A Randomised Controlled Trial of Iodide Supplementation in Preterm Infants Follow-up at 2 Years (I2S2)

Primary Outcome Measures:

• 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. [ Time Frame: 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 Outcome Measures:

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

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.