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. The investigators 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 the investigators also know of any adverse pregnancy outcomes, as well as any developmental problems for the baby and in early childhood.

Background: Pregnant women may be particularly vulnerable to iodine deficiency as requirements increase to support fetal 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 fetus, severe iodine deficiency results in reduced birthweight, increased mortality and neurodevelopmental issues. Several studies suggest 40% of pregnant mothers in the United Kingdom (UK) may not meet the World Health Organization (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 fetal 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: The investigators will utilize the Born in Bradford (BiB) birth cohort which recruited over 12000 pregnant women between 2007- 2009, and has deposited in a biobank 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 (Strengths and Difficulties Questionnaire, SDQ). Linkage with educational outcomes has been achieved, including Early Years Foundation Stage (EYFS) outcomes and Standard Assessment Tests (SATS) at both Key Stage 1 (KS1) and Key Stage 2 (KS2).

The investigators 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.

The investigators 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.

The investigators will also conduct a longitudinal substudy to ascertain how iodine status varies between trimesters (The Hiba study). 200 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 triiodothyronine (fT3), thyroglobulin, Glomerular Filtration Rate (GFR) based on serum creatinine, visual inspection of the thyroid using standard methods, dietary intake using a validated online 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. The investigators 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).

Inclusion criteria:

• Female (Both Born in Bradford and Hiba longitudinal cohorts)
• Able to provide informed consent (Both Born in Bradford and Hiba longitudinal cohorts)
• Confirmed pregnant at 26-28 week Oral Glucose Tolerance Test (OGTT) (Born in Bradford cohort)
• Confirmed 9-15 weeks pregnant at 12 week dating scan (Hiba longitudinal cohort)
• Aged 18-40 years (Hiba longitudinal cohort)
• No medical or known first degree family history of a thyroid condition (Hiba longitudinal cohort).

Exclusion criteria:

• Inability to provide informed consent (Both Born in Bradford and Hiba longitudinal cohorts)
• Current or former medical history of thyroid disease (Hiba longitudinal cohort)
• Use of thyroid related medications (Hiba longitudinal cohort)

The Born in Bradford cohort profile is published here: [doi:10.1093/ije/dys112] All women booked for delivery at the Bradford Royal Infirmary at 26-28 weeks gestation. All of the recruited women who provided urine samples are included in our Born in Bradford analysis.

The Hiba longitudinal study replicates this process, but at the 12 week dating scan.

Born in Bradford welcomes collaboration with other researchers. The BiB website has details of how to submit expressions of interest and has short proformas for these. All suggestions will be reviewed by the BiB Executive Group on a monthly basis, and we aim to get back to potential collaborators within 8 weeks.

Ongoing.

Submit expressions of interest on a short proforma. All suggestions will be reviewed by the BiB Executive Group.