Mild-to-Moderate Gestational Iodine Deficiency Processing Disorder.

This synopsis paper aims to identify if a common pattern of learning and social difficulties can be conceptualized across recent longitudinal studies investigating the influence of mild-to-moderate gestational iodine deficiency (GID) on offspring's optimal cognitive and psycho-social development. The main studies investigated are: The Southampton Women's Study (SWS)-United Kingdom; the Avon Longitudinal Study of Parents and Children (ALSPAC)-United Kingdom; the Gestational Iodine Cohort Longitudinal Study-Tasmania, Australia, and the Danish National Birth Cohort Case-Control Study-Denmark. In contrast to severe GID where there is a global negative impact on neurodevelopment, mild-to-moderate intrauterine iodine deficiency has subtler, but nonetheless important, permanent cognitive and psycho-social consequences on the offspring. This paper links the results from each study and maintains that mild-to-moderate GID is associated with a disorder that is characterized by speed of neural transmitting difficulties that are typically associated with working memory capacity difficulties and attention and response inhibition. The authors maintain that this disorder is better identified as Gestational Iodine Deficiency Processing Disorder (GIDPD), rather than, what to date has often been identified as 'suboptimal development'. The Autistic Spectrum Disorder (ASD), Attention Deficit, Hyperactivity Disorder (ADHD), language and literacy disorders (learning disabilities and dyslexia) are the main manifestations associated with GIDPD. GIDPD is identified on IQ measures, but selectively and mainly on verbal reasoning IQ subtests, with individuals with GIDPD still operating within the 'normal' full-scale IQ range. Greater consideration needs to be given by public health professionals, policy makers and educators about the important and preventable consequences of GID. Specifically, more emphasis should be placed on adequate iodine intake in women prior to pregnancy, as well as during pregnancy and when lactating. Secondly, researchers and others need to further extend, refine and clarify whether GIDPD, as a nosological (medical classification) entity, is a valid disorder and concept for consideration.

Correction: Hynes et al. "Reduced Educational Outcomes Persist into Adolescence Following Mild Iodine Deficiency in Utero, Despite Adequacy in Childhood: 15-Year Follow-Up of the Gestational Iodine Cohort Investigating Auditory Processing Speed and Working Memory" Nutrients 2017, 9 (12), 1354.

The authors wish to make a correction to the published version of their paper [...].

Women Remain at Risk of Iodine Deficiency during Pregnancy: The Importance of Iodine Supplementation before Conception and Throughout Gestation.

In Australia, pregnant women are advised to take an iodine supplement (I-supp) (150 µg/day) to reduce risks to the foetus associated with iodine deficiency (ID). To examine the impact of this recommendation on iodine status, and to identify factors that contribute to adequacy during gestation, supplement use and Urinary Iodine Concentration (UIC) was measured in 255 pregnant women (gestation range 6 to 41 weeks) in Tasmania. The median UIC (MUIC) of 133 µg/L (Inter-quartile range 82⁻233) was indicative of ID, being below the 150⁻249 µg/L range for adequacy during pregnancy. Women taking an iodine-containing-supplement (I-supp) had a significantly higher MUIC (155 µg/L) (n = 171) compared to the combined MUIC (112.5 µg/L) (n = 84) of those who had never (120 µg/L) (n = 61) or were no longer taking an I-supp (90 µg/L) (n = 23) (p = 0.017). Among women reporting I-supp use, the MUIC of those commencing the recommended 150 µg/day prior to conception was significantly higher than those starting supplementation following pregnancy confirmation: 196 (98⁻315) µg/L (n = 45) versus 137.5 (82.5⁻233.5) µg/L (n = 124), p = 0.032. Despite recommendations for iodine supplementation pregnant Tasmanian women remain at risk of ID. Commencing an I-supp of 150 µg/day prior to conception and continuing throughout pregnancy is required to ensure adequacy. Timely advice regarding the importance of adequate iodine nutrition, including supplementation is needed to reduce the risk of irreversible in utero neurocognitive damage to the foetus.

Reduced Educational Outcomes Persist into Adolescence Following Mild Iodine Deficiency in Utero, Despite Adequacy in Childhood: 15-Year Follow-Up of the Gestational Iodine Cohort Investigating Auditory Processing Speed and Working Memory.

There is increasing evidence that even mild gestational iodine deficiency (GID) results in adverse neurocognitive impacts on offspring. It's unclear, however, if these persist long-term and whether they can be ameliorated by iodine sufficiency in childhood. We followed a unique cohort (Gestational Iodine Cohort, n = 266) where gestation occurred during a period of mild population iodine deficiency, with children subsequently growing-up in an iodine replete environment. We investigated whether associations between mild GID and reductions in literacy outcomes, observed at age 9-years, persisted into adolescence. Comparisons were made between offspring of mothers with gestational urinary iodine concentrations (UICs) ≥ 150 µg/L and < 150 µg/L. Educational outcomes were measured using Australian National Assessment Program-Literacy and Numeracy (NAPLAN) tests. Children whose mothers had UICs < 150 µg/L exhibited persistent reductions in spelling from Year 3 (10%, -41.4 points (95% Confidence Interval -65.1 to -17.6, p = 0.001)) to Year 9 (5.6%, -31.6 (-57.0 to -6.2, p = 0.015)) compared to children whose mothers had UICs ≥ 150 µg/L. Associations remained after adjustment for biological factors, socioeconomic status and adolescent UIC. Results support the hypothesis that mild GID may impact working memory and auditory processing speed. The findings have important public health implications for management of iodine nutrition in pregnancy.

Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow-up of the gestational iodine cohort.

CONTEXT: Severe iodine deficiency (ID) during gestation is associated with neurocognitive sequelae. The long-term impact of mild ID, however, has not been well characterized. OBJECTIVE: The purpose of this study was to determine whether children born to mothers with urinary iodine concentrations (UICs) <150 µg/L during pregnancy have poorer educational outcomes in primary school than peers whose mothers did not have gestational ID (UIC ≥150 µg/L). DESIGN: This was a longitudinal follow-up (at 9 years old) of the Gestational Iodine Cohort. Pregnancy occurred during a period of mild ID in the population, with the children subsequently growing up in an iodine-replete environment. SETTING AND PARTICIPANTS: Participants were children whose mothers attended The Royal Hobart Hospital (Tasmania) antenatal clinics between 1999 and 2001. MAIN OUTCOME MEASURES: Australian national curriculum and Tasmanian state curriculum educational assessment data for children in year 3 were analyzed. RESULTS: Children whose mothers had UIC <150 µg/L had reductions of 10.0% in spelling (-41.1 points, 95% confidence interval [CI], -68.0 to -14.3, P = .003), 7.6% in grammar (-30.9 points, 95% CI, -60.2 to -1.7, P = .038), and 5.7% in English-literacy (-0.33 points, 95% CI, -0.63 to -0.03, P = .034) performance compared with children whose mothers' UICs were ≥150 µg/L. These associations remained significant after adjustment for a range of biological factors (maternal age at birth of child, gestational length at time of birth, gestational age at time of urinary iodine collection, birth weight, and sex). Differences in spelling remained significant after further adjustment for socioeconomic factors (maternal occupation and education). CONCLUSIONS: This study provides preliminary evidence that even mild iodine deficiency during pregnancy can have long-term adverse impacts on fetal neurocognition that are not ameliorated by iodine sufficiency during childhood.

Maternal alcohol intake and offspring pulse wave velocity.

BACKGROUND: Intrauterine exposure to alcohol may affect cardiovascular development, increasing risk of cardiovascular malformations. Intrauterine exposure to light maternal alcohol intake has been reported to affect human umbilical arterial contractility, and adult sheep exposed in utero have had altered cerebrovascular reactivity. In human adults, alcohol intake affects arterial stiffness. OBJECTIVES: We investigated whether intrauterine exposure to alcohol was associated with childhood pulse wave velocity (PWV), a measure of arterial stiffness. METHODS: On postnatal day 4, mothers of 147 twin pairs born in Tasmania from 1991 to 1993 reported alcohol intake during each trimester of pregnancy. At 9 years, child PWV was assessed over carotid-femoral and femoral-dorsalis pedis arterial segments by applanation tonometry. RESULTS: Carotid-femoral PWV was 0.2 m/s (95% CI 0.06, 0.4) higher (indicating stiffer vessels) in children whose mothers drank alcohol in the 2nd trimester rather than abstained, after adjusting for potential confounding factors. A similar effect was not seen for femoral-dorsalis pedis PWV. Findings were independent of child blood pressure which correlated strongly with PWV. Alcohol intake varied little between trimesters, so it was not possible to assess the effect of timing of exposure. CONCLUSIONS: Carotid-femoral PWV in adults is predictive of cardiovascular morbidity and mortality. The degree of continuity between childhood and adulthood PWV is unknown, but as we found an association between prenatal alcohol exposure and carotid-femoral PWV at 9 years, a permanent change in vessel wall structure or function is possible. These findings need to be confirmed in other and larger cohorts, and mechanistic animal studies are needed.

The lack of effect of isoflavones on high-density lipoprotein cholesterol concentrations in adolescent boys: a 6-week randomised trial.

BACKGROUND: A substantial fall in high-density lipoprotein cholesterol (HDL-C) during puberty in boys, but not girls, has been reported in Western populations. The fall in boys is believed to be due to hormonal changes--androgens have been shown to be associated with lower HDL-C, whereas oestrogens are associated with higher HDL-C. The fall in HDL-C during puberty was not observed, however, in a study of Moslem boys in Israel, nor in a group of Japanese boys. A diet high in phyto-oestrogens may account for the lack of a fall in HDL-C in these populations. OBJECTIVE: To examine the effect of dietary supplementation with phyto-oestrogens on the HDL-C concentration of adolescent boys from a Western population. We hypothesised that dietary supplementation of 50 mg of the isoflavones daidzein and genistein would produce a 12% higher HDL-C concentration than in controls at the end of a 6-week intervention period. DESIGN: A randomised controlled trial. SETTING: Hellyer College in Burnie (Tasmania, Australia). SUBJECTS: Adolescent boys (aged 16-18 years) were recruited through a letter sent to parents. A total of 132 eligible participants enrolled and five subjects withdrew from the trial. RESULTS: No significant increase in HDL-C was observed in the treatment group (-0.02 mmol l(-1), standard error (SE)=0.03, P = 0.53) or the placebo group (0.05 mmol l(-1), SE = 0.03, P = 0.11). CONCLUSIONS: Factors other than isolated dietary isoflavones may be responsible for the lack of fall in HDL-C during puberty in Japanese and Moslem boys.

A prospective study of urinary electrolytes and bone turnover in adolescent males.

BACKGROUND & AIMS: The role of excessive salt on bone metabolism in children is uncertain. The aim of this 6-week prospective study was to describe the association between urinary electrolytes and bone turnover markers in a convenience sample of adolescent boys (N = 136, mean age 16 yr). METHODS: Urinary electrolytes (sodium, potassium, calcium and magnesium) were assessed on spot overnight urines on three occasions to minimise regression dilution bias. Bone turnover was assessed by bone specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) at baseline and follow up. RESULTS: In multivariate analysis, urinary sodium (but not other electrolytes) was positively associated with both PYR and BAP both before and after taking short-term growth into account (both p < 0.05) and explained 3-6% of the variation in bone turnover markers. Urinary sodium was associated with urinary magnesium (r = +0.26, p < 0.05) but only weakly with calcium (r = +0.18, p = 0.08). Urinary potassium was significantly associated with urinary magnesium (r = -0.24, p < 0.05). CONCLUSION: High urinary sodium (which largely reflects dietary sodium intake in our location) results in a high bone turnover state in adolescent boys which is most likely detrimental for bone. Other urinary electrolytes are not related to bone turnover but may influence bone via other pathways.

Vitamin D insufficiency in adolescent males in Southern Tasmania: prevalence, determinants, and relationship to bone turnover markers.

There are limited data on vitamin D insufficiency in healthy children. The aim of this study was to describe the prevalence and determinants of vitamin D insufficiency and its association with bone turnover in adolescent boys (N = 136, mean age 16 years). Sun exposure and physical activity were assessed by questionnaire. Vitamin D stores were assessed by serum 25-hydroxyvitamin D3 (25[OH]D3). Bone turnover was assessed by bone-specific alkaline phosphatase (BAP) and urinary pyridinoline (PYR) to creatinine (Cr) ratio (mmol PYR/micromol Cr). The mean 25(OH)D3 level was low (44 nmol/l; 68% < 50 nmol/l; range, 16-87) and was associated with self-reported sun exposure on winter weekends (r = 0.23, p = 0.01), school holidays (r = 0.22, p = 0.01), and weekdays (r = 0.17, p = 0.05). It was also associated with number of sports (r = 0.34, p < 0.001) and vigorous activity (r = 0.22, p = 0.01) but not television, computer, and video watching (r = -0.04, p = 0.68). In multivariate analysis, number of sports but not total sun exposure remained significantly associated with 25(OH)D3. Furthermore, 25(OH)D3 was significantly associated with BAP in cutpoint analysis (cutpoint 55 nmol/l, p = 0.03) but not continuous analysis (r = -0.12, p = 0.16) and PYR in both forms (r = -0.23, p = 0.01, cutpoint 43 nmol/l, p = 0.01). In conclusion, vitamin D insufficiency is common in healthy adolescent boys in winter in our setting, is primarily derived from sports-related sun exposure, and is associated with bone turnover markers. These data suggest that a 25(OH)D3 level of at least 43-55 nmol/l is required for optimal bone health in children.

Persistent iodine deficiency in a cohort of Tasmanian school children: associations with socio-economic status, geographical location and dietary factors.

OBJECTIVE: To determine the adequacy of iodine nutrition of Tasmanian primary school-aged children and to examine possible associations with socio-economic status (SES), location and dietary factors. METHODS: Urinary iodine levels and measures of SES, geographical information and dietary habits were surveyed in a population-based sample of 170 children (4 to 12 years) at baseline (1998/99) and at follow-up (2000/01). RESULTS: Median urinary iodine concentration in 1989--99 and 2000--01 were 75 microg/L (range 15 microg/L to 240 microg/L) and 76 microg/L (range 18 microg/L to 480 microg/L) respectively. No significant associations with SES or geographical location were found. More frequent or recent intake of foods that are likely to be dietary sources of iodine tended to be associated with greater prevalence of adequate urinary iodine, particularly consumption of yoghurt and 'fruche' (p=0.04). CONCLUSIONS: After several decades of iodine sufficiency, Tasmanian primary school-aged children are again mildly iodine-deficient by WHO criteria. Despite reduction in iodophor use by the dairy industry in the past decade, consumption of dairy products continues to be associated with higher levels of iodine nutrition. IMPLICATIONS: The lack of association of iodine levels with SES and geographical location within Tasmania found in our study, and the results of studies of iodine levels in Melbourne and Sydney, suggest that inadequate iodine nutrition is a widespread problem in south-eastern Australia. Our study suggests that milk-containing products continue to be an important source of iodine for children.