Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand; Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands.
Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands; St John's Research Institute, Bangalore, India.
Lancet Diabetes Endocrinol. 2017 Nov;5(11):853-863. doi: 10.1016/S2213-8587(17)30332-7. Epub 2017 Oct 10.
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.
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.
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).
Daily iodine supplementation in mildly iodine-deficient pregnant women had no effect on child neurodevelopment at age 5-6 years.
Swiss National Science Foundation, Nestlé Foundation, Wageningen University and Research, and ETH Zurich.
孕妇碘缺乏可能与后代智商（IQ）分数降低有关。我们评估了在学龄儿童碘充足的地区，轻度碘缺乏的孕妇补充碘对其后代神经发育的影响。
在这项随机、安慰剂对照试验中，印度班加罗尔和泰国曼谷的孕妇被随机（1:1）分配接受每天口服 200μg 碘或安慰剂，直至分娩。随机分配使用计算机生成的序列，并按地点分层。主要结局是在儿童 5-6 岁时使用韦氏学前和小学智力量表第三版（WPPSI-III）的言语和表现 IQ 评分以及行为评定量表执行功能-学前版（BRIEF-P）的全球执行综合评分。该试验是双盲的；在中期分析时，部分参与者会暴露身份，但直到 5-6 岁时，所有参与者和几乎所有研究者仍对分组情况保持盲态。使用混合效应模型进行意向治疗分析。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00791466。
2008 年 11 月 18 日至 2011 年 3 月 12 日期间，832 名孕妇进入试验，平均妊娠 10.7 周（SD 2.7）；中位数尿碘浓度为 131μg/L（IQR 81-213）。每月通过药片计数评估，补充剂的平均依从率为 87%。用 WPPSI-III 对 313 名儿童（碘组，n=159；安慰剂组，n=154）进行言语和表现 IQ 分析，用 BRIEF-P 对 315 名儿童（碘组，n=159；安慰剂组，n=156）进行整体执行功能分析。碘组言语 IQ 的平均 WPPSI-III 评分为 89.5（9.8），安慰剂组为 90.2（9.8）（差值-0.7，95%CI-2.9 至 1.5；p=0.77），表现 IQ 的平均 WPPSI-III 评分为碘组 97.5（12.5），安慰剂组 99.1（13.4）（差值-1.6，-4.5 至 1.3；p=0.44）。碘组的 BRIEF-P 全球执行综合评分平均为 90.6（26.2），安慰剂组为 91.5（27.0）（差值-0.9，-6.8 至 5.0；p=0.74）。妊娠和分娩期间，两组的不良事件发生率无差异：碘组有 24 名女性和安慰剂组有 28 名女性报告了不良事件（碘组：流产，n=20；空孕囊，n=2；宫内死亡，n=2；安慰剂组：流产，n=22；空孕囊，n=1；宫内死亡，n=2；新生儿早期死亡，n=1；新生儿死亡，n=2）。
在轻度碘缺乏的孕妇中每天补充碘对儿童 5-6 岁时的神经发育没有影响。
瑞士国家科学基金会、雀巢基金会、瓦赫宁根大学和研究中心以及苏黎世联邦理工学院。
