Study On New Technique Of Prenatal Ultrasound Screening And Diagnosis Of Maxillofacial Structural Malformations In First-trimester

1Background and Subject sourcesFirst trimester (11to13+6weeks’) ultrasound was rised in the early1990s, which was initially used to screening21-trisomy, and then extended to screening13-trisomy and18-trisomy, with current ultrasound equipment and improving sonographictechnique,it is now possible to detect more than80%of fetal anomalies.Early preganancy ultrasound screening makes the vast majority of fetal anomalies diagnosis ahead of time, reducing the impact of induction of labor for pregnant women physiological and psychological, especially in some foreign countries, to avoid the gestational age of induction of labor by the ethical implications of constraints, so in early pregnancy ultrasound screening becomes an important direction of the prenatal ultrasound.Shenzhen Maternity&Child Healthcare Hospital developed ultrasound screening fetal malformations in early pregnancy (11to13+6weeks’) in2006, and establish detailed guildline of ultrasound examination in this period.The main content includes the screening for aneuploid in early pregnancy(fetal NT, nasal bone, ductus venosus), brain, facial region, heart, limb, abdominal wall malformation, aiming at summarizing a series of early methodology of prenatal diagnosing fetal malformations in the research process. In the context,we make a research on a part of the National Key Technology R&D Program in the11th Five year Plan of topics’Study on new technique of prenatal ultrasound screening and diagnosis’(Number:2006BAI05A04) of China.2Objective and significanceTo evaluate the value of the ultrasonographic method of fetal congenital facial disease using cross-sectional view of the fetal lateral ventricle with probe tilting ventral slightly technique in screening fetal facial malformations antenatally in early pregnancy, in order to exploring the display rate of facial anatomical structure and the feasibility of screening facial malformation using this method in early pregnancy, and summarize the ultrasonographic appearances of fetal facial malformations to provide reliable technical standards and ultrasonic guildline in screening facial structure in early pregnancy.3Research data and methods3.1Data source:In a14-month period from November2010to the end of December2011, women attending their first-trimester sonographic screening for aneuploidy to our referral center for prenatal diagnosis were invited to participate in this prospective study. Pregnant couples are local residents. Singleton pregnancies or twin pregnancies.Patients were recruited consecutively, including parents basic information and personal medical history, current pregnancy records and reproductive history. This study was approved by the Institutional Review Board of the Shenzhen Maternity&Child Healthcare Hospital, which is an affiliation of the Southern Medical University,China.Ultrasound results in early pregnancy of each enrolled fetus were compared with mid-trimester ultrasound results or after birth. The fetus of severe deformities and facial malformation who were diagnosised by ultrasound, we informed their parents about fetal outcome, let the parents decide whether to continue pregnancy. With the consent of the pregnant women, we conducted post-natal ultrasound and pathological examination for labored fetuses. Information on second-trimester sonographic findings, antenatal course and pregnancy outcome, including the detection of chromosomal abnormalities, congenital defects or the presence of physical dysmorphic features at birth, was obtained by reviewing the cytogenetics laboratory logbook, delivery records and neonatal discharge summaries in cases delivering in our institution, or by contacting the referring obstetrician or the parents themselves in those delivering elsewhere.3.2The first trimester sonographic protocol used in our center strictly follows the guidelines established by The Fetal Medicine Foundation, UK, and was approved by our Institutional Review Board. All examinations were conducted By two physicians who qualified by FMF. Briefly, Sonographic examination is performed transabdominal using high resolution ultrasound equipment (Acuson512,4.0～6.0MHz). In addition, evaluation of the fetal anatomy for gross fetal anomalies is also performed as recommended by The Fetal Medicine Foundation. Assessment of the contents of the brain, face, chest, stomach, bladder, liver, umbilical artery, heart and upper limbs, lower limbs and so on.The examiner checked the measured data and assess the contents of fill in a form.To evaluate the value of the ultrasonographic method of fetal congenital facial disease using cross-sectional view of the fetal lateral ventricle with probe tilting ventral slightly technique in screening fetal facial malformations. Screening method are as follows:A good sagittal section of the fetus, as for measurement of fetal crown-rump length, should be obtained and the NT should be measured with the fetus in the natural position. Only the fetal head and upper thorax should be included in the image for measurement of NT, then rotating the probe90°to obtain the cross-sectional view of the fetal brain, then slightly tilting its orientation from the fetal forehead to fetal ventral to obtain to display cerebellum, intracranial translucency (IT), ears, eyes, retronasal triangle and lips.(1)Median sagittal section of the facial:this image can clearly show the profile, the echogenic nasal bonewhich parallelled with its upper skin, maxilla, dot-like mandible, thalamus and strip back of the nuchal translucency.(2)Cross-sectional view of the fetal lateral ventricle:Evaluation of the brain included a cross-sectional view of the fetal head, which in normal circumstances shows2paired echogenic structures filling most of the lateral ventricles, corresponding to the choroid plexuses. Because the choroid plexus is narrow in its medial portion and prominent at both the frontal and caudal ends, the apposition of both choroid plexuses in the midline at this particular gestational age produces a characteristic appearance resembling a butterfly.This feature is not present in first-trimester fetuses with holoprosencephaly, however, because that condition is associated with severe distortion of the lateral ventricles and choroid plexuses.(3)Cross-sectional view of the fetal cerebellum:Ultrasound image in the transverse plane of the fetal face showing thalamus, midbrain, brain stem. The fourth ventricle presents as an intracranial translucency between the brain stem and the choroid plexus.(4)Eyes level coronal section:After obtaining fetal midsagittal section, then rotating the transducer90°, and slightly tilting its orientation to the posterior fossa beam to display bilateral frontal bone which present as the plate echo, symmetrical, and "eight" shape, we can see frontal suture between frontal bones which located above the eyes. Bilateral orbits present as hyperecho with hypoecho eye and lens. Bilateral zygomatic locate just below the eyes, are strong echo points. The ears locate in the side of head, with the upper edge flat level of the maxilla, like a short line echo.(5)Retronasal triangle section:This image can be achieved by obtaining a sagittal view of the fetal face that includes the nasal bone,then rotating the transducer90°and slightly tilting its orientation to bring the frontal processes of the maxilla and primary palate into the same plane.Alternatively, the retronasal triangle can be visualized by obtaining a transverse view of the fetal cranium and moving the transducer down to the face to achieve a coronal view in which the above anatomical landmarks are visualized.The hypoecho gap between the points of mandible is the mandibular gap.(6)Upper lip level coronal section:This image can be achieved by obtaining a retronasal triangle section of the fetal face, then slightly tilting the orientation of the transducer to bring the upper lip, lower lip and mandible into the same plane. Nasal bone continued to show strong echo point. There are four parallel echogenic lines, respectively, the upper lip, lower lip, mandible and closed line of lips. When the fetus opened mouth, we can display lip more clearly. If suboptimal views of the nuchal translucency thickness or nasal bone are obtained due to fetal position, we asked patients to get up for a20-30min rest for another examination, if we can not get optimal views several times and then as a check fails. The screening time is no more than2min in a normal fetus, and no more than15min in facial malformation fetus.All images were stored in machines and workstations, and were analyzed by the other two doctors off-line, assessment of the sections to observe the anatomical structure, to the views of the two doctors agreed to a unified standard, when the divided views, the third doctor to assess.3.3Statistical methods:To group all patients into three group based on fetal gestational age which was measured by ultrasound:group1:11to11+6weeks; groups2:12to12+6weeks; groups3:13to13+6weeks. Use statistical software packages of SPSS13.0, measurement data were expressed as mean±standard deviation, count data were expressed as rate, that statistically significant differences in the rate was evaluated by χ2test, P<0.05was considered significant.4Result4.1General conditionA total of644fetus datasets from639pregnancies (including7sets of twins,2monozygotic twins,5dizygotic twins; one was acardiac twins sequence, one was thanatophoric, one was embryo damage) were enrolled in this study, of which6with facial malformation were identified prospectively and1was miss diagnosis in first trimester. All fetus were classified into three groups by gestational age as group1(11to11+6weeks) in72cases (11.2%), group2(12to12+6weeks) in379(58.9%), and; groups3(13to13+6weeks) in193(30%).The median maternal age was29.03years (range20-43), the median gestational age88.22days (range77-97). All patients were followed up,19cases were induced labor in early pregnancy (15cases of malformations, abnormal soft mark in one cases, twins due to the structure of the other fetal abnormalities induced labor two cases), one fetus were induced abortion cases during pregnancy because the fetus thalassemia4.2Information of fetal superficial facial anatomic structures Superficial facial anatomic structures of the fetal faces were clearly displayed and correctly recognized on the four routine planes (median sagittal section of the facial, eyes level coronal section, retronasal triangle section and upper lip level coronal section) in620cases (96.3%).the display rate was97.2%in group11to11+6weeks,97.1%in group12to12+6weeks,94.3%in group13to13+6weeks. There is no significant difference among groups in early pregnancy fetal facial display rate(χ2=2.992, v=3, P=0.224).There are24cases which can not get optimal view of fetal facial (2cases in11to11+6weeks,11cases in12to12+6weeks,11cases in13to13+6weeks), the main reason may include:influence of fetal position(such as fetal persistent prone position or lateral position, the beam can not reach the fetal face); frequent fetal movement, to increase the inspection difficulty; fetal head is parallel to the maternal abdominal wall.4.3Facial malformation in first trimesterThere were7facial malformation in our study, the incidence is10.9/1000.6cases were detected at first trimester, including3cases of bilateral cleft lip and palate,1case of unilateral cleft lip and palate,1case of facial cleft and1case of median cleft lip and palate with proboscis. One isolated cleft lip was miss diagnosed in first trimester. The median maternal age was26.71years (range23～31), the median gestational age89.86days (range84-97), the mean NT4.5mm. The diagnoses were confirmed after subsequent labor or induced labor. The sensitivity, specificity, positive and negative predictive values were85.7%,100%,100%and99.8%respectively(Not including24patients whose face can not displayed).5of6cases of facial malformation diagnosis in first trimester were associated with other structural abnormalities (5/6,83.3%),3cases (33.3%) with more than three deformities (1case with gastroschisis, lack of right upper limb, scoliosis; one cases with gastroschisis, scoliosis, abnormal hand fingers, short umbilical cord; one cases of the holoprosencephaly, significantly increased size of right heart, scoliosis), the first two cases were considered combined with limb body wall complex; one cases (16.7%) with two deformities (with holoprosencephaly and tetralogy of fallot); one cases (16.7%) with omphalocele, one cases (16.7%) of isolated bilateral cleft lip and palate.In the group of seven cases of facial malformation, four cases are associated with other structural malformations with NT≥3mm,2cases of limb body wall complex, one case of omphalocele, one case of TOF, so we can not excluded if there is a clear correlation between the NT thickness and facial malformations;1patient with holoprosencephaly, tricuspid regurgitation, reverse of A wave, scoliosis, was suspected a13-trisomy,but the patient did not undergo karyotype analysis; two cases of simple cleft lip and palate had NT values within the normal range. This group of patients did not indicate a correlation between facial deformity and NT, result of the sample size and most of our positive cases which were associated with other etiological obviously can lead to thickening of the NT.5ConclusionOur study was first proposed combination of median sagittal section of the facial, eyes level coronal section, retronasal triangle section and upper lip level coronal section to screen fetal facial malformations in our country and abroad. The displaying rate of facial structure is about96.2%, which was completely unaffected by gestational age.We can detect This method can effectively screen serious facial deformity during early pregnancy, but the sensitivity for isolated cleft lip and palate need further study. Detection rate for facial deformity was87.5%.The sample size and high-risk population in our study is small, so fewer types of facial malformations were included. The value of this method need further study in low-risk population.