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Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants

  • Review
  • Intervention




Parenteral nutrition solutions, formula milks, and human breast milk contain insufficient iodine to meet recommended intakes for preterm infants. Iodine deficiency may exacerbate transient hypothyroxinaemia in preterm infants and this may be associated with adverse respiratory or neurological outcomes.


To assess the evidence from randomised controlled trials that dietary supplementation with iodine reduces mortality and morbidity in preterm infants.

Search methods

We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005), MEDLINE (1966 - November 2005), EMBASE (1980 - November 2005), CINAHL (1982 - November 2005), conference proceedings, and previous reviews.

Selection criteria

Randomised or quasi-randomised controlled trials that compared a policy of supplementing enteral or parenteral feeds with iodine (more than 30 micrograms per kilogram per day) versus placebo or no supplementation in preterm infants.

Data collection and analysis

The standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference. The primary outcomes for this review were neonatal mortality, death before hospital discharge, and longer term neurodevelopmental outcomes including severe neurodevelopmental disability.

Main results

We found only one randomised controlled trial (N = 121) that fulfilled the review eligibility criteria (Rogahn 2000). The participants were infants born before 33 weeks' gestation (but most were of birth weight greater than 1000 grams). The primary aim of this trial was to assess the effect of iodine supplementation on thyroid function. The investigators did not detect any statistically significant effects on the plasma levels of thyroxine (free and total), triiodothyronine, or thyrotrophin in preterm infants (measured up to 40 weeks' post-conceptional age). Only one infant died and the trial was therefore underpowered to detect an effect on mortality. The trial did not assess the effect of the intervention on neurodevelopmental morbidity. There was not a statistically significant difference in the incidence of chronic lung disease.

Authors' conclusions

There are insufficient data at present to determine whether providing preterm infants with supplemental iodine (to match fetal accretion rates) prevents morbidity and mortality in preterm infants. Future randomised controlled trials of iodine supplementation should focus on extremely preterm and extremely low birth weight infants, the group at greatest risk of transient hypothyroxinaemia. These trials should aim to assess the effect of iodine supplementation on clinically important outcomes including respiratory morbidity and longer term neurodevelopment.








本文依照Cochrane Neonatal Review Group之策略進行搜尋,包括Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2005) 、MEDLINE (1966至2005年11月) 、EMBASE (1980至2005年11月) 、CINAHL (1982至2005年11月) 、會議記錄與先前的綜合評論。


研究比較早產兒經腸道或靜脈補充碘 (至少30 micrograms/kg/day) 與接受安慰劑或不給予任何藥物的隨機或半隨機對照實驗。


本文依循Cochrane Neonatal Review Group之標準程序,由兩位研究員分別評估研究的品質並摘錄其內容,再以相對風險、風險差與加權平均差來作數據分析。主要結果是新生兒之死亡率、出院前死亡與長期之神經發展預後 (包括嚴重神經發育障礙) 。


文獻搜尋到一篇隨機對照實驗 (Rogahn 2000) 符合條件,共包含122名早產兒,懷孕週數小於33週 (但多數出生體重大於1000 gm) ,主要評估補充碘對甲狀腺功能的影響,檢測直到懷孕週數40週時,結果發現兩組早產兒血中甲狀腺素 (游離態與總量) 、三碘甲狀腺素與甲促素 (thyrotropin) 濃度並無顯著差異。實驗中僅1名新生兒死亡,因而無法探討對死亡率的影響,同時該研究並未評估此種治療對早產兒的神經發展後遺症的影響,至於慢性肺疾病的發生率並無顯著差異。


對於早產兒補充碘 (配合胎兒生長速率) 是否有助於預防死亡與併發症,目前尚無充足證據可供評斷,未來的隨機對照實驗應針對一過性低甲狀腺素血症風險最高的極度早產或極低體重早產兒,評估碘的補充對於呼吸系統併發症及長期神經發展等重要臨床預後的影響。



此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。



Plain language summary

Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants

There is currently insufficient evidence to suggest that supplementing the diet of preterm infants with iodine is beneficial. Iodine is essential for the production of thyroid hormones. Thyroid hormones are important for brain development in newborn infants. Preterm infants often have low levels of iodine and of thyroid hormones in the first few weeks after birth. This may in part be due to a lack of iodine in their diet. We found only one trial that assessed the effect of giving preterm babies extra iodine. This study did not find any evidence that providing extra iodine increased the level of thyroid hormones. The trial did not assess the effect of providing extra iodine on brain development. Further trials are needed.