Iodine status in pregnancy and child neurodevelopment: the influence of genetic variation, selenium status and thyroid function on the relationship

Lead Research Organisation: University of Surrey
Department Name: Nutrition & Metabolism

Abstract

Iodine is an essential trace mineral required to make thyroid hormones that are crucially important for the development of the brain and nervous system of the baby during pregnancy. Though UK authorities believe that iodine intake is adequate, my work and that of others has recently shown that there is a degree of iodine deficiency in the UK, notably in young and pregnant women.

In a preliminary study, we have shown that the level of iodine deficiency in the UK is affecting cognition in the offspring. We measured iodine status in a sub-set of women who were part of the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC recruited pregnant women in the 1990s to investigate the effect of environmental factors in pregnancy on child development. Urinary iodine concentration measured during pregnancy showed the group to be mildly-to-moderately iodine deficient by WHO criteria. Children of the 61% of women deficient in iodine had a higher risk of being in the bottom 25% of intelligence quotient (IQ) scores at age 8 and reading accuracy scores at age 9, than children whose mothers were not deficient in iodine.

The overarching aim of this project is to investigate factors that influence maternal iodine status and the consequent effect on child neurodevelopmental outcomes. The project will also develop methods of identifying iodine deficiency in individuals in the clinical setting.

The project will extend the ALSPAC work to include a greater number of outcomes (e.g. hearing and behaviour) and to explore other influences on the observed relationships, such as genetic variation in relevant pathways, maternal selenium status and maternal thyroid function. There are no data on genetic variation in relevant pathways that may influence urinary excretion of iodine and therefore affect the iodine concentration of a urine sample (UIC). This is an important consideration for research that uses UIC to classify women as having adequate or deficient levels of iodine, as we have done in our ALSPAC study. The ALSPAC data set includes the results of a large genome-wide association study (GWAS) of the mothers and this data will be used to evaluate whether there are genetic variations in pathways that are associated with iodine levels in the urine and if these genetic variations then have a subsequent effect on the relationship with child outcomes.

In addition to iodine, selenium is also important for thyroid function and, much like iodine, selenium intake is low in the UK. It is therefore possible that maternal selenium status interacts with maternal iodine status to affect thyroid function and childhood outcomes, though this has not been explored; these relationships will be investigated in relation to child developmental outcomes in ALSPAC. I will also investigate whether the low dose of selenium that was used in the "Selenium in Pregnancy Intervention" (SPRINT), had an effect on thyroid antibodies and maternal thyroid function during pregnancy, a time when adequate thyroid hormone supply is critical for brain development.

Though the findings from ALSPAC are important for understanding the role that iodine and related factors have in fetal brain development, their importance is limited by its being an observational study that cannot prove causality. I will be involved with two trials of iodine supplementation on measures of child cognition; one trial will be in pregnancy and the other in schoolchildren.

Finally, as there is currently no method for diagnosing iodine deficiency in individuals, I will explore alternative biomarkers of iodine status in pregnancy and develop a screening tool that can be used in clinical practice to identify those women at risk of iodine deficiency.

Technical Summary

Iodine, through thyroid hormones, is crucial for brain development, particularly during pregnancy. Though the UK is considered iodine-sufficient, my work and that of others has shown mild-to-moderate iodine deficiency in UK pregnant women. We have shown that the level of iodine deficiency in the UK is affecting child cognition. Urinary iodine was measured in 951 women of the Avon Longitudinal Study of Parents and Children (ALSPAC) and the group was mildly-to-moderately iodine deficient. Children of the 61% of women deficient in iodine had a higher risk of being in the bottom quartile of IQ scores at age 8, reading accuracy at age 9, and key stage 2 maths scores than children whose mothers were not deficient in iodine.

The overarching aim of this project is to investigate factors that influence maternal iodine status and the consequent effect on child neurodevelopmental outcomes. The project will also develop methods of identifying iodine deficiency in individuals in the clinical setting.

The project will investigate genetic variation in pathways of iodine and thyroid metabolism on measured iodine status in pregnancy and the consequent effect on child outcomes in ALSPAC. Associations between maternal selenium, iodine status and thyroid function will be studied in ALSPAC. The effect of selenium supplementation on maternal thyroid function and iodine status will be evaluated using data from a low-dose (60mcg/day) selenium supplementation trial in UK pregnant women (SPRINT). The fellowship will provide research time required to be involved in two randomised controlled trials - in pregnant women and schoolchildren - to assess the effect of iodine supplementation on child cognition. Finally, as there is currently no method for diagnosing iodine deficiency in individuals, the project will explore alternative biomarkers of individual iodine status assessment in pregnancy and methods to identify those at risk of deficiency in the clinical setting.

Planned Impact

WHO WILL BENEFIT FROM THIS RESEARCH?
1) Pregnant women
2) Future generations
3) School children
4) Department of Health
5) The commercial private sector
6) The dairy industry

HOW WILL THEY BENEFIT?
1) Pregnant women will receive evidenced-based dietary information to improve their intake of iodine and prevent iodine deficiency. They will also have the possibility of being screened for iodine deficiency by clinicians, thus enabling appropriate advice to be provided.
2) Future generations as the research has the potential to show that iodine status in pregnancy, in combination with maternal thyroid function and selenium status, is associated with neurodevelopment.
3) If the iodine supplementation in schoolchildren shows that there is a benefit on cognition and therefore school performance, school children will benefit from greater academic attainment and therefore greater earning potential. This would have a benefit on the whole country, as an increase in IQ is associated with GDP.
4) Policy makers and government will have evidence-based information to inform the public and develop policies to their benefit. The UK does not currently monitor the iodine status of the population, and this is partly because the adverse consequences of mild iodine deficiency are not well documented, thus there is little obvious benefit to the cost associated with urinary iodine concentration monitoring. This fellowship has the potential to provide further evidence of the risks associated with mild iodine deficiency in the UK and therefore provide Government bodies with the evidence required. In Australia and New Zealand, there has been a re-emergence of iodine and in 2009, it became mandatory for Australian and New Zealand bakers to replace ordinary salt with iodised salt in bread baking and there has been a notable improvement of iodine status of the population. The Fellowship, through the iodine supplementation study in schoolchildren, may provide the evidence that the UK should follow the example of New Zealand and Australia.
5) Dietary supplement companies will have an impetus to develop a specific iodine supplement as there is currently no such supplement on sale in the UK. There will be an opportunity to develop functional foods sold on the basis of increased iodine content.
6) Milk is considered to be the principal source of iodine in the UK and the Fellowship is likely to provide further evidence that this is the case. In addition, the fellowship may show the benefits of improved iodine supply, which the dairy industry can then use to market their products as rich iodine sources and thus of nutritional benefit.

TIME FRAME
Government action, such as the mandatory use of iodised salt in bread-making, will take some time but the publication of results from the Fellowship will hopefully provide an impetus for change. Advising pregnant women to take an iodine-containing supplement (as is done in the US, Australia and New Zealand) will also take time to implement as this will require waiting for the results of the trial (WISP) in 2020. However, dietary advice to pregnant women can be changed promptly following the publication of my results. Other countries provide information on iodine during pregnancy, for example New Zealand and Australia, and therefore UK pregnancy advice can rapidly be brought in line with these countries by using the results generated from the dietary aspect of the Fellowship project. The screening tool can start to be implemented following publication of the methodology, and combined with improved information on iodine available to health professionals and pregnant women, it is possible that the iodine status of UK pregnant women could be improved within 2-3 years of the publication of results. The commercial sector and the dairy industry will be able to benefit very quickly from the findings of the fellowship project by making changes in product formulations and information on websites respectively.

Publications

10 25 50
 
Description Citations in systematic review - first of two publications cited in a recent systematic review of iodine status in the UK population
Geographic Reach National 
Policy Influence Type Citation in systematic reviews
URL https://www.ncbi.nlm.nih.gov/pubmed/30596360
 
Description Citations in systematic review - second of two publications cited in a recent systematic review of iodine status in the UK population
Geographic Reach National 
Policy Influence Type Citation in systematic reviews
URL https://www.ncbi.nlm.nih.gov/pubmed/30596360
 
Description Article for Dietetics Today 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact An article was written for the British Dietetic Association publication Dietetics Today. The Editor chose to publish the article both in the print copy (sent to members of the BDA) and also online as an open access article. This was because the article was considered to be of interest to the profession and general public.

Not known.
Year(s) Of Engagement Activity 2014
URL https://www.bda.uk.com/dt/onlinearticles
 
Description Article for The Conversation 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article written for The Conversation on our research that showed milk-alternative drinks had a low iodine concentration in comparison to cows' milk. This article was picked up by the media and circulated online.
Year(s) Of Engagement Activity 2017
URL https://theconversation.com/most-milk-substitutes-are-low-in-iodine-heres-why-it-matters-83589
 
Description Comment for media 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Provided a comment on iodine research paper published in the Lancet Diabetes and Endocrinology (10 August 2015). Comment used by BBC online.
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/news/health-33827594
 
Description Dietetic Journal Clubs 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation at two dietetic journal clubs in the South East of the UK. This sparked discussion and questions from the health professionals.

Impact not yet identified
Year(s) Of Engagement Activity 2013,2014
 
Description Expert comment for media 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Provided an expert comment to Science Media Centre on a press release relating to iodine in organic milk (27/4/15). Comments were used by various news outlets (e.g. Telegraph, The Daily Mail).
Year(s) Of Engagement Activity 2015
URL http://www.sciencemediacentre.org/expert-reaction-to-iodine-in-milk-and-iq/
 
Description Filming for RAI3 television programme 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview on iodine and IQ for investigative news program PRESADIRETTA on which aired on prime time on the Italian State Broadcaster Rai3.
Year(s) Of Engagement Activity 2019
 
Description Interview for Wired UK on iodine content of milk-alternative drinks 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Interview for Wired UK magazine on research into iodine content of milk-alternative drinks.
Year(s) Of Engagement Activity 2018
URL https://www.wired.co.uk/article/non-dairy-milk-alternatives-oatly-soy-oat-rice-vegan
 
Description Interview for print article in the media 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interviewed on the issue of iodine deficiency in the UK by journalist at the Guardian. Article was published in December 2015.
Year(s) Of Engagement Activity 2015
URL http://www.theguardian.com/lifeandstyle/2015/dec/07/pregnant-mothers-and-the-dangers-of-iodine-defic...
 
Description Interview on BBC Radio 4 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Interview for BBC Radio 4 In Their Element series - "Awesome iodine", February 2018
Year(s) Of Engagement Activity 2018
URL https://www.bbc.co.uk/programmes/b09plrg0
 
Description Interview on BBC Radio Surrey 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Interview on iodine research (including iodine in milk-alternative drinks) for BBC Surrey, November 2018
Year(s) Of Engagement Activity 2018
 
Description Network Health Dietitans Magazine article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Article written for a magazine that is targetted at UK dietitians with the aim of raising awareness of iodine nutrition in the UK. Title: Iodine deficiency in the UK; a dietetic perspective

No impact yet identified
Year(s) Of Engagement Activity 2013
 
Description Patient event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Invited to speak at the British Thyroid Foundation London Branch meeting on "thyroid funciton, iodine and goitrogens". Approximately 90 patients attended this event in November 2013.

No impact yet
Year(s) Of Engagement Activity 2013
URL http://www.btf-thyroid.org/index.php/support/local-support-groups-100/london/meeting-information
 
Description Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation on iodine in the Dairy Council Diet Zone at the British Dental Industry Association (BDIA) conference, NEC Birmingham, Oct. 2015.
Year(s) Of Engagement Activity 2015
 
Description Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation at the joint SENSE (Self-Employed Nutritionists' Support and Enlightenment) and NII (Nutritionists in Industry) meeting, London, Sept. 2015. Presented research on iodine to an audience of nutritionists, including those working in industry.
Year(s) Of Engagement Activity 2015
URL http://www.sense-nutrition.org.uk/recent.htm
 
Description Radio interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interviewed for BBC Radio 4 programme as part of the "In their elements series" for an episode on "awesome iodine". Contacted by a number of interested members of the public for more information; general interest on social media channels (including health professionals) as a result of the programme.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/programmes/b09plrg0
 
Description Updating the fact sheet on iodine (published by the British Dietetic Association) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Dr Bath and Professor Rayman wrote a fact-sheet on iodine in 2013 that was published by the British Dietetic Association (BDA). In May 2016 Dr Bath revised and updated the fact sheet to reflect recent evidence and data. The fact sheet is available on the website of the BDA and is used as a source of information on iodine for the general public. UK dietitians link to the fact sheet on social media when asked about dietary sources of iodine. There is also a link to the fact sheet from the UK Iodine Group website.
Year(s) Of Engagement Activity 2016
URL https://www.bda.uk.com/foodfacts/Iodine.pdf
 
Description Website development 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact As role on UK Iodine Group, developed website on iodine for the general public and health professionals (as information lacking). Maintain the website and update with news items and blog posts (explaining recent published research).
Year(s) Of Engagement Activity 2015
URL http://www.ukiodine.org/