Iodine, as a component of the thyroid hormones, is crucial for brain development and is therefore especially important during pregnancy when the brain is developing most rapidly. While randomised controlled trials of pregnant women in regions of severe iodine deficiency have shown that prenatal iodine deficiency causes impaired cognition, less is known of the effects in regions of mild deficiency. This is relevant to the UK as the World Health Organisation now classifies the UK as mildly iodine deficient, based on a national study of 14-15 year old schoolgirls in 2011. We have previously published a study using samples and data from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC) that found an association between low iodine status in early pregnancy (urinary iodine-to-creatinine ratio
Iodine is required for adequate thyroid hormone production, which is essential for brain development, particularly in the first trimester of pregnancy. Milk is the principal source of iodine in UK diets, and while small studies in Europe have shown organic milk to have a lower iodine concentration than conventional milk, no such study has been conducted in Britain. In view of the increasing popularity of organic milk in the UK, we aimed to compare the iodine concentration of retail organic and conventional milk and to evaluate regional influences in iodine levels. Samples of organic milk (n 92) and conventional milk (n 80), purchased from retail outlets in sixteen areas of the UK (southern England, Wales and Northern Ireland), were analysed for iodine using inductively coupled plasma MS. The region of origin of the milk was determined from information on the label. Organic milk was 42·1 % lower in iodine content than conventional milk (median iodine concentration 144·5 v. 249·5 ng/g; P
Bath SC, Rayman MP (2012) Antenatal thyroid screening and childhood cognitive function, New England Journal of Medicine 366 (17) pp. 1640-1641
Bath SC, Steer CD, Emmett PM, Golding J, Rayman MP (2013) DOES MATERNAL IODINE STATUS IN UK PREGNANT WOMEN INFLUENCE CHILD NEURODEVELOPMENT?, ANNALS OF NUTRITION AND METABOLISM 63 pp. 1865-1865 KARGER
Bath SC, Jolly KB, Rayman MP (2013) Iodine supplements during and after pregnancy, JAMA - Journal of the American Medical Association 309 (13)
Mao J, Bath SC, Pop VJM, Vader HL, Redman CWG, Rayman MP (2013) Effect of Selenium Supplementation on Thyroid Function in UK Pregnant Women: a Randomised, Controlled Pilot Trial, PROCEEDINGS OF THE NUTRITION SOCIETY 72 (OCE4) pp. E293-E293 CAMBRIDGE UNIV PRESS
Mao J, Bath SC, Vanderlelie JJ, Perkins AV, Redman CWG, Rayman MP (2016) No effect of modest selenium supplementation on insulin resistance in UK pregnant women, as assessed by plasma adiponectin concentration, BRITISH JOURNAL OF NUTRITION 115 (1) pp. 32-38 CAMBRIDGE UNIV PRESS
Bath SC, Walter A, Taylor A, Rayman MP (2008) Iodine status of UK women of childbearing age, Journal of Human Nutrition and Dietetics 21 pp. 379-380
Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CW (2014) Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial., Br J Nutr 112 (1) pp. 99-111
Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 ¼g/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.
Bath SC, Combet E, Scully P, Zimmermann MB, Hampshire-Jones KHC, Rayman MP (2015) A multi-centre pilot study of iodine status in UK schoolchildren, aged 8-10 years, EUROPEAN JOURNAL OF NUTRITION 55 (6) pp. 2001-2009 SPRINGER HEIDELBERG
Bath SC, Button S, Rayman MP (2014) Availability of iodised table salt in the UK - is it likely to influence population iodine intake?, Public Health Nutr 17 pp. 450-454
OBJECTIVE: Iodine deficiency has recently been found in UK young and pregnant women, which is of concern given the importance of adequate iodine intake in pregnancy for fetal brain development. The WHO recommends that iodine deficiency in a population should be corrected through salt iodisation but there is a lack of UK data on iodised-salt availability, a situation that the present study aimed to address. DESIGN: Availability of iodised salt for household use was determined by a shelf survey in five supermarket chains in each of sixteen UK areas (in Southern England, Wales and Northern Ireland) encompassing a total of seventy-seven supermarkets. All branches of a sixth supermarket chain that had 2·3 % of the market share sold exclusively iodised salt. Weighted iodised-salt availability was calculated taking the market share of supermarkets into account. SETTING: The UK. SUBJECTS: Not applicable. RESULTS: Iodised salt was available in thirty-two of the seventy-seven supermarkets (41·6 %). After accounting for market share and including all six UK supermarket chains, the weighted availability of iodised salt was 21·5 %. The iodine concentration of the major UK brand of iodised salt is low, at 11·5 mg/kg. CONCLUSIONS: In contrast to other countries, iodised household table salt is unlikely to contribute meaningful amounts to UK iodine intake as (i) availability is low, (ii) table salt is only a small percentage of total UK salt intake and (iii) UK public-health campaigns have encouraged reduced salt consumption. As iodine intake in the UK is dependent entirely on food choices, regular monitoring of iodine status is essential.
Bath SC, Furmidge-Owen VL, Redman CW, Rayman MP (2015) Gestational changes in iodine status in a cohort study of pregnant women from the United Kingdom: season as an effect modifier., The American journal of clinical nutrition 101 (6) pp. 1180-1187
BACKGROUND: Iodine is required throughout pregnancy for thyroid hormone production, which is essential for fetal brain development. Studies of iodine status in pregnant women from the United Kingdom (UK) have focused on early gestation (
Bath SC, Rayman MP (2013) Iodine deficiency in the UK: An overlooked cause of impaired neurodevelopment?, Proceedings of the Nutrition Society 72 (2) pp. 226-235
This review describes historical iodine deficiency in the UK, gives current information on dietary sources of iodine and summarises recent evidence of iodine deficiency and its association with child neurodevelopment. Iodine is required for the production of thyroid hormones that are needed for brain development, particularly during pregnancy. Iodine deficiency is a leading cause of preventable brain damage worldwide and is associated with impaired cognitive function. Despite a global focus on the elimination of iodine deficiency, iodine is a largely overlooked nutrient in the UK, a situation we have endeavoured to address through a series of studies. Although the UK has been considered iodine-sufficient for many years, there is now concern that iodine deficiency may be prevalent, particularly in pregnant women and women of childbearing age; indeed we found mild-to-moderate iodine deficiency in pregnant women in Surrey. As the major dietary source of iodine in the UK is milk and dairy produce, it is relevant to note that we have found the iodine concentration of organic milk to be over 40% lower than that of conventional milk. In contrast to many countries, iodised table salt is unlikely to contribute to UK iodine intake as we have shown that its availability is low in grocery stores. This situation is of concern as the level of UK iodine deficiency is such that it is associated with adverse effects on offspring neurological development; we demonstrated a higher risk of low IQ and poorer reading-accuracy scores in UK children born to mothers who were iodine-deficient during pregnancy. Given our findings and those of others, iodine status in the UK population should be monitored, particularly in vulnerable subgroups such as pregnant women and children. Copyright © The Authors 2013.
Bath SC, Rayman MP, Steer CD, Golding J, Emmett P (2013) 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), The Lancet
Background: As a component of thyroid hormones, iodine is essential for fetal brain development. Although the UK has long been considered iodine replete, increasing evidence suggests that it might now be mildly iodine deficient. We assessed whether mild iodine deficiency during early pregnancy was associated with an adverse effect on child cognitive development. Methods: We analysed mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort by measuring urinary iodine concentration (and creatinine to correct for urine volume) in stored samples from 1040 first-trimester pregnant women. We selected women on the basis of a singleton pregnancy and availability of both a urine sample from the first trimester (defined as d13 weeks' gestation; median 10 weeks [IQR 9-12]) and a measure of intelligence quotient (IQ) in the offspring at age 8 years. Women's results for iodine-to-creatinine ratio were dichotomised to less than 150 ¼g/g or 150 ¼g/g or more on the basis of WHO criteria for iodine deficiency or sufficiency in pregnancy. We assessed the association between maternal iodine status and child IQ at age 8 years and reading ability at age 9 years. We included 21 socioeconomic, parental, and child factors as confounders. Findings: The group was classified as having mild-to-moderate iodine deficiency on the basis of a median urinary iodine concentration of 91·1 ¼g/L (IQR 53·8-143; iodine-to-creatinine ratio 110 ¼g/g, IQR 74-170). After adjustment for confounders, children of women with an iodine-to-creatinine ratio of less than 150 ¼g/g were more likely to have scores in the lowest quartile for verbal IQ (odds ratio 1·58, 95% CI 1·09-2·30; p=0·02), reading accuracy (1·69, 1·15-2·49; p=0·007), and reading comprehension (1·54, 1·06-2·23; p=0·02) than were those of mothers with ratios of 150 ¼g/g or more. When the less than 150 ¼g/g group was subdivided, scores worsened ongoing from 150 ¼g/g or more, to 50-150 ¼g/g, to less than 50 ¼g/g. Interpretation: Our results show the importance of adequate iodine status during early gestation and emphasise the risk that iodine deficiency can pose to the developing infant, even in a country classified as only mildly iodine deficient. Iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention. Funding: None. © 2013 Elsevier Ltd. All rights reserved.
Bath SC (2014) Direct or indirect iodine supplementation of infants?, The Lancet Diabetes and Endocrinology 2 (3) pp. 184-185
Bath SC, Button S, Rayman MP Iodised salt availability in the United Kingdom, 70
As intra-thyroidal iodine stores should be maximised before conception to facilitate the increased thyroid hormone production during pregnancy, women who are planning to become pregnant should ideally consume 150 ¼g iodine/d (US RDA). As few UK data exist for this population group, a cross-sectional study was carried out at the University of Surrey to assess the iodine intake and status of women of childbearing age. Total iodine excretion was measured from 24 h urine samples in fifty-seven women; iodine intake was estimated by assuming that 90 % of ingested iodine was excreted. The average iodine intake was also estimated from 48 h food diaries that the participants completed. The median urinary iodine concentration value (63·1 ¼g/l) indicated the group to be mildly iodine deficient by WHO criteria. By contrast, the median 24 h urinary iodine excretion value (149·8 ¼g/24 h) indicated a relatively low risk of iodine deficiency. The median estimated iodine intake, extrapolated from urinary excretion, was 167 ¼g/d, whereas it was lower, at 123 ¼g/d, when estimated from the 48 h food diaries. Iodine intake estimated from the food diaries and 24 h urinary iodine excretion were strongly correlated (r 0·75, P
Mao J, Pop VJ, Bath SC, Vader HL, Redman CW, Rayman MP (2014) Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency., Eur J Nutr 55 (1) pp. 55-61
PURPOSE: Selenium is an essential trace mineral and a component of selenoproteins that are involved in the production of thyroid hormones and in regulating the immune response. We aimed to explore the effect of low-dose selenium supplementation on thyroid peroxidase antibody (TPO-Ab) concentration and thyroid function in pregnant women from a mild-to-moderate iodine-deficient population. METHODS: Samples and data were from a secondary analysis of Selenium in PRegnancy INTervention (SPRINT), a double-blind, randomized, placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation. Women were randomized to receive 60 µg/day selenium or placebo until delivery. Serum thyroid peroxidase antibodies (TPO-Ab), thyrotropin (TSH) and free thyroxine (FT4) were measured at 12, 20 and 35 weeks and thyroglobulin antibodies (Tg-Ab) at 12 weeks. RESULTS: 93.5% of participants completed the study. Se supplementation had no more effect than placebo in decreasing TPO-Ab concentration or the prevalence of TPO-Ab positivity during the course of pregnancy. In women who were either TPO-Ab or Tg-Ab negative at baseline (Thy-Ab(-ve)), TSH increased and FT4 decreased significantly throughout gestation (P
Bath SC, Steer CD, Emmett PM, Golding J, Rayman MP (2013) Dietary factors that influence maternal iodine status in UK pregnant women, PROCEEDINGS OF THE NUTRITION SOCIETY 72 (OCE4) pp. E292-E292 CAMBRIDGE UNIV PRESS
Bath SC, Combet E, Scully P, Zimmermann M, Rayman MP (2014) Iodine status in UK schoolchildren, PROCEEDINGS OF THE NUTRITION SOCIETY 73 (OCE1) pp. E37-E37 CAMBRIDGE UNIV PRESS
Bath SC, Redman CW, Rayman MP (2015) Can toenail iodine concentration be used as a biomarker of iodine status?, PROCEEDINGS OF THE NUTRITION SOCIETY 74 (OCE2) pp. E176-E176 CAMBRIDGE UNIV PRESS
Bath SC, Walter A, Taylor A, Wright J, Rayman MP (2014) Iodine deficiency in pregnant women living in the South East of the UK: the influence of diet and nutritional supplements on iodine status., Br J Nutr pp. 1-10
Iodine is a key component of the thyroid hormones which are crucial for brain development. Adequate intake of iodine in pregnancy is important as in utero deficiency may have lifelong consequences for the offspring. Data on the iodine status of UK pregnant women are sparse, and there are no such data for pregnant women in the South East of the UK. A total of 100 pregnant women were recruited to a cross-sectional study carried out at the Royal Surrey County Hospital, Guildford, at their first-trimester visit for an ultrasound scan. The participants provided a spot-urine sample (for the measurement of urinary iodine concentration (UIC) and creatinine concentration) and 24 h iodine excretion was estimated from the urinary iodine:creatinine ratio. Women completed a general questionnaire and a FFQ. The median UIC (85·3 ¼g/l) indicated that the group was iodine deficient by World Health Organisation criteria. The median values of the iodine:creatinine ratio (122·9 ¼g/g) and of the estimated 24 h iodine excretion (151·2 ¼g/d) were also suggestive of iodine deficiency. UIC was significantly higher in women taking an iodine-containing prenatal supplement (n 42) than in those not taking such a supplement (P
Mao J, Bath SC, McCabe P, Redman CWG, Rayman MP (2015) Effect of selenium supplementation on adiponectin concentration as a marker of type-2 diabetes risk in UK pregnant women, PROCEEDINGS OF THE NUTRITION SOCIETY 74 (OCE2) pp. E172-E172 CAMBRIDGE UNIV PRESS
Bath SC, Steer C, Golding J, Emmett PM, Rayman MP Maternal iodine status during pregnancy and the impact on cognitive outcomes in the offspring, (70)
Emmett P, Bath S, Steer C, Golding J, Rayman M (2013) IODINE STATUS, ANNALS OF NUTRITION AND METABOLISM 63 pp. 75-76 KARGER
Bath SC, Rayman MP (2013) Is iodine deficiency during pregnancy a public health concern in the UK?, Nutrition Bulletin 38 (4) pp. 400-404
Bath SC, Rayman MP (2014) Development of an evidenced-based iodine food fact sheet for use in the UK, European Journal of Nutrition and Food Safety 4 (3)
Bath SC, Nezianya CJ, Rayman MP (2015) A label-based assessment of the iodine content of milk-alternative drinks available in the UK, PROCEEDINGS OF THE NUTRITION SOCIETY 74 (OCE5) pp. E303-E303 CAMBRIDGE UNIV PRESS
In December, 2016, the Iodine Global Network (IGN) published its new map of global iodine nutrition based on median urinary iodine concentration (mUIC) in school-aged children.1 Notably, the status of the UK, which was classified as mildly iodine deficient in 2014?15 (mUIC 50?99 ¼g/L), had become adequate by 2016 (mUIC 100?299 ¼g/L).1 The reason for this apparently rapid improvement lies in the different data sources used; data that showed mild deficiency in 2014?15 came from spot-urine samples from 737 girls aged 14?15 years from nine UK centres (mUIC 80·1 ¼g/L),2 whereas the 2016 data were based on spot-urine samples from 458 boys and girls aged 4?18 years, which were collected in year 6 of the UK National Diet and Nutrition Survey (NDNS).
Iodine, as a component of the thyroid hormones, is required for brain and neurological development; its deficiency during pregnancy and early life is associated with poorer cognitive function in the offspring1. This has implications at both the individual level (e.g. lower IQ1), and at the country level (e.g. economic potential2). Iodine deficiency affects many pregnant women in Europe3 and although this is a public-health concern, there is a lack of consistency across countries both in the supply of iodine (e.g. iodised salt programs) and the monitoring of population iodine status
It is well known that severe iodine deficiency during pregnancy affects fetal brain development and has implications for cognition in later life, including reduced intelligence quotient (IQ) scores.1 However, the effects of mild-to-moderate deficiency during pregnancy are less well known. Findings of observational studies in mildly-to-moderately iodine-deficient pregnant women have shown an association with lower IQ, reading ability,2 and spelling scores in offspring.3 Although several randomised controlled trials of iodine supplementation in pregnancy have been done in regions of mild-to-moderate iodine deficiency, they did not measure neurodevelopment in offspring.
Seafood intake in pregnancy has been positively associated with childhood cognitive outcomes which could potentially relate to the high vitamin-D content of oily fish. However, whether higher maternal vitamin D status [serum 25-hydroxy-vitamin D, 25(OH)D] in pregnancy is associated with a reduced risk of offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065 mother-child pairs were studied from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who had data for both serum total 25(OH)D concentration in pregnancy and at least one measure of offspring neurodevelopment (pre-school development at 6?42 months; ?Strengths and Difficulties Questionnaire? scores at 7 years; IQ at 8 years; reading ability at 9 years). After adjustment for confounders, children of vitamin-D deficient mothers (
Iodine deficiency is present in certain groups of the UK population, notably in pregnant women; this is of concern as iodine is required for fetal brain development. UK milk is rich in iodine and is the principal dietary iodine source. UK sales of milk-alternative drinks are increasing but data are lacking on their iodine content. As consumers may replace iodine-rich milk with milk-alternative drinks, we aimed to measure the iodine concentration of those available in the UK. Using ICP-MS, we determined the iodine concentration of seven types of milk-alternative drink (soya, almond, coconut, oat, rice, hazelnut, and hemp) by analysing 47 products purchased in November/December 2015. For comparison, winter samples of conventional (n=5) and organic (n=5) cows? milk were included. The median iodine concentration of all of the unfortified milk-alternative drinks (n=44) was low, at 7.3 ¼g/kg, just 1.7% of our value for winter conventional cows? milk (median 438 ¼g/kg). One brand (not the market leader), fortified its soya, oat, and rice drinks with iodine and those drinks had a higher iodine concentration than unfortified drinks, at 280, 287, 266 ¼g/kg respectively. The iodine concentration of organic milk (median 324 ¼g/kg) was lower than that of conventional milk. Although many milk-alternative drinks are fortified with calcium, at the time of this study, just three of 47 drinks were fortified with iodine. Individuals who consume milk-alternative drinks that are not fortified with iodine in place of cows? milk may be at risk of iodine deficiency unless they consume alternative dietary iodine sources.
O'Kane S. Maria, Pourshahidi L. Kirsty, Mulhern Maria S., Strain J.J., Mackle Emer M., Koca Duygu, Schomburg Lutz, Hill Sarah, O?Reilly Jennifer, Kmiotek Diana, Deitrich Christian, Bath Sarah C., Yeates Alison J. (2017) Cow's milk consumption increases iodine status in women of childbearing age in a randomized controlled trial, Journal of Nutrition 148 (3) pp. 401-408
American Society for Nutrition
Background: Recent evidence has highlighted the prevalence of mild-to-moderate iodine deficiency
in women of childbearing age and pregnant women, with important public health ramifications owing
to the role of iodine, required for thyroid hormone production, in neurodevelopment. Cow?s milk
contributes the greatest amount to iodine intakes in several countries.
Objective: The objective of this study was to investigate the effect of increased cow?s milk
consumption on iodine status, thyroid hormone concentrations and selenium status.
A 12 week, randomized-controlled trial was conducted in 78 low-moderate milk consuming
skimmed milk per week, while the control group continued their usual milk consumption (baseline
median (IQR): 140 (40-240) mL/d). At baseline, week 6 and week 12 participants provided a spot51
urine sample [urinary iodine concentration (UIC); creatinine] and a fasting blood sample [thyroid
hormone concentrations; serum total selenium; selenoprotein P]. This study was registered at
ClinicalTrials.gov Study (Ref: NCT02767167).
At baseline, the median (IQR) UIC of all participants was 78.5 (39.1-126.1)¼g/L. Changes in
the median UIC from baseline to week 6 (35.4 vs. 0.6 ¼g/L; P=0.014) and week 12 (51.6 vs. -3.8
¼g/L; P=0.045) were significantly greater in the intervention group compared with the control group.
However, despite being higher within the intervention group at weeks 6 and 12, the change in the
iodine:creatinine ratio from baseline was not significantly different between groups at either week 6
(P=0.637) or 12 (P=0.178). There were no significant differences in thyroid hormone concentrations
or selenium status between groups at any time point.
The present study has demonstrated that the consumption of additional cow?s milk can
significantly increase UIC in women of childbearing age. These results suggest that cow?s milk is a
potentially important dietary source of iodine in this population group.
Severe iodine deficiency during pregnancy has been associated with pregnancy/neonatal loss, and adverse pregnancy outcomes; however, the impact of mild?to?moderate iodine insufficiency, though prevalent in pregnancy, is not well-documented. We assessed whether mild iodine deficiency during pregnancy was associated with pregnancy/infant loss, or with other adverse pregnancy outcomes. We used samples and data from the Avon Longitudinal Study of Parents and Children (ALSPAC), from 3140 singleton pregnancies and from a further 42 women with pregnancy/infant loss. The group was classified as mildly-to-moderately iodine deficient with a median urinary iodine concentration of 95.3 µg/L (IQR 57.0?153.0; median urinary iodine-to-creatinine ratio (UI/Creat) 124 µg/g, IQR 82-198). The likelihood of pregnancy/infant loss was not different across four UI/Creat groups (250 µg/g). The incidence of pre-eclampsia, non-proteinuric gestational hypertension, gestational diabetes, glycosuria, anaemia, post-partum haemorrhage, preterm delivery, mode of delivery, being small for gestational age, and large for gestational age did not differ significantly among UI/Creat groups, nor were there any significant differences in the median UI/Creat. We conclude that maternal iodine status was not associated with adverse pregnancy outcomes in a mildly-to-moderately iodine-deficient pregnant population. However, in view of the low number of women with pregnancy/infant loss in our study, further research is required.
Iodine is an essential micronutrient incorporated into thyroid hormones. Although iodine deficiency can lead to a broad spectrum of disorders throughout life, it is most critical in the early stages of development, as the foetal brain is extremely dependent on iodine supply. During the last two decades, our understanding of thyroid physiology during gestation has substantially improved. Furthermore, thyroid hormone receptors have been identified and characterised in placental and embryonic tissues, allowing us to elucidate the maternal-foetal transfer of thyroid hormones. Experimental studies have demonstrated that the cyto-architecture of the cerebral cortex can be irreversibly disturbed in iodine deficiency causing abnormal neuron migratory patterns which are associated with cognitive impairment in children. In this context, the role of iodine as key factor in the programming of foetal and infant neurodevelopment, needs to be revisited with a special focus on areas of mild to moderate iodine deficiency. The objective of this review is to summarize the available evidence from both animals and human studies, for the effect of iodine deficiency (particularly, of maternal hypothyroxinemia) on brain development and neurological or behavioural disorders, such as lower intelligence quotient (IQ) or attention deficit hyperactivity disorder (ADHD).
Levie D, Korevaar T, Bath Sarah, Dalmau-Bueno A, Murcia M, Espada M, Dineva Mariana, Ibarluzea J, Sunyer J, Tiemeier H, Rebagliato M, Rayman Margaret, Peeters R, Guxens M (2018) Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: a Meta-analysis of Individual-participant Data, Journal of Clinical Endocrinology and Metabolism 00224
Oxford University Press
Low maternal free thyroxine (FT4) has been associated with poor child neurodevelopment in some single-centre studies. Evidence remains scarce for potential adverse effects of high FT4 and whether associations differ in countries with a different iodine status.
To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status.
Design, Setting and Participants:Meta-analysis of individual-participant data compromising 9,036 mother-child pairs from three prospective population-based birth cohorts: INMA (Spain), Generation R (The Netherlands) and ALSPAC (United Kingdom). Exclusion criteria were multiple pregnancies, fertility treatments, thyroid interfering medication usage, and known thyroid disease.
Main outcomes:Child non-verbal IQ at 5-8 years of age, verbal IQ at 1.5-8 years of age, and autistic traits within the clinical range at 5-8 years of age.
Results: FT4 97.5th percentile was associated with a 1.9 (1.0 to 3.4) fold higher risk of autistic traits. No independent associations were found with thyrotropin.Low maternal FT4 was consistently associated with lower IQ across cohorts. Further studies should replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay
It is well known that severe iodine deficiency during pregnancy may cause impaired brain development in the child, with effects on cognitive and motor function, hearing and speech. Whether mild-to-moderate deficiency also affects neurological development is less well known, but in the last decade a number of observational studies have been conducted to answer this question and these studies are reviewed in this article. The picture is now emerging that even mild-to-moderate iodine deficiency during pregnancy may be associated with subtle impairments in cognition and school performance, though the evidence from randomised controlled trials is still lacking. As global efforts to eradicate iodine deficiency in populations continue, it is more likely that mild-to-moderate, rather than severe, iodine deficiency will be the issue of concern in pregnancy, and therefore further research in regions of mild-to-moderate deficiency is required to strengthen the research base and to inform public-health policy.
Dineva Mariana, Rayman Margaret P., Levie Deborah, Guxens Mònica, Peeters Robin P., Vioque Jesus, González Llúcia, Espada Mercedes, Ibarluzea Jesús, Sunyer Jordi, Korevaar Tim I. M., Bath Sarah C. (2019) Similarities and differences of dietary and other determinants of iodine status in pregnant women from three European birth cohorts, European Journal of Nutrition 59 pp. 371-387
© Springer-Verlag GmbH Germany
As a component of thyroid hormones, adequate iodine intake is essential during pregnancy for fetal neurodevelopment. Across Europe, iodine deficiency is common in pregnancy, but data are lacking on the predictors of iodine status at this life stage. We, therefore, aimed to explore determinants of iodine status during pregnancy in three European populations of differing iodine status.
Data were from 6566 pregnant women from three prospective population-based birth cohorts from the United Kingdom (ALSPAC, n = 2852), Spain (INMA, n = 1460), and The Netherlands (Generation R, n = 2254). Urinary iodine-to-creatinine ratio (UI/Creat, µg/g) was measured in spot-urine samples in pregnancy (d 18-weeks gestation). Maternal dietary intake, categorised by food groups (g/day), was estimated from food-frequency questionnaires (FFQs). Multivariable regression models used dietary variables (energy-adjusted) and maternal characteristics as predictors of iodine status.
Median UI/Creat in pregnant women of ALSPAC, INMA, and Generation R was 121, 151, and 210 µg/g, respectively. Maternal age was positively associated with UI/Creat in all cohorts (P Â 0.001), while UI/Creat varied by ethnicity only in Generation R (P Â 0.05). Of the dietary predictors, intake of milk and dairy products (per 100 g/day) was positively associated with UI/Creat in all cohorts [ALSPAC (B = 3.73, P Â 0.0001); INMA (B = 6.92, P = 0.002); Generation R (B = 2.34, P = 0.001)]. Cohort-specific dietary determinants positively associated with UI/Creat included fish and shellfish in ALSPAC and INMA, and eggs and cereal/cereal products in Generation R.
The cohort-specific dietary determinants probably reflect not only dietary habits but iodine-fortification policies; hence, public-health interventions to improve iodine intake in pregnancy need to be country-specific.
Levie Deborah, Korevaar Tim I M, Bath Sarah C, Murcia Mario, Dineva Mariana, Llop Sabrina, Espada Mercedes, van Herwaarden Antonius E, de Rijke Yolanda B, Ibarluzea Jesús M, Sunyer Jordi, Tiemeier Henning, Rayman Margaret P, Guxens Mònica, Peeters Robin P (2019) Association of maternal iodine status with child IQ: a meta-analysis of individual-participant data, The Journal of Clinical Endocrinology & Metabolism 104 (12) pp. pp 5957-5967
Oxford University Press (OUP)
While 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.
To study the association between maternal iodine status during pregnancy and child IQ and to identify vulnerable time-windows of exposure to suboptimal iodine availability.
Meta-analysis of individual-participant data from three prospective population-based birth cohorts: Generation R (The Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002-2006, 2003-2008, and 1990-1992, respectively.
6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancy, fertility treatment, medication affecting the thyroid, and pre-existing thyroid disease.
Main Outcome Measure
Child non-verbal and verbal IQ assessed at 1.5-8 years of age.
There was a positive curvilinear association of the urinary iodine-to-creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat Â 150 µg/g was not associated with lower non-verbal IQ [-0.6 points, 95% CI -1.7 to 0.4, P=0.246] or lower verbal IQ [-0.6, 95% CI -1.3 to 0.1, P=0.082]. Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation.
Fetal brain development is vulnerable to mild-to-moderate iodine deficiency, particularly in the first trimester. Our results show that any potential randomized, controlled trial investigating the effect of iodine supplementation in mild-to-moderate iodine deficient women on child neurodevelopment, should start with supplementation not later than the first trimester.
Iodine intake is required for thyroid hormone
production, which is essential for neurological development. A
large proportion of UK women of childbearing age are likely
to have insufficient iodine intake, and should they become
pregnant, there would be a risk to fetal neurodevelopment.
However, there are no useful biomarkers to measure iodine
status in an individual; urinary iodine concentration can only
be used for population assessment. The aim of this study was
therefore to validate an iodine intake screening tool that had
previously been developed, against a reference measure for
estimating iodine intake. We hypothesized that the short
screening tool (28 questions) would be able to correctly classify
daily iodine intake as low (Â140 lg), adequate (140 lg -
600 lg) or excessive (Ã600 lg).
Healthy females aged 18?50 years, were recruited
from the University of Surrey population and contacts of the
researchers. They were asked to complete the iodine screening
tool and a 4-day dietary record using estimated measures of
intake. The screening tool was coded to calculate daily iodine
intake based on estimated iodine content per portion and frequency
of consumption. Dietary records were analysed in
Nutritics to give an average daily iodine intake. Values from
the tool and the dietary record were compared using a Spearman
Rank correlation and Bland-Altman analysis. Cohen's j
was used to assess iodine intake classification from the two
methods of assessment. A sensitivity analysis was performed to
exclude outliers and highlight variations in individual components
of the screening tool. The project received a favourable
ethical opinion from the Faculty of Health and Medical
Sciences Ethics Committee (University of Surrey).
Twenty-one female participants (mean age 33 ± 4)
were recruited. There was no significant difference (p = 0.566)
between median iodine intake from the screening tool
(155 lg/day, interquartile range (IQR): 70?180 lg) and dietary
records (100 lg/day, IQR: 88?176 lg). There was a moderate
correlation (rs=0.540, p = 0.012) and moderate agreement for
categorisation of participants based on iodine intake (j=0.521,
p = 0.017) with 67% of those with low intakes according to
the reference measure also being categorized as low using the
screening tool (Table 1); none of the participants had excessive
iodine intake. The exclusion of brown seaweed improved
sensitivity of the tool (to 75%) by removing outliers. Bland-
Altman analysis indicated high accuracy but large limits of
The percentage of women correctly classified was
similar or higher than other validation studies of food frequency
questionnaires (FFQs) using dietary records as a reference
measure (45% - 66%)1?3. The Cohen?s j value is also
higher than those from those studies (0·15 - 0·3), indicating a
greater agreement regarding classification.
The screening tool is a quick, simple and moderately
accurate method of classifying individuals into low and
normal intakes of iodine using 4-day dietary records as a reference
Levie Deborah, Korevaar Tim I.M., Mulder Tessa A., Bath Sarah C., Dineva Mariana, Lopez-Espinosa Maria-Jose, Basterrechea Mikel, Santa Marina Loreto, Rebagliato Marisa, Sunyer Jordi, Rayman Margaret P., Tiemeier Henning, Peeters Robin P., Guxens Mònica (2019) Maternal Thyroid Function in Early Pregnancy and Child Attention-Deficit Hyperactivity Disorder An Individual-Participant Meta-Analysis, Thyroid
Mary Ann Liebert
Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (FT4) concentrations during the first 18 weeks of pregnancy with child Attention-Deficit Hyperactivity Disorder (ADHD).
Methods: 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INMA (N=1073, Spain), Generation R (N=3812, The Netherlands) and ALSPAC (N=2784, United Kingdom). Exclusion criteria were multiple pregnancies, fertility treatments, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the DSM-IV criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses.
Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither FT4 nor TSH was associated with a higher risk of ADHD [Odds ratio (OR), 95% Confidence Interval (CI): 1.1 (1.0-1.3), P=0.060 and OR 0.9, 95% CI 0.9-1.1, P=0.385, respectively] or with high symptom scores. When investigating effect modification by gestational age, a higher FT4 was associated with symptoms above the 90th percentile but only in the first trimester [for FT4 per 1SD: OR 1.2 (95% CI 1.0-1.4), P=0.027]. However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed.
Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD.
Mullan Karen, Hamill Lesley, Doolan Katy, Young Ian, Smyth Peter, Flynn Albert, Walton Janette, Meharg Andrew A., Carey Manus, McKernan Claire, Bell Marcia, Black Neil, Graham Una, McCance David, McHugh Cathy, McMullan Paul, McQuaid Siobhan, O?Loughlin Aonghus, Tuthill Antoinette, Bath Sarah C., Rayman Margaret, Woodside Jayne V. (2019) Iodine status of teenage girls on the island of Ireland, European Journal of Nutrition pp. 1-9
The trace element iodine is a vital constituent of thyroid hormones. Iodine requirements increase during pregnancy, when even mild deficiency may affect the neurocognitive development of the offspring. Urinary iodine concentration (UIC) is the means of assessing iodine status in population surveys; a median UIC of 100?199 µg/L is deemed sufficient in a non-pregnant population. Milk is the main dietary source of iodine in the UK and Ireland.
We surveyed the iodine status of 903 girls aged 14?15 years in seven sites across the island of Ireland. Urine iodine concentration was measured in spot-urine samples collected between March 2014 and October 2015. Food group intake was estimated from iodine-specific food-frequency questionnaire. Milk-iodine concentration was measured at each site in summer and winter.
The median UIC overall was 111 µg/L. Galway was the only site in the deficient range (median UIC 98 µg/L). All five of the Republic of Ireland sites had UIC d 105 µg/L. In the two sites surveyed twice, UIC was lower in summer vs winter months [117 µg/L (IQR 76?165) vs 130 µg/L (IQR 91?194) (p Â 0.01)]. Milk samples collected from Galway and Roscommon had a lower mean iodine concentration than those from Derry/Londonderry (p Â 0.05). Milk intake was positively associated with UIC (p Â 0.001).
This is the largest survey of its kind on the island of Ireland, which currently has no iodine-fortification programme. Overall, the results suggest that this young female population sits at the low end of sufficiency, which has implications if, in future, they enter pregnancy with borderline status.
Levie Deborah, Bath Sarah, Guxens Monica, Korevaar Tim I.M, Dineva Mariana, Fano Eduardo, Ibarlueza Jesus M., Llop Sabrina, Murica Mario, Rayman Margaret P., Sunyer Jordi, Peeters Robin P., Tiemieer Henning (2020) Maternal iodine status during pregnancy is not consistently associated with attention-deficit hyperactivity disorder or autistic traits in the child, Journal of Nutrition
Oxford University Press
Background: Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood.
Objective: We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits.
Methods: Collaborative study of three population-based birth cohorts: Generation R (N=1634), INMA (N=1293), and ALSPAC (N=2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 ? 7.7 years for ADHD symptoms and 4.5 ? 7.6 years for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat)
Conclusion: There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits.
Adequate iodine intake during pregnancy is essential to maintain optimal maternal thyroid function which is crucial for fetal neurodevelopment. Though, globally, iodine deficiency is considered to be the single, most important, preventable cause of brain damage, many pregnant women are still iodine-deficient.
The research work presented in this thesis aimed to investigate several aspects of maternal iodine nutrition, including: (i) the determinants of iodine status in pregnancy; ii) the effect of advancing gestation on urinary-iodine concentration which is the most commonly-used biomarker of population iodine-status; iii) the usefulness of serum thyroglobulin as a functional biomarker of longer-term iodine nutrition in pregnancy; iv) the effect of maternal iodine deficiency in pregnancy, as measured in multiple spot-urine samples, on child cognition; v) the effect of iodine supplementation of mildly-to-moderately iodine-deficient pregnant women on thyroid function and child cognition.
In the first study, data from three European birth-cohorts were used. Milk and dairy products were found to be an important, common, dietary determinant of iodine status in pregnancy; cohort-specific determinants were also identified. In the second study, three spot-urine iodine measurements from each trimester were used in longitudinal analysis which showed an increase in urinary-iodine concentration across pregnancy. The third study showed that thyroglobulin was negatively associated with urinary-iodine concentration in an iodine-sufficient and a mildly iodine-deficient pregnant population; this suggested that thyroglobulin could be used as a complementary indicator of population iodine status. In the fourth study, iodine deficiency at multiple gestational time-points was associated with lower non-verbal intelligence quotient in children at 8 years. In the final study, evidence of the effects of iodine supplementation of mildly-to-moderately iodine-deficient pregnant women on thyroid function and child cognition was reviewed systematically; the results highlighted the lack of good-quality evidence from randomised-controlled trials to support recommendations for iodine supplementation in pregnancy in these areas. Public-health strategies aimed at educating pregnant women and women of childbearing age on the importance of iodine and the ways that they can meet iodine requirements through diet are needed. An accurate assessment of iodine status in pregnancy would be valuable for public-health monitoring and future research.
Background: Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent;
this is of concern as observational studies have shown negative associations with child
neurodevelopment. Though 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.
Objective: 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 such recommendations in these areas.
Design: A systematic review of randomised controlled trials (RCTs), non-RCT interventions
and observational studies was conducted. To identify relevant papers 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
Results: In total, 37 publications were included ? ten RCTs, four 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 three RCTs, it prevented or
diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed
child neurodevelopment; only one was adequately-powered. Meta-analyses of two RCTs
showed no effect on child cognitive [mean difference (MD) (95%CI): -0.18 (-1.22, 0.87)],
language [MD (95%CI): 1.28 (-0.28, 2.83)] or motor scores [MD (95%CI): 0.28 (-1.10,
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 areas of moderate deficiency
future trials by including appropriate measures of pre-conceptional iodine intake.