Breastfeeding mothers often report perceived insufficient milk (PIM) believing their infant is crying too much, which leads to introducing formula and the early abandonment of breastfeeding. We sought to determine if infant crying was associated with reported PIM (yes/no) and number of problems associated with lactation (lactation problem score [LPS] 6‐point Likert scale) before formula introduction. Primiparous breastfeeding mothers were recruited at birth and visited at 1, 2 and 4 weeks. Among those fully breastfeeding at 1 week (N = 230), infant crying variables based on maternal reports were not associated with PIM at 1 week, but LPS was. However, a mother's expectation that her infant would cry more than other infants was associated with increased odds of reporting PIM at 2 and 4 weeks, as were delayed onset of lactation and previous LPS. At 1 week, crying variables (frequency, difficulty in soothing) were associated with LPS along with percent weight change. Delayed onset of lactation, infant care style, number of breastfeeds and previous LPS were longitudinally associated with change in LPS from 1 to 2 weeks and 2 to 4 weeks. Our data suggest that reported infant crying is associated with PIM and LPS in the first 4 weeks of life. Guidance on what to expect in crying behaviour and the impact of infant care style may be beneficial in reducing PIM and LPS in the first month.
Deborah Levie, Sarah Bath, Monica Guxens, Tim I.M Korevaar, Mariana Dineva, Eduardo Fano, Jesus M. Ibarlueza, Sabrina Llop, Mario Murica, Margaret P. Rayman, Jordi Sunyer, Robin P. Peeters, Henning Tiemieer Maternal iodine status during pregnancy is not consistently associated with attention-deficit hyperactivity disorder or autistic traits in the child, In: 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) < 150 μg/g – in all mother-child pairs, and in those with a urinary-iodine measurement at ≤ 18 weeks and ≤ 14 weeks of gestation – with the risk of ADHD or a high autistic-trait score (≥ 93rd percentile cut-off), using logistic regression. The cohort-specific effect estimates were combined by random effects meta-analyses. We also investigated whether UI/Creat modified the association of maternal free thyroxine (FT4) or thyroid stimulating hormone (TSH) concentrations with ADHD or autistic traits. Results: UI/Creat <150 μg/g was not associated with ADHD [odds ratio (OR): 1.2; 95% CI: 0.7, 19 2.2; P=0.56] or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6-1.1; P=0.22). UI/Creat <150 20 μg/g in early pregnancy (i.e., ≤ 18 weeks or ≤ 14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P=0.017) was not modified by iodine status. 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.
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 (<16 wk). Data on the effect of advancing gestation on urinary iodine excretion are conflicting, with suggestions of both an increase and a decrease.
The aims were to evaluate iodine status in a cohort of UK pregnant women and to explore how it changes throughout gestation.
We used samples and data from 230 UK pregnant women who were recruited to the Selenium in PRegnancy INTervention study. Iodine concentration was measured in spot-urine samples that were collected at ∼12, 20, and 35 wk of gestation; creatinine concentration was also measured to correct for urine dilution. A linear mixed model was used to explore the effect of gestational week on iodine-to-creatinine ratio, with change in season, body mass index, daily milk intake, and maternal age controlled for.
The median urinary iodine concentration from urine samples collected at all time points (n = 662) was 56.8 μg/L, and the iodine-to-creatinine ratio was 116 μg/g, thus classifying this cohort as mildly-to-moderately iodine deficient. The median iodine-to-creatinine ratios at 12, 20, and 35 wk were 102.5, 120.0, and 126.0 μg/g, respectively. Only 3% of women were taking iodine-containing prenatal supplements. The iodine-to-creatinine ratio increased with advancing gestation, and there was a significant interaction between gestational week and season (P = 0.026). For a 1-wk increase in gestation, the iodine-to-creatinine ratio increased by a factor of 1.05 (95% CI: 1.02, 1.08) in winter and by a factor of 1.04 (95% CI: 1.00, 1.08) in summer.
This group of UK pregnant women was mildly-to-moderately iodine deficient at all trimesters, which is of public health concern. The finding that the iodine-to-creatinine ratio increased over the course of gestation may not be generalizable to populations with different iodine status from ours and merits further investigation. This trial was registered at www.isrctn.com as ISRCTN37927591.
Deborah Levie, Tim I M Korevaar, Sarah C Bath, Mario Murcia, Mariana Dineva, Sabrina Llop, Mercedes Espada, Antonius E van Herwaarden, Yolanda B de Rijke, Jesús M Ibarluzea, Jordi Sunyer, Henning Tiemeier, Margaret P Rayman, Mònica Guxens, Robin P Peeters (2019)Association of maternal iodine status with child IQ: a meta-analysis of individual-participant data, In: The Journal of Clinical Endocrinology & Metabolism104(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 ˂ 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.
S. Maria O'Kane, L. Kirsty Pourshahidi, Maria S. Mulhern, J.J. Strain, Emer M. Mackle, Duygu Koca, Lutz Schomburg, Sarah Hill, Jennifer O’Reilly, Diana Kmiotek, Christian Deitrich, Sarah C. Bath, Alison J. Yeates (2017)Cow's milk consumption increases iodine status in women of childbearing age in a randomized controlled trial, In: Journal of Nutrition148(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. Methods: A 12 week, randomized-controlled trial was conducted in 78 low-moderate milk consuming (<250ml/d) healthy women (18-45 years). The intervention group were asked to consume 3L of semi49 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). Results: At baseline, the median (IQR) UIC of all participants was 78.5 (39.1-126.1)μg/L. Changes in the median UIC from baseline to week 6 (35.4 vs. 0.6 μg/L; P=0.014) and week 12 (51.6 vs. -3.8 μg/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. Conclusions: 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.
We have been asked to comment on differences in trace element concentrations between organic and conventional milk found in the recent meta-analysis by Średnicka-Tober and colleagues(1). Such a comment is important because in fact the most significant difference revealed between organic and conventional milk, in terms of contribution to nutrient requirements, is that of iodine. In many countries, and particularly in the UK where iodised salt is rarely used(2), milk is the single biggest contributor to iodine intake(3). By contrast, milk is a relatively inconsequential source of fatty acids, particularly of those desirable long-chain n-3 PUFAs. This calls into question the emphasis placed on the n-3 PUFAs both in the paper and the press release. We will concentrate our comment on the difference in iodine, selenium and iron concentration. We will use the standard meta-analysis data presented by the authors as these are weighted according to the size of the studies (unweighted meta-analyses are generally not considered appropriate) and were the only analyses to find significant differences in mineral concentrations between organic and conventional milk samples. For the same reason, we will use the weighted mean percentage differences derived from the standard meta-analyses.
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.
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 (<50, 50–149, 150–250, >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.
P Emmett, S Bath, C Steer, J Golding, M Rayman (2013)IODINE STATUS, In: ANNALS OF NUTRITION AND METABOLISM63pp. 75-76
SC Bath, E Combet, P Scully, M Zimmermann, MP Rayman (2014)Iodine status in UK schoolchildren, In: PROCEEDINGS OF THE NUTRITION SOCIETY73(OCE1)pp. E37-E37
CAMBRIDGE UNIV PRESS
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).
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 μg/l) indicated that the group was iodine deficient by World Health Organisation criteria. The median values of the iodine:creatinine ratio (122·9 μg/g) and of the estimated 24 h iodine excretion (151·2 μg/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< 0·001). In the adjusted analyses, milk intake, maternal age and iodine-containing prenatal supplement use were positively associated with the estimated 24 h urinary iodine excretion. Our finding of iodine deficiency in these women gives cause for concern. We suggest that women of childbearing age and pregnant women should be given advice on how to improve their iodine status through dietary means. A national survey of iodine status in UK pregnant women is required. © The Authors 2013.
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 μg/L), had become adequate by 2016 (mUIC 100–299 μg/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 μg/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).
D Levie, T Korevaar, Sarah Bath, A Dalmau-Bueno, M Murcia, M Espada, Mariana Dineva, J Ibarluzea, J Sunyer, H Tiemeier, M Rebagliato, Margaret Rayman, R Peeters, M Guxens (2018)Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: a Meta-analysis of Individual-participant Data, In: Journal of Clinical Endocrinology and Metabolism00224
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 <2.5th percentile was associated with a 3.9 [95% confidence interval -5.7 to -2.2)] point lower non-verbal IQ and a 2.1 (-4.0 to -0.1) point lower verbal IQ. A suggestive association of hypothyroxinemia with a higher risk of autistic traits was observed. 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
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 (˂140 lg), adequate (140 lg - 600 lg) or excessive (˃600 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 agreement.
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 measure.
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 (< 50.0 nmol/L) were more likely to have scores in the lowest quartile for gross motor development at 30 months (OR 1.20 95% CI 1.03, 1.40), fine motor development at 30 months (OR 1.23 95% CI 1.05, 1.44), and social development at 42 months (OR 1.20 95% CI 1.01, 1.41) than vitamin-D sufficient mothers (≥ 50.0 nmol/L). No associations were found with neurodevelopmental outcomes, including IQ, measured at older ages. However, our results suggest that deficient maternal vitamin D status in pregnancy may have adverse effects on some measures of motor and social development in children under 4 years. Prevention of vitamin D deficiency may be important for preventing suboptimal development in the first 4 years of life.
Mariana Dineva, Margaret P. Rayman, Deborah Levie, Mònica Guxens, Robin P. Peeters, Jesus Vioque, Llúcia González, Mercedes Espada, Jesús Ibarluzea, Jordi Sunyer, Tim I. M. Korevaar, Sarah C. Bath (2019)Similarities and differences of dietary and other determinants of iodine status in pregnant women from three European birth cohorts, In: European Journal of Nutrition59pp. 371-387
© Springer-Verlag GmbH Germany
Purpose 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. Methods 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 (≤ 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. Results 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 ˂ 0.001), while UI/Creat varied by ethnicity only in Generation R (P ˂ 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 ˂ 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. Conclusions 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.
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 meta-analyses. 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, 1.66)]. 4 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 (median UIC<100 µg/L). The maternal intra-thyroidal iodine stores should be considered in future trials by including appropriate measures of pre-conceptional iodine intake.
Karen Mullan, Lesley Hamill, Katy Doolan, Ian Young, Peter Smyth, Albert Flynn, Janette Walton, Andrew A. Meharg, Manus Carey, Claire McKernan, Marcia Bell, Neil Black, Una Graham, David McCance, Cathy McHugh, Paul McMullan, Siobhan McQuaid, Aonghus O’Loughlin, Antoinette Tuthill, Sarah C. Bath, Margaret Rayman, Jayne V. Woodside (2019)Iodine status of teenage girls on the island of Ireland, In: European Journal of Nutritionpp. 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 ≤ 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 ˂ 0.01)]. Milk samples collected from Galway and Roscommon had a lower mean iodine concentration than those from Derry/Londonderry (p ˂ 0.05). Milk intake was positively associated with UIC (p ˂ 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.
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 <150 μg/g) and lower verbal IQ and reading scores in the offspring. Though the women in ALSPAC were recruited in the early 1990s, the results of the study are still relevant as their iodine status was similar to that reported in recent studies of UK pregnant women. This review discusses the evidence that mild-to-moderate iodine deficiency during pregnancy has deleterious effects on child neurodevelopment and relates that evidence to the data on iodine status in the UK. It has highlighted a need for nationwide data on iodine status of pregnant women and that a randomised controlled trial of iodine supplementation in pregnant women in a region of mild-to-moderate iodine deficiency with child outcomes as the primary endpoint is required.
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.
Deborah Levie, Tim I.M. Korevaar, Tessa A. Mulder, Sarah C. Bath, Mariana Dineva, Maria-Jose Lopez-Espinosa, Mikel Basterrechea, Loreto Santa Marina, Marisa Rebagliato, Jordi Sunyer, Margaret P. Rayman, Henning Tiemeier, Robin P. Peeters, Mònica Guxens (2019)Maternal Thyroid Function in Early Pregnancy and Child Attention-Deficit Hyperactivity Disorder An Individual-Participant Meta-Analysis, In: 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.
Background Though iodine deficiency in pregnancy is a matter of public-health concern, a functional measure of iodine status is lacking. The thyroid-specific protein, thyroglobulin (Tg), which reflects thyroid size, has shown promise as a functional measure in studies of children and adults, but data in pregnancy are sparse. In a cohort of mildly-to-moderately iodine-deficient pregnant women, we aimed to explore whether serum Tg is a sensitive functional biomarker of iodine status and to examine longitudinal change in Tg with gestational age. Method 230 pregnant women were recruited at an ante-natal clinic at 12 weeks of gestation to the Selenium in PRegnancy INTervention (SPRINT) study, in Oxford, UK. Repeated measures of urinary iodine-to-creatinine ratio, serum TSH and Tg at 12, 20, and 35 weeks of gestation were collected. Women were dichotomised by their iodine-to-creatinine ratio, (<150 or ≥150 μg/g) to group them broadly as iodine-deficient or iodine-sufficient. Women with thyroid antibodies were excluded; data and samples were available for 191 women. Results Median Tg concentration was 21, 19, and 23 μg/L in the first, second, and third trimesters, respectively. In a linear mixed model, controlling for confounders, Tg was higher in the <150 μg/g than in the ≥150 μg/g group (p<0.001) but there was no difference in TSH (p=0.27). Gestational week modified the effect of iodine status on TSH (p=0.01) and Tg (p=0.012); Tg did not increase with gestational week in the ≥150 μg/g group but did in the <150 μg/g group, and TSH increased more steeply in the <150 μg/g group. Conclusions Low iodine status (<150 μg/g) in pregnancy is associated with higher serum Tg, suggesting that the thyroid is hyper-stimulated by iodine deficiency, which causes it to enlarge. Tg is a more sensitive biomarker of iodine status in pregnancy than is TSH.
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
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 μg/kg, just 1.7% of our value for winter conventional cows’ milk (median 438 μg/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 μg/kg respectively. The iodine concentration of organic milk (median 324 μg/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.
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.
Selenium and iodine are trace elements that are maximally concentrated in the thyroid. Iodine is a substrate for thyroid hormone synthesis, while the selenoproteins protect the thyroid from the oxidative stress incurred. We measured plasma selenium concentration in 241 pregnant women in 1st trimester, previously reported to have iodine deficiency. Mean age was 30.3 years (SD 5.4), BMI 26.2 kg/m2 (SD 4.9) and 53% reported taking supplements. Median urinary-iodine concentration was 73 μg/L (IQR 37-122) (WHO recommendation, ≥150 μg/L). Mean plasma-selenium concentration was 75 μg/L (SD 7.7) which is below the 80-125 μg/L reported to be optimal. Four-day food diaries revealed a selenium intake of 43μg/day (SD 15.9), also below the 55-70 μg/day reported to be optimal. This is the first report of selenium status in pregnancy on the island of Ireland. The possible combined effects of iodine and selenium deficiencies in pregnancy merit further investigation.
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 < 0·001). There was no difference in the iodine concentration of either conventional or organic milk by area of purchase. However, a difference was seen in iodine concentration of organic milk by region of origin (P < 0·001). The lower iodine concentration of organic milk has public-health implications, particularly in view of emerging evidence of iodine deficiency in UK population sub-groups, including pregnant women. Individuals who choose organic milk should be aware that their iodine intake may be compromised and should ensure adequate iodine intake from alternative sources.