Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants

  • Review
  • Intervention

Authors


Abstract

Background

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

Objectives

To determine whether prophylactic thyroid hormones given to preterm infants without congenital hypothyroidism result in clinically important changes in neonatal and long term outcomes.

Search methods

The standard search strategy of the Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE, PREMEDLINE, and searches of abstracts of conference proceedings, citations of published articles and expert informants.

Selection criteria

All trials using random or quasi-random patient allocation in which prophylactic thyroid hormone treatment was compared to control in premature infants.

Data collection and analysis

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

Four studies enrolling 318 infants were included. All studies enrolled preterm infants on the basis of gestational age criteria. All studies commenced treatment in the first 48 hours, but used different regimens, dose and durations of treatment. All four studies used thyroxine (T4). Valerio 2004 incorporated one arm with an early short course of T3, then T4 for 6 weeks. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997; Vanhole 1997). All studies were small with the largest (van Wassenaer 1997) enrolling 200 infants.

No significant difference was found in neonatal morbidity, mortality or neurodevelopmental outcome in infants who received thyroid hormones compared to control. van Wassenaer 1997 reported no significant difference in abnormal mental development at 6, 12, 24 months (RR 0.67, 95% CI 0.28, 1.56) or five years (RR 0.66, 95% CI 0.22, 1.99) or cerebral palsy assessed at five years (RR 0.72, 95% CI 0.28, 1.84). Meta-analysis of two studies (van Wassenaer 1997, Vanhole 1997) found no significant difference in the Bayley MDI (WMD -1.14, 95% CI -5.46, 3.19) and PDI (WMD 0.22, 95% CI -4.80, 5.24) at 7 - 12 months. van Wassenaer 1997 reported no significant difference in the Bayley MDI (MD -3.50, 95% CI -11.21, 4.21) and PDI (MD 3.10, 95% CI -3.31, 9.51) at 24 months, IQ scores at 5 years (MD -2.10, 95% CI -7.91, 3.71) and children in special schooling at 10 years (RR 0.88, 95% CI 0.43, 1.83). Meta-analysis of all four trials found no significant difference in mortality to discharge (typical RR 0.76, 95% CI 0.46 to 1.24). van Wassenaer 1997 reported no significant difference in death or cerebral palsy at five years (RR 0.70, 95% CI 0.43 to 1.14). No significant differences were reported for neonatal morbidities, including the need for mechanical ventilation, duration of mechanical ventilation, air leak, CLD in survivors at 28 days or 36 weeks, intraventricular haemorrhage, severe intraventricular haemorrhage, periventricular leucomalacia, patent ductus arteriosus, sepsis, necrotising enterocolitis or retinopathy of prematurity.

Authors' conclusions

This review does not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality, neonatal morbidity or improve neurodevelopmental outcomes. An adequately powered clinical trial of thyroid hormone supplementation with the goal of preventing the postnatal nadir of thyroid hormone levels seen in very preterm infants is required.

摘要

背景

早產兒在產後給予預防性甲狀腺素以預防罹病和死亡率

觀察性研究顯示,早產新生兒出生後數週內的暫時性低甲狀腺素濃度(暫時性低血甲狀腺素症)和異常的神經發展結果有關聯。補充甲狀腺素可預防上述情形。

目標

評估對於沒有先天性低血甲狀腺素症的早產兒給予預防性的甲狀腺素補充,是否對新生兒時期和長期結果產生臨床上重要的改變

搜尋策略

使用考科藍新生兒審查小組的標準搜索策略。這包括了對於Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) EDLINE (1966  March 2006), EMBASE, PREMEDLINE,進行中討論會的摘要、以及發表文章的引文和專家意見的搜索。

選擇標準

選擇所有對早產兒給予預防性甲狀腺素治療的隨機或半隨機對照試驗,比較治療與對照組的效果。

資料收集與分析

利用考科藍協作和其新生兒審查小組的標準方法,評估實驗的品質、數據擷取,並應用相對危險(RR)和加權平均差異(WMD)來解釋數據。

主要結論

收錄了四個共納入318位嬰兒的試驗。所有的早產兒根據妊娠週數為收案標準。所有的試驗都在48小時內開始治療,但是使用了不同的治療處方、劑量和時間。所有四個試驗使用了thyroxine (T4)。Valerio 2004還包含一組早期短暫使用了T3,然後再6個星期T4的試驗組。只有兩個有追蹤神經發展的試驗方法學較好(van Wassenaer 1997; Vanhole 1997)。所有的試驗規模都不大,其中最大的(van Wassenaer 1997)招收了200個嬰兒。和對照組比較起來,接受甲狀腺素的新生兒在罹病率、死亡率及神經發展結果上都沒有顯著的差異。van Wassenae 997 報導在出生後6、12、24個月(RR 0.67, 95% CI 0.28, 1.56)或5年時(RR 0.66, 95% CI 0.22, 1.99)的異常智能發展,或在五歲時評估是否有腦性麻痺(RR 0.72, 95% CI 0.28, 1.84),結果並沒有顯著差異的。兩個試驗(van Wassenaer 1997, Vanhole 1997)的統合分析發現第7到12個月的Bayley MDI (WMD −1.14, 95% CI −5.46, 3.19)及PDI (WMD 0.22, 95% CI −4.80, 5.24)沒有顯著差異。van Wassenaer 1997報導第24個月的Bayley MDI (MD −3.50, 95% CI −11.21, 4.21)、 DI (MD 3.10, 95% CI −3.31, 9.51)、第五年的IQ分數(MD −2.10, 95% CI −7.91, 3.71)以及第10年是否會在特教學校的孩子(RR 0.88, 95% CI 0.43, 1.83)的分析結果上都沒有顯著差異。所有四個試驗的統合分析發現在出院的死亡率上並沒有差異(typical RR 0.76, 95% CI 0.46 to 1.24)。 an Wassenaer 1997 報導第五年的腦性麻痺或死亡率沒有顯著差異(RR 0.70, 95% CI 0.43 to 1.14)。在新生兒罹病率的報導上也沒有顯著差異,這些罹病率包括了:需要使用呼吸器、呼吸器的使用時間、氣漏、存活者在第28和36週的慢性肺疾病(CLD)、腦室內出血、嚴重腦室內出血、腦室周邊白化軟化症、開放性動脈導管、敗血症、壞死性腸炎或早產兒視網膜病變。

作者結論

這個回顧不支持在早產兒使用預防性甲狀腺素來減少新生兒死亡率及罹病率,或改善神經發展結果。目前仍需要一個有足夠說服力,且針對使用甲狀腺素補充來預防極早產兒(very preterm infants)中出生後血甲狀腺素最低點為目的之臨床試驗。

翻譯人

本摘要由高雄醫學大學附設醫院李智雄翻譯。

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

總結

由隨機對照試驗的資料進行系統性回顧,並無法提供常規性給予甲狀腺素治療能夠有效避免早產的問題或改善他們的發展結果的證據。中樞神經系統、心臟和肺臟的發展和成熟需要甲狀腺素。出生時沒有足夠甲狀腺素的孩童可能發展出嚴重的智能退化。目前相信在34週前出生的早產兒在出生後數週的甲狀腺素低下(暫時性低血甲狀腺素症)可能造成了這個異常發展。這些試驗的回顧,並未能發現常規性於早產兒中使用甲狀腺素能夠有效減少短暫的低假甲狀腺素濃度造成的問題的證據。

Plain language summary

Prophylactic postnatal thyroid hormones for prevention of morbidity and mortality in preterm infants

A systematic review of the data from randomised controlled trials provides no evidence that routine thyroid hormone therapy is effective in preventing problems in preterm babies or improves their developmental outcomes. 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 after birth (transient hyperthyroxinaemia) in preterm babies born before 34 weeks may contribute to this abnormal development. The review of trials found no evidence that using thyroid hormones routinely in preterm babies is effective in reducing the risk of problems caused by transiently low levels of thyroid hormones.