Fetal head-to-trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To determine the pattern of early growth disturbance in chromosomally abnormal fetuses by comparing the volume of the fetal head to that of the trunk. METHODS: The fetal trunk and head volume was measured using three-dimensional (3D) ultrasound in 145 chromosomally abnormal fetuses at a median gestational age of 12 (range, 11 + 0 to 13 + 6) weeks. The head volume was measured separately and then subtracted from the total head and trunk volume to obtain the volume of the fetal trunk. The head-to-trunk ratios were then calculated and the Mann-Whitney U-test was used to determine the significance of differences from 500 chromosomally normal fetuses. RESULTS: The fetal head volume for crown-rump length (CRL) was significantly smaller than normal in trisomy 21, trisomy 13 and Turner syndrome (P < 0.001, P < 0.001 and P = 0.001, respectively), whereas no significant differences were found in trisomy 18 and triploidy (P = 0.139 and P = 0.070, respectively). The fetal trunk volume for CRL was significantly smaller in all chromosomal abnormalities (P < 0.001) except Turner syndrome (P = 0.134). The head-to-trunk ratio for CRL was significantly larger in trisomy 18, trisomy 13 and triploidy (P < 0.001), but normal in trisomy 21 (P = 0.221) and Turner syndrome (P = 0.768). CONCLUSIONS: In trisomy 21 and Turner syndrome, the growth deficit was symmetrical with the head and trunk being equally affected, whereas in triploidy and trisomies 18 and 13 there was asymmetrical growth restriction with the trunk being more severely compromised than the head.     

Three-dimensional evaluation of mid-facial hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the mid-facial hypoplasia of fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation, by three-dimensional (3D) evaluation of the maxilla and the nasal bones. METHODS: A 3D volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median 12) weeks of gestation in 80 fetuses that were subsequently found to have trisomy 21 and in 862 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal face and to demonstrate the maxilla, the adjacent rami of the mandible and the nasal bones. The maxillary depth, defined as the distance between the alveolus of the maxilla in the midline anteriorly and the midpoint of the line joining the rami posteriorly, was measured. Ossification of the nasal bones was considered to be normal if both bones were more echogenic than the overlying skin. RESULTS: In the chromosomally normal group the maxillary depth increased linearly with crown-rump length (CRL) from 3.1 mm at a CRL of 45 mm to 4.8 mm at a CRL of 84 mm, and in the trisomy 21 fetuses the depth was significantly smaller than normal (mean difference = - 0.3 mm, P < 0.001). There was no significant association between the delta maxillary depth and delta nuchal translucency thickness in either the trisomy 21 or the chromosomally normal fetuses. Impaired ossification of the nasal bones was observed in 3.1% of the chromosomally normal fetuses and in 60.0% of those with trisomy 21. The mean maxillary depth was significantly smaller in fetuses demonstrating impaired ossification than in those with normal ossification of the nasal bones (mean difference = -0.2 mm; 95% CI, -0.3 to -0.1, P = 0.001). CONCLUSIONS: In a high proportion of fetuses with trisomy 21 there is sonographic evidence of mid-facial hypoplasia at 11 + 0 to 13 + 6 weeks of gestation.     

Brachycephaly and frontal lobe hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To investigate the incidence of brachycephaly and frontal lobe hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median, 12 + 5) weeks of gestation in 100 fetuses that were subsequently found to have trisomy 21 and in 300 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal head and to demonstrate the biparietal and suboccipitobregmatic views. We measured the biparietal diameter (BPD), the occipitofrontal diameter (OFD) and the frontothalamic distance (FTD) between the inner table of the frontal bone and the posterior thalami. RESULTS: In the chromosomally normal group the BPD, OFD and FTD increased linearly with crown-rump length (CRL) from 16.7 mm, 19.0 mm and 12.1 mm at a CRL of 45 mm to 26.7 mm, 31.7 mm and 18.7 mm, respectively, at a CRL of 84 mm. In the trisomy 21 fetuses, compared to normal fetuses, there was shorter BPD (mean difference = -0.63 mm; 95% CI, -0.97 to -0.30 mm, P < 0.0001), OFD (mean difference = -1.41 mm; 95% CI, -1.75 to -1.07 mm, P < 0.0001) and FTD (mean difference = -0.77 mm; 95% CI, -1.02 to -0.54 mm; P < 0.0001) and higher BPD to OFD ratio (mean difference = 0.022; 95% CI, 0.012 to 0.032, P < 0.0001) but no significant difference in the FTD to OFD ratio (mean difference = 0.004; 95% CI, -0.006 to 0.013, P = 0.448). CONCLUSIONS: In fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation there is evidence of brachycephaIy but not of frontal lobe hypoplasia.     

Frontomaxillary and mandibulomaxillary facial angles at 11 + 0 to 13 + 6 weeks in fetuses with trisomy 18.

OBJECTIVE: To define the relative position of the maxilla and mandible in fetuses with trisomy 18 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before karyotyping at 11 + 0 to 13 + 6 weeks of gestation in 36 fetuses subsequently found to have trisomy 18, and 200 chromosomally normal fetuses. The frontomaxillary facial (FMF) angle and the mandibulomaxillary facial (MMF) angle were measured in a mid-sagittal view of the fetal face. RESULTS: In the chromosomally normal group both the FMF and MMF angles decreased significantly with crown-rump length (CRL). In the trisomy 18 fetuses the FMF angle was significantly greater and the angle was above the 95(th) centile of the normal range in 21 (58.3%) cases. In contrast, in trisomy 18 fetuses the MMF angle was significantly smaller than that in normal fetuses and the angle was below the 5(th) centile of the normal range in 12 (33.3%) cases. CONCLUSIONS: Trisomy 18 at 11 + 0 to 13 + 6 weeks of gestation is associated with both mid-facial hypoplasia and micrognathia or retrognathia that can be documented by measurement of the FMF angle and MMF angle, respectively.     

Gestational sac volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring the gestational sac volume (GSV) at 11 to 13 + 6 weeks of gestation in screening for chromosomal defects. METHODS: The GSV was measured using three-dimensional (3D) ultrasound in 500 consecutive singleton pregnancies immediately before chorionic villus sampling (CVS) for fetal karyotyping at 11 to 13 + 6 (median 12) weeks of gestation. RESULTS: The fetal karyotype was normal in 417 pregnancies and abnormal in 83. In the chromosomally normal group, the mean GSV increased significantly with gestational age from a mean of 69 mL at 11 weeks to 144 mL at 13 + 6 weeks (the standard deviation was 27 mL). In the chromosomally abnormal group, the mean GSV for gestational age was not significantly different from normal in fetuses with trisomy 21, trisomy 18 and Turner syndrome, but it was smaller in those with triploidy and trisomy 13. However, the mean GSV for crown-rump length (CRL) was significantly larger in trisomy 18, smaller in triploidy and trisomy 13, and not different from normal in trisomy 21 and Turner syndrome. The mean CRL for gestational age was significantly smaller than normal in trisomy 18, triploidy and trisomy 13. CONCLUSIONS: The measurement of the GSV at 11 to 13 + 6 weeks of gestation is unlikely to provide useful prediction of the major chromosomal defects. In trisomy 13 and triploidy, the small GSV may be due to early onset fetal growth restriction and reduced amniotic fluid volume. In trisomy 18, the increase in GSV is probably due to the presence of associated fetal abnormalities that interfere with fetal swallowing.     

Fetal trunk and head volume measured by three-dimensional ultrasound at 11 + 0 to 13 + 6 weeks of gestation in chromosomally normal pregnancies.

OBJECTIVE: To establish the relationship between fetal trunk and head volume measured by three-dimensional (3D) ultrasound and gestational age at 11 + 0 to 13 + 6 weeks of gestation. METHODS: The fetal trunk and head volume were measured using 3D ultrasound in 417 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 (median, 12 + 0) weeks of gestation. Regression analysis was used to determine the significance of the association between fetal volume and gestational age. The Bland-Altman analysis was used to compare the measurement agreement and bias for a single examiner and between different examiners. RESULTS: The fetal trunk and head volume increased linearly with gestation from a mean of 5.8 mL at 11 + 0 weeks to 33.3 mL at 13 + 6 weeks and 1 SD was 4.4 mL. There was also a significant linear association between fetal volume and crown-rump length (CRL), from a mean of 5.1 mL at a CRL of 45 mm to 37.5 mL at a CRL of 84 mm and 1 SD was 2.7 mL. However, within this gestational range, a doubling in CRL, from a mean of 48 mm at 11 + 0 weeks to 79 mm at 13 + 6 weeks, was associated with a 5-6-fold increase in fetal volume. The mean difference in fetal volume between paired measurements by the same sonographer was -0.87 mL (95% limits of agreement, -2.31 to 4.05 mL) and the mean difference between paired measurements by two sonographers was -1.09 mL (-5.49 to 3.32 mL). CONCLUSIONS: 3D ultrasound can provide a reproducible measurement of the fetal trunk and head volume in early pregnancy. At between 11 + 0 and 13 + 6 weeks there is a 5-6-fold increase in fetal volume but only a doubling in CRL.     

Frontomaxillary facial angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To investigate the frontomaxillary facial (FMF) angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before karyotyping at 11 + 0 to 13 + 6 weeks of gestation in 23 fetuses with trisomy 13. The FMF angle, defined as the angle between the upper surface of the maxilla and the frontal bone in a midsagittal view of the fetal face, was measured and compared to the angle in 500 chromosomally normal fetuses. RESULTS: In 10 of 12 (83.3%) fetuses with trisomy 13 and holoprosencephaly, the FMF angle was above the 95(th) centile of the normal range. In the 11 fetuses with no holoprosencephaly, the FMF angle was not significantly different from normal. There was no significant difference in the FMF angle between the trisomy 13 fetuses with and without facial cleft. CONCLUSIONS: In fetuses with trisomy 13, the FMF angle at 11 + 0 to 13 + 6 weeks of gestation is increased only in cases with associated holoprosencephaly.     

Femur and humerus length in trisomy 21 fetuses at 11-14 weeks of gestation.

OBJECTIVE: To determine the value of measuring fetal femur and humerus length at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: Femur and humerus lengths were measured using transabdominal ultrasound in 1018 fetuses immediately before chorionic villus sampling for karyotyping at 11-14 weeks of gestation. In the group of chromosomally normal fetuses, regression analysis was used to determine the association between long bone length and crown-rump length (CRL). Femur and humerus lengths in fetuses with trisomy 21 were compared with those of normal fetuses. RESULTS: The median gestation was 12 (range, 11-14) weeks. The karyotype was normal in 920 fetuses and abnormal in 98, including 65 cases of trisomy 21. In the chromosomally normal group the fetal femur and humerus lengths increased significantly with CRL (femur length = - 6.330 + 0.215 x CRL in mm, r = 0.874, P < 0.0001; humerus length = - 6.240 + 0.220 x CRL in mm, r = 0.871, P < 0.0001). In the Bland-Altman plot the mean difference between paired measurements of femur length was 0.21 mm (95% limits of agreement - 0.52 to 0.48 mm) and of humerus length was 0.23 mm (95% limits of agreement - 0.57 to 0.55 mm). In the trisomy 21 fetuses the median femur and humerus lengths were significantly below the appropriate normal mean for CRL by 0.4 and 0.3 mm, respectively (P = 0.002), but they were below the respective 5th centile of the normal range in only six (9.2%) and three (4.6%) of the cases, respectively. CONCLUSION: At 11-14 weeks of gestation the femur and humerus lengths in trisomy 21 fetuses are significantly reduced but the degree of deviation from normal is too small for these measurements to be useful in screening for trisomy 21.     

Aberrant right subclavian artery at 11 + 0 to 13 + 6 weeks of gestation in chromosomally normal and abnormal fetuses.

OBJECTIVES: To establish the feasibility of examining the subclavian artery at 11 + 0 to 13 + 6 weeks of gestation, and to determine the prevalence of aberrant right subclavian artery (ARSA) in chromosomally normal and chromosomally abnormal fetuses. METHODS: Fetal echocardiography was performed prospectively in 516 patients before chorionic villus sampling at 11 + 0 to 13 + 6 weeks of gestation. Transabdominal sonography was carried out, and color flow mapping was used to identify the right subclavian artery and determine whether this was normal or aberrant (ARSA). Second-trimester fetal echocardiography was also carried out in a subgroup of 183 fetuses. RESULTS: The median gestational age was 12 weeks and the median crown-rump length was 68 mm. Successful assessment of the right subclavian artery was achieved in 425/516 (82.4%) cases and the rate of failure to do so was significantly associated with decreasing fetal crown-rump length (r = 0.174, P < 0.001) and increasing maternal body mass index (r = 0.275, P < 0.001). An ARSA was observed in 2/353 (0.6%) fetuses with a normal karyotype, in 4/51 (7.8%) cases with trisomy 21 and in 2/20 (10.0%) with other chromosomal defects. In a subgroup of 183 fetuses examined in both the first and second trimester there were three cases of ARSA observed at both scans and an additional case in which ARSA was detected only at the second scan. CONCLUSIONS: Assessment of the position of the right subclavian artery is feasible at the 11 + 0 to 13 + 6-week scan and ARSA is more common in chromosomally abnormal than normal fetuses. However, ARSA in the first trimester is unlikely to be a useful marker of trisomy 21.     

Likelihood ratio for trisomy 21 in fetuses with tricuspid regurgitation at the 11 to 13 + 6-week scan.

OBJECTIVE: To determine the likelihood ratio for trisomy 21 in fetuses with tricuspid regurgitation at the 11 to 13 + 6-week scan. METHODS: Fetal echocardiography was carried out by specialist pediatric cardiologists in 742 singleton pregnancies at 11 to 13 + 6 weeks' gestation and pulsed wave Doppler was used to ascertain the presence or absence of tricuspid regurgitation. To avoid confusion with other adjacent signals, a strict definition of tricuspid regurgitation was used, in that it had to occupy at least half of systole and reach a velocity of over 80 cm/s. The fetal crown-rump length (CRL) and the nuchal translucency (NT) thickness were measured and the presence of any congenital heart abnormality noted. Follow-up of the pregnancy was carried out to determine the presence of chromosomal abnormalities. The likelihood ratio for trisomy 21 in fetuses with and without tricuspid regurgitation was determined. RESULTS: The tricuspid valve was successfully examined in 718 (96.8%) cases. Tricuspid regurgitation was present in 39 (8.5%) of the 458 chromosomally normal fetuses, in 82 (65.1%) of the 126 with trisomy 21, in 44 (53.0%) of the 83 with trisomy 18 or 13, and in 11 (21.6%) of the 51 with other chromosomal defects. The prevalence of tricuspid regurgitation was also associated with fetal CRL, delta NT and the presence of cardiac defects. Logistic regression analysis, irrespective of cardiac defects, demonstrated that in the chromosomally normal fetuses significant independent prediction of the likelihood of tricuspid regurgitation was provided by fetal delta NT (odds ratio (OR), 1.26; 95% CI, 1.34-1.41; P < 0.0001), while in trisomy 21 fetuses prediction was provided by CRL (OR, 0.94; 95% CI, 0.89-0.99; P = 0.021). The likelihood ratio for trisomy 21 for tricuspid regurgitation was derived by dividing the likelihood in trisomy 21 by that in normal fetuses. In the chromosomally normal fetuses, the prevalence of tricuspid regurgitation in those with cardiac defects was 46.9% and 5.6% in those without cardiac defects, and the likelihood ratio of tricuspid regurgitation for cardiac defects was 8.4. CONCLUSION: At 11 to 13 + 6 weeks' gestation, there is a high association between tricuspid regurgitation and trisomy 21, as well as other chromosomal defects. The prevalence of tricuspid regurgitation increases with fetal NT thickness and is substantially higher in those with, than those without, a cardiac defect.     

Likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan.

OBJECTIVE: To update the likelihood ratio for trisomy 21 in fetuses with absent nasal bone at the 11-14-week scan. METHODS: Ultrasound examination of the fetal profile was carried out and the presence or absence of the nasal bone was noted immediately before karyotyping in 5918 fetuses at 11 to 13+6 weeks. Logistic regression analysis was used to examine the effect of maternal ethnic origin and fetal crown-rump length (CRL) and nuchal translucency (NT) on the incidence of absent nasal bone in the chromosomally normal and trisomy 21 fetuses. RESULTS: The fetal profile was successfully examined in 5851 (98.9%) cases. In 5223/5851 cases the fetal karyotype was normal and in 628 cases it was abnormal. In the chromosomally normal group the incidence of absent nasal bone was related first to the ethnic origin of the mother, being 2.2% for Caucasians, 9.0% for Afro-Caribbeans and 5.0% for Asians; second to fetal CRL, being 4.7% for CRL of 45-54 mm, 3.4% for CRL of 55-64 mm, 1.4% for CRL of 65-74 mm and 1% for CRL of 75-84 mm; and third to NT, being 1.6% for NT < or = 95th centile, 2.7% for NT > 95th centile-3.4 mm, 5.4% for NT 3.5-4.4 mm, 6% for NT 4.5-5.4 mm and 15% for NT > or = 5.5 mm. In the chromosomally abnormal group there was absent nasal bone in 229/333 (68.8%) cases with trisomy 21 and in 95/295 (32.2%) cases with other chromosomal defects. Logistic regression analysis demonstrated that in the chromosomally normal fetuses significant independent prediction of the likelihood of absent nasal bone was provided by CRL, NT and Afro-Caribbean ethnic group, and in the trisomy 21 fetuses by CRL and NT. The likelihood ratio for trisomy 21 for absent nasal bone was derived by dividing the likelihood in trisomy 21 by that in normal fetuses. CONCLUSION: At the 11-14-week scan the incidence of absent nasal bone is related to the presence or absence of chromosomal defects, CRL, NT and ethnic origin.     

Umbilical cord diameter at 11-14 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring umbilical cord diameter (UCD) at 11-14 weeks of gestation in screening for chromosomal defects. METHODS: The UCD was measured in 1323 fetuses immediately before chorionic villus sampling for karyotyping at 11-14 weeks of gestation. In the group of chromosomally normal fetuses, regression analysis was used to determine the association between UCD and crown-rump length (CRL). UCD was compared in normal fetuses and those with chromosomal abnormalities. RESULTS: The median gestation was 12 (range, 11-14) weeks. The UCD was successfully measured in all cases. The fetal karyotype was normal in 1150 pregnancies and abnormal in 173, including 97 cases of trisomy 21. In the chromosomally normal group the UCD increased significantly with CRL from a mean of 2.9 mm at a CRL of 45 mm to 4.4 mm at a CRL of 84 mm. The UCD in the group of fetuses with trisomy 21 was significantly smaller than normal. Conversely, there were no significant differences from normal in the UCD of fetuses with other chromosomal abnormalities. CONCLUSION: At 11-14 weeks of gestation the UCD of fetuses with trisomy 21 is significantly smaller than normal but the magnitude of the difference is too small for useful inclusion of this measurement in screening.     

First-trimester placental volume as a marker for chromosomal anomalies: preliminary results from an unselected population.

OBJECTIVE: To compare first-trimester placental volume in chromosomally abnormal and normal pregnancies. METHODS: Placental volumes were routinely recorded at the time of nuchal translucency thickness measurement at 10-13 weeks of gestation. This was done using customized three-dimensional ultrasound equipment and measurements were then converted to the placental quotient (placental volume/fetal crown-rump length). The possible difference in placental quotient between chromosomally normal and abnormal pregnancies was examined. RESULTS: A total of 2863 pregnancies was evaluated, including 17 with major chromosomal defects (nine cases of trisomy 21, four of trisomy 18, two of trisomy 13, and one each of Turner syndrome and 48,XXY + 21). The median placental quotient in the chromosomally abnormal group (0.67) was significantly lower than that in the normal fetuses (0.98). In nine of the 17 affected pregnancies the quotient was below the 10th centile of the normal range. CONCLUSIONS: Assessment of placental volume may prove to be useful in first-trimester risk assessment for chromosomal anomalies.     

Placental volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects.

OBJECTIVE: To determine the potential value of measuring the placental volume at 11 to 13 + 6 weeks of gestation in screening for chromosomal defects. METHODS: The placental volume was measured using three-dimensional ultrasound in 500 consecutive singleton pregnancies immediately before chorionic villus sampling for fetal karyotyping at 11 to 13 + 6 (median, 12) weeks of gestation. RESULTS: The fetal karyotype was normal in 417 pregnancies and abnormal in 83. In the chromosomally normal group the mean placental volume increased significantly with gestation from a mean of 51 mL (5th and 95th centiles: 31.2 and 82.4 mL) at 11 weeks to 91 mL (5th and 95th centiles: 55.7 and 147.2 mL) at 13 + 6 weeks. In the chromosomally abnormal group the mean placental volume for gestational age was not significantly different from normal in trisomy 21 and Turner syndrome, but it was smaller in trisomies 13 and 18. CONCLUSIONS: The measurement of the placental volume at 11 to 13 + 6 weeks of gestation is unlikely to be a useful predictor of the major chromosomal defects. In trisomies 13 and 18 the small placental volume may be due to early-onset fetal growth restriction, which could be the consequence of impaired placental function.     

Absent nasal bone at 11-14 weeks of gestation and chromosomal defects.

OBJECTIVE: To examine the association between absence of the nasal bone at the 11-14-week ultrasound scan and chromosomal defects. METHODS: Ultrasound examination was carried out in 3829 fetuses at 11-14 weeks' gestation immediately before fetal karyotyping. At the scan the fetal crown-rump length (CRL) and nuchal translucency (NT) thickness were measured and the fetal profile was examined for the presence or absence of the nasal bone. Maternal characteristics including ethnic origin were also recorded. RESULTS: The fetal profile was successfully examined in 3788 (98.9%) cases. In 3358/3788 cases the fetal karyotype was normal and in 430 it was abnormal. In the chromosomally normal group the incidence of absent nasal bone was related firstly to the ethnic origin of the mother (2.8% for Caucasians, 10.4% for Afro-Caribbeans and 6.8% for Asians), secondly to fetal CRL (4.6% for CRL of 45-54 mm, 3.9% for CRL of 55-64 mm, 1.5% for CRL of 65-74 mm and 1.0% for CRL of 75-84 mm) and thirdly, to NT thickness, (1.8% for NT < 2.5 mm, 3.4% for NT 2.5-3.4 mm, 5.0% for NT 3.5-4.4 mm and 11.8% for NT > or = 4.5 mm. In the chromosomally abnormal group the nasal bone was absent in 161/242 (66.9%) with trisomy 21, in 48/84 (57.1%) with trisomy 18, in 7/22 (31.8%) with trisomy 13, in 3/34 (8.8%) with Turner syndrome and in 4/48 (8.3%) with other defects. CONCLUSION: At the 11-14-week scan the incidence of absent nasal bone is related to the presence or absence of chromosomal defects, CRL, NT thickness and ethnic origin.     

妊娠11~13+6周胎儿侧脑室脉络丛参数初步研究及异常病例分析

目的分析正常妊娠11~13⁺⁶周胎儿侧脑室脉络丛相关参数及其价值。 方法选取2017年1月至2021年1月在安徽医科大学第二附属医院超声诊断科行早孕期胎儿结构筛查的正常胎儿277例（妊娠11~13⁺⁶周）,测量胎儿双侧侧脑室脉络丛长径、面积及大脑镰长度（CF-L）,侧脑室脉络丛长径、面积,采用配对t检验分析左、右侧有无差异;侧脑室脉络丛平均长径（CP-L）、侧脑室脉络丛总面积（CP-A）、CP-L/CF-L与头臀长（CRL）的相关性采用Pearson相关性分析;以CRL作为自变量,CP-L、CP-A、CP-L/CF-L作为因变量,应用简单线性回归模型探索分析变量之间的关系,并建立CRL与相关参数测量值的线性回归方程;同时分析2017年1月至2022年3月在安徽医科大学第二附属医院超声诊断科行早孕期胎儿结构筛查发现的侧脑室脉络丛异常的11例胎儿（妊娠11~13⁺⁶周）的侧脑室脉络丛参数。 结果正常妊娠11~13⁺⁶周胎儿左侧与右侧侧脑室脉络丛长径、面积差异均无统计学意义（P均＞0.05）。CP-L与CRL呈线性正相关（r=0.681,P＜0.001）,线性回归方程为：CP-L=0.134×CRL＋0.577;CP-A与CRL呈线性正相关（r=0.736,P＜0.001）,线性回归方程为：CP-A=0.251×CRL-0.267;CP-L/CF-L与CRL呈线性负相关（r=-0.514,P＜0.001）,线性回归方程为：CP-L/CF-L=-0.047×CRL＋1.011。早孕期侧脑室脉络丛异常者共11例,其中3例为双侧侧脑室脉络丛融合,1例为无侧脑室脉络丛,1例为侧脑室脉络丛不对称,另6例为侧脑室脉络丛小。 结论妊娠11~13⁺⁶周时,CP-L、CP-A、CP-L/CF-L与CRL呈线性相关,为侧脑室脉络丛检查提供一个可参考范围,具有一定的临床意义。     

Fetal heart rate in chromosomally abnormal fetuses.

OBJECTIVES: To determine the effects of chromosomal defects on fetal heart rate at 10-14 weeks of gestation. METHODS: Fetal heart rate at 10-14 weeks of gestation in 1061 chromosomally abnormal fetuses was compared to that from 25,000 normal pregnancies. The chromosomally abnormal group included 554 cases of trisomy 21, 219 cases of trisomy 18, 95 of trisomy 13, 50 of triploidy, 115 of Turner syndrome and 28 of sex chromosome abnormalities other than Turner syndrome. RESULTS: In the normal group, fetal heart rate decreased from a mean value of 170 beats per minute (bpm) at 35 mm of crown-rump length to 155 bpm at 84 mm crown-rump length. In trisomy 21, trisomy 13 and Turner syndrome fetal heart rate was significantly higher, in trisomy 18 and triploidy the heart rate was lower and in other sex chromosome defects it was not significantly different from normal. Fetal heart rate was above the 95th centile of the normal range in 10%, 67% and 52% of fetuses with trisomy 21, trisomy 13 and Turner syndrome, respectively. The fetal heart rate was below the 5th centile in 30% of fetuses with triploidy and 19% of those with trisomy 18. CONCLUSIONS: Trisomy 21, trisomy 13 and Turner syndrome are associated with fetal tachycardia, whereas in trisomy 18 and triploidy there is fetal bradycardia. Inclusion of fetal heart rate in a first-trimester screening program for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness is unlikely to provide useful improvement in sensitivity.     

Uterine artery Doppler at 11-14 weeks of gestation in chromosomally abnormal fetuses.

OBJECTIVE: To determine whether the major chromosomal abnormalities are associated with impaired placentation in the first trimester of pregnancy. METHODS: This was a prospective study of 692 singleton pregnancies undergoing fetal karyotyping at 11-14 weeks of gestation. Uterine artery Doppler was carried out and the mean pulsatility index was calculated just before chorionic villus sampling. RESULTS: The fetal karyotype was normal in 613 pregnancies and abnormal in 79, including 39 cases of trisomy 21, 11 of trisomy 18, 11 of trisomy 13, eight of Turner syndrome and 10 with other defects. There were no significant differences in the median value of uterine artery mean PI between any of the individual groups. Although in the combined group of trisomy 18, trisomy 13 and Turner syndrome fetuses, the median pulsatility index (1.60) was significantly higher than in the chromosomally normal group (median pulsatility index, 1.51; P = 0.021), in the majority of abnormal fetuses (24 of 30) mean pulsatility index was below the 95th centile of the normal group (mean pulsatility index, 2.34). There was no significant association between uterine artery mean pulsatility index and fetal nuchal translucency thickness or fetal growth deficit. CONCLUSIONS: The high intrauterine lethality and fetal growth restriction associated with the major chromosomal abnormalities are unlikely to be the consequence of impaired placentation in the first trimester of pregnancy.     

Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free beta-hCG and PAPP-A. METHODS: The study population comprised 77 trisomy 21 and 232 chromosomally normal fetuses from singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. In all cases the fetal karyotype was determined by chorionic villus sampling (CVS), which was carried out at the request of the parents after first-trimester screening for trisomy 21 by fetal NT and maternal serum free beta-hCG and PAPP-A. Immediately before chorionic villus sampling, fetal echocardiography was performed and the presence or absence of tricuspid regurgitation was determined by pulsed wave Doppler ultrasonography.The distribution of fetal NT, maternal serum free beta-hCG and PAPP-A in trisomy 21 fetuses with absent and present tricuspid regurgitation was examined. We examined two screening strategies: first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free beta-hCG and PAPP-A followed by second-stage assessment of tricuspid regurgitation only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first stage. RESULTS: Tricuspid regurgitation was observed in 57 (74.0%) of the trisomy 21 fetuses and in 16 (6.9%) of the chromosomally normal fetuses. There were no significant differences in median maternal age, median gestational age, free beta-hCG multiples of the median (MoM) and PAPP-A MoM in trisomy 21 fetuses with and without tricuspid regurgitation. The modeled detection rates of trisomy 21 for fixed false positive rates of 1%, 2% and 5% in screening by maternal age, fetal NT thickness and maternal serum free beta-hCG and PAPP-A and assessment of tricuspid flow in all cases were 87%, 90% and 95%. In the two-stage approach, the estimated detection rate was 91% and the false positive rate was 2.6%. CONCLUSIONS: There is no relationship between tricuspid regurgitation and the levels of maternal serum free beta-hCG and PAPP-A in cases with trisomy 21. An integrated sonographic and biochemical test at 11 + 0 to 13 + 6 weeks can potentially identify about 90% of trisomy 21 fetuses for a false-positive rate of 2-3%.     

Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.