阮毅燕 潘新年 王金秋等
[摘要] 目的 觀察新生兒低血糖與腦損傷發(fā)生的關(guān)系,為臨床低血糖性腦損傷的防治提供理論依據(jù)。 方法 回顧性分析2009年1月~2010年12月在廣西壯族自治區(qū)婦幼保健院新生兒科住院的90例新生低血糖患兒的臨床資料,按有無腦損傷分為腦損傷組及無腦損傷組,分別為39例和51例。比較早產(chǎn)兒與足月兒、母、嬰圍生因素及臨床表現(xiàn)在兩組間的差異。 結(jié)果 早產(chǎn)兒低血糖發(fā)生率為83.3%,顯著高于足月兒的16.7%,差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01);低血糖性腦損傷發(fā)生率為43.33%;母親妊娠期糖尿病嬰兒低血糖性腦損傷發(fā)病率顯著高于母親無妊娠期糖尿病嬰兒,差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01)。腦損傷組在胎齡、5 min及10 min Apgar評(píng)分均顯著低于無腦損傷組,差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01);有癥狀的低血糖患兒腦損傷顯著高于無癥狀者,差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01)。腦損傷組血糖最低值顯著低于無腦損傷組,差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01);低血糖持續(xù)時(shí)間顯著長(zhǎng)于無腦損傷組,差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01)。 結(jié)論 早產(chǎn)兒易發(fā)生低血糖;母親妊娠期糖尿病、胎齡小、出生5 min及10 min Apgar評(píng)分、血糖最低值、低血糖持續(xù)時(shí)間與腦損傷發(fā)生率密切相關(guān)。
[關(guān)鍵詞] 新生兒;低血糖;腦損傷
[中圖分類號(hào)] R587.3 [文獻(xiàn)標(biāo)識(shí)碼] A [文章編號(hào)] 1673-7210(2015)08(c)-0116-04
[Abstract] Objective To investigate the relationship between neonatal hypoglycemia and brain injury, so as to provide a theoretical basis for clinical treatment of hypoglycemic brain injury. Methods From January 2009 to December 2010, 90 cases of children with neonatal hypoglycemia were admitted to the retrospective analysis in neonatal department of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. They were divided into brain injury group and non-brain injury group according to the presence of brain injury, 39 cases and 51 cases respectively, the differences of preterm infants and term infants, perinatal factors of mother and baby, clinical manifestation between the two groups were compared. Results The incidence of hypoglycemia in premature infants was 83.3%, significantly higher than that of term infants (16.7%), the differences were statistically significant (P < 0.01); the incidence of hypoglycemic brain injury was 43.33%. The incidence of hypoglycemic brain injury in infants whose mother had gestational diabetes was significantly higher than that of mother without gestational diabetes, the differences were statistically significant (P < 0.01). Gestational age, 5 min and 10 min Apgar scores in brain injury group were significantly lower than the non-brain injury group, the differences were statistically significant (P < 0.01). Brain injury in children with symptomatic hypoglycemia was significantly higher than that in asymptomatic children, the difference was statistically significant (P < 0.01), the lowest value of blood glucose in brain injury group was significantly lower than that in non-brain injury group, the difference was statistically significant (P < 0.01), and the duration of hypoglycemia was significantly longer than the non- brain injury group, the difference was statistically significant (P < 0.01). Conclusion Premature infants are prone to hypoglycemia, and the incidence of brain injury are closely related with mothers with gestational diabetes, small gestational age, 5 min and 10 min Apgar scores, the lowest value of blood glucose, the duration of hypoglycemia.
[Key words] Neonate; Hypoglycemia; Brain injury
新生兒低血糖是一種臨床常見的糖代謝問題,大多數(shù)低血糖新生兒癥狀隱匿,且易與新生兒其他疾病相混淆。既往研究資料顯示,新生兒低血糖如果未能及時(shí)發(fā)現(xiàn)和妥善地處理,有可能導(dǎo)致永久性腦損傷,嚴(yán)重者會(huì)導(dǎo)致腦性癱瘓、癲癇等[1-2]。本研究選擇廣西壯族自治區(qū)婦幼保健院(以下簡(jiǎn)稱“我院”)新生兒科住院的90例低血糖患兒的臨床資料進(jìn)行分析,尋找導(dǎo)致低血糖性腦損傷的可能危險(xiǎn)因素,為新生兒低血糖所致腦損傷的預(yù)防及臨床治療提供依據(jù)。
1 資料與方法
1.1 一般資料
選擇2009年1月~2010年12月在我院新生兒科住院的低血糖新生兒90例,其中男59例,女31例,男女之比1.9∶1;胎齡29~40周,平均(33.70±2.56)周;體重1.03~3.20 kg,平均(1.80±0.39)kg;糖尿病母親嬰兒14例;妊娠高血壓母親嬰兒12例。該研究經(jīng)我院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn),所有入組患兒均由家長(zhǎng)簽署知情同意書。
1.2 觀察指標(biāo)及診斷標(biāo)準(zhǔn)
臨床表現(xiàn)可無癥狀或表現(xiàn)為反應(yīng)差、吸吮力差、嗜睡、體溫低下、發(fā)紺、呼吸異常、易激惹、震顫、抽搐、肌張力低等。收集所有入組病例的胎齡、出生體重、Apgar評(píng)分、臨床表現(xiàn)及母親圍生期資料,動(dòng)態(tài)監(jiān)測(cè)治療前后患兒血糖值變化及低血糖持續(xù)時(shí)間。應(yīng)用微量血糖儀監(jiān)測(cè),取足跟血檢測(cè)血糖,同時(shí)抽靜脈血立刻送化驗(yàn)室檢測(cè)全血血糖水平作對(duì)照,二者檢測(cè)結(jié)果比較差異無統(tǒng)計(jì)學(xué)意義。所有患兒均常規(guī)行頭顱MRI檢查。低血糖指1次全血或血漿葡萄糖水平≤2.2 mmol/L[3]。低血糖性腦損傷:①符合低血糖診斷標(biāo)準(zhǔn);②合并低血糖伴隨的臨床表現(xiàn)或低血糖時(shí)和血糖糾正后一段時(shí)間表現(xiàn)有神經(jīng)系統(tǒng)功能障礙;③頭顱MRI有明顯腦損傷改變;④除外缺氧缺血性腦病、顱內(nèi)感染、敗血癥、腦發(fā)育異常、嚴(yán)重的顱內(nèi)出血、內(nèi)分泌疾病及先天性代謝性疾病所致的腦病。
1.3 治療方法
血糖 < 1.5 mmol/L或有臨床表現(xiàn)的患兒立即靜脈推注10%葡萄糖1~2 mg/kg,然后予以葡萄糖6~8 mg/(kg·min)靜脈輸注維持至正常血糖;凡血糖為1.5~2.2 mmol/L的患兒予以葡萄糖6~8 mg/(kg·min)靜脈輸注維持至血糖正常。所有患兒治療后或每次調(diào)整葡萄糖靜脈輸注速度后均于半小時(shí)后監(jiān)測(cè)血糖,如果治療后血糖恢復(fù)正常則每4~6小時(shí)監(jiān)測(cè)血糖1次,若連續(xù)3次血糖測(cè)定均≥2.8 mmol/L,則下調(diào)葡萄糖靜脈輸注速度;如果治療后血糖仍不能維持正常,則繼續(xù)每半小時(shí)復(fù)查血糖并調(diào)節(jié)葡萄糖靜脈輸注速度,直至血糖正常。對(duì)于持續(xù)或反復(fù)發(fā)作的嚴(yán)重低血糖患兒如治療后血糖仍不能維持正常,則加用氫化可的松治療。
1.4 統(tǒng)計(jì)學(xué)方法
采用SPSS 19.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析,計(jì)量資料數(shù)據(jù)用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,兩組間比較采用t檢驗(yàn);計(jì)數(shù)資料用率表示,組間比較采用χ2檢驗(yàn),以P < 0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 分娩情況
本組90例低血糖患兒中,早產(chǎn)兒占83.3%(75/90),顯著高于足月兒16.7%(15/90),差異有高度統(tǒng)計(jì)學(xué)意義(χ2=80.000,P < 0.01)。39例發(fā)生腦損傷,腦損傷發(fā)生率為43.33%(39/90)。其中早產(chǎn)兒腦損傷發(fā)生率為45.3%(34/75),較足月兒33.3%(5/15)增高,但兩組間差異無統(tǒng)計(jì)學(xué)意義(χ2=0.733,P > 0.05)。
2.2母圍生因素與低血糖性腦損傷關(guān)系
腦損傷組中,母親患妊娠期糖尿病者顯著高于無腦損傷組,兩組間差異有高度統(tǒng)計(jì)學(xué)意義(P < 0.01);母親患妊娠高血壓、剖宮產(chǎn)兩組比較差異均無統(tǒng)計(jì)學(xué)意義(P > 0.05)。見表1。
2.3 嬰兒圍生因素與腦損傷關(guān)系
腦損傷組胎齡、5 min及10 min Apgar評(píng)分顯著低于無腦損傷組,差異均有高度統(tǒng)計(jì)學(xué)意義(P < 0.01),出生體重及1 min Apgar評(píng)分兩組比較差異均無統(tǒng)計(jì)學(xué)意義(P > 0.05)。見表2。
2.4 臨床表現(xiàn)與腦損傷關(guān)系
與無腦損傷組比較,腦損傷組出現(xiàn)臨床癥狀者增多,最低血糖值降低,低血糖持續(xù)時(shí)間長(zhǎng),兩組間差異均有高度統(tǒng)計(jì)學(xué)意義(P < 0.01)。見表3。
3 討論
葡萄糖是腦細(xì)胞代謝的主要能量來源,新生兒腦代謝最旺盛,由于腦組織不儲(chǔ)備糖原,且不能利用各種戊糖底物作為腦細(xì)胞代謝的部分能量,因此有賴于血糖的不斷補(bǔ)充和供應(yīng)。低血糖可使腦細(xì)胞失去基本能量來源,如不及時(shí)糾正會(huì)造成腦損傷。本組資料中,低血糖性腦損傷發(fā)生率為43.33%。動(dòng)物實(shí)驗(yàn)已經(jīng)證實(shí),在低血糖性腦損傷發(fā)生過程中,存在細(xì)胞內(nèi)鈣離子超載和突觸釋放過多的谷氨酸,產(chǎn)生細(xì)胞毒性損傷的病變過程,也有選擇性神經(jīng)元壞死現(xiàn)象,并且影響到小膠質(zhì)細(xì)胞的免疫防護(hù)作用。而早產(chǎn)兒及小于胎齡兒糖原儲(chǔ)備更少,腦相對(duì)較大,腦細(xì)胞代謝需糖量亦大,肝糖原異生酶發(fā)育不成熟,糖原分解功能差,皮下脂肪及游離脂肪少,供能底物少,更易發(fā)生低血糖[4]。本組90例低血糖患兒中,早產(chǎn)兒占83.3%,顯著高于足月兒。雖早產(chǎn)兒腦損傷發(fā)生率與足月兒比較差異無統(tǒng)計(jì)學(xué)意義,但顯示出升高的趨勢(shì),進(jìn)一步分析發(fā)現(xiàn),腦損傷組胎齡顯著低于無腦損傷組。
母親的慢性高血糖癥導(dǎo)致胎兒在母體中同樣有慢性高血糖癥狀,因此引起胎兒胰島素生成增加發(fā)生胎兒高胰島素血癥。當(dāng)胎兒娩出后,母體的高血糖來源突然中斷,患兒本身又存在高胰島素血癥,導(dǎo)致新生兒低血糖發(fā)生,故母親糖尿病是新生兒低血糖性腦損傷的高危因素[5]。本組資料中,腦損傷組母親患妊娠期糖尿病者顯著高于無腦損傷組,與既往研究相符[6]。新生兒窒息的缺氧、缺血病理過程對(duì)機(jī)體代謝的主要影響之一是糖代謝紊亂[7]。本研究中盡管單獨(dú)應(yīng)用Apgar評(píng)分定義新生兒窒息有其局限性,但Apgar評(píng)分是目前大多數(shù)產(chǎn)科應(yīng)用最多的評(píng)估窒息的方法。本組資料中,腦損傷組5 min及10 min Apgar評(píng)分均顯著低于無腦損傷組,1 min Apgar評(píng)分兩組間差異無統(tǒng)計(jì)學(xué)意義,提示長(zhǎng)時(shí)間窒息未及時(shí)復(fù)蘇者可導(dǎo)致腦損傷發(fā)生。缺氧缺血時(shí)無氧酵解加速了腦組織內(nèi)葡萄糖的消耗,低血糖時(shí)則抑制了低氧時(shí)的腦血管擴(kuò)張,阻斷了通過其他途徑改善供氧的代償機(jī)制,新生兒腦缺氧缺血和低血糖兩因素疊加加重腦損傷[8]。有文獻(xiàn)報(bào)道,新生兒缺血缺氧性腦病同時(shí)血糖 < 2.6 mmol/L,影響24個(gè)月齡時(shí)神經(jīng)系統(tǒng)發(fā)育[9]。
新生兒低血糖發(fā)生時(shí)多為無癥狀或者暫時(shí)性的,但當(dāng)新生兒出現(xiàn)嗜睡、驚厥、呼吸暫停等神經(jīng)功能紊亂癥狀時(shí),提示此時(shí)新生兒已出現(xiàn)腦損傷[10]。本研究中,腦損傷組以癥狀性低血糖者為多,表明新生兒癥狀性低血糖對(duì)低血糖性腦損傷的提示作用,與既往研究相符[11]。Montassir等[12]隨訪低血糖患兒神經(jīng)系統(tǒng)發(fā)育情況,發(fā)現(xiàn)神經(jīng)系統(tǒng)發(fā)育異常的患兒血糖 < 15 mg/L(0.74 mmol/L)的發(fā)生率明顯高于神經(jīng)系統(tǒng)發(fā)育正常的患兒,低血糖持續(xù)時(shí)間異常組高于正常組,和本組資料結(jié)果基本相符,提示低血糖性腦損傷的發(fā)生與低血糖水平和低血糖持續(xù)時(shí)間密切相關(guān),這是由于低血糖過程會(huì)造成患兒腦部能量代謝的缺乏,且長(zhǎng)時(shí)間的低血糖狀態(tài)會(huì)導(dǎo)致腦部神經(jīng)處于低營(yíng)養(yǎng)狀態(tài)下,因此低血糖水平與低血糖持續(xù)時(shí)間也是腦損傷的重要因素[13-14]。
新生兒低血糖性腦損傷及其后遺癥并無有效治療方法,所以重在預(yù)防新生兒低血糖[15]。通過識(shí)別母親妊娠、分娩及新生兒出生時(shí)的高危因素,早期篩查血糖十分必要。同時(shí),及時(shí)發(fā)現(xiàn)低血糖的臨床癥狀并正確治療,維持正常穩(wěn)定的血糖濃度,以預(yù)防神經(jīng)系統(tǒng)后遺癥的發(fā)生。目前,新生兒低血糖的防治已有規(guī)范化的處理方案[16]。
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(收稿日期:2015-04-27 本文編輯:任 念)