2016-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647718摘要：背景：新生兒延長性黃疸是相當常見的問題，由於近年來衛生福利部積極推動母乳哺育政策，我國嬰兒母乳哺育率明顯提升。因此新生兒延長性黃疸超過出生後兩週甚至四週者相當常見。有部份嬰兒延長性黃疸是因為嚴重的膽汁滯留所引起，卻常被誤以為是母乳哺育所造成黃疸，以致延誤早期診治時機，而失去生命，或需要換肝。膽汁滯留症之中以膽道閉鎖為兒童肝病最常見之致死原因，及換肝的主因。在國民健康署的支持下，我們於2004年開始推展世界第一個『全國性嬰兒大便辨識卡篩檢膽道閉鎖症』之工作，獲得國際之肯定與了解，許多國家均來函請求引進此系統。我們也證明因此系統之實施，使膽道閉鎖兒之小於60天手術率、3年及5年存活率，均有明顯進步。但是相較於日本東北大學所報告的日本膽道閉鎖兒之10年存活率，台灣膽道閉鎖嬰兒，在實施全國性大便顏色卡篩檢之後的年代出生者，只追蹤至5年的時間仍不夠長，是否有機會在10年的存活率達到七成以上仍未知，值得探討。另自2009年起我們將兒童健康手冊中大便卡不正常顏色由原本的三色增為六色，大便卡因此提昇為九色嬰兒大便辨識卡，我們擬探討膽道閉鎖兒在出生30天大之前與出生30天後發現異常顏色大便對治療與預後的差異比較，做為以大便辨識卡篩檢膽道閉鎖症之成效探討，期盼能幫助家長及醫護人員能早期發現、及早診治。只使用嬰兒大便辨識卡進行篩檢膽道閉鎖仍有所不足，自2012年開始，我們努力研發建立新直接/總膽紅素微量檢測法，期望補足可能未注意或誤認大便顏色的情形，提升早期篩檢膽汁滯留症的精確性。目前一般醫師對黃疸嬰兒通常以腳根微量採血，但仍循古老觀念只檢測總膽紅素。而多數醫師若要同時檢測直接膽紅素及總膽紅素，仍然以抽取嬰兒靜脈血的方式檢驗，這是家長較難接受的。因此我們希望以微量抽血方式減少嬰兒抽血量，以增加家長對於嬰兒抽血的意願。我們雖然在過去的三年裡，開始籌劃及建立『同時檢驗直接及總膽紅素，並求其比值以微量檢測法』，並於北中南各地開始推廣。然大多數醫護人員受到過去數十年傳統只驗總膽紅素不驗直接膽紅素的影響，對延長性黃疸嬰兒同時檢驗直接及總膽紅素的觀念認知仍極為不足。另受限於檢驗設備、人力成本等問題，且須於門診對家長解說，加上須與檢醫部門及行政單位協調等費時費力之工作，此小兒微量檢測法的新觀念尚待努力推廣。若能使病嬰在出生後及早發現及診斷膽道閉鎖，及早接受葛西氏手術，能顯著地改善這些病童的預後情形，不論任何的方式採血，此『同時檢驗直接及總膽紅素並求其比值』的檢測觀念，在全國持續推廣與執行實在是非常重要的。本計畫之目的及研究方法如下：【目的】：1.提供嬰兒大便卡諮詢專線之維護與正常運作及辦理醫事人員與機構之教育推廣。2.長程追蹤世界第一個以全國性『嬰兒大便辨識卡篩檢膽道閉鎖症之篩檢系統』對病童五年及十年存活率之影響。2.希望藉由推廣『以微量檢驗法同時檢測直接/總膽紅素及嬰兒大便辨識卡』，篩檢延長性黃疸嬰兒，鑑別母乳哺育黃疸與膽汁滯留症之黃疸，提升早期發現及診斷膽道閉鎖，早期施行葛西手術，減少肝臟功能受損情形，提昇原肝存活率。【研究方法】：1.透過各式管道對民眾做教育宣導，結合媒體、文宣品或演講活動，讓民眾注意嬰兒延長性黃疸篩檢及鑑別診斷之重要性與就醫檢測之最佳時機;並加強資源缺乏區域的推廣。2.探討參與嬰兒延長性黃疸鑑別診斷課程之醫院，執行小兒微量檢測同時檢驗直接及總膽紅篩檢膽道閉鎖的現況或成效分析讓所有的延長性新生兒黃疸的嬰兒都能以極少的血量與簡便的方法檢測，持續推廣不論以任何的採血方式，都必須同時檢驗直接及總膽紅素並求其比值的觀念。3.建立新的“檢驗網＂以供全國各地民眾查詢或基層診所醫療人員轉檢，為了補足目前在診所及地區醫院就診嬰兒無此篩檢服務，擬建立目前已可配合以微量檢測方式檢驗直接膽紅素及總膽紅素的醫療院所或檢驗所名單，並以全國各地區及醫療院所層級分類。4.持續進行醫療專業人員之教育訓練“以微量檢驗法同時檢測直接及總膽紅素並求其比值鑑別嬰兒延長性黃疸”的觀念，建立種子老師制度，並研製適合不同對象宣導之衛教內容，如民眾版、專業人士版，並製作成統一簡報教材或衛教單張，提供適當教育訓練簡報教材，進行分眾宣導，每年至少2場；人數至少300人/年。5.分析國內嬰兒肝膽疾病之發生率、發現異常大便顏色的天數、接受手術天數與比率及長程追蹤五年及十年存活率、換肝等資訊之相關性。6.以大便卡諮詢專線(02-2382-0886)，提供諮詢及通報之功能，協助一般民眾及嬰兒照顧者對嬰兒大便顏色、黃疸及膽道閉鎖等相關問題之正確認知，異常大便顏色及膽道閉鎖個案的通報功能; 針對諮詢內容進行相關統計分析，就常見問題研擬Q&A做為民眾、醫事人員教育訓練之參考。7.強化全國醫療機構以「預防注射網路通報系統」進行嬰兒膽道閉鎖症之篩檢通報率；透過提供誘因，鼓勵醫事人員正確使用網路篩檢通報，以利及時掌握大便顏色異常個案，給予輔導或轉介。8. 探討國內各醫療院所以九色嬰兒大便辨識卡於篩檢膽道閉鎖與膽汁滯留症之篩檢執行情況、困難及改善建議。<br> Abstract: [Bockground]:Prolonged neonatal jaundice is a common problem in infancy, Recently due to the active promotion of breast feeding by the Ministry of Heath and Welfare, the breast feeding rate increased remarkably. Therefore prolonged neonatal jaundice exceeds two to four weeks is guite common. Part of the prolonged jaundice in those infants is due to cholestasis, which often misrecognized as breast feeding jaundice. Biliary atresia is the most common canse of liver death or liver transglantation in children. Delay in diagnosis of cholestasis may delay the early treatment of biliary atresia, leading to death or liver transplantation.Under the support of health promotion administration, we initiated the world first nationwide infant stood color card screening program for biliary atresia in 2004. The good results of this screening program obtained international recognition and understanding. Many countries thus asked for our permission to use this screening system. We provide evidence to prove that this screening sytem enhanced the rate of early surgery before 60 days old, and the 3 and 5-year surviral rates. Yet comparing to the results of Tohoku university in Japan, which follow-up the 10-year survival rates in infants of biliary atresia, our infants of biliary atresia only had data of 5-year follow-up after the launch of Nationwide stool color screening program. It is very important to investigate whether the 10-year survival rate can reach 70% or even greater. Further more, we increased the abnormal stool color from 3 to 6 colors, thus changing the card from 6 to 9-colored stoold color card. We will study, under stool color card screening program, whether the discovery of abnormal stool color before versus after 30 days will affect the outcome of biliary atresia. It seems that stool color card screening may enhance ealy diagnosis and treatment of biliary. But the enhancing effect faces some limitation for further advancement. Starting from 2012, we established a additional new screening method, i.e. direct/total bilirubin micromethod, aiming to have additional promotion effect to screen cholestasis in infancy among infants with prolonged jaundice, This method is very accurate. Currently, infants with prolonged jaundice were only monitored by checking total bilirubin level of the heel blood using micromethod. Occasionally doctors take venous blood to check direct/total bilirubin levels. In order to increase the acceptance rate of checking direct/total bilirubin, we started the micro-methed to reduce the blood amount taken for the tect. In the past three years,we promote “Simultaneous determination of direct/total bilirubin and its ratio, using micro-method” in infants with prolonged jaundice at Northern, Middle, and Southern Taiwan. However, due to the traditional concept in the past decades, which only check total but not direct bilirubin, the knowledge for the new and accurate method of “simultaneous determination of direct/total bilirubin and its ratio” for infants with prolonged jaundice is still seldom recognized. Additional factors include, due to the limitation of the lab equipment and personnel cost, time to explain it to the parents, and coordination between laboratory and administration department in the hospital. In order to early diagnose and treatr biliary atresia, we will continue to promote the concept of “early simultaneous determination for direct /total bilirubin and its ration”, using either micro-method or taking venous blood in infants with prolonged jaundice in the whole Taiwan.[Aims and Method][Aims]1.To provide & maintain the function of “Stool Color Card Advisory Hotling”, and to conduct continuing education for medical personnel and organization.2.Long-term follow-up the world first “Nationwide Infant stool color card screening program for biliary atresia” and to study Its effect on the 5-and 10-year survical rate.3.Through promoting “Simultaneous determination of direct /total bilirabm and stool color card screening program” to screen infants with prolonged jaundice, we will be able to differentiate between cholestasis and breast feeding jaundice, to enhance early diagnosis of biliary atresia, early Kasai operation, to reduce liver injury and to enhance survival rate with native liver.[Methods]1.1.A variety of outreach to educate the public, combining media, promotion material, or lectures will be used to enhance the attention of people on the importance to screen infants with prolonged jaundice for the early detection and management for biliary atresia; with special emphasis for the promotion in remote areas.2.The status of conducting micro-method to determine direct/total bilirubin in hospitals, which participated the continuing education course of the differential diagnosis of infantile prolonged jaundice, will be studied. The concept of simultaneous determination of direct/ total bilirubin and its ratio” using either micro-method or traditional veno-puncture will be promoted in the whole Taiwan.3.A new “Medical Laboratory Network” will be established for people or primary health care personnel to transfer blood sample for testing of direct/to tal bilirubin, if the test is not available in their repions. A list of hospitals, clinics, and laboratories, with the levels of the hospitals & clinic, which can provide service for the determination of direct/total bilirubin will be established.4.Educating medical personnel for the concept of “Using micro-method to determine direct/total bilirubin and its ratio” will be continued. Seed teacher system will be established. Health education with materials and leaflets targeting different subjects, for general popution or for medical personnel, will be conducted. Each year at least two classes will be held, for totally at least 300 persons/year.5.Information on the incidence, age at discovery of abnormal stool color, age and rate of Kasaioperation, and 5 and 10-year survival rate, and rate of liver transplantation will be analyzed. 6.A “Stool Color Card Advisory Hotline” (02-2382-0886) providing consultation and reporting function, helping general population and infant caretakers to accurately recognize infant stool color, jaundice, and biliary atresia, to understand related knowledge, and to report abnormal stool color and cases of biliary atresia. The contents of the consultation through this hotline will be analyzed for the reference to focus to design a Q & A for the education of general population and medical personnel. 7.Medical personnel will be encouraged to use “Immunization online reporting system” to report abnormal infant stool color for the screening of biliary atresia. Through some in centives. the medical personal will be encouraged to accurately use the online screening and reporting system, so the information of abnormal stool color infants will be immediated obtained and, timely assistance or referral will be given.8.The status, difficulty, and suggestions from hospitals & clinics in Taiwan for the 9-colored stool color card to screen biliary atresia and cholestasis in infants will be investigated.新生兒黃疸膽汁滯留症膽道閉鎖嬰兒大便辨識卡直接及總膽紅素比值neonatal jaundicecholestatsisbiliary atresiainfant stool color carddirect/total bilirubin and its ratio