Title: Assessing iodine status and associated health outcomes in British women during pregnancy
Funder: Department of Health and Social Care

Abstract: Background: Pregnant women may be particularly vulnerable to iodine deficiency as requirements increase to support foetal development. There is limited information concerning how maternal iodine status changes during pregnancy. Severe iodine deficiency is associated with deleterious health outcomes during pregnancy including gestational diabetes, preeclampsia, stillbirth, and increased mortality. For the foetus, severe iodine deficiency results in reduced birthweight, increased mortality and neurodevelopmental issues. Several studies suggest 40% of pregnant mothers in the UK may not meet the WHO definition of iodine sufficiency. Although the effects of severe iodine deficiency are known, the impact of mild-to-moderate deficiencies on maternal health and associated foetal and childhood development are not well understood. Aims: 1) To provide up-to-date information on iodine status in pregnant women in the UK, including changes during pregnancy and lactation, and the role of diet. 2) To quantify any associations between iodine status during pregnancy, pregnancy outcomes, and cognitive and motor development of the child. 3) To compare the iodine status of mothers in the Born in Bradford cohort to a more nationally representative sample. Research plan and methods: We will utilize the Born in Bradford (BiB) birth cohort which recruited over 12000 pregnant women between 2007- 2009, and has biobanked 6971 spot urine samples collected at 26-28 weeks gestation. Data are available on health outcomes during pregnancy including gestational diabetes, preeclampsia, blood pressure, length of gestation, mortality, mental health. Child outcome measures at birth include weight, length, head circumference, small-for-gestational-age. Childhood developmental measures include height, weight, growth trajectories, motor skills, literacy, numeracy and mental health. We will measure all maternal urine samples in BiB to allow sufficient power to detect potential modest-sized associations. This will be conducted using inductively coupled plasma mass spectrometry (ICPMS). All maternal baseline characteristics and associated outcome data are available for extraction from the primary BiB database. We will apply multiple logistic regression and multiple linear regression to ascertain potential associations between maternal iodine status and health and developmental outcomes. Cubic splines will be used to model any nonlinear dose-response associations, making no assumptions regarding any predefined thresholds. We will also conduct a longitudinal substudy to ascertain how iodine status varies between trimesters. 300 pregnant women will be recruited at 12 week dating scans and the following collected: baseline characteristics, urine samples for iodide analysis, blood for thyroid stimulating hormone (TSH), free thyroxine (fT4) and triodothyronine (fT3), Glomerular Filtration Rate (GFR) based on serum creatinine, visual inspection of the thyroid using standard methods, dietary intake using a 24h recall tool (myfood24). Data collection will be repeated at 26 and 36 weeks gestation, and 6, 18 and 30 weeks postpartum. The proposed substudy will clarify how iodine status alters in pregnancy and lactation, and any associated thyroid hormone changes. We will identify key sources of iodine in the diet and ascertain dietary patterns associated with different iodine status. To compare results to a more nationally representative sample, spot urines will be analysed from approximately 650 women in the SCOPE birth-cohort (London, Leeds and Manchester). Research team: The research team comprises a molecular epidemiologist (Hardie) with extensive experience of nutritional biomarkers, a biostatistician with expertise in birth cohorts, child health and nutrition (Greenwood), the BiB study lead (Wright), nutritional epidemiologist (Cade), and obstetrician (Simpson) and endocrinologist (Stewart). The team will be supported by four external expert advisors (Zimmermann, Alwan, Mon-Williams, Ajjan). Potential impact: These studies will describe the nature and any associated health impact of iodine status during pregnancy for British women and their children. This will inform public health policy in the UK regarding dietary advice and the potential need for iodine supplementation during pregnancy.

Lay abstract: Iodine is a key micronutrient in the diet, essential for healthy growth, and is particularly important during pregnancy and breastfeeding when demands are increased to support the developing baby. Many people are thought to lack all the iodine they need, and this is a greater issue during and shortly after pregnancy when the body s iodine requirements are greatest. Iodine deficiency complications are potentially serious for both mother and child. Iodine deficiency can lead to thyroid enlargement, lower production of important hormones produced by the thyroid, pregnancy complications in the mother, and impaired growth and developmental problems in babies and children. This research will focus on providing an up-to-date estimate of how many pregnant women do not have enough iodine, and what different levels of iodine might mean in terms of health risks during pregnancy and for childhood development. We will investigate how iodine levels vary over the course of pregnancy and lactation, how this is affected by diet, associated changes in thyroid size and function, and what levels of iodine are linked with greater risk of subsequent health problems. The research will take advantage of existing urine samples collected from mothers during pregnancy in the Born in Bradford birth cohort study, where we also know of any adverse pregnancy outcomes, as well as any developmental problems for the baby and in early childhood.

Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH