| Abstract: | 早產兒 (premature infants)，為新生兒加護病房最主要的病患族群。根據衛生福利部國民健康署公布的資料，全世界每年約有 1,500萬名早產新生兒，而早產併發症是導致 5歲以下兒童死亡的首要原因。早產兒出生後，除了醫療介入之外，營養的支持也是決定早產兒是否能順利長大出院的關鍵因素。早產兒中又以出生體重低於 1250公克或懷孕週數小於 30週的族群最容易產生營養不良，常需要以靜脈營養支持輔助。除此之外，早產兒因肺部未發育成熟，出生後常需要高濃度氧氣治療以維持血中氧氣含量，然而高濃度氧氣也會引起許多併發症，最常被提及的就是早產兒慢性肺疾病和視網膜病變。營養素的補充治療過去也常被提及可改變早產兒的高氧併發症的發生率。所有的兒科醫師都希望能夠知道早產兒最佳的營養補充策略。
過去幾年來，早產兒的靜脈營養治療建議不斷的更新，彰化基督教兒童醫院的新生兒加護病房也在 2005年12月以及 2010年1月改變了早產兒出生後靜脈營養的輸注策略，這些營養治療透過營養治療小組都有留下營養及水分給予量紀錄。因此，第一個研究以回溯性研究模式觀察及比較兩個不同時期早產兒的生長速度以及併發症的差異，並分析每週抽血數值的結果。結果發現：2010年1月以後營養治療介入的族群在出生後第一週接受了較多的脂肪和能量輸注，在第二和第四週接受了較多的蛋白質、脂肪和能量輸注，並且有較快的生長速度，體重和營養治療的相關性也比較好，但是在高氧治療下併發症的發生率並未明顯改善。
因此，我們考慮是否除了蛋白質、脂肪和能量的補充之外，提供額外的維生素可否改善高氧治療的併發症。過去的研究中，維生素A、C、E曾被嘗試用於治療高氧治療的併發症，但僅維生素A被認為可能有幫助。維生素B-6的化學結構含有氫氧基 (-OH) 及胺基 (-NH2)，這些官能基在體內自由基結合，而有抗氧化的能力；維生素 B-6 也參與穀胱甘?合成，而穀胱甘?及其相關的抗氧化酵素已知是體內重要的抗氧化防禦系統；此外，維生素 B-6 也被提到會調節體內的發炎反應。早產兒的抗氧化防禦系統本身較差，加上高氧治療過程可能會引起氧化壓力和發炎反應，因此維生素 B-6 有機會可以改善早產兒高氧治療的併發症。目前有關維生素 B-6 應用於治療早產兒高氧治療併發症研究並不多。由於早產兒是易受傷害族群，過去研究中發現新生大鼠暴露於高氧環境中肺部也會有類似早產兒慢性疾病的變化，故決定以新生大鼠當作實驗的對象。我們將新生大鼠分派為四組，分別為對照組、維生素 B-6 組、高氧組、維生素 B-6 加上高氧組，結果發現高氧治療在第3天到16天會增加新生大鼠肺部多形核白血球 (polymorphonuclear granulocyte)和巨噬細胞 (macrophage)的浸潤，也會增加肝臟均質液氧化壓力指標丙二醛 (malondialdehyde)的濃度；維生素B-6補充在第3天和第6天會增加新生大鼠血清中發炎激素的反應，而會減少第6天和第9天肝臟均質液丙二醛的濃度，除此之外，維生素B-6的補充顯著增加了高氧環境中新生大鼠的存活率。
總結上述兩個研究，可以了解營養的介入治療在早產兒的重要性，增加及提早從靜脈營養給予蛋白質和脂肪，可以改善早產兒的預後和生長速度。而透過適量的維生素 B-6 的補充，可能可以進一步調控體內的發炎反應和降低器官的氧化壓力，可為預防早產兒產生高氧治療的併發症提供一個有潛力的治療方式。
Premature infants are the main group of patients in neonatal intensive care units (NICUs). According to information from the Health Promotion Administration of Taiwan’s Ministry of Health of Welfare, 15 million infants are born prematurely every year worldwide, and premature complications are the main cause of death of children aged under 5 years. Apart from medical intervention, nutritional care is critical for premature infants. Premature infants with a birth weight of <1250 g or gestational age of <30 weeks are the major groups that develop malnutrition after birth and are in most need of parenteral nutrition support. Moreover, because of immature lung development, premature infants often require hyperoxia treatment to maintain blood oxygen saturation. However, hyperoxia treatment can lead to the development of many complications in these patients, such as bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). Some nutrient supplement have been reported to modify the risk of hyperoxia complications in premature infants. For the neonatologist, optimal nutritional practices are always warranted.
Nutritional guidelines for the parenteral nutrition of premature infants has changed in the past years. The NICU team at Changhua Christian Children’s Hospital in Changhua, Taiwan, changed its parenteral nutritional practices in December 2005 and January 2010. Moreover, the daily nutrient and total fluid intakes of each patient are recorded by the parenteral nutrition dietician team in daily practice. For this dissertation, we first conducted a retrospective study to compare changes in premature growth velocity and complications and analyzed weekly laboratory results. Results revealed that patients born after January 2010 consumed more fat and energy in week 1 and more protein, fat, and energy in weeks 2 and 4 compared with those born between December 2005 and December 2009. Furthermore, growth velocity was higher in patients born after January 2010, and the association between nutrient intake and body weight increased. However, the risk of hyperoxia complications did not change after implementation of nutritional practices.
Therefore, we considered the use of vitamins to improve the outcomes of hyperoxia complications in addition to supplements of protein, fat, and energy. Vitamins A, C, and E have been studied for preventing hyperoxia complications in the past decades, and only vitamin A has been found to improve the risk of chronic lung disease in premature infants. Vitamin B-6 is a chemical compound with hydroxyl (-OH) and amine (-NH2) groups on the pyridine ring; these functional groups combine with free radicals and exhibit antioxidant ability. Furthermore, vitamin B-6 is involved in the synthesis of glutathione, which plays a crucial role in cellular defense against reactive free radicals. Moreover, vitamin B-6 was reported to modify the inflammatory response in human bodies. To date, only a few studies have been conducted to determine the application of vitamin B-6 supplementation on hyperoxia complications in premature infants. Because premature infants belong to a vulnerable group, we attempted to imitate clinical conditions by exposing neonatal rats to a hyperoxia environment, which is a typical research model for neonatal chronic lung disease. Neonatal rats were randomly divided into four groups: the control group, hyperoxia group (O2 group), vitamin B-6 group (B-6 group), and hyperoxia combined with vitamin B-6 group (O2 + B-6 group). The O2 group was found to have lung polymorphonuclear granulocytes and macrophage infiltration, increased liver hemopoiesis, and higher malondialdehyde (MDA) levels in liver homogenates from 3 to 16 days after birth. The O2 + B-6 group had significantly increased serum inflammatory cytokines on either the sixth or ninth day and decreased liver MDA levels before the sixth day compared with the O2 group. In addition, vitamin B-6 supplementation considerably improved the survival rate in hyperoxia-exposed neonatal rats.
In summary, the results from our two studies indicated the importance of nutrition care in premature infants; adequate nutritional intervention could improve their prognosis and growth. Furthermore, vitamin B-6 supplementation can improve hyperoxia complications through modification of the inflammatory response and oxidative stress, and thus, it is a potent choice in the future treatment of premature infants. |
