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

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.

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.

hypothyroxinemia, preterm infants, iodine, neurodevelopmental outcome, Iodine supplementation, Randomised controlled trial

sodium iodide 30 micrograms/kg/day, daily dose, from randomisation (within 42 hours of birth) to 34 corrected weeks gestation

Sodium Chloride 30 micrograms/kg/day, daily dose, from randomisation (from within 42 hours of birth)to 34 corrected weeks gestation

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.

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.

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.

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.

Nutritional status collected on postnatal day 7, 14, 28 and 34 corrected weeks (as indicated by neonatal drug chart

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

Williams F, Hume R, Ogston S, Brocklehurst P, Morgan K, Juszczak E; I2S2 team. A summary of the iodine supplementation study protocol (I2S2): a UK multicentre randomised controlled trial in preterm infants. Neonatology. 2014;105(4):282-9. doi: 10.1159/000358247. Epub 2014 Feb 27.