeeding women and their infants during the first 24 wk after childbirth.

OBJECTIVE: The aim of this study was to observe the variation of iodine concentration in breast milk and urine in exclusively breastfeeding women and their infants during the first 24 wk after childbirth. METHODS: In all, 634 exclusively breastfeeding mother-infant pairs were enrolled at hospital and followed at the 1, 4, 8, 12, 16, and 24 wk postpartum. Spot infant urinary iodine concentration (I-UIC), maternal urinary iodine concentration UIC (M-UIC), and breast milk iodine concentration (BMIC) in bilateral breasts were measured. RESULTS: During the first 24 wk, the median I-UIC was 216 (139-362) and 122 (68-217) µg/L in lactating mothers, both indicating iodine sufficiency. A strong correlation and no difference were found between BMIC in bilateral breasts. The mean BMIC (M-BMIC) of the two breasts was 165 (112-257) µg/L with a Bland-Altman index of 2.1%. Positive correlations were found between M-BMIC and I-UIC (r = 0.353, P < 0.001), between M-BMIC and M-UIC (r = 0.339, P < 0.001), and between I-UIC and M-UIC (r = 0.222, P < 0.001). M-BMIC was significantly higher than M-UIC (P < 0.001) and lower than I-UIC (P < 0.001). M-BMIC declined from week 1 to week 8 postpartum, both I-UIC and M-UIC dropped from week 1 to week 4 postpartum and stabilized thereafter. CONCLUSION: The iodine nutrition in lactating women and infants were adequate during the first 24 wk after childbirth. M-BMIC declined from week 1 to week 8 postpartum. Both I-UIC and M-UIC dropped from week 1 to week 4 postpartum. Further studies are needed to explore a more definitive BMIC and UIC range for an optimal iodine status in lactating women and breastfed infants.

Intra-individual and inter-individual variations in iodine intake and excretion in adult women: implications for sampling.

Iodine intake and excretion vary widely; however, these variations remain a large source of geometric uncertainty. The present study aims to analyse variations in iodine intake and excretion and provide implications for sampling in studies of individuals or populations. Twenty-four healthy women volunteers were recruited for a 12-d sampling period during the 4-week experiment. The duplicate-portion technique was used to measure iodine intake, while 24-h urine was collected to estimate iodine excretion. The mean intra-individual variations in iodine intake, 24-h UIE (24-h urinary iodine excretion) and 24-h UIC (24-h urinary iodine concentration) were 63, 48 and 55 %, respectively, while the inter-individual variations for these parameters were 14, 24 and 32 %, respectively. For 95 % confidence, approximately 500 diet samples or 24-h urine samples should be taken from an individual to estimate their iodine intake or iodine status at a precision range of ±5%. Obtaining a precision range of ±5% in a population would require twenty-five diet samples or 150 24-h urine samples. The intra-individual variations in iodine intake and excretion were higher than the inter-individual variations, which indicates the need for more samples in a study on individual participants.

Serum Iodine Is Correlated with Iodine Intake and Thyroid Function in School-Age Children from a Sufficient-to-Excessive Iodine Intake Area.

BACKGROUND: An alternative feasible and convenient method of assessing iodine intake is needed. OBJECTIVE: The aim of this study was to examine the utility of serum iodine for assessing iodine intake in children. METHODS: One blood sample and 2 repeated 24-h urine samples (1-mo interval) were collected from school-age children in Shandong, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), total iodine (StI), and non-protein-bound iodine (SnbI) concentrations and urine iodine (UIC) and creatinine (UCr) concentrations were measured. Iodine intake was estimated based on two 24-h urine iodine excretions (24-h UIE). Associations between serum iodine and other factors were analyzed using the Spearman rank correlation test. Receiver operating characteristic (ROC) curves were used to illustrate diagnostic ability of StI and SnbI. RESULTS: In total, 1686 children aged 7-14 y were enrolled. The median 24-h UIC for the 2 collections was 385 and 399 µg/L, respectively. The median iodine intake was estimated to be 299 µg/d and was significantly higher in boys than in girls (316 µg/d compared with 283 µg/d; P < 0.001). StI and SnbI were both positively correlated with FT4 (ρ = 0.30, P < 0.001; and ρ = 0.21, P < 0.001), Tg (ρ = 0.21, P < 0.001; and ρ = 0.19, P < 0.001), 24-h UIC (ρ = 0.56, P < 0.001; and ρ = 0.47, P < 0.001), 24-h UIE (ρ = 0.46, P < 0.001; and ρ = 0.49, P < 0.001), urine iodine-to-creatinine ratio (ρ = 0.58, P < 0.001; and ρ = 0.62, P < 0.001), and iodine intake (ρ = 0.49, P < 0.001; and ρ = 0.53, P < 0.001). The areas under the ROC curves for StI and SnbI for the diagnosis of excessive iodine intake in children were 0.76 and 0.77, respectively. The optimal StI and SnbI threshold values for defining iodine excess in children were 101 and 56.2 µg/L, respectively. CONCLUSIONS: Serum iodine was positively correlated with iodine intake and the serum FT4 concentration in children. It is a potential biomarker for diagnosing excessive iodine intake in children. This trial was registered at clinicaltrials.gov as NCT02915536.

Serum iodine concentration in pregnant women and its association with urinary iodine concentration and thyroid function.

OBJECTIVE: This study aims to evaluate the association of serum iodine concentration (SIC) with urinary iodine concentration (UIC) and thyroid function in pregnant women, as well as to provide the reference range of SIC of pregnant women in iodine-sufficiency area. METHODS: Pregnant women were enrolled in the Department of Obstetrics, Tanggu Maternity Hospital, Tianjin from March 2016 to May 2017. Fasting venous blood and spot urine samples were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), UIC and SIC were measured. RESULTS: One thousand and ninety-nine participants were included in this study. The median UIC was 156 µg/L. The median SIC was 108 µg/L, and the 95% reference interval for SIC was 65.6-164.7 µg/L. SIC was positively correlated with UIC (r = 0.12, P < 0.001), FT3 (r = 0.23, P < 0.001), and FT4 (r = 0.50, P < 0.001) and was inversely correlated with TSH (r = -0.14, P < 0.001). Pregnant women with a SIC < 79.9 µg/L had a higher risk of hypothyroxinemia compared to those with higher SIC (OR = 2.44, 95% CI: 1.31-4.75). Those having SIC > 138.5 µg/L were more likely to have thyrotoxicosis than those with lower SIC values (OR = 13.52, 95% CI: 4.21-43.36). CONCLUSIONS: Serum iodine level is associated with UIC and thyroid function in pregnant women. Low SIC was associated with increased risk for iodine deficiency and hypothyroxinemia, while high SIC was related to excess and thyrotoxicosis.