2013-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645942摘要： 極低出生體重早產兒（妊娠週數＜37 週，出生體重＜1,500 公克）是容易發生不良發展預後的族群。隨著新生兒階段存活率的日益上升，雖然嚴重發展障礙（例如：嚴重智能遲緩、聽力損傷、視力損傷、及腦性麻痺）的發生率維持在8%至10%之間，但輕度發展功能損傷（例如：學習障礙、智力商數偏低、注意力不足過動症、神經心理發展損傷、感知動作協調不良、及內向性行為問題）的比例，在近15 年來大幅提升至50%至70%之間。回顧過去西方文化背景的文獻與我們針對台灣族群所進行的研究結果，顯示早期介入有助於增進早產兒的短期或長期的發展表現，然而，與介入療效相關的生物社會路徑及基因易感受性則尚不清楚。 此五年期計劃採用多中心及臨床隨機試驗的研究設計，研究目的為探討以家庭為中心之早產兒介入計劃對於極低出生體重早產兒的療效，以及探討基因及環境因子對於介入後兒童發展的中介或調節機制。在前驅實驗當中，我們向144 名曾經參與早期介入計畫的母親（分屬於常規照護組、門診介入組、家訪介入組）進行滿意度的調查，詢問其針對介入服務與效益的建議。門診介入組以及家訪介入組的母親在增進處理發展相關問題能力與親職自信方面，普遍反應較常規照護組的母親高的滿意度，此外，門診介入組的母親較常規照護組的母親對於介入服務的內容與頻率感到滿意，且亦較家訪介入組的母親對於增加兒童健康發展知識感到滿意；就改善介入內容的意見，門診介入組的母親認為可增加對於互動遊戲以及居家環境中學習教材的說明，家訪介入組的母親認為可示範親職互動的技巧，並提供兒童情緒發展的資訊。因此我們將改善過去的介入服務，建立一套同時著重兒童及家庭發展的＂以家庭為中心之早產兒介入計劃＂，介入計畫將於住院階段至矯正年齡12 個月間，以床邊、門診及居家訪視的方式進行，提供共12 次的服務，介入內容將包含環境的改善、兒童發展技巧的教導、餵食教導、嬰兒按摩、親子互動的教導、父母的社會支持及早產兒衛教等。 本計劃將收集250 位在北部及南部三家醫學中心出生的極低出生體重早產兒，並隨機分配至實驗組及控制組。有關介入療效的評估包含主要(兒童健康、生長及發展及次要預後(父母及家庭互動)，其中兒童發展預後包含神經行為(心智、語言、動作及行為方面)及神經生理功能的測量(腦電波及腦波誘發電位)，父母預後包含親職壓力及生活品質的測量，而家庭互動變項則包含親子互動品質的評估及家庭環境的經驗測量，神經生理功能與家庭互動變項將被檢驗是否為介入療效及兒童發展預後的中介因子。此外，本研究將採集所有孩童的口腔細胞檢體，並合併過去153名極低出生體重早產兒的基因資料，以進行與認知、感覺動作以及行為情緒系統之神經傳導相關，且可能與多項發展與精神疾病有關的多巴胺相關基因之基因型檢測，並探討多巴胺相關基因之多型性對於介入後兒童發展之潛在調節作用。本研究的結果將提供重要的訊息，幫助了解有效之早產兒介入計劃的生物社會路徑以及基因易感受性，並將有助於針對臺灣早產兒設計個別化的介入方案，以提昇其發展預後。<br> Abstract: Preterm birth with very low birth weight (VLBW) (gestational age <37 weeks, birth weight <1,500 g)is a significant public health issue worldwide. Despite the remarkable achievements in neonatal survival,the incidence of major developmental disabilities (e.g., severe mental retardation, hearing loss, blindness,and cerebral palsy) has remained relatively constant at 8% to 12% and the prevalence estimates of low severity dysfunctions (e.g., learning disabilities, borderline to low average intelligent quotient scores, attention-deficit hyperactivity disorder, specific neuropsychological deficits, poor perceptual-motor skills and internalizing behavioral problems) appear to increase to as high as 50% to 70% in VLBW preterm infants over the past 15 years. Review of the intervention studies in Western societies and our intervention study in Taiwan for preterm infants show that comprehensive and intensive services may yield short- or long-term benefits on child development; however, the underlying biosocial pathways andpossible genetic predisposition for effective intervention remain unclear. The aim of this five-year study is therefore to examine the effectiveness of a family centered intervention program (FCIP) in VLBW preterm infants in Taiwan using a multi-site randomized clinical trial and to assess the genetic and environmental factors that moderate or mediate intervention effects onchild development. In a preliminary study, we have surveyed 144 mothers in our prior intervention study regarding the services and benefits of three programs: usual care program (UCP), clinic-based intervention program (CBIP) and home-based intervention program (HBIP) as well as the recommendations on further revision. Mothers of the CBIP and HBIP showed higher levels of satisfaction than those of the UCP with the effects in enhancing the development-related problem solving ability and maternal confidence. Mothers of the CBIP were more satisfied with the content and frequency of services than those of the UCP, and had higher levels of satisfaction than those of the HBIP with the effects in advancing the knowledge of child health and development. Specifically, mothers of the CBIP required more demonstration of play activities and more information on the learning materials in home environment; while mothers of the HBIP needed more demonstration of dyadic interaction skills andmore information on child emotional development. We will modify the intervention services in our previous study into the FCIP to contain ecologically pervasive child- and parent-focused servicesincluding environmental modulation, teaching of child developmental skills, feeding support, massage, teaching of interactional activities, and parent support and education. The 12-session intervention is intensive that will be delivered from hospitalization to 12 months CA via ward, clinic and home visits. A total of 250 VLBW preterm infants will be prospectively recruited at three medical centers in northern and southern Taiwan and will be randomly assigned to the FCIP or UCP group. Outcome assessments will include primary (child medical, growth and development) and secondary measures (parent and transactions within the family). Child development will be assessed by means of the neurobehavioral (cognitive, language, motor and behavior aspects) and neurophysiological methods(electroencephalogram/event-related potentials). Parent outcomes will include psychological stress and quality of life. Transactions within the family will be measured using the quality of dyadic interaction and affordances in home environment. The neurophysiological and transactions data will be examined for whether they mediate intervention effects on child development. In addition, these infants and 153VLBW preterm infants in our prior intervention study will be collected buccal cells for assessment of the polymorphisms of dopamine-related genes, which are involved in the neurotransmission of cognitive, sensori-motor and behavioral-emotional systems and postulated to be associated with severaldevelopmental and psychiatric illnesses. The polymorphisms of dopamine-related genes will be examined for potential moderating influence on the effects of the intervention for child development. The results of this project will provide important insights into the underlying biosocial pathways and possible genetic predisposition for effective intervention in VLBW preterm infants. The findings will also help designindividualized intervention for preterm infants in Taiwan to enhance their developmental outcomes.環境基因介入神經發展路徑早產兒environmentgeneinterventionneurodevelopmentpathwaypreterm infants