Transient Hypothyroxinemia
Conditions
Keywords
hypothyroxinemia, preterm infants, iodine, neurodevelopmental outcome, Iodine supplementation, Randomised controlled trial
Brief summary
The purpose of this trial is to determine whether iodide supplementation of neonates born under 31 weeks gestation improves neurodevelopment measured at two years of age.
Detailed description
Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 μg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed as a UK multicentre randomised controlled trial to establish whether iodine supplementation of preterm infants benefits neurodevelopment.
Interventions
DRUGsodium iodide
sodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation
DRUGSodium Chloride
Sodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation
Sponsors
University of Dundee
National Institute for Health Research, United Kingdom
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Hours to 42 Hours
Healthy volunteers
No
Inclusion criteria
* All infants born under 31 weeks gestation
Exclusion criteria
* Mother exposed to excess iodine during pregnancy or delivery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Appreciable neurodevelopmental impairment at 2 years corrected age. As measured by the three main domains of the Bayley III score: i.e. cognitive score, language composite score and motor composite score. | at 2 years corrected age | P ≤0.05 will be the level used to indicate statistical significance.Deaths and those infants with severe neurodevelopment disability will be scored 55 in the cognitive domain, 46 in the motor domain and 47 in the language domain. The primary outcome will be ordered as cognitive score, motor composite score and language composite score in all results presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurodevelopment impairment as a composite of death or a Bayley III score of <85 in any of the score's three main subsets domains: cognitive, language and motor composites. | 2 years corrected age | — |
| Neurodevelopmental impairment assessed as a difference between the iodine supplemented and placebo groups in each of the four subset scores of the Bayley III i.e. receptive communication, expressive communication, fine motor or gross motor. | 2 years corrected age | — |
| Type and severity of illness: necrotising enterocolitis | 2 years corrected age | Type and severity of illness: necrotising enterocolitis |
| Type and severity of illness:persistent ductus arteriosus | 2 years corrected age | Type and severity of illness:persistent ductus arteriosus |
| Type and severity of illness: respiratory distress | 2 years corrected age | Type and severity of illness: respiratory distress |
| Type and severity of illness:chronic lung disease (need for oxygen at 36 weeks corrected age) | 2 years corrected age | Type and severity of illness: chronic lung disease (need for oxygen at 36 weeks corrected age) |
| Cranial ultrasound changes | 2 years corrected age | cranial ultrasound changes |
| Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age. | 2 years corrected age | — |
| Hearing and vision impairment | 2 years corrected age | Hearing and vision impairment as indicated by parental questionnaire |
| Postnatal drug use | 2 years corrected age | diamorphine, dexamethasone, dopamine, caffeine and indomethacin |
| Nutritional status | 2 years corrected age | Nutritional status collected on postnatal day 7, 14, 28 and 34 corrected weeks (as indicated by neonatal drug chart |
| BAPM level of care | 2 years corrected age | BAPM level of care |
| Highest recorded bilirubin levels | 2 years corrected age | highest recorded bilirubin levels; and death - immediate and underlying causes. |
| Death - immediate and underlying causes. | 2 years corrected age | Death - immediate and underlying causes. |
| Acquired infection | 2 years corrected age | Acquired infection as indicated by medical notes during neonatal period |
Countries
United Kingdom
Outcome results
None listed