Clinical outcome of fetuses with sonographic diagnosis of isolated micrognathia

OBJECTIVE: To describe the clinical outcome of fetuses with the prenatal sonographic diagnosis of isolated micrognathia. METHODS: A retrospective review of fetuses and infants with the prenatal diagnosis of isolated micrognathia for April 1990 to August 2001 was undertaken. Isolated micrognathia was considered if no other anatomic, growth, or amniotic fluid abnormalities were detected by a detailed ultrasound examination. Sources of outcome data included maternal and neonatal medical records, prenatal genetics records, and karyotype results. RESULTS: Fifty-eight fetuses with the diagnosis of micrognathia were identified. Fifteen fetuses (26%) had isolated micrognathia by prenatal sonogram. After neonatal examination, 14 of 15 were found to have at least one additional abnormality. Eleven had a cleft of the soft and/or hard palate. Seven (54%) of 13 live-born neonates had mild to severe airway obstruction that required intervention. Four (31%) of 13 experienced feeding difficulties of varying duration. Follow-up data were available for 1 to 10 years. Eight (62%) of 13 children are reported to be doing well. Five (38%) of 13 children are reported to have mild to severe developmental delay. CONCLUSION: If micrognathia is the only sonographic finding identified, physicians and families should be prepared for possible respiratory difficulty at delivery, the presence of a cleft palate, and/or developmental delay.     

Antenatal ultrasonic findings of craniofacial malformations.

Fetal craniofacial malformations were identified sonographically in 13 cases. Holoprosencephaly and median cleft syndrome were the most frequent findings. Cleft lip, cleft palate, single nostril, cyclopia and hypotelorism were also seen. Seven of the 13 cases (54%) had polyhydramnios. Amniocentesis was performed on 12 fetuses, and 5 of them showed autosomal trisomy. Accordingly, when craniofacial malformation is recognized antenatally, a careful survey of the fetus for other associated structural anomalies and cytogenetic study are indicated to aid in diagnosis and subsequent obstetric and neonatal management. Also screening for fetal craniofacial malformation is recommended during mid-trimester ultrasound examinations.     

Sonographic features of trisomy 18 at midpregnancy

OBJECTIVE: To evaluate the sonographic characteristics of the fetuses with trisomy 18 at 16-22 weeks of gestation. METHODS: The subjects were recruited from pregnant women undergoing prenatal sonographic examinations at 16-22 weeks of gestation and subsequently proven to be trisomy 18. The results of ultrasound findings were retrospectively reviewed in 25 cases with chromosomes which were confirmed as trisomy 18. RESULTS: All cases had at least one abnormal sonographic finding. There was only one case that had no structural abnormality, but fetal growth restriction was documented. The common sonographic findings included fetal growth restriction, choroid plexus cysts, cardiac anomalies, clenched hand, omphalocele and cleft lip. Fetal growth restriction was the most common finding demonstrated in nearly half of all cases. Other less common findings were diaphragmatic hernia, abnormal head shape, polyhydramnios, single umbilical artery. CONCLUSION: Nearly all fetuses with trisomy 18 had characteristic sonographic patterns of abnormalities demonstrated at midpregnancy. Detailed ultrasound at midpregnancy could effectively screen fetuses with trisomy 18 for further genetic testing.     

Prenatal sonographic findings in 207 fetuses with trisomy 21

OBJECTIVE: The objective was to evaluate the contribution of second trimester ultrasound examination to the prenatal diagnosis of trisomy 21 in 207 fetuses with this aneuploidy. The type and frequency of abnormal sonographic findings were determined. Possible multiple malformation patterns, characteristic of trisomy 21 were sought. STUDY DESIGN: Singleton fetuses that had prenatal sonography during the second trimester, then underwent cytogenetic evaluation in our institution, made up the study population. The sonographic findings of 207 fetuses with trisomy 21 were analyzed. RESULTS: Between 1990 and 2004, fetal karyotyping was performed in 22,150 patients for different indications. An abnormal karyotype was diagnosed in 514 cases (2.3%); among them 207 fetuses with trisomy 21 were detected (40.3%). Abnormal sonography was seen in 63.8% of the cases. Structural anomalies were detected in 28.5% of the trisomy 21 fetuses, among them cardiac defects (15.9%), central nervous system anomalies (14.5%), and cystic hygromas (6.8%) were the most common. Of the minor markers, increased nuchal translucency (28%), pyelectasis (20.3%), and shorter extremities (8.7%) were common findings. CONCLUSIONS: Appropriate diagnosis of structural anomalies, looking for relatively easily detectable minor markers and incorporating fetal echocardiography into the second trimester sonographic protocol, may increase the contribution of mid-trimester ultrasound examination to diagnosing trisomy 21.     

Chromosomal defects and associated malformations in fetal cleft lip with or without cleft palate

OBJECTIVE: To describe the incidence, associated features including chromosomal defects in fetuses, with cleft lip and/or palate and assess the need for karyotyping. METHODS: Retrospective study of 62 cases of prenatally diagnosed facial cleft lip and/or palate in a tertiary fetal medicine unit between January 1991 and December 1999. Chromosome analysis was performed in all fetuses with associated ultrasound findings and in 14 (39%) fetuses with isolated facial clefts. RESULTS: Associated abnormalities were detected in 26 (42%) of the 62 fetuses of which 22 (35%) fetuses had multiple other abnormalities. Central nervous system abnormalities and limb malformations were the most common. Three fetuses had genetic syndromes confirmed after birth. All fetuses with isolated clefts were chromosomally normal, whereas 15 of the 26 with additional abnormalities (58 or 24% of the total group) had chromosomal defects (eight cases of trisomy 13, five of trisomy 18, one unbalanced translocation between chromosomes 7 and 8, and one deletion 4p-). All 22 women who chose not to undergo fetal karyotype analysis delivered phenotypically normal infants. There were five midline clefts; each of them was associated with additional sonographic findings and four were associated with holoprosencephaly. CONCLUSION: Isolated facial clefting is not associated with an increased risk for chromosomal defect. Amniocentesis is recommended when facial cleft is found in association with additional ultrasonographic abnormalities as it is unnecessary for isolated clefts.     

中晚孕期18-三体综合征胎儿的超声特征

目的:研究中晚孕期18-三体综合征胎儿超声影像的变化。方法:回顾分析经羊膜腔穿刺、脐血管穿刺胎儿染色体分析确诊为18-三体的胎儿24例的临床资料和超声影像特征。结果:24例18-三体胎儿中,22例超声影像有变化,占全部病例的91.7%;最常见的超声变化是心脏畸形,共15例,占62.5%;其它常见的异常有脉络膜囊肿、脐带异常、肢体异常、宫内生长迟缓、脑室扩大、小脑延髓池扩大等;还可见颅骨变形、颜面裂、颈项皮肤增厚、消化道闭锁、腹壁缺损、膈疝、肾盂轻度积水、羊水过多等。结论:超过90%的18-三体胎儿中晚孕期可发现超声影像改变,中晚孕期胎儿超声检查是产前筛查18-三体胎儿的有效手段。     

Pseudocyst of the umbilical cord: prenatal sonographic appearance and clinical significance

OBJECTIVE: To assess the clinical significance of umbilical cord pseudocysts detected prenatally by sonography. METHODS: The prenatal sonographic findings, karyotype, and perinatal outcome in 13 fetuses with umbilical cord pseudocysts were reviewed retrospectively. RESULTS: Umbilical cord pseudocysts were diagnosed at a median gestation of 27 weeks (range 15-37). Pseudocysts were single in eight cases with cyst diameters ranging from 20 to 50 mm, and double in one case. In the remaining four cases, multiple small cystic masses measuring less than 8 mm were identified. Additional sonographic findings were noted in 11 cases; ten of these fetuses had prenatal karyotyping, which showed trisomy 18 in five cases, trisomy 13 in one case, and a 46,XX, inv ins(18;21) complement in one case. Among the seven chromosomally abnormal fetuses, umbilical cord pseudocysts were multiple in four fetuses and single in three. All chromosomally abnormal fetuses and two euploid fetuses with associated structural defects died in utero or in the neonatal period. There were no perinatal complications in either of the fetuses with isolated pseudocysts. CONCLUSION: The prenatal sonographic appearance of umbilical cord pseudocysts varied widely. These umbilical cord cystic masses were associated strongly with chromosomal disorders and structural defects, regardless of their sonographic appearance in utero.     

Cardiac and extra-cardiac anomalies as indicators for trisomies 13 and 18: a prenatal ultrasound study

The purpose of the present study was to establish sonographic markers for prenatal diagnosis of trisomies 13 and 18. Retrospective analysis of sonographic morphology was therefore carried out in seven fetuses with trisomy 13, and 16 fetuses with trisomy 18. Gestational age ranged between 17 and 39 weeks (median 28 weeks). Polyhydramnios and symmetrical growth retardation were present in 14 of 23 fetuses. A cardiac anomaly was diagnosed in all 23 fetuses, the majority representing a ventricular septal defect (n = 8) or double outlet right ventricle (n = 8). Extra-cardiac anomalies were characterized by a high incidence of limb deformities (polydactyly, clenched hands, club feet; n = 15) and omphalocele (n = 7). We conclude that the combined appearance of cardiac and extra-cardiac anomalies should prompt fetal karyotyping. Cardiac anomalies in combination with fetal limb deformities and omphalocele are suspicious for trisomies 13 and 18.     

Latent class analysis applied to patterns of fetal sonographic abnormalities: definition of phenotypes associated with aneuploidy.

The aim of the present study was to generate different latent variables that classify the major chromosome aneuploidies using frequency and patterns of fetal sonographic abnormalities in a large database. A total of 1867 fetuses with sonographic abnormalities recorded in a database at New England Medical Center from January 1995 to March 1998 were available for the statistical analysis. Included within this group were 61 aneuploid fetuses, including 11 with 45,X, 30 with trisomy 21, 14 with trisomy 18 and 6 with trisomy 13, 40 structural malformations and/or sonographic markers were detected in these 61 aneuploid fetuses. The ability of malformations and sonographic markers to generate different groups of phenotypes was evaluated by means of latent class analysis, using the 61 affected cases. Four different classes were generated with the hypothetical assumption that each of them could satisfactorily identify a respective fetal aneuploidy represented in the study group. Among 40 fetal malformations and/or sonographic markers, the most important findings in generating specific karyotypic groups were cystic hygroma (class 1), duodenal atresia (class 2), holoprosencephaly (class 3) and omphalocele (class 4), respectively. Accuracy of the classification was 72 per cent for Turner syndrome (class 1), 74 per cent for Down syndrome (classes 1 and 2), 88 per cent for trisomy 13 (class 3) and 93 per cent for trisomy 18. The frequency of associated malformations detected sonographically can help to define a phenotype that is likely to be representative of a specific aneuploidy. Before the definitive karyotype is available or, in cases in which patients refuse an invasive prenatal diagnostic procedure, this may improve antenatal clinical management.     

Prenatal karyotyping in malformed fetuses

Experience with prenatal karyotyping of 237 fetuses with sonographic evidence of malformation is reported. Abnormal karyotype was found in 40 cases (16.8 per cent): chromosomal aberrations were found in 19 of the 178 fetuses with an isolated structural anomaly (10.6 per cent) and in 21 of the 59 fetuses with multiple malformations (35.6 per cent). Detailed cytogenetic and morphological information concerning fetuses affected by omphalocele, duodenal atresia, hydrocephalus, multicystic kidney, unilateral hydronephrosis and cystic hygroma is reported. The need for a very careful ultrasound evaluation of fetal anatomy in these pregnancies is stressed, as the risk of a chromosomal anomaly depends mainly on the existence of more than one ultrasonically diagnosed structural defect.     

Abnormal pregnancy sonogram and chromosomal anomalies: four years' experience with rapid karyotyping

Over a four-year period, 140 pregnancies with different malformations detected by ultrasound were examined cytogenetically. Gestational age ranged from 13 to 36 weeks. Twenty-six fetuses (18.6 per cent) had abnormal karyotypes, including trisomies, triploidy, monosomy X, and structural anomalies. Similar malformations were found in fetuses with different chromosomal anomalies, indicating that the types of malformations are not specific for particular chromosomal anomalies. Chromosomal analysis was performed on amniotic fluid culture and by direct karyotyping of placental biopsies. Direct karyotyping is suggested to be the most rapid approach, especially if sonographic anomalies are detected close to the 24th week of gestation, shortly before delivery, and in cases of significant oligohydramnios.     

Natural history of 70 fetuses with a prenatally diagnosed orofacial cleft

OBJECTIVE: This study is an analysis of neonatal outcome in 70 fetuses diagnosed over a 10-year period as having cleft lip with or without cleft palate (CL-P) by ultrasonographic examination. METHODS: We describe the natural history of these 70 fetuses with orofacial clefts and select those who may be candidates for fetal surgery. The sonograms of 70 fetuses with orofacial clefts were evaluated for the nature of the CL-P and for the nature of the associated anomalies. Additionally, karyotyping was performed in 63 of 70 patients (90%). RESULTS: The frequency of additional anomalies and the mortality rate varied with the type of cleft. Also, the frequency and type of chromosomal abnormalities varied with the type of cleft. The overall mortality rate was 63% (n = 44). 3 of the surviving 26 fetuses had severe associated anomalies. In 13 of the remaining 23 cases, the fetal age at diagnosis (> or =22 weeks) excluded the fetuses from the potential benefits of fetal intervention. CONCLUSION: Of 70 fetuses with prenatally diagnosed orofacial clefts, only 10 (14%) were candidates for fetal CL-P surgery.     

Diagnosis of polyhydramnios in early gestation: indication for prenatal diagnosis?

Previously published reports have indicated that idiopathic polyhydramnios may be associated with trisomies 18 and 21 and that chromosomal analysis is indicated. Furthermore, the natural history and fetal outcome of polyhydramnios diagnosed in early gestation have not been well delineated. We identified 138 pregnancies with polyhydramnios prior to 26 weeks' gestation. Of 131 complete cases, 21 were diagnosed as severe, 18 as moderate, and 92 as mild polyhydramnios. Congenital abnormalities were noted in 18 of 21 severe cases (86 per cent). Two of the remaining three cases were twin-to-twin transfusion. Thirteen of 18 cases with moderate polyhydramnios (72 per cent) were associated with anomalies; six of the remaining cases were twin-to-twin transfusion. Sixteen of 92 cases of mild polyhydramnios (17 per cent) were associated with congenital abnormalities. In 69 of 76 cases of mild hydramnios not associated with anomalies (91 per cent), the hydramnios resolved prior to delivery. Only 2 of 16 (13 per cent) associated with anomalies resolved. In 4 of 5 cases (80 per cent) with moderate hydramnios and no anomalies, the amniotic fluid volume was normal on subsequent ultrasound. No case of moderate polyhydramnios associated with anomalies or maternal conditions nor any case of severe polyhydramnios resolved. There were seven cases of chromosomal abnormalities in this series; all were associated with sonographic findings in addition to the presence of polyhydramnios. On the basis of these data, we doubt the benefit of amniocentesis following the early diagnosis of idiopathic polyhydramnios in the absence of other ultrasound findings.     

142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。     

Prenatal imaging of facial clefts by magnetic resonance imaging with emphasis on the posterior palate

OBJECTIVE: To evaluate the role of Magnetic Resonance Imaging (MRI) in the prenatal diagnosis of facial clefts. MATERIALS AND METHODS: Six fetuses with a sonographic diagnosis of cleft lip and palate underwent MRI at a median age of 30 weeks (range 28-32). The defect was bilateral in two cases. RESULTS: Fetal MRI confirmed the presence of a cleft involving at least the anterior palate in all cases. Distinction between unilateral and bilateral clefts could be made in all cases and was always confirmed after birth. Sagittal views of the fetal face were found to be particularly useful in identifying the degree of extension of the cleft into the palate. The diagnosis was confirmed after birth. CONCLUSION: Our results suggest that MRI may be ancillary to ultrasound in prenatal investigation of a fetus with cleft lip, allowing a better staging of the lesion by demonstrating the degree of involvement of the palate.     

Prenatal diagnosis of complete trisomy 9: a case report and review of the literature

Complete trisomy 9 is a very rare chromosome aneuploidy, associated with specific patterns of multisystem dysmorphism and a wide spectrum of congenital anomalies. We present a case of complete trisomy 9 with prenatal sonographic findings in the second trimester. The combination of sonography and karyotyping from cordocentesis enabled us to establish the prenatal diagnosis. An additional clinical feature of this syndrome that has not been reported previously is an aortopulmonary communication. A review of the literature specifically dealing with prenatal sonographic findings with complete trisomy 9 is also presented.     

Prenatal detection of facial clefts

OBJECTIVES: To determine (1) the antenatal detection rate for isolated cleft lip and/or cleft palate during the routine anomaly scan; (2) the correlation between prenatal diagnosis and postnatal findings, and (3) the association of apparently isolated cleft lip and/or cleft palate with other anomalies, in particular chromosomal abnormalities. METHOD: A population-based retrospective analysis of all cases of isolated cleft lip and/or cleft during an 8-year period in an academic teaching hospital in the UK. RESULTS: Thirty-nine cases of isolated cleft lip and/or cleft palate were identified among deliveries at the hospital. Twenty-eight cases had a routine anomaly scan. Fourteen cases were detected prenatally (sensitivity 50%). None of the isolated cleft palates was detected, while 14 of 20 cases of cleft lip (70%) were detected. One of the isolated cases of cleft lip was associated with trisomy 21, while 3 of the isolated cleft palate cases were associated with the Pierre Robin syndrome. In all cases, an antenatal diagnosis of cleft was confirmed following delivery or post-mortem examination (specificity 100%). CONCLUSIONS: Ultrasound is a useful tool in screening for cleft lip with or without cleft palate, but not for cleft palate alone. Even with an isolated cleft lip, there is an increased risk of chromosomal abnormality. The role of prenatal education and support is extremely important in the preparation of prospective parents and can help alleviate the shock which occurs when there is an unexpected cleft at birth.     

18-三体综合征胎儿超声声像特征分析

目的分析18-三体综合征胎儿超声声像特征,以期早期诊断与处理。方法回顾分析经染色体核型分析确诊的18-三体儿12例超声检查的资料。结果全部18-三体儿存在二个或以上异常超声声像表现。其中,胎儿生长受限、羊水过多表现率最高,各为58.3%;其次是心脏畸形,50.0%;再其次是脉络丛囊肿、单脐动脉、脑发育不全、上肢发育异常。在〈28周的胎儿中,超声异常的表现率最高的是心脏畸形、脉络丛囊肿,各为66.7%,其次是胎儿生长受限、羊水过多,各为50.0%。胎儿生长受限主要表现为股骨长度发育落后于正常。结论超声检查是产前筛查18-三体儿的有效手段。     

Prenatal diagnosis of craniofacial malformations with ultrasonography

Although the utility of ultrasound in the prenatal diagnosis of many congenital anomalies is well established, its accuracy in detecting craniofacial malformations has not been examined in a large series. Sonographic examinations of 223 patients at risk for fetuses with craniofacial malformations were performed between 18 and 40 weeks. The risk factors included a familial history of craniofacial malformations, extrafacial anomalies diagnosed on ultrasound, fetal chromosomal aberrations, and maternal drug intake. Sonographic diagnosis was possible in 151 (67.7%) patients on the first scan and in 47 (21.1%) patients on the second scan and was not possible in 25 patients (11.2%). Of the 198 cases diagnosed antenatally, craniofacial malformation was detected in 14 and confirmed postnatally. No false positive diagnoses were made. A negative diagnosis of craniofacial malformation was made in 184 cases with two false negative results (1.0%). Anomalies diagnosed sonographically included anophthalmia, anterior cleft lip and/or palate, hypotelorism, hypertelorism, and micrognathia. The results of this study demonstrate that ultrasound is an accurate and reliable tool for the prenatal diagnosis of craniofacial malformations.