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.

中文翻译：

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孕妇补充碘对儿童神经发育的影响：一项随机，双盲，安慰剂对照试验

背景

怀孕期间的碘缺乏症可能与后代的智商（IQ）得分降低有关。在中学生缺碘的地区，我们评估了碘缺乏症轻度孕妇补充碘对其子代神经发育的影响。

方法

在这项随机，安慰剂对照的试验中，印度班加罗尔和泰国曼谷的孕妇被随机分配（1：1）每天一次口服200μg碘或安慰剂直至分娩。用计算机生成的序列进行随机化，并按位点分层。共同主要结果是韦氏儿童学前和智力量表第三版（WPPSI-III）的口头和绩效智商得分，以及执行功能-学龄前儿童行为评级清单（BRIEF-P）中的全球执行综合得分。 5-6岁的儿童。审判是双盲的。在2岁时进行了一些揭露，以进行中期分析，但参与者和几乎所有研究者都对5-6岁时的小组任务保持掩盖。分析的目的是使用混合效应模型进行治疗。ClinicalTrials.gov，编号NCT00791466。

发现

在2008年11月18日至2011年3月12日之间，有832名妇女以平均胎龄10·7周（SD 2·7）进入试验。尿碘中位数浓度为131μg/ L（IQR 81–213）。根据每月的片剂计数评估，补充剂的平均依从率为87％。使用WPPSI-III对313名儿童（碘组，n = 159；安慰剂组，n = 154）的语言和表现智商进行了分析，对315名儿童（碘组，n = 159；安慰剂组，n = 156）进行了总体执行功能评估。简报 言语智商的WPPSI-III口头智商平均得分为89·5（SD 9·8），安慰剂组为90·2（9·8）（差异-0·7，95％CI -2·9至1·5; p = 0·77），碘治疗组的IQ为97·5（12·5），安慰剂组为99·1（13·4）（差异-1·6，-4 ·5至1·3； p = 0·44）。碘治疗组的BRIEF-P全球高管综合平均评分为90·6（26·2），安慰剂治疗组为91·5（27·0）（差异-0·9，-6·8至5·0 ； p = 0·74）。妊娠期间或分娩时两组之间的不良事件发生频率没有差异：碘组中有24名妇女和安慰剂组中有28名妇女报告了不良事件（碘组：流产，n = 20；卵子枯萎，n = 2；子宫内死亡，n ＝ 2；安慰剂组：流产，n ＝ 22；卵子枯萎，n ＝ 1；子宫内死亡，n ＝ 2；新生儿早期死亡，n ＝ 1；和新生儿死亡，n ＝ 2）。子宫内死亡，n = 2；安慰剂组：流产，n = 22；枯萎的卵子，n = 1；子宫内死亡，n = 2；新生儿早期死亡，n = 1；和新生儿死亡，n = 2）。子宫内死亡，n = 2；安慰剂组：流产，n = 22；枯萎的卵子，n = 1；子宫内死亡，n = 2；新生儿早期死亡，n = 1；和新生儿死亡，n = 2）。

解释

轻度缺碘孕妇每天补充碘对5-6岁的儿童神经发育没有影响。

资金

瑞士国家科学基金会，雀巢基金会，瓦赫宁根大学和研究以及苏黎世联邦理工学院。