Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants

M Ibrahim, J Sinn, W McGuire
Cochrane Database of Systematic Reviews 2006, (2): CD005253

BACKGROUND: Parenteral nutrition solutions, formula milks, and human breast milk contain insufficient iodine to meet recommended intakes for preterm infants. Iodine deficiency may exacerbate transient hypothyroxinaemia in preterm infants and this may be associated with adverse respiratory or neurological outcomes.

OBJECTIVES: To assess the evidence from randomised controlled trials that dietary supplementation with iodine reduces mortality and morbidity in preterm infants.

SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 - November 2005), EMBASE (1980 - November 2005), CINAHL (1982 - November 2005), conference proceedings, and previous reviews.

SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared a policy of supplementing enteral or parenteral feeds with iodine (more than 30 micrograms per kilogram per day) versus placebo or no supplementation in preterm infants.

DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference. The primary outcomes for this review were neonatal mortality, death before hospital discharge, and longer term neurodevelopmental outcomes including severe neurodevelopmental disability.

MAIN RESULTS: We found only one randomised controlled trial (N = 121) that fulfilled the review eligibility criteria (Rogahn 2000). The participants were infants born before 33 weeks' gestation (but most were of birth weight greater than 1000 grams). The primary aim of this trial was to assess the effect of iodine supplementation on thyroid function. The investigators did not detect any statistically significant effects on the plasma levels of thyroxine (free and total), triiodothyronine, or thyrotrophin in preterm infants (measured up to 40 weeks' post-conceptional age). Only one infant died and the trial was therefore underpowered to detect an effect on mortality. The trial did not assess the effect of the intervention on neurodevelopmental morbidity. There was not a statistically significant difference in the incidence of chronic lung disease.

AUTHORS' CONCLUSIONS: There are insufficient data at present to determine whether providing preterm infants with supplemental iodine (to match fetal accretion rates) prevents morbidity and mortality in preterm infants. Future randomised controlled trials of iodine supplementation should focus on extremely preterm and extremely low birth weight infants, the group at greatest risk of transient hypothyroxinaemia. These trials should aim to assess the effect of iodine supplementation on clinically important outcomes including respiratory morbidity and longer term neurodevelopment.

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