本文選題：超聲 + 產(chǎn)前診斷�。� 參考：《山東大學(xué)》2014年博士論文

【摘要】：研究背景與研究目的 產(chǎn)前超聲在胎兒時期能夠顯示的膽道系統(tǒng)異常主要包括：膽道囊性發(fā)育異常(biliary cystic malformation, BCM)、膽囊不顯示(non-visualization of gallbladder, NVGB)、旦囊大小異常、膽囊腔內(nèi)異�；芈暭澳懩椅恢卯惓�。 多年來國外超聲研究的相關(guān)文獻(xiàn)數(shù)量有限,不同研究所得到的結(jié)論往往差別也較大。針對東方人群的系統(tǒng)研究鮮見報道。 我國已開展胎兒產(chǎn)前診斷工作十余年,在超聲篩查和診斷胎兒畸形的工作中,對胎兒膽道系統(tǒng)異常的相關(guān)研究一直是薄弱環(huán)節(jié)。對胎兒膽道系統(tǒng)的超聲診斷缺乏規(guī)范的研究和標(biāo)準(zhǔn)。 BCM產(chǎn)前異常表現(xiàn)主要為膽管樹的囊狀擴(kuò)張。包括囊性膽道閉鎖(cystic biliary atresia, CBA)和膽總管囊腫(choledochal cyst, CC,屬于先天性膽管擴(kuò)張癥范疇)兩大類疾病。因診斷經(jīng)驗的差異,在產(chǎn)前超聲檢查中,易與腸系膜囊腫、肝囊腫、大膽囊,左位膽囊、十二指腸閉鎖,及胎兒右上腹部的其它囊性病變相混淆。囊腫與膽囊相通或與擴(kuò)張肝管相通,是產(chǎn)前超聲判斷其膽系來源的決定性征象。而在產(chǎn)前超聲檢查中,上述超聲征象在BCM類疾病中常常顯示不清晰。 胎兒可導(dǎo)致NVGB的相關(guān)因素之中,膽囊收縮是最常見的原因。而臨床對于胎兒膽囊收縮的規(guī)律、可能持續(xù)的時間、發(fā)生機制知之甚少。 最近胎兒NVGB結(jié)合羊水中消化酶檢測技術(shù)已逐漸應(yīng)用于臨床以輔助膽道閉鎖(biliary atresia, BA)等嚴(yán)重疾病的產(chǎn)前診斷,雖然對BA的診斷特異性有限,但到目前為止,尚未發(fā)現(xiàn)新的可替代輔助診斷方法。東方人相對來說是BA的高發(fā)人群,因此建立國人羊水GGT的正常參考值是必要的。 為了進(jìn)一步了解胎兒膽道系統(tǒng)異常的超聲表現(xiàn)及掌握有診斷價值的診斷征象,本論文就以下問題進(jìn)行了深入探討。 1.如何評價現(xiàn)有超聲征象對BCM類疾病的檢出效率,及如何提高BCM的產(chǎn)前檢出率。 2.CC和CBA產(chǎn)前超聲表現(xiàn)雖然相似,產(chǎn)前超聲掃查時應(yīng)如何鑒別。 3.導(dǎo)致胎兒膽囊NVGB相關(guān)因素的深入研究。 4.研究膽囊收縮在NVGB中的發(fā)生率及胎兒膽囊收縮的持續(xù)時間。 5.為提高BA產(chǎn)前診斷水平,有必要建立我們自己的羊水GGT參考值。 第一部分：胎兒囊性膽道發(fā)育不良的超聲表現(xiàn)及具有診斷價值的超聲征象篩選 目的：1.從常見BCM相關(guān)超聲征象中,篩選出對產(chǎn)前診斷BCM具有較高特異度及敏感度的征象及其組合。2.總結(jié)胎兒BCM的超聲表現(xiàn)及臨床結(jié)局。 方法：1.以2009年5月至2013年11月期間,30例發(fā)生于中上及右上腹部囊性病變的胎兒作為研究對象。以產(chǎn)前及產(chǎn)后超聲診斷,或手術(shù)、尸解病理結(jié)果為依據(jù),將病例分為BCM(16例)及非BCM(NBCM,14例)兩組。比較產(chǎn)前超聲診斷BCM的相關(guān)征象在兩組中的表達(dá)率。這些征象包括：囊腫位于胎兒右上腹部(A)、囊腫上端緊貼肝門下方(B)、囊腫并非膽囊(C)、囊腫內(nèi)無分隔(D)、囊腫與膽囊相通(E)、囊腫與肝管相通(F)、囊腫下緣止于上腹正中、脊柱前方(G)、囊腫上端接近膽囊頸部(H)。通過診斷試驗評價各征象及征象組合的診斷效能。以診斷指數(shù)作為參考依據(jù),篩選出最有應(yīng)用價值的征象及征象組合。2.總結(jié)BCM病例的產(chǎn)前超聲表現(xiàn),并總結(jié)隨訪病例的臨床結(jié)局。 結(jié)果：1.征象A、D在BCM及NBCM兩組間表達(dá)無統(tǒng)計學(xué)差異；其余征象組間表達(dá)差異有統(tǒng)計學(xué)意義(P0.05)。2.診斷試驗表明：單項征象B、F、G及19個征象組合具有診斷效能。診斷指數(shù)1.9000的征象組合為B和H、E或F、E或G、B和D、F或G、E或F或G；后三組達(dá)到2.0000。3.共9例BCM隨訪至出生后,8例為CC,1例為CBA。產(chǎn)前超聲共6例表達(dá)F征,其中4例出生后伴有阻塞性黃疸。4.CC囊腫出生前后均有不同程度增大,CC病例的膽囊大小形態(tài)正常。1例III型CBA囊腫產(chǎn)前超聲變化不明顯,而生后體積逐漸變小,胎兒膽囊顯示不清。 結(jié)論：1.如果胎兒肝門下方出現(xiàn)囊腫,在排除其為膽囊的可能性的前提下,即可考慮為膽系來源囊腫可能；而如果觀察到囊腫與膽囊、肝管相通或囊腫下端逐漸向胎兒上腹中部,脊柱前方走行時可進(jìn)一步明確其膽系來源可能。2.BCM病例產(chǎn)前超聲伴有肝管擴(kuò)張者,生后有可能出現(xiàn)阻塞性黃疸。3.產(chǎn)前超聲表現(xiàn)為BCM合并NVGB或膽囊發(fā)育不良,且囊腫在出生后有減小趨勢時,應(yīng)考慮到CBA可能性。 第二部分超聲在胎兒膽囊異常的應(yīng)用研究 目的：1.研究胎兒膽囊異常的臨床意義。2.研究胎兒膽囊收縮的持續(xù)時間。 方法：1.對2009年1月～2013年12月期間,我科診出的胎兒膽囊異常者分類,進(jìn)行超聲隨訪,結(jié)合臨床及其它輔助檢查手段獲得病因診斷。2.32例孤立性NVGB的胎兒按固定周期進(jìn)行密切產(chǎn)前及生后超聲隨訪�？偨Y(jié)并分析NVGB初診至膽囊再度顯示之間的時間間期(A-B間期)。 結(jié)果：1.研究期間共檢出胎兒膽囊異常者共347例,在門診病例中的檢出率約0.6%。NVGB308例,占胎兒膽囊異常病例總數(shù)的88.8%(308/347);膽囊腔內(nèi)異�；芈�27例(其中3例產(chǎn)前超聲繼NVGB之后出現(xiàn)),占7.8%(27/347)；膽囊位置異常15例,占4.3%(15/347),均無明顯性別差異。2.在308例胎兒NVGB中,89.9%超聲初診于晚孕期。27例合并其他超聲異常,占NVGB總數(shù)的8.8%(27/308)其中12例合并多發(fā)異常。隨訪NVGB病例215例,90.7%初診于晚孕期。3例胎兒NVGB,最終證實病因為先天性膽道發(fā)育異常,分別為先天性無膽囊、肝小葉間膽管缺乏及III型囊性膽道閉鎖(cystic biliary atresia, CBA),占隨訪病例的1.4%。3.胎兒膽囊腔內(nèi)異常回聲27例,平均孕周(35.7±2.5)周(范圍29～39周)。其中3例(3.7%)合并其他結(jié)構(gòu)異常,其余25例膽囊腔內(nèi)異�；芈暰S訪至消失,21例(84%)消失于生后1周內(nèi)。4.膽囊位置異常15例。永久性右臍靜脈(Persistent right umbilical vein, PRUV)10例,其中50%合并心臟或血管發(fā)育異常。左位膽囊2例,預(yù)后良好。內(nèi)臟反位(Situs viscera inversus, SVI)3例,均引產(chǎn),1例為21-三體。5.A-B間期(NVGB初診至膽囊再度顯示的時間問期)為3天～71天。28.1%(9/32)病例A-B問期≤7天,46.9%(15/32)病例A-B間期在8天～21天之間,25%(8/32)病例A-B間期21天。產(chǎn)前膽囊再顯示者21例。11例胎兒膽囊于產(chǎn)后再顯示,顯示實現(xiàn)均于生后1周以內(nèi)。經(jīng)隨訪32例由膽囊收縮所致的NVGB胎兒預(yù)后良好,A-B間期長短對胎兒預(yù)后沒有明顯影響。 結(jié)論：1.NVGB是最常見的胎兒膽囊異常表現(xiàn)。2.盡管胎兒生理性膽囊收縮是孕晚期胎兒NVGB最常見原因,但仍有存在膽道系統(tǒng)發(fā)育異常(1.4%)及合并多發(fā)超聲異常(3.9%)的可能,臨床不容忽視。3.肝小葉間膽管缺乏可能是胎兒膽囊持續(xù)不顯示的病因之一,其臨床意義有待深入研究。4.胎兒膽囊腔內(nèi)異常回聲均出現(xiàn)于晚孕期之后(尤其是孕32周至足月),均于產(chǎn)前產(chǎn)后自行消失,84%于生后1周內(nèi)消失,預(yù)后良好。5.胎兒膽囊的形態(tài)和位置異常可合并多發(fā)異常及染色體異常。因此胎兒膽囊的超聲觀察具有重要臨床意義。6.胎兒膽囊的持續(xù)收縮多是生理現(xiàn)象,A-B間期的長短對胎兒預(yù)后無明顯影響,其生理機制有待深入研究。 第三部分：妊娠20周～24周正常胎兒羊水GGT酶值測定及價值 目的：建立20周～24周胎兒羊水GGT正常值,以作為膽道閉鎖產(chǎn)前診斷的參考值。 方法：試驗采用橫斷設(shè)計。羊水采集自2009年6月～2010年4月期間,符合羊水穿刺指征,需進(jìn)行胎兒染色體檢查的孕婦。同時應(yīng)滿足以下條件：胎兒染色體結(jié)果正常,孕婦身體健康,孕婦及配偶無染色體異常,產(chǎn)前超聲檢查無明顯胎兒結(jié)構(gòu)異常(包括羊水量異常),無染色體異常胎兒分娩時,或病因不明的異常孕產(chǎn)史。羊水標(biāo)本抽取后立即送檢染色體核型及GGT的定量分析。計算各孕周羊水GGT測值的x±s、1%-99%可信區(qū)間,并對LogGGT值與孕周的相關(guān)性進(jìn)行Pearson檢驗。 結(jié)果：研究期間共采集符合標(biāo)準(zhǔn)的孕20周～24周胎兒羊水110例。其中女性胎兒73例。隨孕周增長GGT酶值的x、中位數(shù)、LogGGT均有隨孕周逐漸減低的趨勢,LogGGT值與孕周呈負(fù)相關(guān)。 結(jié)論：隨孕周增長GGT酶值有逐漸減低的趨勢；胎兒孕20周-24周羊水GGT正常值的建立有望對進(jìn)一步關(guān)于膽道閉鎖的產(chǎn)前診斷及CC與CBA產(chǎn)前的鑒別診斷提供新的輔助診斷參考依據(jù)。
[Abstract]:Research background and research purpose
The abnormalities of the biliary tract system that the prenatal ultrasound can display in the fetal period mainly include: biliary cystic malformation (BCM), the gallbladder does not display (non-visualization of gallbladder, NVGB), the size of the sac is abnormal, the abnormal echo of the gallbladder and the abnormal position of the gallbladder.
Over the years, the number of relevant literatures on ultrasound studies abroad is limited, and the conclusions from different research institutes are often different.
In China, the prenatal diagnosis of fetal prenatal diagnosis has been carried out for more than ten years. In the work of screening and diagnosis of fetal malformation, the study of abnormal fetal biliary system has been a weak link. The ultrasonic diagnosis of fetal biliary system is lack of standard research and standard.
The abnormal prenatal manifestation of BCM is the cystic dilatation of the bile duct tree. The two major diseases include cystic biliary atresia (cystic biliary atresia, CBA) and choledochal cyst (choledochal cyst, CC, and congenital cholangiectasis). Due to the difference of diagnostic experience, the mesenteric cyst, hepatic cyst, large gallbladder, and left position in the prenatal hyper acoustic examination Gallbladder, duodenal atresia, and other cystic lesions in the right upper abdomen of the fetus are confused. The cyst is interlinked with the gallbladder or interlinked with the dilated hepatic duct. It is a decisive sign of the source of the biliary system by prenatal ultrasound. In the prenatal ultrasound, the above ultrasound signs are often not clear in the BCM disease.
The most common cause of the cholecystokinin is that the fetus can lead to NVGB, and there is little knowledge about the mechanism of the fetal gallbladder contraction, the possible duration and the mechanism of the gall bladder contraction.
Recently, fetal NVGB combined with amniotic fluid (amniotic fluid) digestive enzyme detection technology has been applied to clinical diagnosis of severe diseases such as biliary atresia (biliary atresia, BA) and other serious diseases. Although the diagnosis of BA is limited, up to now, no new alternative diagnostic methods have been found. The Oriental is a relatively high risk population of BA. It is necessary to establish the normal reference value of Chinese amniotic fluid GGT.
In order to further understand the ultrasonographic manifestations of fetal biliary tract system abnormalities and grasp the diagnostic signs of diagnostic value, the following issues were discussed in depth.
1. how to evaluate the detection efficiency of the existing ultrasonic signs for BCM diseases and how to improve the detection rate of BCM.
Prenatal sonographic findings of 2.CC and CBA are similar. How to identify prenatal ultrasound scanning?
3. in-depth study of NVGB related factors in fetal gallbladder.
4. to study the incidence of gallbladder contraction in NVGB and the duration of fetal gallbladder contraction.
5. in order to improve the level of prenatal diagnosis of BA, it is necessary to establish our own GGT reference value for amniotic fluid.
Part I: ultrasonographic features and diagnostic value of fetal cystic dysplasia of bile.
Objective: 1. to screen out the signs of high specificity and sensitivity for prenatal diagnosis of BCM and the combination of.2. to summarize the ultrasonic manifestations and clinical outcomes of fetal BCM from the common BCM related ultrasonographic signs.
Methods: 1. from May 2009 to November 2013, 30 fetuses born in the upper and right upper abdominal cystic lesions were studied. The cases were divided into BCM (16 cases) and two groups of non BCM (NBCM, 14 cases) with prenatal and postpartum ultrasound diagnosis, or surgery, and the pathological results were obtained. The correlation of prenatal ultrasonography in the diagnosis of BCM was compared in the two groups. These signs include: the cyst is located in the right upper abdomen of the fetus (A), the upper end of the cyst is close to the hepatic portal (B), the cyst is not the gallbladder (C), the cyst is separated from the gallbladder (D), the cyst and the gallbladder are interlinked (E), the cyst and the liver Guan Xiangtong (F), the lower margin of the cyst in the upper abdomen (G), and the upper end of the cyst near the neck of the gallbladder (H). Through diagnostic test evaluation The diagnostic efficiency of the various signs and the combination of signs. The diagnostic index was used as the reference basis to screen out the most valuable signs and signs combination.2. to summarize the prenatal ultrasound manifestations of BCM cases, and to sum up the clinical outcome of the follow-up cases.
Results: there was no statistical difference between the 1. signs of A and D in the two groups of BCM and NBCM; the difference between the other signs was statistically significant (P0.05).2. diagnostic test showed that the single sign of B, F, G and 19 signs had diagnostic efficiency. The combination of the diagnostic index 1.9000 was B and H. 0000.3. 9 cases were followed up to postnatal, 8 cases CC, 1 cases of CBA. prenatal ultrasound and 6 cases of F, of which 4 cases were born with obstructive jaundice.4.CC cyst at birth and before and after birth. The size of the gallbladder in CC case is normal.1 case of III type CBA cyst prenatal ultrasound alteration is not obvious, and the postnatal volume gradually smaller, fetal gallbladder. The display is not clear.
Conclusion: 1. if there is a cyst beneath the hilum of the fetal liver, it is possible to consider the possibility of biliary cyst in the precondition of removing the gallbladder, and if the cyst is connected to the gallbladder, the hepatic duct or the lower end of the cyst to the upper middle of the fetus, the possible.2.BCM case of the biliary tract may be further clarified. Prenatal ultrasound with hepatic duct dilatation may occur after birth of obstructive jaundice with.3. prenatal ultrasound in BCM with NVGB or gallbladder dysplasia, and the possibility of CBA should be considered when the cyst has a decreasing trend after birth.
The second part is the application of ultrasound in fetal gallbladder abnormality.
Objective: 1. to study the clinical significance of fetal gallbladder abnormality..2. study the duration of fetal gallbladder contraction.
Methods: 1. from January 2009 to December 2013, the group of fetal gallbladder abnormalities diagnosed by our department were classified, followed up with ultrasound, combined with clinical and other auxiliary examinations to obtain the etiological diagnosis of.2.32 cases of isolated NVGB. The close prenatal and postnatal ultrasound visits were carried out according to the fixed period of the fetus. The first diagnosis of NVGB to the gallbladder re display was summarized and analyzed. Time interval (A-B interval) between them.
Results: 1. a total of 347 cases of fetal gallbladder abnormalities were detected in the 1. study period. In the outpatient cases, the detection rate was about 0.6%.NVGB308 cases, accounting for 88.8% (308/347) of the total number of abnormal gallbladder cases, 27 cases of abnormal echo in the gallbladder (3 cases of prenatal ultrasound after NVGB), 7.8% (27/347), and 15 cases of gallbladder location, accounting for 4.3% (15/347), all of them were all cases (15/347). There were no significant gender differences in 308 cases of fetal NVGB, 89.9% ultrasound first diagnosed in late pregnancy.27 cases combined with other ultrasound abnormalities, accounting for 8.8% (27/308) of the total number of NVGB (27/308) of which 12 cases were associated with multiple abnormalities. 215 cases of NVGB cases were followed up, 90.7% first diagnosed in late pregnancy.3 case fetal NVGB, and finally confirmed that the disease was congenital biliary dysplasia, respectively, congenital absence of congenital biliary tract development. The gallbladder, the hepatic interlobular bile duct deficiency and the type III cystic biliary atresia (cystic biliary atresia, CBA), accounted for 27 cases of abnormal echo echo in the gallbladder of the follow-up cases, the average gestational age (35.7 + 2.5) weeks (29~39 weeks). 3 cases (3.7%) were combined with other structural abnormalities, and the other 25 cases of abnormal echo in the gallbladder were followed up to disappear, 21 cases (84%). There were 15 cases of abnormal.4. gallbladder disposition within 1 weeks after birth. 10 cases of permanent right umbilical vein (Persistent right umbilical vein, PRUV), of which 50% had cardiac or vascular dysplasia. 2 cases of left gallbladder had good prognosis. 3 cases of visceral reverse position (Situs viscera inversus, SVI) were induced, 1 cases were first diagnosed to gallbladder again. .28.1% (9/32) case A-B of 3 days to 71 days was less than 7 days, 46.9% (15/32) A-B interval was 8 to 21 days, 25% (8/32) A-B interval was 21 days. The postnatal gallbladder re display of 21 cases of.11 case of fetal gallbladder was re displayed postpartum, showing that the realization was within 1 weeks after birth. After follow-up, 32 cases of NVGB fetus caused by gallbladder contraction were followed up. The prognosis is good, and the length of A-B interval has no significant effect on the prognosis of the fetus.
Conclusion: 1.NVGB is the most common abnormal manifestation of fetal gallbladder (.2.). Although fetal physiological gallbladder contraction is the most common cause of fetal NVGB in the late pregnancy, there is still a possibility of abnormal development of biliary tract (1.4%) and multiple ultrasound abnormalities (3.9%), which may not be ignored in the clinic, which may not be the continuous undisplay of the fetal gallbladder. One of the causes of the disease is to study the clinical significance of the abnormal echo in the gallbladder of.4. fetus after the late pregnancy (especially in 32 weeks to full term), all of which disappear spontaneously before and after birth and after birth, 84% in 1 weeks after birth. The prognosis is good for the form and position of the gall bladder of the fetus of.5., which may be combined with multiple abnormalities and chromosomal abnormalities. The ultrasonic observation of the gallbladder has important clinical significance. The continuous contraction of the gall bladder in the.6. is a physiological phenomenon. The length of the A-B interval has no obvious influence on the prognosis of the fetus, and its physiological mechanism needs to be further studied.
The third part: determination and value of GGT enzyme value in normal fetuses from 20 weeks to 24 weeks of gestation.
Objective: to establish the normal GGT value of fetal amniotic fluid 20 weeks to 24 weeks, so as to provide reference value for prenatal diagnosis of biliary atresia.
Methods: the transection design was used. The amniotic fluid was collected from June 2009 to April 2010. The pregnant women who were in accordance with the indications of amniotic fluid puncture were required to carry out the fetal chromosome examination. The following conditions should be met: the fetal chromosome results were normal, pregnant women were healthy, pregnant women and spouses had no dyed body abnormalities, and prenatal ultrasound examination had no obvious fetal structural difference. Often (including abnormality of amniotic fluid), no chromosomal abnormal fetal birth, or abnormal pregnancy history of unknown etiology. The karyotype and GGT quantitative analysis of amniotic fluid samples were taken immediately after the extraction of amniotic fluid samples. The X + s, 1%-99% confidence interval of the GGT values of amniotic fluid in each week were calculated, and the correlation between the LogGGT value and the pregnancy week was tested by Pearson test.
Results: during the study, 110 cases of fetal amniotic fluid were collected from 20 weeks to 24 weeks of pregnancy, of which 73 were female. With the growth of GGT enzyme, the median of X, the median, LogGGT decreased gradually with the gestational weeks, and the LogGGT value was negatively correlated with the gestational weeks.
Conclusion: the GGT enzyme value gradually decreases with the growth of gestational weeks, and the establishment of the normal value of amniotic fluid GGT at 20 weeks -24 weeks in fetal pregnancy is expected to provide a new diagnostic reference for the further diagnosis of biliary atresia and the differential diagnosis of CC and CBA prenatal.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R714.5;R445.1

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