Exploration of thyroglobulin as a biomarker of iodine status in iodine-sufficient and mildly iodine-deficient pregnant women.

PURPOSE: Urinary iodine-to-creatinine ratio (UI/Creat) reflects recent iodine intake but has limitations for assessing habitual intake. Thyroglobulin (Tg) concentration, which increases with thyroid size, appears to be an indicator of longer-term iodine status in children and adults, however, less is known in pregnancy. This study investigated the determinants of serum-Tg in pregnancy and its use as an iodine-status biomarker in settings of iodine-sufficiency and mild-to-moderate deficiency. METHODS: Stored blood samples and existing data from pregnant women from the Netherlands-based Generation R (iodine-sufficient) and the Spain-based INMA (mildly-to-moderately iodine-deficient) cohorts were used. Serum-Tg and iodine status (as spot-urine UI/Creat) were measured at median 13 gestational weeks. Using regression models, maternal socio-demographics, diet and iodine-supplement use were investigated as determinants of serum-Tg, as well as the association between UI/Creat and serum-Tg. RESULTS: Median serum-Tg was 11.1 ng/ml in Generation R (n = 3548) and 11.5 ng/ml in INMA (n = 1168). When using 150 µg/g threshold for iodine deficiency, serum-Tg was higher in women with UI/Creat < 150 vs ≥ 150 µg/g (Generation R, 12.0 vs 10.4 ng/ml, P = 0.010; INMA, 12.8 vs 10.4 ng/ml, P < 0.001); after confounder adjustment, serum-Tg was still higher when UI/Creat < 150 µg/g (regression coefficients: Generation R, B = 0.111, P = 0.050; INMA, B = 0.157, P = 0.010). Iodine-supplement use and milk intake were negatively associated with serum-Tg, whereas smoking was positively associated. CONCLUSION: The association between iodine status and serum-Tg was stronger in the iodine-deficient cohort, than in the iodine-sufficient cohort. Serum-Tg might be a complementary (to UI/Creat) biomarker of iodine status in pregnancy but further evidence is needed.

Iodine status during child development and hearing ability: a systematic review.

Iodine, through the thyroid hormones, is required for the development of the auditory cortex and cochlea (the sensory organ for hearing). Deafness is a well-documented feature of endemic cretinism resulting from severe iodine deficiency. However, the range of effects of suboptimal iodine intake during auditory development on the hearing ability of children is less clear. We therefore aimed to systematically review the evidence for the association between iodine exposure (i.e. intake/status/supplementation) during development (i.e. pregnancy and/or childhood) and hearing outcomes in children. We searched PubMed and Embase and identified 330 studies, of which thirteen were included in this review. Only three of the thirteen studies were of low risk of bias or of good quality, this therefore limited our ability to draw firm conclusions. Nine of the studies (69 %) were in children (one RCT, two non-RCT interventions and six cross-sectional studies) and four (31 %) were in pregnant women (one RCT, one cohort study and two case reports). The RCT of iodine supplementation in mildly iodine-deficient pregnant women found no effect on offspring hearing thresholds. However, hearing was a secondary outcome of the trial and not all women were from an iodine-deficient area. Iodine supplementation of severely iodine-deficient children (in both non-RCT interventions) resulted in improved hearing thresholds. Five of six cross-sectional studies (83 %) found that higher iodine status in children was associated with better hearing. The current evidence base for the association between iodine status and hearing outcomes is limited and further good-quality research on this topic is needed.

Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women.

BACKGROUND: Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent; this is of concern because observational studies have shown negative associations with child neurodevelopment. Although neither the benefits nor the safety of iodine supplementation in pregnancy in areas of mild-to-moderate deficiency are well researched, such supplementation is increasingly being recommended by health authorities in a number of countries. OBJECTIVES: By reviewing the most recent published data on the effects of iodine supplementation in mildly-to-moderately deficient pregnant women on maternal and infant thyroid function and child cognition, we aimed to determine whether the evidence was sufficient to support recommendations in these areas. METHODS: A systematic review of randomized controlled trials (RCTs), non-RCT interventions, and observational studies was conducted. To identify relevant articles, we searched the PubMed and Embase databases. We defined mild-to-moderate iodine deficiency as a baseline median urinary iodine concentration (UIC) of 50-149 µg/L. Eligible studies were included in meta-analyses. RESULTS: In total, 37 publications were included-10 RCTs, 4 non-RCT interventions, and 23 observational studies. Most studies showed no effect of iodine supplementation on maternal or infant thyroid-stimulating hormone and free thyroxine. Most RCTs found that supplementation reduced maternal thyroglobulin and in 3 RCTs, it prevented or diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed child neurodevelopment; only 1 was adequately powered. Meta-analyses of 2 RCTs showed no effect on child cognitive [mean difference (MD): -0.18; 95% CI: -1.22, 0.87], language (MD: 1.28; 95% CI: -0.28, 2.83), or motor scores (MD: 0.28; 95% CI: -1.10, 1.66). CONCLUSIONS: There is insufficient good-quality evidence to support current recommendations for iodine supplementation in pregnancy in areas of mild-to-moderate deficiency. Well-designed RCTs, with child cognitive outcomes, are needed in pregnant women who are moderately deficient (median UIC < 100 µg/L). Maternal intrathyroidal iodine stores should be considered in future trials by including appropriate measures of preconceptional iodine intake.This review was registered at www.crd.york.ac.uk/prospero as CRD42018100277.

Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data.

CONTEXT: Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. OBJECTIVE: To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability. DESIGN: Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively. SETTING: General community. PARTICIPANTS: 6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancies, fertility treatment, medication affecting the thyroid, and preexisting thyroid disease. MAIN OUTCOME MEASURE: Child nonverbal and verbal IQ assessed at 1.5 to 8 years of age. RESULTS: There was a positive curvilinear association of urinary iodine/creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat <150 µg/g was not associated with lower nonverbal IQ (-0.6 point; 95% CI: -1.7 to 0.4 points; P = 0.246) or lower verbal IQ (-0.6 point; 95% CI: -1.3 to 0.1 points; P = 0.082). Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation. CONCLUSIONS: Fetal brain development is vulnerable to mild to moderate iodine deficiency, particularly in the first trimester. Our results show that potential randomized controlled trials investigating the effect of iodine supplementation in women with mild to moderate iodine deficiency on child neurodevelopment should begin supplementation not later than the first trimester.