Sueppong Gowachirapant1, Nidhi Jaiswal2, Alida Melse-Boonstra3, Valeria Galetti4, Sara Stinca4, Ian Mackenzie5, Susan Thomas6, Tinku Thomas6, Pattanee Winichagoon7, Krishnamachari Srinivasan6, Michael B Zimmermann8. 1. Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand; Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. 2. Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands; St John's Research Institute, Bangalore, India. 3. Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. 4. Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland. 5. Hearing Impairment Research Group, Liverpool School of Tropical Medicine, Liverpool, UK. 6. St John's Research Institute, Bangalore, India. 7. Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand. 8. Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland. Electronic address: michael.zimmermann@hest.ethz.ch.
Abstract
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 μg 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 μg/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. FUNDING: Swiss National Science Foundation, Nestlé Foundation, Wageningen University and Research, and ETH Zurich.
RCT Entities:
BACKGROUND:Iodinedeficiency 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 μg 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 μg/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. FUNDING: Swiss National Science Foundation, Nestlé Foundation, Wageningen University and Research, and ETH Zurich.
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