Plain English Summary
Background and study aims.
There is evidence from previous studies that low thyroid function during pregnancy may affect the intelligence quotient (IQ) of the child. However there have been no prospective studies to confirm this. We carried out a study to answer the question: Does testing thyroid function in early pregnancy and treating those women with underactive thyroids improve the IQ of their children?
Who can participate?
We recruited 22000 women pregnant with one baby (singleton pregnancies) before 16 weeks gestation who were not taking thyroid medication.
What does the study involve?
Blood samples were randomly allocated to a screen group and a control group. Thyroid testing was done immediately in all samples from the screen group. The control group samples were stored until the woman delivered the baby and the thyroid test was then carried out. Note: at the time of this trial (2002) there was no routine screening of thyroid function in pregnant women. The screen group women who were found to have an underactive thyroid received Levothyroxine daily for the length of the pregnancy. The control group received no treatment during pregnancy. The women who had an underactive thyroid diagnosed after delivery were referred to their general practitioner for standard care.
What are the possible benefits and risks of participating?
The women participating had a 50% chance of having thyroid function measured during early pregnancy (compared to 0% chance in normal practice). They then had the opportunity to see if the thyroxine intervention improved the IQ of their child compared to the children born to mothers from the control group. Side effects of thyroxine include palpitations and tiredness. Thyroid testing was done in women taking thyroxine 6 weeks after starting and again at 30 weeks of pregnancy. Less than 5% of women required a dose adjustment.
Where is the study run from?
The study was run from the University Hospital of Wales, Cardiff University. There were approximately 8 centres including one in Turin, Italy.
When is the study starting and how long is it expected to run for?
The study started in 2002 and ended in 2010.
Who is funding the study?
Who is the main contact?
Professor JH Lazarus
Prof John H Lazarus
University Hospital of Wales
Professor of Clinical Endocrinology/
+44 (0)29 20 742193
Randomised controlled trial of the effect of gestational thyroid hormone intervention therapy on childhood development
Aim is to evaluate strategy of screening of thyroid function in early pregnancy.
Trent Multi-Centre Research Ethics Committee gave approval on the 24th June 2004 (ref: MREC/04/4/026)
Multicentre, randomised controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Please note that, as of 18 January 2007, this trial is closed to recruitment: follow up continuing
Sera obtained from pregnant women before 16 weeks gestation. Sera randomised to 'screen' (T4 and Thyroid Stimulating Hormones [TSH] measured at time of randomisation) and 'control' (hormones measured post delivery) groups. Thyroxine intervention given to screen group with low T4/high TSH and to control group postpartum.
This is the only prospective randomised intervention trial of thyroxine in early pregnancy.
Primary outcome measures
Intelligence Quotient (IQ) of children in screen and control groups.
Secondary outcome measures
No secondary outcome measures
Overall trial start date
Overall trial end date
Participant inclusion criteria
All pregnant women (aged 18 - 45 years) before 16 weeks gestation
Target number of participants
22,000 - recruitment closed on 31st May 2006
Participant exclusion criteria
1. Twin pregnancy
2. Thyroid treatment (T4 or antithyroid drugs)
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
The Wellcome Trust (UK) (grant ref: GRO65143MA)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22316443
Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, Chiusano E, John R, Guaraldo V, George LM, Perona M, Dall'Amico D, Parkes AB, Joomun M, Wald NJ, Antenatal thyroid screening and childhood cognitive function., N. Engl. J. Med., 2012, 366, 6, 493-501, doi: 10.1056/NEJMoa1106104.