Harding Kimberly B, Peña-Rosas Juan Pablo, Webster Angela C, Yap Constance My, Payne Brian A, Ota Erika, De-Regil Luz Maria
Research and Evaluation, Micronutrient Initiative, 180 Elgin Street, Suite 1000, Ottawa, ON, Canada, K2P 2K3.
Evidence and Programme Guidance, Department of Nutrition for Health and Development, World Health Organization, 20 Avenue Appia, Geneva, GE, Switzerland, 1211.
Cochrane Database Syst Rev. 2017 Mar 5;3(3):CD011761. doi: 10.1002/14651858.CD011761.pub2.
BACKGROUND: Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences. OBJECTIVES: To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results. MAIN RESULTS: We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period. AUTHORS' CONCLUSIONS: There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review.
背景:碘是甲状腺激素生物合成所需的一种必需营养素,甲状腺激素负责调节生长、发育和新陈代谢。孕期和哺乳期对碘的需求量大幅增加。如果在这些时期需求未得到满足,甲状腺激素的产生可能会减少,不足以满足母体、胎儿和婴儿的需求。补充碘可能有助于满足孕期和产后增加的碘需求,并预防或纠正碘缺乏及其后果。 目的:评估孕前、孕期或产后妇女单独或与其他维生素和矿物质联合补充碘对其自身及其子女结局的益处和危害。 检索方法:我们检索了Cochrane妊娠与分娩试验注册库(2016年11月14日)和世界卫生组织国际临床试验注册平台(ICTRP)(2016年11月17日),联系了该领域的专家,并检索了检索到的研究及其他相关论文的参考文献列表。 选择标准:个体或整群随机的随机和半随机对照试验,比较孕前、孕期或产后注射或口服碘补充剂(如片剂、胶囊、滴剂),无论碘化合物、剂量、频率或持续时间如何。 数据收集与分析:两位综述作者独立评估试验的合格性、偏倚风险、提取数据并进行准确性检查。我们采用GRADE方法评估主要结局证据的质量。我们预计试验间存在高度异质性,因此使用随机效应模型汇总试验结果,并在解释汇总结果时保持谨慎。 主要结果:我们纳入了14项研究,排除了48项研究。我们确定了5项正在进行或未发表的研究,2项研究正在等待分类。11项涉及2700多名妇女的试验为本综述中的比较提供了数据(3项试验未报告主要或次要结局)。 母体主要结局:碘补充剂使产后甲状腺功能亢进不良反应的可能性降低了68%(平均风险比(RR)0.32;95%置信区间(CI)0.11至0.91,3项试验,轻度至中度碘缺乏环境,543名妇女,无统计学异质性,低质量证据),并使孕期消化不耐受不良反应的可能性增加了15倍(平均RR 15.33;95%CI 2.07至113.70,1项试验,轻度缺乏环境,76名妇女,极低质量证据)。孕期或产后甲状腺功能减退组间无明显差异(孕期:平均RR 1.90;95%CI 0.57至6.38,1项试验,365名妇女,低质量证据,产后:平均RR 0.44;95%CI 0.06至3.42,3项试验,540名妇女,无统计学异质性,低质量证据)、早产(平均RR 0.71;95%CI 0.30至1.66,2项试验,376名妇女,有统计学异质性,低质量证据)或孕期或产后甲状腺过氧化物酶抗体(TPO-ab)升高的母体不良反应(平均RR 0.95;95%CI 0.44至2.07,1项试验,359名妇女,低质量证据,平均RR 1.01;95%CI 0.78至1.30,3项试验,397名名妇女,无统计学异质性,低质量证据),或孕期甲状腺功能亢进(平均RR 1.90;95%CI 0.57至6.38,1项试验,365名妇女,低质量证据)。所有为这些结局提供数据的试验均在轻度至中度碘缺乏的环境中进行。 婴儿/儿童主要结局:与未接受碘补充剂的婴儿相比,接受碘补充剂的婴儿围产期死亡的可能性降低了34%,但这一差异无统计学意义(平均RR 0.66;95%CI 0.42至1.03,2项试验,457次评估,低质量证据)。所有围产期死亡均发生在一项在严重碘缺乏环境中进行的试验中。低出生体重组间无明显差异(平均RR 0.56;95%CI 0.26至1.23,2项试验,377名婴儿,无统计学异质性,低质量证据)、新生儿甲状腺功能减退/促甲状腺激素(TSH)升高(平均RR 0.58;95%CI 0.11至3.12,2项试验,260名婴儿,极低质量证据)或新生儿甲状腺过氧化物酶抗体(TPO-ab)升高的不良反应(平均RR 0.61;95%CI 0.07至5.70,1项试验,108名婴儿,极低质量证据)。所有为这些结局提供数据的试验均在轻度至中度碘缺乏地区进行。没有试验报告新生儿期之后的甲状腺功能减退/TSH升高或任何不良反应。 作者结论:没有足够的数据就孕期前、孕期或产后妇女常规补充碘的益处和危害得出任何有意义的结论。现有证据表明,补充碘可降低产后甲状腺功能亢进的可能性,并增加孕期消化不耐受不良反应的可能性——这两者均被视为潜在的不良反应。然而,由于研究设计的局限性和宽泛的置信区间,我们认为这些结局的证据质量低或极低。此外,由于我们的荟萃分析中试验数量少且纳入的妇女数量有限,这些结果必须谨慎解释。对其他重要的母体或儿童结局没有明显影响,不过由于数据有限和试验质量低,这些结果也必须谨慎解释。此外,几乎所有证据都来自轻度或中度碘缺乏的环境,因此可能不适用于严重缺乏的环境。需要更多关于孕期前、孕期和产后补充碘对母婴结局影响的高质量随机对照试验。然而,在严重缺乏碘的环境中将碘与安慰剂或不治疗进行比较可能不符合伦理。在孕妇和哺乳期妇女通常服用含碘产前补充剂的环境中进行试验也可能不可行。需要了解开始补充碘的最佳时机以及补充方案和剂量。未来的试验应考虑本综述中的结局,并对新生儿期之后的儿童进行随访。未来的试验应采用足够的样本量,评估潜在的不良反应(包括消化不耐受的性质和程度),并以允许评估偏倚风险、全面提取数据并按本综述指定的亚组进行分析的方式报告。
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