“

The BTF award is crucial for kick-starting new areas of research with the potential to benefit thyroid health – thank you so much for this opportunity and I am excited to see where this pilot data leads us in the future.'

”

British Thyroid Foundation Research Award 2019: Measurement of environmental modulators of thyroid hormone biosynthesis, and investigation of their aetiological role in congenital hypothyroidism

Our 2019 BTF Research Award was awarded to Dr Nadia Schoenmakers from the Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge. The Award has funded the development of techniques to measure environmental pollutants that may disrupt thyroid function and a pilot study using these techniques to investigate the role of environmental pollutants, and micronutrients in babies with thyroid underactivity at birth (congenital hypothyroidism, CH).

Having recently presented her preliminary findings, we asked Dr Schoenmakers about her research:

What was the background to your study?

Congenital hypothyroidism (CH) (thyroid underactivity from birth) affects 1 in 2000 newborns. In some cases, the thyroid gland has developed normally, but it cannot produce adequate amounts of thyroid hormone (thyroxine). This form of CH is known as gland-in-situ (GIS). 

Although there is sometimes a genetic reason why babies have GIS CH, in most cases we cannot find an underlying cause. We therefore wanted to investigate whether levels of chemicals and nutrients that babies are exposed to during pregnancy may be involved. We already know that minerals such as iodine, iron and selenium play important roles in thyroid hormone production. Iodine is an integral component of thyroid hormones and iodine deficiency leads to hypothyroidism. This may be made worse if levels of iron and selenium are also suboptimal. 

We also know that environmental pollutants e.g. perchlorate, thiocyanate and nitrate may interrupt thyroid function. These chemicals are found in the atmosphere, as well as in food, soil and water. This means we are exposed to them widely in our daily lives. Perchlorate can persist in groundwater and has been detected in foods including dairy products, eggs, vegetables and even tablets such as vitamins. Thiocyanate is produced from cigarette smoke and is naturally present in food such as brassicas e.g. cabbages, Brussels sprouts, broccoli etc. Nitrates are used in fertilisers but naturally occurring nitrate is also found in green leafy vegetables, roots, oilseeds, grains, tubers, and nuts. 

However, we do not know what role these environmental factors play in the development of GIS CH. Additionally, although levels of environmental pollutants may be measured in urine samples, this is technically challenging and not routinely available in the UK. 

What was the aim of your research?

We initially wanted to develop techniques to measure levels of environmental chemicals that may influence thyroid function. This would subsequently enable us to integrate measurement of these pollutants with more readily-evaluable micronutrients in mothers and newborns, to see whether they are associated with CH. We also wanted to gain better insights into maternal and neonatal nutritional status; something that has not been widely studied in the UK.

Which groups of patients were involved in the study?

We recruited babies with who had been diagnosed with CH and their mothers when they first attended Great Ormond Street Hospital for investigation. We also recruited similarly-aged babies without CH and their mothers (the control group) from the Rosie maternity unit at Cambridge University Hospitals.

In total, we studied 30 mother-baby pairs with CH and 53 without CH. 

How did you conduct the research?

We first developed and validated assays to measure urinary levels of perchlorate, thiocyanate and nitrate which we used to make measurements in mother and baby pairs with and without CH. We also measured iodine levels in both urine and breast milk and assessed blood levels of thyroid hormones and micronutrients including selenium, folate and iron in mothers. Participants were also asked to complete a food frequency questionnaire to assess dietary iodine intake. This questionnaire was developed by Dr Sarah Bath at the University of Surrey, with whom we are collaborating for analysis of results.

What were your findings?

• Mothers in both study groups have a similar, mild iodine deficiency. However, their babies are not iodine deficient. In breastfed babies this may be because, despite iodine deficiency, mothers can maintain high levels of breast milk iodine which gives their babies sufficient iodine. 
• We successfully developed reliable testing methods for measuring urinary levels of perchlorate, thiocyanate and nitrite. We found no difference in levels of these chemicals, in cases or controls. 
  
• Mothers of babies with CH have lower folate and selenium levels than mothers of controls 
  and a substantial proportion have folate and/or selenium deficiency, compared with clinical reference ranges. Fewer mothers of CH cases took vitamin or folate supplements during pregnancy. This is a concern, both for thyroid health and general materno-foetal health in this group.

What role did the BTF funding play?

The BTF Research Award was vital for kick-starting this important study.  We now have the technology to quantify exposure to these important thyroid-disrupting chemicals through urinary measurements. Additionally, we have taken the first steps towards evaluating concentrations of these chemicals together with micronutrient levels, in mothers and their babies with and without CH. In retrospect, although we want to identify differences that may contribute to the development of CH, I think we have underestimated just how important the control data may be in its own right. Our study is proving a great way of exploring nutritional status in the immediate period after giving birth, with particular focus on thyroid health, which has also not been explored in the UK. This research has subsequently helped us to attract funding from the Wellcome Trust to support further studies. 

What are the next steps in your research?

Using funding from the Wellcome Trust, we have begun to extend the study to include more participants so that we can perform more complex analyses. In particular, we are interested in understanding whether combinations of micronutrient deficiencies or chemical exposures may contribute to particular subtypes of CH. We would also like to include participants from additional hospitals to increase the diversity of the study population.

This expansion is very exciting as our planned studies will help us further our understanding of this hitherto little-studied aspect of both foetal and maternal health. Depending on our findings, this may also lead to future recommendations around the use of supplements to prevent or treat thyroid dysfunction and provide insights into the health impact of thyroid-disrupting chemicals.

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