Iodine Status in Pregnancy and Associated Health Outcomes
Condition: Cognitive Developmental Delay; Birth Weight
MeSH terms: Birth Weight
Study type: Observational

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:

        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).
    

Intervention name(s): Maternal iodine status
Intervention type(s): Other
Intervention description(s): 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.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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.
      
Biospecimen description: 
      7000 urine samples from the Born in Bradford cohort. 200 urine and blood samples during
      pregnancy and lactation from the Hiba longitudinal cohort.
    
Keywords: Iodine; Cognitive function; Birth outcomes; Pregnancy