To Summarize The Indirect Ultrasound Characteristic Of Absent Corpus Callosum And To Explore A New Approach For Screening Fetal Absent Of Corpus Callosum At 11-13+6 Weeks

Absent of corpus callosum (ACC) is a complex disease, which can result from disruption in any one of the multiple steps of callosal development, such as cellular proliferation and migration, axonal growth or glial patterning at the midline. In the general population, the incidence of ACC is 0.1‰～7‰, while the incidence is as high as 2%-4%in the neurodevelopment delayed population. Corpus callosum as the largest myelinated nerve fiber connection in the hemisphere, its radiation is extensive, the fiber projection areas of it as followings:prefrontal lobe, premotor and supplementary motor areas, primary motor areas, primary sensory cortex, parietal lobe, occipital lobe, and temporal lobe. Since closely contact with brain lobes and cortex district, the corpus collosum damage can lead to appropriate involvement of dysfection regional, such as the corpus callosum absent in addition to being hemispheric information transfer is limited, it can also be complicated by other neurological disorders, such as epilepsy, autism disorder, abnormal motor behaviors, learning disabilities, social skills impairment, mild-severe neurological or metal retardation, otherwise it is often associated with other syndromes or genetic disease. The approximately 67% with nerous system abnormalities can be combined with ACC.Then ACC is highly correlated with more than fifty kinds of genetic syndromes, in born errors of metabolic such as fetal alcohol syndrome(FAS), and a variety of chromosome aberrations. According to the associated malformations, ACC can be divided into groups as complex ACC or simple ACC, while the complex ACC is more commom in society. Approximately 45.8% ACC embraces neurological disorder, and 17.8% choromosome abnormalities in the complex ACC or simple ACC. Therefore, gave birth to a child with ACC is a significant stress and financial burden to the family. The direct financial loss caused by birth defects is up to 800 million yuan every years in China, and the medical expenses for rainsing a disabled child is 150 billion yuan in public expenditure yearly. Thus to explore a safe and effective approach for screening fetal ACC is not only a great challenge faced by prenatal ultrasound currently, but also to protect our limited medical resources, and to raise important issues related to quality of the population.Now that the MRI is the preferred method todiagnose ACC, as its advantages of multi-dimension and multi-level imaging, without limitation of amniotic fluid and maternal BMI, and other characteristics affecting fetal position. But the pregnant women in our country always refused to do MRI, for the reason that it expensive cost and the limited exam period. Although ultrasound has some limitations compared with MRI, it is still an irreplacement examination to obstetric clinic, with security, convenient, real-time imaging, repeated dynamic observation and other advantages. The diagnosis of ACC can be exactly confirmed by experienced sonography and the accuracy rate is as same as MRI. In other words, for the reason that ultrasonography is economical, security, repeatable, effectiveness and feasibility, it has been an important role in improving the quality of population, stabling the development of society.The corpus callosum is the later development in nervous system, it began to development from 8-10 gastational weeks to 18-20 gastational weeks. According to the embryonic period, ACC can be categories as complete ACC and partial ACC. In the early 1980s, intrauterine diagnosis ACC has been reported, and the direct and indirect sonographic features is not reported until researchers summarized the neonate ACC by neonatal brain sonograms in 1990s. The direct prenatal ultrasound sonographic features of ACC are:the hypoechoic thin and banding between two hyperecho in the fetal brain mid-sagittal completely absent (CACC) or partial absent (PACC); the hypoechoic between two lateral ventricle anterior horn in the series fetal brain coronal are completely absent. The indirect prenatal ultrasound sonographic features of ACC are:the brain mid-sagittal section:pericallosal artery semi-circular shpe is disappeared, cingulated gyrus in disorder;the brain series transverse section: cavum septum pellucidum absent, ventriculomegaly (teardrop-shaped), lateral ventricle abduction (Bull’s horn sign), third ventricle widened and upped, increased separation of the interhemispheric fissure "triplication of the mid-line echo". The amniotic fluid volume is moderate in second trimester (18-24 weeks), and most structures have been fully developed during this time, so it is recognized as the best period for fetal structural abnormalities screening. The overall rate of fetal malformations detection is 45% in second trimester, and the good time to prenatal diagnosis ACC is also in second trimester, which is diagnosed by direct sonographic features and detected by indirect features. But the ACC direct sonographic features is usually difficult to obtained directly, so the indirect sonographic features are more often used by sonography to detecting ACC in clinical. However, these indirect prenatal sonography features is not presented in all affected fetus, so there are some doubts that which indirect feature is the most common one, and what correlation exists between the indirects, and whether differences exists in prenatal ultrasound indirect signs of different categories of ACC, and all abve is unclear so far.In addition, the prenatal ultrasound diagnosis of ACC is being more than 20 years, but the diagnosis gestational age which is in second trimester is no significant advance. First tremister (11-13+6 weeks) ultrasound screening is rised in the early 1990s, and after more than 10 years of exploration, first tremister ultrasound have developed rapidly, especially in the abnormal detection. The previous study in our research center show that the sensitivity of fetal anomalies was 75.9% for first trimester ultrasound, the specificity was 98.5%, and the positive predictive value was 65.6%.2011 United Kingdom FMF President Nicolaides raise screening during early pregnancy the fetus malformation with holoprosencephaly, exencephaly, anencephaly, umbilical hernia, and diaphragmatic hernia, gastroschisis, body stalk anomaly, single ventricle anomalies, megalocystis, lethal skeletal dysplasia, and other severe deformities. All of this show that screening for prenatal abnormalities during early pregnancy is viable. However, there are few reference regarding first trimester screen corpus callosum.This study is intended for make prenatal diagnosis ACC as the research object, by summerize the indirect sonography features of ACC, to explore the frequency of the indirect sonography features, to explore the relationship between different types of ACC. Moreover this research is also intended for make normal fetuses, absent of corpus callosum, holoprosencephaly fetuses as research objects, to retrospective analysis the midbrain and falx in fetus brain of first trimester NT images, with this to explore a new indicators for absent of corpus callosum high-risk populations in first trimester. This project proposed by the above research, to detect high-risk ACC fetus more earlier, and to reduce the rate of false negalive rate, and to reduce the rate of birth defects in newborn, and make a greater contribution to improving the quality of national population in our country.Part One To Summarize the indirect ultrasound characteristic of absent corpus callosum[Purpose]The prenatal direct ultrasound features of ACC is difficult to access directly, and the diagnosis of ACC is often confirmed by indirect features. However, these indirect prenatal sonography features is not presented in all affected fetus, so there are some doubts that which indirect feature is the most common one, and what correlation exists between the indirects, and whether differences exists in prenatal ultrasound indirect signs of different categories of ACC, and all above is unclear so far.[Method]There are 65cases of ACC fetuses conformed to the criteria(CACC=51 cases, and PACC=14 cases). To retrospective the prenatal ultrasound images and indirect features of 65cases, and to explore the correlation between the indirect ultrasound features, and whether there is a difference between different types of ACC indirect ultrasound features. Then summarize the assosicated abnormalities, laboratory test results and consequence of follow-up of the 65cases. All datas are using SPSS20.0 software package for statistical analysis.[Results]1.In the 65cases ACC fetuses,62 cases are termination of labor,4 cases diagnosed as simple ACC are labor at term. The follow-up time of the 7 cases are vary from 2 monthes to 2 years and 1 monthes, and the outcome are good.2.The the rate of diagnosis gestational weeks less than 28weeks is 63.1%.3.Only 15 cases were conducted chromosome examinations, among these 11 cases chromosome karyotype analysis were normal, and 4 cases were abnormal:2 case in 18 chromosome trisomy,1 case in 5-p chromosome deletion, and 1 cases in46,ⅩⅩ,t(1;8)(q32.3;q24.1).4.Among the 65 cases,75.4% ACC fetus were associated with other abnormalities, including 56.9% of intracranial abnormalities,43.1% combined extracranial anomalies. The major intracranial abnormalities are hydrocephalus and Dandy-walker malformation, and the extracanial is heart malformation. The two groups has no significant difference in intracranial and extracranial anomalies anomalies (P> 0.05).5.According to the prenatal ultrasound features of ACC fetuses in our hospital, we summarize the frequency of ACC associated indirect ultrasound features from highest to lowest as followings:ventriculomegaly(93.8%), cavum septum pellucidum absent (78.5%), third ventricle widened and upped(75.4%), lateral ventricle abduction ("Bull’s horn sign") (64.6%), increased separation of the interhemispheric fissure "triplication of the mid-line echo"(60%).,6.The carrelation relationships of the five ACC associated indirectly ultrasound features are all showed positive correlation exclud the ventriculomegaly and "triplication of the mid-line echo" or "Bull’s horn sign". The cavum septum pellucidum absent and "Bull’s horn sign", the "triplication of the mid-line echo" and "Bull’s horn sign", and the cavum septum pellucidum absent andthe third ventricle widened and upped are all showed a significant positive correlation (r=0.760,0.714, 0.504, P均<0.0001), and the "Bull’s horn sign" and cavum septum pellucidum absent showed the most closely correlated.7.There exited significant difference of cavum septum pellucidum abnormal between CACC and PACC (P< 0.05), and CACC is cavum septum pellucidum absent, and PACC is cavum septum pellucidum present. The rest prenatal indirectly ultrasound signs were more frequency present in CACC compared with PACC (P< 0.05).8.The most common situation in CACC is cavum septum pellucidum absent, ventriculomegaly, the third ventricle widened and upped, "triplication of the mid-line echo", "Bull’s horn sign" are all present at the same time and the rate is 62.8%; and the following situation is cavum septum pellucidum absent, ventriculomegaly, third ventricle widened and uppered present at the same time and the rate is 17.6%. Additionaly in PACC, the cavum septum pellucidumis usually present, and only the ventriculomegaly present is the most common situation and the rate is 43%.[Conclusion]1.Use the ultrasound to diagnose ACC in prenatal is feasible, and the best time is the second trimester.2.ACC fetuses also associated with other abnormalities or choromasome abnormal, and these can make an deep influence in the outcome.3.The pericallosal artery abnormalities is the most frequency features present in ACC, and when we observed these features the suspected of should be proposed. Otherwise the cavum septum pellucidum absent is usually appeared with "Bull’s horn sign" or "triplication of the mid-line echo", and the "triplication of the mid-line echo" is more closely combined with "Bull’s horn sign". So that the indirectly ultrasound features has an most important values to prenatal diagnosis ACC.4.CACC and PACC shows difference in the present of indirectly ultrasound features, and the CACC which is more easier to diagnosed in prenatal is usually associated with the indirectly features, while the PACC is less associated with it.These conclusions show that the ACC indirect ultrasound signs associated with a very large value for the prenatal diagnosis of fetal ACC. If these signs appear gives an geart alert to diagnosis ACC. In addition, ACC is often associated with external fetal nervous system and other nervous system abnormalities, prenatal diagnosis of ACC suggestive significance to find some less common, easily missed abnormalities, and has an important role to reduce the rate of birth defects and improve the overall quality of the population.Part two To explore a new approach for screening fetal absent of corpus callosum at 11-13+6 weeks and established the normal range for fetues midbrain diameter and falx diameterChapter 1 To established the normal range for fetues midbrain diameter and falx diameter[Purpose]In this study, we exploring the possibility of the first trimester (11-13+6 weeks) screening high-risk fetal ACC by ultrasound in normal fetal brain.[Method]This is a retrospective study, in whichtotally 620 normal singleton fetuses between 11 to 13+6 gastational weeks were enrolled in the study. During the first trimester the fetal brain were measured midbrain diameter (MD), falx diameter (falx diameter, FD), and midbrain to falx diameter ratio(MD/FD ratio), then studied the relationship between these and gestational age and crown-rump length(CRL). Thenormal reference ranges of these related structuralparameters at various CRLwere established. A scatter diagram of each parameter against CRL was plotted out. The optimal formula was selected out according to the correlation and regression analysis. All data using SPSS 20.0 software package for statistical analysis.[Results]Among 620 normal fetuses, therelationship of fetal brain mid-sagittal section between the structure of the brain withvarious gestational age is:MD and MD/FD increased with increasing gestational age (F=60.951,85.516, P<.001), while MD/ FD decreased (F=273.193, P<0.001). MD, FD value, MD/FD ratio showed a correlation between CRL, as significantly positive linear correlations were found between parameters of MD, FD values and CRL (r=0.528 and r=0.811, P<0.001), while FD was inversely linear correlated with CRL (r=-0.506, P<0.001). Moreoverfetal brain mid-sagittal MD values normal reference range in first trimester is (5.26-6.19) cm, the FD noemal reference range is (8.04-10.41) cm, and the MD/ FD ratiois (0.56-0.70). Additionlly fetal falx showed a rapid growth phase in 12-13 gestational weeks, whilefetal midbrain is in 11-12 gestational weeks (P<0.001).[Conclusion]There exists some correlationship between midbrain structural and CRL.Established the normal reference ranges gives a possibility to explore morenervous system disease in first trimester.Chapter 2 To explore a new approach for screening fetal absent of corpus callosum at 11-13+6 weeks[Purpose]To explore the feasibility to screening the ACC fetus in first trimester.[Method]This was a retrospective study for stored images of the midsagittal view of the fetal brain at 11-13+6 weeks’gestation, and the fetuses which diagnosis as absent of corpus callosum (ACC) or Holoprosencephaly (HPE) is detected in 01,Jan,2011 to 31,Oct,2013 in our hospital. Both groups were measured fetal brain sagittal section of MD, FD values, and MD/FD ratio respectively, and the results are compared with the privous analysis of the narmal range. All datas are using SPSS20.0 software package for statistical analysis.[Result]A total of five fetuses were enrolled in ACC group, and 13 fetuses were included into HPE groups. There are no significant difference in MD, FD values and MD/FD ratio of two group (P>0.05). In the fetuses with ACC and HPE, compared to the normal controls, the mean MD value and MD/FD ratio were significantly increased by the reference range for CRL.(P<0.05). The mean MD/FD ratio of ACC and HPE were significantly decreased (p<0.05). In all these 5 cases of ACC and 13 cases of HPE the ratio were more than 1, whereas in all normal cases the ratio was less than 1.[Conclusion]In the midsagittal view of the fetal brain at 11-13+6 weeks, the majority of fetuses with ACC and HPE have measurable abnormalities in the midbrain and falx area of the brain. In another words, the MD, FD value and MD/FD ratio could be a very promising noninvasive prenatal screening for corpus callosum abnormal.