Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: an RCT

Background: The recommendation for enteral iodide intake for preterm infants is 30–40 μg/kg/day and 1μg/kg/day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared to placebo, iodide supplementation of preterm infants improves neurodevelopment.

Methods: A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks’ gestation. Trial solutions (sodium iodide or sodium chloride; dose 30μg/kg/day) were given within 42 hours of birth to the equivalent of 34 weeks’ gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin and thyroid binding globulin were measured on four specific postnatal days. The primary outcome was neurodevelopmental status at two years’ of age, measured using the Bayley-III scales. The primary analyses are by intention-to-treat and data are presented also for survivors.

Results: 1,273 infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. 131 infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference Cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; Motor composite score, 0.21, 95% CI -2.23 to 2.65; Language composite score, -0.05, 95%CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the Language composite score and one subtest score.

Conclusions: Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

Trial Registration and Funding: CTA No. 21584/0251/001, and registration No. NCT00638092. Funded by MRC and managed by NIHR on behalf of the MRC-NIHR partnership.