Iodine Status in Pregnancy and Associated Health Outcomes

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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: 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. To quantify any associations between iodine status during pregnancy, pregnancy outcomes, and cognitive and motor development of the child. 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).

Official Title
-----------------
Assessing Iodine Status and Associated Health Outcomes in British Women During Pregnancy

Conditions
-----------------
Cognitive Developmental Delay, Birth Weight

Intervention / Treatment
-----------------
* Other: Maternal iodine status


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Maternal iodine status|Urinary iodine concentration during pregnancy at 26 weeks' gestation (Bord in Bradford study) and at 12, 26 and 36 weeks' gestation, 6, 18 and 30 weeks postpartum (Hiba longitudinal study). This is primarily in the form of Iodine to Creatinine ratio, to take spot urine volume into account. There is no intervention in this observational study.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Born in Bradford: Early Years Foundation Stage (EYFS) profiles | The EYFS average points total over 17 domains (score range 17 to 41) and summarised using achievement of Good Level of Development (GLD) (binary). | Ages 3 to 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Born in Bradford: Key Stage 1 (KS1) educational outcomes | Year 1 phonics screening test (score range 0 to 40) and KS1 SATS scores in Reading, Writing, Mathematics and Science (working securely at level 2b or beyond pre-2016 or working at the expected standard or beyond for 2016 onwards, binary) will be presented. | Ages 5 to 8 | 
| Born in Bradford: Letter identification | Letter identification (standardised) | Ages 3 to 5 | 
| Born in Bradford: Receptive vocabulary | Receptive vocabulary using the British Picture Vocabulary Scale (BPVS)(standardised) | Ages 3 to 5 | 
| Born in Bradford: Social functioning | Social functioning using the Strengths and Difficulties Questionnaire (SDQ) total difficulty score and split by domains (e.g. internalising and externalising) | Ages 3 to 5 | 
| Born in Bradford: Fine motor skills | Fine motor skills using the Clinical Kinematic Assessment Tool (CKAT) overall battery score, along with Tracking, Aiming and Tracing CKAT sub-scores. | Ages 3 to 5 | 
| Born in Bradford: Birth weight centile | The main birth outcome of interest is birth weight centile, calculated using the version 8.0.1 of the Bulk centile calculator provided by the Gestation Network based at the Perinatal Institute for Maternal and Child Health | At birth | 
| Born in Bradford: Apgar score | Apgar score (ordinal). | At 1 minute and 5 minutes after birth. | 
| Born in Bradford: Diagnosis of autism | Confirmed diagnosis of autism based on Read codes in linked General Practitioner records. | Up to age 11. | 
| Born in Bradford: Diagnosis of attention deficit hyperactivity disorder (ADHD) | Confirmed diagnosis of attention deficit hyperactivity disorder (ADHD) based on Read codes in linked General Practitioner records. | Up to age 11. | 
| Hiba longitudinal study: Urinary iodine status | The main outcome of interest is urinary iodine status (primarily in the form of iodine to creatinine ratio to take account of spot urine volumes) changes during pregnancy and lactation (continuous) | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 
| Hiba longitudinal cohort: thyroid stimulating hormone (TSH) | Changes in thyroid stimulating hormone (TSH) during gestation and lactation. | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 
| Hiba longitudinal cohort: triiodothyronine (fT3) | Changes in triiodothyronine (fT3) during gestation and lactation. | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 
| Hiba longitudinal cohort: free thyroxine (fT4) | Changes in free thyroxine (fT4) during gestation and lactation. | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 
| Hiba longitudinal cohort: thyroglobulin | Changes in thyroglobulin during gestation and lactation. | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 
| Hiba longitudinal cohort: thyroid size | Changes in thyroid size, measured by palpation, using a standard protocol, during gestation and lactation. | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 
| Hiba longitudinal cohort: maternal dietary iodine intake (micrograms) | Identification of highest ranking food items in terms of contribution to iodine in the maternal diet as measured using the myfood24 tool | 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Iodine, Cognitive function, Birth outcomes, Pregnancy