| Part one: Prenatal diagnosis for fetal cleft lip/palate by ultrasonographyObjective: To evaluate the clinical significance of prenatal diagnosis for fetal cleft lip/palate by ultrasonography.Methods: The ultrasonographic characteristics and associated anomalies were retrospectively analyzed in 603 fetuses,who were diagnosed as cleft lip/palate by prenatal two-dimensional(2D)ultrasonography and three-dimensional(3D)ultrasonography in the Affiliated Suzhou Hospital of Nanjing Medical University during January 2014 to June 2017.Fetal face was examined by 2D ultrasonography in sections such as nose and lip coronal plane,upper lip transverse plane,lower lip transverse plane,facial sagittal plane,et al.If fetal cleft lip/palate was suspected by 2D ultrasonography,three-dimensional(3D)ultrasonography was combined for further diagnosis,classification and extent of the cleft.Three-dimensional ultrasonography technologies such as render mode,Omni View technology,tomographic ultrasound imaging(TUI),volume contrast imaging(VCI),etc.were utilized.The cleft lip/palate was traditionally classified as cleft lip(CL)(unilateral or bilateral),cleft lip and palate(CLP)(unilateral or bilateral)and cleft palate(CL).Fetuses with cleft lip/palate need detailed scan to exclude ‘soft markers’ and other structural abnormalities.According to any other anomalies,fetuses with cleft lip/palate was divided into two groups,nonsyndromic cleft and syndromic cleft.The former included isolated cleft and cleft accompanied with ‘soft markers’.The latter was associated with other structural malformations.All fetuses were followed until birth or induced abortion.Results: Among 71 831 fetuses,603 fetuses were diagnosed as cleft lip/palate by prenatal 2D ultrasonography and 3D ultrasonography,including 76 cases of cleft lip,505 cases of cleft lip and palate,21 cases of median cleft associated with holoprosencephaly and 1 case of irregular cleft caused by Amniotic Band Syndrome.Fetuses with cleft lip/palate were mainly diagnosed during 20 to 28 weeks’ gestation.The ultrasonographic characteristic of cleft lip was anechoic area in the upper lip,which was discontinuous.For cleft lip and palate,the discontinuities of both upper lip and alveolar was detected by prenatal 2D ultrasonography.When combined with 3D ultrasonography such as Omni View technology,TUI,etc.,cleft lip and palate was detected efficiently,especially for cleft of secondary palate.Among 501 nonsyndromic fetuses,461 were isolated cleft lip/palate,while the other 40 had ‘soft markers’.The most common ‘soft marker’ was single umbilical artery.Eighty syndromic fetuses were associated with other structural abnormalities,the most common of which was congenital heart disease.Among 603 fetuses,79 fetuses underwent genetic testing and 12 cases were abnormal,mainly with trisomy 18 and trisomy 13.Four hundred and sixty-seven fetuses were induced abortion and 136 cases continued pregnancy to birth.During follow-up,2 cases who were originally diagnosed as cleft lip(degreeⅠ)by prenatal ultrasonography came out to be normal after birth.Three cases of cleft lip and palate were misdiagnosed as cleft lip only.Two cases of cleft lip(degreeⅠ)and 44 cases of cleft palate were missed diagnosis by prenatal ultrasonography.The diagnostic accordance rate of prenatal ultrasonography for cleft lip/palate was 92.43%(598/647).Conclusion: Prenatal ultrasonography is the modality of choice for the diagnosis of fetal cleft lip/ palate.It has high diagnostic accuracy for cleft lip and cleft lip and palate.However,it doesn’t detect cleft palate.It also has false positive diagnosis and false negative diagnosis of cleft lip(degreeⅠ),which should be avoided as far as possible.Diagnosis of fetal cleft lip/palate promotes detailed scan for associated anomalies and genetic testing should be suggested when necessary.Part two: The application of three-dimensional ultrasonography Omni View technology in diagnosis of fetal cleft lip/palateObjective: To evaluate the clinical significance of three-dimensional ultrasonography Omni View technology in diagnosis of fetal cleft lip/palate,especially for cleft of secondary palate.Methods: One hundred and three fetuses,suspected as cleft lip were examined by two-dimensional(2D)ultrasonography and three-dimensional(3D)ultrasonography Omni View technology.The fetal face was examined by 2D ultrasonography in routine sections such as nose and lip coronal plane,upper lip transverse plane,lower lip transverse plane and facial sagittal plane.Then 3D volume data was acquired and stored.4D View offline software(version 10.3)was utilized.Anatomical lines were drawn by Omni View technology in the A plane,which was the reference plane and should be facial midsagittal plane.Retronasal triangle(RNT)coronal plane was obtained by drawing the line through fetal nasal bone,primary palate and mandibular.When the curved line or polyline was drawn along the palate,a transverse plane was obtained to show the upper lip,alveolar(primary palate)and secondary palate,from anterior to posterior.All fetuses were followed until birth or induced abortion.Fetal cleft lip/ palate was classified as cleft lip(CL),cleft lip and alveolus(CLA)and cleft lip and palate(CLP)(including cleft of primary palate and of secondary palate).The diagnostic accordance rate was calculated and compared between 2D ultrasonography and 3D ultrasonography Omni View technology.Results: Thirty-four,66 and 3 cases were diagnosed as CL,CLA,CLP by 2D ultrasonography,respectively.Thirty-one,27 and 45 fetuses were diagnosed as CL,CLA,CLP by 3D ultrasonography Omni View technology,respectively.Twenty-nine,25 and 49 cases were confirmed as CL,CLA,CLP,respectively,by examination or surgery after birth or autopsy after abortion.All 103 fetuses had cleft lip.Both 2D ultrasonography and 3D ultrasonography Omni View technology could detect all cleft lip.The diagnostic accordance rate of CLA by 2D ultrasonography and 3D ultrasonography Omni View technology were 80%(20/25)and 92.0%(23/25),respectively.The difference had no statistical significance(p=0.41).However,for CLP,the diagnostic accordance rate of 2D ultrasonography and 3D ultrasonography Omni View technology were 6.12%(3/49)and 91.84%(45/49),respectively.The difference had obvious statistical significance(p<0.001).Conclusion: Both 2D ultrasonography and 3D ultrasonography Omni View technology have high diagnostic accordance rate for cleft lip(CL)and cleft lip and alveolus(CLA).Whereas 3D ultrasonography Omni View technology has a much higher diagnostic accordance rate of cleft lip and palate(CLP)(including cleft of primary palate and of secondary palate).As a new method of imaging,3D ultrasonography Omni View technology is useful for prenatal diagnosis of fetal cleft lip/palate,especially for cleft of secondary palate.Part three: Ultrasonographic measurement of fetal facial profile markers during first trimester(11 to 13+6 weeks’ gestation)Objective: The aim of this pilot study was to evaluate the repeatability of ultrasonographic measurement for fetal facial markers such as inferior facial angle(IFA),maxilla-nasion-mandibular(MNM)angle,mandibulo-maxillary line(MML)and frontal space(FS)distance,to analyze the correlation between these markers and fetal crown rump length(CRL),and to provide the reference range for these markers during first trimester(11 to 13+6 weeks’ gestation).Methods: Three hundred and ten stored two-dimensional(2D)ultrasonographic images,used for fetal nuchal translucency(NT)thickness measurement were retrospectively selected from 310 normal fetuses.Fetal facial markers were measured through View Point 6 software by two experienced sonographers,who had got The Fetal Medicine Foundation(FMFa)certification for NT scan.The images should be strictly on fetal midsagittal section.Intra-operator and inter-operator repeatability was examined by using 95% limits of agreement(95% Lo A).The distribution and variation trend of the parameters were analyzed.Inferior facial angle(IFA)was the angle between two lines,the reference line was orthogonal to the vertical part of the forehead at the level of the synostosis of the nasal bones,and the other line joined the tip of the mentum and the anterior border of the more protruding lip(either upper or lower lip).Maxilla-nasion-mandibular(MNM)angle was defined as the angle between maxilla-nasion line and mandible-nasion line in the midsagittal plane.A mandibulo-maxillary line(MML)was created by connecting the anterior edge of the mental protuberance and anterior edge of the maxilla.The MML was then extended upwards.When it ran posteriorly to the forehead,its position was called ‘positive’,and when located anteriorly,it’s called ‘negative’.When it passed lengthwise through the frontal bone,it was called ‘zero’.Frontal space(FS)distance was the perpendicular distance between MML and the skin at the point of largest excursion of the fetal forehead.In cases of ‘negative’ MML,the distance was measured in the same fashion but should be multiplied by-1.Results: The parameters were measured in the images of 303 normal fetuses.The gestational age ranged from 11+5 to 13+6 weeks,with the CRL between 49 mm and 84 mm.For each parameter,the repeatability for intra-operator and inter-operator was good.IFA value ranged from 38.44° to 127.29° during first trimester,with the mean(standard deviation)value of 83.73(14.95)°.The reference range of IFA was 54.43°~113.03°.Therefore,micrognathia/ retrognathia should be suspected when an IFA value was below 54.43°(mean-2SD).The correlation between IFA value and CRL had a borderline statistical significance(p=0.056).The MNM angle had no significant correlation to CRL(p=0.44),with the mean(SD)value of 4.58(2.33)°.The reference range was 1.17°~9.66°.The determination of position of MML were same both intra-operator and inter-operator,including 268 ‘positive’,27 ‘zero’ and 8 ‘negative’.The mean FS distance was 2.73mm(SD 1.57).FS distance was dependent on CRL(FS=6.25-0.054*CRL,r=-0.256,p<0.001).Conclusion: It is reliable for prenatal ultrasonography to measure the markers such as IFA,MNM angle and FS distance during first trimester.These markers represent fetal facial profile especially the relative position of maxilla and mandibular.The reference range of these markers are preliminarily constructed,which provide objective quantitative reference for further diagnosis of fetal cleft lip/palate and micrognathia/retrognathia during first trimester. |
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