A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants Follow-up at 2 Years

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants With Follow-up at 2 Years

Conditions
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Transient Hypothyroxinemia

Intervention / Treatment
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* Drug: sodium iodide
* Drug: Sodium Chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All infants born under 31 weeks gestation Exclusion Criteria: Mother exposed to excess iodine during pregnancy or delivery

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 42 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iodine<br>This is the hypothetical active arm | Drug: sodium iodide<br>* sodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation<br>|
| Placebo Comparator: Placebo<br>this is the hypothetical placebo | Drug: Sodium Chloride<br>* Sodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | at 2 years corrected age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood levels of T4, TSH and TBG on day 7, 14, 28 and 34 weeks corrected age. |  | 2 years corrected age | 
| 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 | Type and severity of illness: necrotising enterocolitis | 2 years corrected age | 
| Type and severity of illness:persistent ductus arteriosus | Type and severity of illness:persistent ductus arteriosus | 2 years corrected age | 
| Type and severity of illness: respiratory distress | Type and severity of illness: respiratory distress | 2 years corrected age | 
| Type and severity of illness:chronic lung disease (need for oxygen at 36 weeks corrected age) | Type and severity of illness: chronic lung disease (need for oxygen at 36 weeks corrected age) | 2 years corrected age | 
| Cranial ultrasound changes | cranial ultrasound changes | 2 years corrected age | 
| Acquired infection | Acquired infection as indicated by medical notes during neonatal period | 2 years corrected age | 
| Cranial ultrasound changes | Type and severity of illness: necrotising enterocolitis, persistent ductus arteriosus, respiratory distress , chronic lung disease (need for oxygen at 36 weeks corrected age), cranial ultrasound changes, acquired infection; hearing and vision impairment; postnatal drug use (e.g. diamorphine, dexamethasone, dopamine, caffeine and indomethacin); nutritional status; BAPM level of care; highest recorded bilirubin levels; and death - immediate and underlying causes. | 2 years corrected age | 
| Hearing and vision impairment | Hearing and vision impairment as indicated by parental questionnaire | 2 years corrected age | 
| Postnatal drug use | diamorphine, dexamethasone, dopamine, caffeine and indomethacin | 2 years corrected age | 
| Nutritional status | Nutritional status collected on postnatal day 7, 14, 28 and 34 corrected weeks (as indicated by neonatal drug chart | 2 years corrected age | 
| BAPM level of care | BAPM level of care | 2 years corrected age | 
| Highest recorded bilirubin levels | highest recorded bilirubin levels; and death - immediate and underlying causes. | 2 years corrected age | 
| Death - immediate and underlying causes. | Death - immediate and underlying causes. | 2 years corrected age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypothyroxinemia, preterm infants, iodine, neurodevelopmental outcome, Iodine supplementation, Randomised controlled trial