Intervention Review

Thyroid hormones for preventing neurodevelopmental impairment in preterm infants

  1. David A Osborn*

Editorial Group: Cochrane Neonatal Group

Published Online: 23 OCT 2001

Assessed as up-to-date: 1 FEB 2009

DOI: 10.1002/14651858.CD001070


How to Cite

Osborn DA. Thyroid hormones for preventing neurodevelopmental impairment in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD001070. DOI: 10.1002/14651858.CD001070.

Author Information

  1. Royal Prince Alfred Hospital, RPA Newborn Care, Camperdown, New South Wales, Australia

*David A Osborn, RPA Newborn Care, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales, 2050, Australia. david.osborn@email.cs.nsw.gov.au.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 23 OCT 2001

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxinemia) and abnormal neurodevelopmental outcome. Thyroid hormone therapy might prevent this morbidity.

Objectives

To assess whether thyroid hormone therapy in preterm infants without congenital hypothyroidism results in clinically important changes in neonatal and long term outcomes in terms of benefits and harms.

Search methods

The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language.

Selection criteria

All trials using random or quasi-random patient allocation, in which thyroid hormone therapy (either treatment or prophylaxis) was compared to control in premature infants.

Data collection and analysis

Primary clinical outcomes included measures of neurodevelopmental outcome and mortality. Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group.

Main results

Nine studies were identified that compared thyroid hormone treatment to control. Four randomized (Chowdhry 1984, van Wassenaer 1997; Vanhole 1997; Smith 2000) and one quasi-randomized study (Amato 1989) met inclusion criteria. All studies enrolled preterm infants < 32 weeks gestation, but used different timing, dose and duration of treatment with thyroid hormones. Four studies used thyroxine, whereas Amato 1989 used triiodothyronine. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997, Vanhole 1997). All studies were of small size with the largest, van Wassenaer 1997, enrolling 200 infants.

Meta-analysis of five studies found no significant difference in mortality to discharge (typical RR 0.70, 95% CI 0.42, 1.17) in infants who received thyroid hormone treatment compared to controls. Meta-analysis of two studies (van Wassenaer 1997; Vanhole 1997) found no significant difference in the Bayley MDI or PDI performed at 7-12 months. van Wassenaer 1997 found no significant differences in the Bayley MDI and PDI at 24 months, incidence of cerebral palsy (RR 0.72, 95% CI 0.28, 1.84), death and cerebral palsy (RR 0.70, 95% CI 0.43, 1.14) or the RAKIT IQ score (WMD -2.10, 95% CI -7.91, 3.71) at 5.7 years of age. Fraction of inspired oxygen was lower in infants receiving triiodothyronine in one small quasi-randomized study, but not in infants receiving thyroxine in a randomized study. Duration of mechanical ventilation and incidence of chronic lung disease were not reduced in infants receiving early thyroid hormone therapy.

Authors' conclusions

This review does not support the use of thyroid hormones in preterm infants to reduce neonatal mortality, improve neurodevelopmental outcome or to reduce the severity of respiratory distress syndrome. An analyses of data from one study (van Wassenaer 1997) which showed benefits in infants 24-25 weeks gestation was not prespecified and should be treated with caution.

The small number of infants included in trials incorporated in this review limits the power of the meta-analysis to detect clinically important differences in neonatal outcomes.

Future trials are warranted and should be of sufficient size to detect clinically important differences in neurodevelopmental outcomes. They should consider enrolling those infants most likely to benefit from thyroid hormone treatment such as infants born at less than 27 weeks gestation.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Thyroid hormones for preventing neurodevelopmental impairment in preterm infants

No evidence from trials that thyroid hormone therapy is effective in preventing problems such as respiratory distress syndrome in preterm babies. Thyroid hormones are needed for the normal growth and maturity of the central nervous system, as well as the heart and lungs. Children born without sufficient thyroid hormones can develop serious mental retardation. It is believed that low levels of thyroid hormones in the first few weeks of life (transient hypothyroxinemia) in preterm babies born before 34 weeks may cause this abnormal development. The review of trials found no evidence that using thyroid hormones in preterm babies is effective in reducing the risk of problems caused by insufficient thyroid hormones.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

在早產兒身上使用的甲狀腺荷爾蒙來預防神經發展受損

根據觀察性研究所得的結果顯示,在早產嬰兒出生後的前幾個星期之中,有暫時性低甲狀腺荷爾蒙濃度(暫時性低甲狀腺素血症),會跟不正常的神經發展之預後之間存在著某種關聯。因此甲狀腺荷爾蒙的療法,或許能夠預防這樣不正常的神經發展的發病率。

目標

在未患有先天性甲狀腺功能低下的早產兒身上,評估甲狀腺荷爾蒙療法是否對其在新生兒時期及長期之預後造成臨床上重大改變之好處與壞處。

搜尋策略

使用Neonatal Review Group標準的搜尋策略。所搜尋的範圍包括:Oxford Database of Perinatal Trials、Cochrane Controlled Trials Register、MEDLINE、先前的文獻回顧,包括交叉對照參考資料、摘要、研討會及座談會手冊、專家意見,並且人工搜尋英文期刊。

選擇標準

所有的試驗病患都是隨機或是半隨機分配,其中甲狀腺荷爾蒙療法(不論是治療或是預防性作用)會跟早產兒的對照組進行比較。

資料收集與分析

首要的臨床結果包含了神經發展之預後與死亡率。對試驗的品質評估、資料擷取、資料的合成等項目,以及使用相對風險(RR)與加權平均差(WMD),這些在進行的時候都是採用了Cochrane Collaboration以及它的新生兒檢審團隊(Neonatal Review Group)的標準作法。

主要結論

共9份研究將甲狀腺荷爾蒙治療與對照組進行比較。其中有4組隨機(Chowdhry 1984、van Wassenaer 1997;Vanhole 1997;Smith 2000)與1組半隨機(Amato 1989)的研究符合了收案標準。這些研究都是收集妊娠週數在32周以下的早產兒,但是使用的甲狀腺荷爾蒙類藥物之時間點、劑量、以及治療的時間長度則有差異。其中有4份研究使用的是甲狀腺素(thyroxine),至於Amato 1989 則是使用triiodothyronine。只有2份研究在神經發展方面的追蹤具有良好的方法學(van Wassenaer 1997、Vanhole 1997)。所有的研究都屬於小型的,其中最大的是 van Wassenaer 1997,共收集了200名嬰兒。針對5份研究所進行統合分析發現,跟對照組比較起來,對於那些接受了甲狀件荷爾蒙治療的嬰兒來說,出院前之死亡率(典型的RR 0.70,95% CI 0.42,1.17)並沒有明顯的差異。由2份研究(van Wassenaer 1997; Vanhole 1997)所得到的統合分析發現,在7 – 12個月的時候,不論是執行Bayley MDI (嬰兒心智發展量表) 或是PDI (嬰兒活動發展量表) ,都沒有明顯的差異。 van Wassenaer 1997發現,在24個月的時候,對於 Bayley MDI 與PDI來說,當中都沒有顯著的差異,另外腦性麻痺的發生率(RR 0.72,95% CI 0.28,1.84)、死亡與腦性麻痺(RR 0.70,95% CI 0.43,1.14),或是年齡在5.7歲時的RAKIT IQ (智商) 評分(WMD −2.10,95% CI −7.91,3.71)也沒有顯著的差異。在其中1份小型的半隨機研究當中,對於接受過 triiodothyronine的嬰兒而言,所需要的氧氣比例是較低的,但是另1分隨機的研究當中,對於接受過甲狀腺素的嬰兒而言,卻沒有這樣的現象。在接受過早期甲狀腺素荷爾蒙治療的嬰兒身上,針對使用機械式呼吸器的時間,以及發生慢性肺部疾病的發生率,都沒有減少。

作者結論

本篇回顧並不能支持我們要在早產兒身上使用甲狀腺素荷爾蒙,以求降低新生兒的死亡率、改善神經發展的結果,或是降低呼吸窘迫症狀的嚴重性。有1份研究(van Wassenaer 1997)當中顯示了24 – 25週之妊娠週數的嬰兒使用甲狀腺素荷爾蒙會有某些好處,而這份研究報告卻沒有特別說明,因此要在這個族群使用甲狀腺素荷爾蒙應該要小心。對於本篇回顧所收集的試驗而言,被挑選進入這些試驗當中的嬰兒數量不多,因而在針對新生兒的結論方面,若是想要偵測出臨床上重要的差異,這樣小的數目就限制了統合分析的效力。對於神經發展方面的預後而言,為了偵測出臨床上的重要差異,我們確信還值得進行許多更深入的試驗,而且這些試驗應該要具備足夠的嬰兒數量。例如不滿27週的妊娠週數就出生的嬰兒就屬於那些比較可能會從甲狀腺素荷爾蒙療法當中獲得助益的對象,應該考慮先將這群嬰兒們納入研究。

翻譯人

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

總結

從這些試驗當中,並沒有辦法得到證據支持甲狀腺素荷爾蒙療法可以有效地預防像是在早產兒身上所發生的呼吸窘迫症狀等問題。對於中樞神經系統的正常生長與發展而言,以及心臟與肺部,甲狀腺素荷爾蒙類都是不可或缺的。在兒童出生的時候,若是缺乏足夠的甲狀腺素荷爾蒙,就可能會產生嚴重的心智障礙。人們相信,對於在34週之前就出生的早產兒來說,生命初期的前幾週若是處在低濃度的甲狀腺素荷爾蒙(暫時性的低甲狀腺素血症)條件下,就有可能會產生這些不正常的發展。在早產兒身上使用甲狀腺素荷爾蒙類的藥物,以求能夠有效地降低甲狀腺素荷爾蒙類不足所帶來的問題,在本篇試驗的回顧發現,並沒有證據能夠加以支持這樣的做法。