Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Iodine deficiency during pregnancy might be associated with reduced intelligence quotient (IQ) score in offspring. We assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on neurodevelopment of their offspring in areas where schoolchildren were iodine sufficient. METHODS: In this randomised, placebo-controlled trial, pregnant women in Bangalore, India, and Bangkok, Thailand, were randomly assigned (1:1) to receive 200 mu g iodine orally once a day or placebo until delivery. Randomisation was done with a computer-generated sequence and stratified by site. Co-primary outcomes were verbal and performance IQ scores on the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) and the global executive composite score from the Behaviour Rating Inventory of Executive Function-Preschool Version (BRIEF-P) in the children at age 5-6 years. The trial was double-blinded; some unmasking took place at age 2 years for an interim analysis, but participants and nearly all investigators remained masked to group assignment until age 5-6 years. Analysis was by intention to treat using mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT00791466. FINDINGS: Between Nov 18, 2008, and March 12, 2011, 832 women entered the trial at a mean gestational age of 10.7 weeks (SD 2.7); median urinary iodine concentration was 131 mu g/L (IQR 81-213). Mean compliance with supplementation was 87%, assessed by monthly tablet counts. 313 children (iodine group, n=159; placebo group, n=154) were analysed for verbal and performance IQ with WPPSI-III and 315 (iodine group, n=159; placebo group, n=156) for overall executive function with BRIEF-P. Mean WPPSI-III scores for verbal IQ were 89.5 (SD 9.8) in the iodine group and 90.2 (9.8) in the placebo group (difference -0.7, 95% CI -2.9 to 1.5; p=0.77), and for performance IQ were 97.5 (12.5) in the iodine group and 99.1 (13.4) in the placebo group (difference -1.6, -4.5 to 1.3; p=0.44). The mean BRIEF-P global executive composite score was 90.6 (26.2) in the iodine group and 91.5 (27.0) in the placebo group (difference -0.9, -6.8 to 5.0; p=0.74). The frequency of adverse events did not differ between groups during gestation or at delivery: 24 women in the iodine group and 28 in the placebo group reported adverse events (iodine group: abortion, n=20; blighted ovum, and n=2; intrauterine death, n=2; placebo group: abortion, n=22; blighted ovum, n=1; intrauterine death, n=2; early neonatal death, n=1; and neonatal death, n=2). INTERPRETATION: Daily iodine supplementation in mildly iodine-deficient pregnant women had no effect on child neurodevelopment at age 5-6 years.