Investigation of the effect of maternal iodine status on cognitive outcomes in the offspring

1. Investigation of the effect of maternal iodine status on cognitive outcomes in the offspring Sarah Bath Professor Margaret Rayman University of Surrey Professor Jean Golding Colin Steer Dr Pauline Emmett University of Bristol

2. Overview Iodine Essential component of T4 and T3 Growth, development and metabolism Brain and neurological development

3. Impaired psychomotor skills2 Reduced I.Q.1 Increased infant mortality1 Reduced mental andmotor skills3 Cretinism1 ADHD4 Why iodine is important 1. Delange 1994; 2. Pop 1999; 3. Pop 2004; 4. Vermiglio 2004

4. Iodine requirements • Pregnancy is the life stage with the highest requirement for iodine • Adult requirement: 150 µg/day (WHO) • Pregnancy requirement: 250 µg/day (WHO) Zimmermann 2009, Endocr Rev 30, 376-408

5. Use of a biomarker for assessment of iodine status • Iodine status is determined from urinary iodine concentration • 90% of iodine ingested is assumed to be excreted • For an individual, 24-hr urinary iodine excretion is the best measure • For a population, a spot-urine sample is used • Urinary creatinine measured to correct for urine volume

6. Areas of endemic goitre in the past Patient with Derbyshire neck Iodine Deficiency in the UK - Historical • Iodine deficiency used to be widespread in Britain with high rate of goitre and even of cretinism in some areas • Goitre was still present in many areas until the 1960s Phillips D 1997; Lee S et al. 1994

7. How goitre was eradicated in the UK Iodine concentration of milk increased Milk consumption increased Three-foldincrease in iodine intakes between 1950s and 1980s

8. mild def. moderatedef. severe def. Percentage of schoolgirls Urinary iodine excretion (μg/L) Current iodine status* • Urinary iodine excretion measured in 737 adolescent girls (14-15 yrs) • Nine centres across the UK • Iodine excretion indicated mild deficiency in the cohort • Concern that iodine deficiency may be widespread in the UK *Vanderpump et al. Lancet 2011

9. 250 Adequate range for population median iodine concentration in pregnancy 2 200 150 Median Urinary I Conc (µg/L) ** 100 50 ** p<0.001 0 Whole Group Iodine supplement users Non iodine supplement users Iodine status of Surrey pregnant women1 1. Bath et al. Proc Nutr Soc 2010; 2. Andersson et al. 2007

10. Does iodine deficiency in the UK matter? Aims: • Evaluate impact of maternal iodine deficiency on cognition in offspring in a region of mild-moderate iodinedeficiency

11. Methods: Participants • Our current study investigated 1000 ALSPAC women • The women were selected on the basis of: • availability of a urine sample at 12 weeks gestation and • their children having a measure of intelligence quotient (IQ) at age eight years

12. Methods: Outcome measures Intelligence Quotient (IQ) • Weschler Intelligence Scale for Children IIIUK (WISC-IIIUK) at age 8 years Reading ability • Neale Analysis of Reading Ability at age 9 years School performance • Key Stage 2 at age 11 years Sub-optimal performance = bottom 25% of scores

13. Results: Iodine status • This cohort of pregnant women were classified as mildly-to-moderately iodine deficient1,2 • Median urinary iodine concentration = 91.8 µg/L • Median iodine:creatinine ratio = 123 µg/g • 61.6%of the women were iodine deficient (< 150 µg/g) when using creatinine-adjusted values • None of the women took iodine-containing supplements or seaweed during pregnancy 1. Andersson et al. Public Health Nutr 2007; 10: 1606-1611; 2. Zimmermann. Thyroid 2007; 17: 829-835.

14. No. of children OR 95% CIP value measured IQ (age 8) Verbal 951 1.36 0.99, 1.86 0.06 Performance 951 1.59 1.17, 2.16 0.003 Total score 951 1.55 1.06, 2.28 0.020 Reading (age 9) Accuracy 849 1.89 1.24, 2.87 0.003 Comprehension 851 1.45 1.05, 2.01 0.020 School attainment (age 11) English 865 1.29 0.94, 1.78 0.12 Maths 869 1.60 1.15, 2.22 0.006 Science 869 1.40 1.02, 1.92 0.039 Results: Cognitive outcomes Risk of being in the bottom quartile of scores if maternal iodine status was deficient rather than sufficient (unadjusted)

15. No. of children OR 95% CIP value measured IQ (age 8) Performance 792 1.46 1.02, 2.10 0.038 Total score 792 1.55 1.06, 2.28 0.025 Reading (age 9) Accuracy 713 1.89 1.24, 2.87 0.003 School attainment (age 11) Maths 725 1.67 1.09, 2.56 0.02 Science 726 1.40 0.94, 2.08 0.10 Results: Cognitive outcomes adjusted for confounders Adjusted* risk of being in the bottom quartile of scores if maternal iodine status was deficient rather than sufficient Confounders: gender, preterm birth, birth weight, ethnicity, breastfeeding, maternal age, smoking, alcohol use, parity, stressful life events, parenting score, maternal depression, n-3 fatty acid and iron intake, fish oil supplements, maternal and paternal education, housing status, crowding, family adversity and HOME score

16. IQ Score Reading Accuracy Results: Effect of degree of iodine deficiency

17. Conclusions from our ALSPAC data • Iodine status in UK pregnant women of the ALSPAC cohort is mildly-to-moderately deficient • This level of deficiency appears sufficient to affect brain development in the offspring as shown by: • Significantly lower total IQ at age 8 • Significantly lower reading accuracy at age 9 • Poorer school performance at age 11, which issignificantly poorer in mathematics • The adverse effects on brain development increase with a higher level of iodine deficiency

18. Acknowledgements Collaborators • ALSPAC Executive • Prof Jean Golding • Colin Steer • Dr Pauline Emmett • Dr John Wright • Analysts • Dr Christine Sieniawska • Dr Andrew Taylor • Mr Alan Walter Dr Alex Richardson Sponsors