含有魚油的脂肪乳劑對早產兒呼吸窘迫與肺支氣管發育不全之免疫調節反應

研究目的：二十二碳六烯酸（DHA）是一種n-3長鏈多不飽和脂肪酸，在動物和人類的研究發現，可能會降低早產兒肺支氣管發育不良(BPD)的風險，但缺乏大型的隨機分配人體試驗。研究方法及資料：從2013年7月1日至2015年6月30日，我們隨機分配了在醫學中心新生兒加護病房有插管的極低出生體重早產兒，體重低於1250克或懷孕週數小於32週，在父母親的知情同意後，隨機分為實驗組和對照組，估計病例數為30位魚油組和30位對照組。出生後48小時內，實驗組將接受全靜脈營養添加魚油的新型脂肪乳劑（SMOF），提供4.8克/ L的EPA和3.5克/ L的DHA； 對照組將接受全靜脈營養含有傳統的大豆油脂肪乳劑（Lipovenoes MCT20％），兩者都是由德國費森尤斯卡比公司製造進口，皆有台灣衛生署批准在嬰幼兒使用。主要結果是觀察血清及支氣管清洗液的發炎細胞激素變化，包括白細胞介素-6（IL-6），白細胞介素-1β（IL-1β）以及早產兒肺支氣管發育不良的發生率是否有差異。研究結果：與對照組相比，實驗組第8天的血清和支氣管清洗液的IL-1β和IL-6數值顯著降低（p <0.05）。實驗組的BPD發生率為13.3％，而對照組為36.7％（p = 0.04;勝算比[OR]，0.36; 95％信賴區間[CI]，0.21-0.86）。實驗組使用呼吸器時間和氧氣使用的持續時間明顯少於對照組（p <0.05）。實驗組第8天的丙氨酸氨基轉移酶水平顯著降低（p = 0.031）結論與建議：在早產兒中，早期給于含有魚油的脂肪乳劑顯著降低了血清和支氣管清洗液中的IL-1β和IL-6水平，並且發現有較短的呼吸器使用時間和較少的早產兒支氣管肺發育不良（BPD），針對這個發現可進一步進行更大型的臨床隨機分配試驗以證實早期給于魚油對早產兒的發炎反應及免疫調節作用。

Background & aims Early inflammation and lower levels of long-chain polyunsaturated fatty acids (LCPUFAs) in preterm infants associated with respiratory distress syndrome and bronchopulmonary dysplasia (BPD). Supplementing very premature infants with intravenous lipid emulsions (LE) that fish oil, which is rich in n-3 LC-PUFAs, may decrease bronchopulmonary dysplasia (BPD) by modulating inflammation and neonatal immune function.Methods We enrolled sixty very low birth weight (VLBW) premature infants requiring ventilator support, randomized in a double-blind manner to 2 groups and received total parenteral nutrition with fish oil containing LE (intervention group, n=30) or soybean oil containing LE (control group, n=30) for 7 days. Blood samples and bronchoalveolar lavage fluid (BALF) were obtained for assay on day 1 and 7 days after LE. The primary outcome was to compare the levels of interleukin (IL)-1β and IL-6 in serum and BALF. Secondary outcomes were to compare mortality and co-morbidities.Results The levels of IL-1β and IL-6 in serum and BALF were significantly lower in the intervention group at day 8 (p < 0.05). The incidence of BPD in the intervention group compared to the control group was 13.3% versus 36.7% (p = 0.04; odds ratio [OR], 0.36; 95% confidence interval [CI], 0.21–0.86). The duration of ventilator support and oxygen use was significantly less in the intervention group than in the control group (p <0.05). The level of alanine aminotransferase was significantly lower in the intervention group on day 8 (p = 0.031). ConclusionsIn very premature infants with respiratory distress syndrome, early administration of fish oil containing LE significantly decreased IL-1β and IL-6 levels in serum and BALF and was associated with shorter duration of ventilator support and less bronchopulmonary dysplasia (BPD).