Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants

 

Abstract

Background

Respiratory distress syndrome (RDS) is caused by a deficiency or dysfunction of pulmonary surfactant. A variety of surfactant products including protein free synthetic surfactant have been developed and tested in the prevention and treatment of RDS.

Objectives

To assess the effect of prophylactic administration of protein free synthetic surfactant (SS) on mortality, chronic lung disease and other morbidities associated with prematurity in preterm newborns at risk for developing RDS. Subgroup analysis were planned according to the degree of prematurity, surfactant product and dosage schedule.

Search methods

Searches were made of the The Cochrane Library, MEDLINE, OVID, EMBASE, CINAHL from 1966 to 2009. In addition, previous reviews including cross references and abstracts from the Society for Pediatric Research were searched. No language restrictions were applied.

Selection criteria

Randomized and quasi-randomized controlled trials that compared the effect of protein free SS administered to high risk preterm newborns at or shortly after birth in order to prevent RDS, mortality and complications of prematurity.

Data collection and analysis

Data regarding clinical outcomes was excerpted from the clinical trials by the reviewers. Data were analyzed according to the standards of the Cochrane Neonatal Review Group.

Main results

Studies of prophylactic administration of protein free SS note a variable improvement in the respiratory status and a decrease in respiratory distress syndrome in infants who receive prophylactic protein free SS. The meta-analysis supports a decrease in the risk of pneumothorax (typical relative risk 0.67, 95% CI 0.50, 0.90), pulmonary interstitial emphysema (typical relative risk 0.68, 95% CI 0.50, 0.93), and neonatal mortality (typical relative risk 0.70, 95% CI 0.58, 0.85). No differences were seen in the risk of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and cerebral palsy. The meta-analysis supports an increase in the risk of patent ductus arteriosus associated with prophylactic SS administration (typical relative risk 1.11, 95% CI 1.00, 1.22), and an increase in the risk of pulmonary hemorrhage (typical relative risk 3.28, 95% CI 1.50, 7.16).

Authors' conclusions

Prophylactic intratracheal administration of protein free synthetic surfactant to infants at risk of developing respiratory distress syndrome has been demonstrated to improve clinical outcome. Infants who receive prophylactic protein free SS have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema, and a decreased risk of neonatal mortality. Infants who receive prophylactic protein free SS have an increased risk of developing patent ductus arteriosus and pulmonary hemorrhage.

 

Plain language summary

Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants

Pulmonary surfactant is a substance that prevents the air sacs of the lungs from collapsing by reducing surface tension. Surfactant is essential to normal lung function in newborn babies. Sometimes it is absent in immature lungs and respiratory distress syndrome (RDS) can develop. Protein free synthetic surfactants have been developed and can be used for babies born prematurely (before 34 weeks) who are at risk of developing RDS. The review of trials found evidence that synthetic surfactant reduced the risk of RDS in babies considered at risk. Babies who receive prophylactic synthetic surfactant have a decreased risk of RDS, pneumothorax (air in the lung cavity) and death. However, babies who receive prophylactic synthetic surfactant have an increased risk of developing lung hemorrhage and patent ductus arteriosus, an open vessel that channels blood from the lungs to the body. Although this can lead to potentially life threatening complications, the overall benefits of surfactant treatment outweigh the risks.

 

摘要

背景

預防性給予早產兒合成性表面張力素以避免發病率和死亡率

呼吸窘迫症(Respiratory distress syndrome, RDS) 肇因於肺表面活性物質不足或功能障礙。有許多表面活性劑產品像是合成性表面張力素已被研發出來，並用於預防及治療RDS。

目標

評估使用預防性給予合成性表面張力素於有風險發展為呼吸窘迫症侯群的(RDS)早產兒。

搜尋策略

檢索了牛津周產期試驗數據庫，Medline(醫學標題表：肺表面張力素; 限制：年齡組，新生兒; 出版物類型，臨床試驗)，前幾次審查包括交叉引用、摘要、會議和研討會論文集，專家信息和日記手搜索的英語。

選擇標準

隨機和類隨機對照試驗比較影響在出生後或出生後不久對於高風險早產兒給予預防性合成表面張力素，以預防呼吸窘迫症和其他早產兒的併發症。

資料收集與分析

和臨床預後有關的數據，包括氣胸、肺間質氣腫、開放性動脈導管、壞死性小腸結腸炎、腦室內出血(任何級別和嚴重腦室內出血)、支氣管肺發育不良等的發生率，死亡率、支氣管肺發育不良或死亡，早產兒視網膜病變(任何視網膜病變，和視網膜病變等級3 – 4)，至一歲死亡率及腦性麻痺是由審閱者摘自臨床試驗的報告內容。數據分析是根據Cochrane新生兒評估組的標準來作。

主要結論

在預防性給予合成表面張力素的研究中，發現到接受預防性給予合成表面張力素的嬰兒其呼吸狀態的改善及減少呼吸窘迫症有不同的差異。該統合分析(metaanalysis)結果顯示可下降氣胸發生的風險(相對危險度0.67，95％CI為0.50，0.90;典型的風險差0.05，95％CI為−0.09，−0.02)，也可下降肺間質氣腫的風險(相對危險度0.68，95％CI為0.50，0.93;典型的風險差0.06，95％CI為−0.11，−0.01)，以及減少新生兒死亡率(相對危險度0.70，95％CI為0.58，0.85; 風險差−0.07，95％CI為−0.11，−0.03)。而腦室內出血、壞死性小腸結腸炎、支氣管肺發育不良、早產兒視網膜病變、腦性麻痺則無差異。該統合分析支持開放性動脈導管風險增加與合成表面張力素預防性給予有關(相對危險度1.11，95％CI為1.00，1.22，風險差0.05，95％CI為0.00, 0.10)，以及增加肺出血風險(相對危險度3.28，95％CI為1.50，7.16，風險差0.03，95％CI為0.01，0.05)。

作者結論

預防性經由氣管內給予合成表面張力素在具有高風險形成呼吸窘迫症的嬰兒身上，已證實能改善臨床表現的預後。接受預防性合成表面張力素的嬰兒可減少氣胸及間質性肺氣腫發生的風險，並降低新生兒死亡率。而嬰兒接受預防性合成表面張力素會增加開放動脈導管和肺出血的風險。

翻譯人

本摘要由高雄醫學大學附設醫院楊詠甯翻譯。

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

總結

合成表面張力素可有效地減少呼吸窘迫症和早產兒死亡率。肺表面張力素是一種能減少表面張力而可防止肺內氣囊塌陷的物質。有時不成熟的肺部缺乏表面張力素便會發生呼吸窘迫症(RDS)。合成表面張力素已發展可使用於有呼吸窘迫症高危險群的早產嬰兒(34週前)。此臨床報告的回顧發現合成表面張力素能有效降低高危險群的嬰兒發生呼吸窘迫症的風險。合成表面張力素能降低呼吸窘迫症、氣胸(在胸腔中的空氣)和死亡的風險。