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.     

Ultrasound diagnosis of fetal abnormalities and cytogenetic evaluation.

Over a 6 1/2 year period, in 288 pregnancies a variety of fetal malformations were detected by ultrasound. Two hundred and ten fetuses (73 per cent) were karyotyped. Gestational age at detection ranged from 11 to 38 weeks. The incidence of an abnormal karyotype in the total series was 14 per cent and 14.7 per cent in the 210 pregnancies in which a karyotype was performed. Single structural anomalies were found in 149 cytogenetically investigated fetuses, of which 25 had a chromosomal abnormality (17 per cent). Multiple structural malformations were present in 61 fetuses, of which 16 had an abnormal karyotype (26 per cent). Trisomy 18 was the most frequent finding. The most constant ultrasound finding in cases of an abnormal karyotype was polyhydramnios and severe IUGR in combination with structural defects. There is a need for extensive detailed ultrasound examination in high-risk pregnancies.     

Evaluation of prenatal diagnosis by a registry of congenital anomalies.

Prenatal diagnosis performed by fetal karyotype and ultrasound scan is now a routine part of antenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In our region, prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non-chromosomal anomalies. Only 6.9 per cent of the pregnancies with fetuses with non-chromosomal anomalies were terminated. The sensitivity of prenatal diagnosis by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiple malformed children, 15.3 and 48.3 per cent respectively, chromosomal anomalies excluded.     

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.     

Anatomic correlates of ultrasound prenatal diagnosis of urinary tract abnormalities

In 52 fetuses, in utero sonographic diagnosis of urinary tract malformations was correlated with their autoptic or surgical findings. 39 malformations were correctly diagnosed prenatally, although 5 other extrarenal-associated anomalies were not detected; 10 diagnoses were incomplete; in 3 cases the characteristics of malformations found at sonography turned out to be different at the post-mortem examination. The following factors impaired sonographic diagnoses: limited number of examinations, gestational age at the time of examination, nature of malformation and, above all, oligohydramnios (which is common in most urinary tract malformations). The correlations between renal malformations and karyotype anomalies are also discussed in relation to the higher incidence present in polymalformative syndromes.     

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.     

Analysis of ultrasonic scans and karyotype of fetuses with holoprosencephaly diagnosed in the Department of Obstetrics & Gynecology of the Postgraduate Center of Medical Education between 1997 & 2005

OBJECTIVES: The aim of our study was to determine the risk of aneuploidy and associated malformations in fetuses with holoprosencephaly. We have also analyzed the gestational age during the first examination. DESIGN: We have studied ultrasound reports of fetuses with holoprosencephaly. MATERIALS AND METHODS: We analyzed 33 cases, diagnosed in the course of the last eight years in our center. All fetuses underwent a detailed ultrasound survey and, in most cases, antenatal karyotyping. In all cases the type of holoprosencephaly was assessed. RESULTS: In analyzed fetuses alobar holoprosencephaly was diagnosed in 24, semilobar in 7 and lobar holoprosencephaly in 2 cases. Associated anomalies were detected in 28 (mostly face defects) and chromosomal abnormalities in 12 cases. The median gestational age at the first examination was 25 weeks. No more than 14 examinations had been performed before 24 week. CONCLUSIONS: Our findings suggest that in case of fetuses with holoprosencephaly, a detailed ultrasound survey and karyotyping are essential to be performed in all cases. For that reason, patients with fetuses with holoprosencephaly should be diagnosed as early as possible in the referral center.     

Evaluation of ultrasonography. Apropos of a continuous series of 1,000 pregnancies

2,648 sonograms were performed in a continuous series of 1,000 patients, all of whom had delivered in the department between March 1, 1988 and September 1, 1988; pregnancies resulting in a spontaneous miscarriage, extra-uterine pregnancy, therapeutic abortion as well as invasive sonographies, are excluded. Most patients underwent two or three sonograms during their pregnancy. 74 per cent of the requests come from specialists. The main indications are either systematic (67.7%) or result from early manifestations (25.1%). 12.6 per cent of the sonograms are performed before 12 weeks of amenorrhea, including 36.7 per cent performed systematically, and could be performed at a later date. 90 per cent of the term modifications were correctly indicated, and there were early manifestations in 60 per cent of the cases. 45.1 per cent of intra-uterine growth delays were detected and there were early manifestations in 50 per cent of the cases. 41.6 per cent of the malformations were diagnosed on sonograms. Renal malformations are easily recognized; this is not true of cardiac malformations. 96 per cent of the patients were justifiably reassured or worried. Ultrasonography presents a good sensitivity for term modifications, macrosomia, placental insertion anomalies. The sensitivity is less for intra-uterine growth delays and fetal malformations.     

The value of sonography in early pregnancy for the detection of fetal abnormalities in an unselected population.

OBJECTIVE: To determine the value of early pregnancy sonography in detecting fetal abnormalities in an unselected obstetric population. DESIGN Prospective cross-sectional study. All women initially underwent transabdominal sonography and when the anatomical survey was considered to be incomplete, transvaginal sonography was also performed (20.1%). Nuchal translucency was measured and karyotyping was performed as appropriate. SETTING: University Department of Obstetrics and Gynaecology. PARTICIPANTS: 6634 sequential unselected women (mean maternal age 29.9 years, range 13-50; mean gestational age 12+4 weeks, range 11+0-14+6), carrying 6443 live fetuses participated in this study. MAIN OUTCOME MEASURE: Detection rate of fetal anomalies and the associated cost per case detected in early pregnancy. RESULTS: The incidence of anomalous fetuses was 1.4% (92/6443) including 43 chromosomal abnormalities. The detection rate for structural abnormalities was 59.0% (37/63, 95% CI 46.5-72.4) and the specificity was 99.9% in early pregnancy. When the first and second trimester scans were combined, the detection for structural abnormalities was 81.0% (51/63, 95% CI 67.7-89.2). Seventy-eight percent (31/40) of chromosomal abnormalities (excluding three cases of XXY) were diagnosed at 11-14 weeks, either because of a nuchal translucency greater than or equal to the 99th centile for gestational age (43%; 17/40, 95% CI 27.4-60.4), or due to the presence of structural abnormalities (35%; 14/40, 95% CI 21.2-52.8). Sixty-five percent (15/23) of cases of trisomy 21 were also diagnosed either because of having a nuchal translucency greater than or equal to the 99th centile (57.0%; 13/23) or due to the presence of a structural abnormality (9.0%; 2/23). Overall, the detection rate of structurally abnormal fetuses was 59% (37/63) in early pregnancy and 81% in combination with the second trimester scan. The cost per abnormality diagnosed in early pregnancy is estimated to be pound sterling 6258 per structurally abnormal fetus, pound sterling 7470 per chromosomal abnormality and pound sterling 4453 per anomalous fetus. CONCLUSION: The majority of fetal structural and chromosomal abnormalities can be detected by sonographic screening at 11-14 weeks, but the second trimester scan should not be abandoned.     

The prenatal diagnosis of Pierre-Robin sequence.

The purpose of this study was to evaluate the spectrum of prenatal sonographic and chromosomal findings, associated anomalies and perinatal and neonatal outcomes in cases with Pierre-Robin sequence. All cases (20) with Pierre Robin sequence, who were born at China Medical College Hospital between 1990 and 1997, were included and analysed in this series. 12 pregnancies (60 per cent) were complicated by polyhydramnios and 9 (45 per cent) were combined with cleft palate. Four cases (20 per cent) with cardiac anomalies were also observed. Two fetuses (10 per cent) had abnormal karyotyping (one trisomy 21, one trisomy 18). All fetuses were delivered at or near term. Male deviation was observed in cases with isolated Pierre-Robin sequence or combined mild anomalies (male female ratio: 13:3). Two neonatal mortalities and three with mental retardation were observed. This investigation provides a basis for counselling patients with fetal micrognathia or neonatal Pierre-Robin sequence. The main prenatal sonographic findings of Pierre-Robin sequence are micrognathia, polyhydramnios and cleft palate. In cases of polyhydramnios, sonographic examination of the facial profile and palate are recommended. After the finding of polyhydramnios, micrognathia, and even cleft palate, clinicians should be aware of the possibility of neonatal Pierre-Robin sequence. Cardiac evaluation and karyotyping is also recommended.     

Right ductus arteriosus: facts and theory

ObjectiveTo report fetal right-sided persistent ductus arteriosus (RPDA) in association with right aortic arch (RAA).Study designExtensive sonographic fetal anatomical scans were consecutively performed on 19,874 private, self-referred pregnant women who wanted early sonographic detection of fetal anomalies.ResultsOf 19,874 transvaginal (TVS) sonographic examinations 40 fetuses had right aortic arch (RAA) and four of them (10%) had RPDA. We also diagnosed seven cases of RPDA with involvement of the left aortic arch where a right-curving pattern (“L” shape) parallel to the right pulmonary artery was suggestive of Rt. DA with left aortic arch. Only one (9%) of the RPDA cases was associated with a cardiac anomaly (double outlet right ventricle). None of the other eight RPDA cases had any discernible anomalies, and all of the fetuses with RPDA had normal karyotypes.ConclusionsIn 10% of the fetuses with right aortic arch the ductal arch was also on the right side. An unusual-looking DA may be a RPDA associated with the left aortic arch.In most cases, the RPDA is a normal variant not associated with other anomalies.     

Intrinsic intrathoracic malformations of the fetus: sonographic detection and clinical presentation

Intrinsic intrathoracic malformations are a rare group of congenital anomalies associated with high fetal and neonatal mortality rates. The antenatal sonographic appearance and the adequacy of diagnosis in 15 affected fetuses were evaluated. An accurate prenatal diagnosis was made in 12 cases; the precise nature of the intrathoracic defect was incorrectly categorized in two fetuses, and the defect was missed entirely in one affected fetus. Antenatal detection and characterization of intrinsic intrathoracic congenital malformations seems possible, but requires a high index of suspicion, familiarity with their sonographic appearances, and meticulous attention to detail.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1.8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.     

Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation-a randomised controlled trial in 39,572 pregnancies

OBJECTIVE: To compare the antenatal detection rate of malformations in chromosomally normal fetuses between a strategy of offering one routine ultrasound examination at 12 gestational weeks (gws) and a strategy of offering one routine examination at 18 gws. DESIGN: Randomised controlled trial. SETTING: Multicentre trial including eight hospitals. POPULATION: A total of 39,572 unselected pregnant women. METHODS: Women were randomised either to one routine ultrasound scan at 12 (12-14) gws including nuchal translucency (NT) measurement or to one routine scan at 18 (15-22) gws. Anomaly screening was performed in both groups following a check-list. A repeat scan was offered in the 12-week scan group if the fetal anatomy could not be adequately seen at 12-14 gws or if NT was >or=3.5 mm in a fetus with normal or unknown chromosomes. MAIN OUTCOME MEASURES: Antenatal detection rate of malformed fetuses. RESULTS: The antenatal detection rate of fetuses with a major malformation was 38% (66/176) in the 12-week scan group and 47% (72/152) in the 18-week scan group (P= 0.06). The corresponding figures for detection at <22 gws were 30% (53/176) and 40% (61/152) (P= 0.07). In the 12-week scan group, 69% of fetuses with a lethal anomaly were detected at a scan at 12-14 gws. CONCLUSIONS: None of the two strategies for prenatal diagnosis is clearly superior to the other. The 12-week strategy has the advantage that most lethal malformations will be detected at <15 gws, enabling earlier pregnancy termination. The 18-week strategy seems to be associated with a slightly higher detection rate of major malformations, although the difference was not statistically significant.     

Risks of funipuncture in fetuses with single umbilical arteries

OBJECTIVE: To estimate procedure-related risks of funipuncture in fetuses with single umbilical arteries (UAs). METHODS: We identified fetuses that had blood samples collected by funipuncture and in which single UAs were detected, prenatally or postnatally. We also recorded maternal demographics, prenatal sonographic findings, gestational age at the time of the procedure, procedure-related complications, and perinatal outcomes. RESULTS: Over 2 years, 14 fetuses identified as having single UAs had funipuncture for prenatal karyotyping at a median gestational age of 29 weeks (range 20-34 weeks). Each had additional abnormal prenatal sonographic findings. The approach to the cord was transplacental in six cases and transamniotic in eight. There were no failed procedures, and 13 of 14 funipunctures were successful on the first attempt. Three fetuses (21%) had complications (bradycardia in two cases and bleeding in one case), a complication rate not greater than that reported in large series of fetuses that had fetal blood sampling. All three complications were associated with the transamniotic approach. There were no procedure-related pregnancy losses within 2 weeks of the procedure in this series. CONCLUSION: Funipuncture does not seem to be associated with increased risk of procedure-related complications or pregnancy losses in fetuses with single UAs, although the risk could be greater with transamniotic than with transplacental sampling.     

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。     

Ontogeny of isolated ultrasound markers for fetal aneuploidy.

OBJECTIVE: To evaluate the natural history of isolated ultrasound markers for fetal aneuploidy observed at 14-16 weeks of affected gestations. STUDY DESIGN: 76 aneuploid gestations were diagnosed among a predominantly low-risk population undergoing targeted ultrasonography in the early second trimester. Indications for evaluation of fetal karyotype included fetal malformations or sonographic markers for aneuploidy, maternal age over 35 years and abnormal serum screening results. Markers were re-evaluated at the time of amniocentesis or at pregnancy termination for fetal anomalies. RESULTS: Sonographic markers for aneuploidy (SMA) were observed in 68 of 76 aneuploid gestations diagnosed in the study group. In 46 cases, SMA were associated with major fetal malformations and in 22 cases, markers were isolated. Only 2 of 22 isolated markers for aneuploidy were documented at the time of amniocentesis. CONCLUSION: Isolated ultrasound markers for aneuploidy are transient and may disappear later on in gestation. Transvaginal sonography at 14-16 weeks of gestation appears to provide the best time window for detection of markers for fetal abnormal karyotype.     

Placental thickness at mid-pregnancy as a predictor of Hb Bart's disease

The measurement of placental thickness can effectively differentiate normal pregnancies from affected pregnancies requiring invasive work-up. The objective was to evaluate the efficacy of placental thickness at mid-pregnancy in predicting fetal Hb Bart's disease in pregnancies at risk. Among 17 254 pregnant women screened for severe thalassaemia between June 1994 and December 1998, 345 pregnancies at risk for having a fetus with Hb Bart's disease underwent ultrasound examinations and cordocentesis at 18-21 gestational weeks. Before cordocentesis, the placental thickness was measured and recorded.The definite fetal diagnosis was performed with high performance liquid chromatography. The efficacy of placental thickness in predicting Hb Bart's disease was evaluated by sensitivity and specificity. Various cut-off values of the placental thickness were used for calculation and the best cut-off value was determined by a receiver-operating characteristic (ROC) curve. Of 345 pregnancies at risk, 70 fetuses with Hb Bart's disease were finally diagnosed. The mean placental thickness (+/-SD) of the normal pregnancies and pregnancies with Hb Bart's fetuses were significantly different, 24.6+/-5.2 mm and 34. 5+/-6.7 mm, respectively (Student's t-test, p<0.001). The sensitivity and specificity of placental thickness in prediction were calculated for various cut-off values. Based on the ROC curve, the best cut-off value was 30 mm (>30 mm considered abnormal), giving a sensitivity of 88.57 per cent, specificity of 90.18 per cent, positive-predictive value of 78.48 per cent and negative-predictive value of 96.87 per cent. For couples at risk, when sonographic placental thickness is normal, the risk of having an Hb Bart's fetus is markedly decreased. The measurement of placental thickness can effectively, though not absolutely, differentiate the normal pregnancies from affected ones requiring invasive work-up.     

Sonography at the time of genetic amniocentesis to screen for fetal malformations

Obstetric ultrasound performed in conjunction with genetic amniocentesis at 14-18 weeks' gestation identified 16 fetuses with structural malformations among 4781 examinations. The outcomes for these 16 fetuses included 12 terminations, two fetal deaths, one related death six months after birth, and one transient abnormality with no apparent significant sequelae. The ultrasound examination failed to detect at least nine other fetuses with structural malformations. The relatively small size and early stage of development of the fetuses at the time of genetic amniocentesis appears to have contributed to the failure of ultrasound to detect these malformations. A brief search for fetal malformations during obstetric ultrasound performed at early genetic amniocentesis appears productive enough to be worthwhile. However, if there is a special indication to search for fetal malformations, the ultrasound examination should probably be repeated later.