Ultrasound Study Of Fetal Facial Contour Index In Early Pregnancy And Its Diagnostic Value For Abnormal Fetuses

Objective:To develop the normal reference range of fetal facial markers from the median sagittal section in Chinese population,to study the correlation with crown-rump length(CRL),and to evaluate early diagnostic value of these facial markers in abnormal fetuses during first trimester(11?13⁺⁶gestational weeks).These facial markers included inferior facial angle(IFA),maxilla-nasion-mandible(MNM)angle,facial maxillary angle(FMA)and profile line(PL)distance.Methods:Fetal ultrasound images were selected from those fetuses who underwent first trimester ultrasound screening during August 2017 to July 2019 at the Affiliated Suzhou Hospital of Nanjing Medical University.Fetuses with normal ultrasound and normal follow-up outcomes were divided into the normal group.Fetuses diagnosed as chromosomal abnormalities by invasive genetic examination or those with facial structure abnormalities suspected by ultrasound and confirmed after induced abortion were categorized as the abnormal group.Two experienced sonographers who had obtained the nuchal translucency(NT)screening qualification certificate from the Fetal Medicine Foundation(FMF^a)measured these facial markers.Bland-Altman Analysis and intraclass correction coefficient(ICC)were used to compare intra-operator and inter-operator repeatability.Pearson correlation test was used to analyze the correlation between fetal facial markers and CRL,and a linear regression equation was established.The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic(ROC)curves.Results:There were total 380 fetuses selected in the normal group,with CRL between 50mm and 84mm.The ICCs(95%CI)of intra-operator 1 repeatability of IFA,MNM angle,FMA,PL distance were 0.944(0.886?0.973),0.804(0.629?0.902),0.834(0.68?0.918)and 0.935(0.868?0.969),respectively.The ICCs(95%CI)of intra-operator 2 repeatability of those parameters were 0.931(0.857?0.967),0.809(0.637?0.904),0.786(0.600?0.892)and 0.906(0.813?0.954),respectively.The ICCs(95%CI)of inter-operator repeatability of IFA,MNM angle,FMA,PL distance were0.885(0.663?0.953),0.829(0.672?0.915),0.77(0.511?0.891)and 0.844 (0.68?0.925),respectively.The repeatability of these markers for intra-operator and inter-operator was good.The measurement range of IFA during first trimester was55.9°?107.89°.The mean IFA was 80.2(standard deviation 7.25)°, IFA=127.601-0.707*CRL,r=-0.598,p<0.001,and it had negative correlation with CRL.The measurement range of MNM angle was 1.66°?9.21°.The overall mean MNM angle was 4.17(SD 1.19)°,MNM angle=-4.112+0.123*CRL,r=0.547, p<0.001,and it had positive correlation with CRL.The measurement range of FMA was 56.29°?89.59°and the mean FMA was 75.36(SD 5.31)°. FMA=55.683+0.293*CRL,r=0.339,p<0.001,it had positive correlation with CRL.The measurement range of PL distance was 1.53?4.37mm,with the mean(SD)value of 2.78(0.54)mm.PL distance=5.136-0.035*CRL,r=-0.399,p<0.001,and it decreased significantly with CRL.In the normal group,facial profile line(FPL)was all‘positive'.The position classification of FPL was consistent both intra-operator and inter-operator. Thirteen abnormal fetal images were selected,and one of them was removed from the group because the nasal bone was absent.Eventually 12 fetuses were in the abnormal group,including 5 cases of trisomy 21,2 cases of trisomy 18 and 5 cases of cleft lip and palate,with CRL between 54mm and 77mm.The IFA values for trisomy21 and trisomy 18 fetuses were 72.3°±7.22°and 64.95°±5.71°,respectively,which were significantly smaller than the normal group(t=2.42,p=0.016;Z=-2.286, p=0.022).The MNM angle of cleft lip and palate fetuses was 9.54°±3.12°,which was significantly greater than the normal group(t=-3.847,p=0.018).The MNM angle of trisomy 18 fetuses was 7.27°±2.83°.The difference with the normal group had critical statistical significance(Z=-1.949,p=0.051).The FMA values of trisomy 18 fetuseswere 66.21°±2.38°,which was significantly smaller than the normal group(Z=-2.145,p=0.032).The PL distance of trisomy 21,trisomy 18,cleft lip and palate fetuses were2.77±0.30mm,3.07±0.85mm and 2.61±0.49mm,respectively.The difference with the normal group had no statistical significance(t=0.05,p=0.96;Z=-0.588,p=0.557; t=0.718,p=0.473).In the abnormal group,twelve fetuses all had‘positive'FPL. The diagnostic sensitivity of IFA for trisomy 21 was 60%.The diagnostic accuracy of IFA,FMA and MNM angle for trisomy 18 was 96.8%,93.9%and 89.9%,respectively,in descending order.The diagnostic accuracy of MNM angle for cleft lip and palate was 98.6%.When the IFA was less than 69.00°or the FMA was less than67.96°,trisomy 18 should be highly suspected.During first trimester,when the MNM angle was greater than 6.83°,cleft lip and palate should be suspected.Conclusions:The repeatability and feasibility of measuring fetal facial profile markers was good during first trimester.The normal reference range of each marker was obtained through large sample data,and the good correlation with CRL was found.IFA had certain significance in detecting trisomy 21 during first trimester.IFA and FMA were reliable indicators for screening trisomy 18 fetuses.The abnormal MNM angle could be used as a sensitive indicator for cleft lip and palate.PL distance and FPL were not the best ultrasound markers for trisomy 21,trisomy 18 and cleft lip and palate during first trimester.