- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03552341
Iodine Status in Pregnancy and Associated Health Outcomes (Hiba)
Assessing Iodine Status and Associated Health Outcomes in British Women During Pregnancy
Study Overview
Status
Conditions
Intervention / Treatment
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).
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
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.
Description
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)
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Born in Bradford: Early Years Foundation Stage (EYFS) profiles
Time Frame: Ages 3 to 5
|
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
Time Frame: Ages 5 to 8
|
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
Time Frame: Ages 3 to 5
|
Letter identification (standardised)
|
Ages 3 to 5
|
Born in Bradford: Receptive vocabulary
Time Frame: Ages 3 to 5
|
Receptive vocabulary using the British Picture Vocabulary Scale (BPVS)(standardised)
|
Ages 3 to 5
|
Born in Bradford: Social functioning
Time Frame: Ages 3 to 5
|
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
Time Frame: Ages 3 to 5
|
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
Time Frame: At birth
|
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
Time Frame: At 1 minute and 5 minutes after birth.
|
Apgar score (ordinal).
|
At 1 minute and 5 minutes after birth.
|
Born in Bradford: Diagnosis of autism
Time Frame: Up to age 11.
|
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)
Time Frame: Up to age 11.
|
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
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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)
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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)
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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)
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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)
Time Frame: 12, 26 and 36 weeks' gestation during pregnancy, and 6, 18 and 30 weeks' postpartum.
|
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.
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Born in Bradford: length of gestation
Time Frame: At birth
|
length of gestation (weeks), presenting pre-term delivery (<37 weeks)
|
At birth
|
Born in Bradford: congenital anomalies
Time Frame: At birth
|
Diagnosis of congenital anomalies from linked congenital anomalies records (binary)
|
At birth
|
Born in Bradford: childhood growth trajectories
Time Frame: From 26 weeks gestation, through to age 11
|
Childhood growth trajectories (weight in kg)
|
From 26 weeks gestation, through to age 11
|
Born in Bradford: Key Stage 2 (KS2) educational outcomes
Time Frame: Ages 8 to 11
|
Key Stage 2 (KS2) SATS scores in English grammar, punctuation and spelling, English reading, and Mathematics.
|
Ages 8 to 11
|
Born in Bradford: maternal mental health
Time Frame: From 26 weeks gestation, through to age 11
|
Patient Health Questionnaire 9 (PHQ-9) depression test questionnaire
|
From 26 weeks gestation, through to age 11
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Darren C Greenwood, PhD, University of Leeds
- Principal Investigator: Laura J Hardie, PhD, University of Leeds
Publications and helpful links
General Publications
- Snart CJP, Keeble C, Taylor E, Cade JE, Stewart PM, Zimmermann M, Reid S, Threapleton DE, Poston L, Myers JE, Simpson NAB, Greenwood DC, Hardie LJ. Maternal Iodine Status and Associations with Birth Outcomes in Three Major Cities in the United Kingdom. Nutrients. 2019 Feb 20;11(2):441. doi: 10.3390/nu11020441.
- Snart CJP, Threapleton DE, Keeble C, Taylor E, Waiblinger D, Reid S, Alwan NA, Mason D, Azad R, Cade JE, Simpson NAB, Meadows S, McKillion A, Santorelli G, Waterman AH, Zimmermann M, Stewart PM, Wright J, Mon-Williams M, Greenwood DC, Hardie LJ. Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort. BMC Med. 2020 Jun 11;18(1):132. doi: 10.1186/s12916-020-01602-0.
- Threapleton DE, Snart CJP, Keeble C, Waterman AH, Taylor E, Mason D, Reid S, Azad R, Hill LJB, Meadows S, McKillion A, Alwan NA, Cade JE, Simpson NAB, Stewart PM, Zimmermann M, Wright J, Waiblinger D, Mon-Williams M, Hardie LJ, Greenwood DC. Maternal iodine status in a multi-ethnic UK birth cohort: Associations with child cognitive and educational development. Paediatr Perinat Epidemiol. 2021 Mar;35(2):236-246. doi: 10.1111/ppe.12719. Epub 2020 Sep 1.
- Threapleton DE, Waiblinger D, Snart CJP, Taylor E, Keeble C, Ashraf S, Bi S, Ajjan R, Azad R, Hancock N, Mason D, Reid S, Cromie KJ, Alwan NA, Zimmermann M, Stewart PM, Simpson NAB, Wright J, Cade JE, Hardie LJ, Greenwood DC. Prenatal and Postpartum Maternal Iodide Intake from Diet and Supplements, Urinary Iodine and Thyroid Hormone Concentrations in a Region of the United Kingdom with Mild-to-Moderate Iodine Deficiency. Nutrients. 2021 Jan 14;13(1):230. doi: 10.3390/nu13010230.
- Cromie KJ, Threapleton DE, Snart CJP, Taylor E, Mason D, Wright B, Kelly B, Reid S, Azad R, Keeble C, Waterman AH, Meadows S, McKillion A, Alwan NA, Cade JE, Simpson NAB, Stewart PM, Zimmermann M, Wright J, Waiblinger D, Mon-Williams M, Hardie LJ, Greenwood DC. Maternal iodine status in a multi-ethnic UK birth cohort: associations with autism spectrum disorder. BMC Pediatr. 2020 Dec 5;20(1):544. doi: 10.1186/s12887-020-02440-y.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PR-R10-0514-11004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Study Data/Documents
-
Individual Participant Data Set
Information comments: Submit expressions of interest on a short proforma. All suggestions will be reviewed by the BiB Executive Group.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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