Phenotype to genotype characterization by array-comparative genomic hydridization (a-CGH) in case of fetal malformations: A systematic review

The aim of the current review is to report a-CGH abnormalities identified in fetuses with prenatally diagnosed fetal malformations in whom a normal karyotype was diagnosed with conventional cytogenetic analysis.A systematic electronic search of databases (PubMed/Medline, EMBASE/SCOPUS) has been conducted from inception to May, 2017. Bibliographic analysis has been performed according to PRISMA statement for review. The following keywords were used: ‘array-CGH’ and ‘fetal malformations” and “prenatal diagnosis”; alternatively, “microarray”, “oligonucleotide array”, “molecular biology”, “antenatal diagnostics”, “fetal diagnostics”, “congenital malformations” and “ultrasound” were used to capture both “a-CGH” and “prenatal”.One-hundred and twelve fetuses with prenatally diagnosed fetal malformations with normal karyotyping and a-CGH abnormalities detected are described. Single or multiple microarray abnormalities diagnosed have been classified in relation to different organ/system affected. The most frequent a-CGH abnormalities were detected in cases of congenital heart diseases (CDHs), multiple malformations and central nervous system (CNS) malformations. Maternal or paternal carrier-state was seen in 19.64% (22/112), of cases while the number of reported de novo mutations accounted for 46.42% (52/112) of all CNVs microarray abnormalities. Array-comparative genomic hydridization (a-CGH) may become an integral and complemantary genetic testing when fetal malformations are detected prenatally in fetuses with normal cytogenetic karyotype. In addition, a-CGH enables the identification of CNVs and VOUS and improves the calculation of recurrent risk and the genetic counseling.     

Prenatal diagnosis and management of congenital heart disease

Thirty-two fetuses were diagnosed as having congenital heart disease (CHD). The major indications for level II echocardiography other than suspected cardiac abnormalities were fetal malformations, nonimmune hydrops and cardiac arrhythmia. Only three patients had a previous history of fetal CHD. No false-abnormal diagnosis of severe CHD was made. Aortic arch anomalies represented the major diagnostic problem among the six correct but incomplete diagnoses. Sixty-one percent of the fetuses were growth retarded, thus confirming the severity of their CHD. Chromosomal anomalies and extracardiac malformations were associated in 19% and 44% of the fetuses, respectively. Obstetric management and fetal prognosis in cases of extracardiac malformations were greatly influenced by the diagnosis of CHD. The poorest perinatal outcome was associated with heart failure. The only intrauterine deaths occurred in that group, and only one neonate survived. The outcome was more favorable in neonates without other malformations or heart failure. Four of ten (40%) of those neonates survived, while the overall perinatal survival rate was 24%.     

Perinatal outcome after ultrasound prenatal diagnosis of persistent right umbilical vein

Objective

Our aim was to describe ultrasound findings and perinatal outcome after prenatal diagnosis of persistent right umbilical vein (PRUV).

Study design

We performed a retrospective analysis of fetuses with an ultrasound-based prenatal diagnosis of PRUV on record at 2 tertiary centers in Madrid, Spain. We describe clinical, maternal, fetal and perinatal variables for all cases.

Results

A total of 20,426 fetuses were delivered between the study centers. We detected 22 cases (0.1%) of PRUV. The male-to-female ratio was 1:1. All cases were intrahepatic type and diagnosed during the second and third trimesters (median, 21 weeks; IQR, 20–29 weeks). Doppler ultrasound revealed normal flow in the ductus venosus in all cases. Nine fetuses (40.9%) had additional ultrasound anomalies but no chromosomal abnormalities. Cardiovascular malformations were the most frequently associated congenital anomalies (4/9), followed by neurological malformations (2/9). In 5 of the cases with no concomitant anomalies, the weight of the newborn was below the tenth percentile for gestational age. Gestational development was normal for the remaining newborns. Delivery was unremarkable, and post-natal evolution was favorable.

Conclusion

Our results point to a potential association between PRUV and other fetal malformations and a very low rate of chromosomal abnormalities. Prenatal diagnosis of PRUV should be followed by detailed anatomical evaluation and echocardiography in order to rule out other structural malformations. The indication for a fetal karyotype study must be made on an individual basis considering PRUV type and other ultrasound findings.     

The exact prenatal diagnosis of abnormalities of the kidneys and efferent urinary system--a possibility for further decreasing perinatal morbidity and mortality

Early detection of fetal malformations has become possible owing to the availability of highly advanced ultrasound systems. Majority of malformations, 30 per cent, has been recordable from urinary system. This system is early of access for the examiner, so that even sophisticated diagnosis of malformation is possible. High accuracy diagnosis has been increasingly helpful in forecasting pregnancy prognosis. Hence, with adequate perinatological management, it will be possible to influence on perinatal morbidity and mortality positively. 70 fetuses with malformations of kidneys and to urinary system have been observed in the context of this study. An assessment was made of diagnostic efficiency, postpartum development and long-range prognosis. Recommendations are derived from the above mentioned findings for perinatological approach in cases of diagnosed malformations of kidneys and the other urinary system.     

The performance of routine ultrasonographic screening of pregnancies in the Eurofetus Study.

OBJECTIVES: The purpose of the Eurofetus Study was to evaluate the accuracy of the antenatal detection of malformations by routine ultrasonographic examination in unselected populations. STUDY DESIGN: All ultrasonographic diagnoses of malformations and the outcomes of the fetuses were prospectively recorded in 61 European obstetric units over a 3-year period (1990-1993). Also recorded were all cases of malformation diagnosed after abortion or birth for the mothers who underwent follow-up in these centers. RESULTS: Of 3685 malformed fetuses, 2262 had received diagnoses during pregnancy (sensitivity, 61.4%). Of a total number of 4615 malformations, 2593 were detected (sensitivity, 56.2%). The detection sensitivity was higher for the major than for the minor abnormalities (73.7% vs 45.7%), and the diagnosis was made earlier in the pregnancy (24.2 weeks vs 27.6, P <. 01). Overall, 55% of the major abnormalities were detected within 24 gestational weeks. Within each severity group the accuracy of detection depended on the system. For the major abnormalities it was better for the central nervous system (88.3%) and urinary tract (84. 8%) but lower for the heart and great vessels (38.8%). Detection of minor abnormalities was also effective for the urinary tract (89.1%) but not for the heart and great vessels (20.8%) or the musculoskeletal system (18%). Detection of abnormalities had an influence on the rate of termination of pregnancy. The rate of live births for the mothers bearing fetuses with major abnormalities was lower than that for the mothers in whom no abnormalities were detected, mainly because of the higher rate of elective terminations of pregnancy in the former group. CONCLUSION: Systematic ultrasonographic screening during pregnancy can now detect a large proportion of fetal malformations, although some still escape detection.     

Perinatal results following the prenatal ultrasound diagnosis of single umbilical artery

OBJECTIVE. To study the perinatal results in our population, following the prenatal ultrasound diagnosis of a single umbilical artery (SUA), as this alteration is associated with fetal malformations, chromosomal abnormality, and poor perinatal results. MATERIALS AND METHODS. A retrospective review of all obstetric ultrasounds carried out between October 2000 and December 2003 in our service, obtaining the postnatal results of the fetuses diagnosed with an SUA. RESULTS. From a total of 5,987 pregnant patients examined by ultrasound scan at 20th week, an SUA was found in 40 cases, representing an incidence of 0.7%. Of these, 84.6% were normal pregnancies at birth and 15.4% presented other malformations and/or chromosomal abnormalities. No aneuploidy was found in pregnancies where there were no other associated findings in the ultrasound scan at 20 weeks. All cases with serious congenital malformations accompanying the SUA were diagnosed prenatally. There was a 5% of perinatal mortality rate among our fetuses with SUA, which represents a mortality rate 10 times greater than the overall rate among our patients. CONCLUSIONS. The ultrasound discovery of an SUA implies the meticulous search for other associated malformations, and in the absence of these, the risk of a chromosomal abnormality is very low, unless it is a high-risk patient. However, the growth and wellbeing of the fetus must be carefully monitored in the last 3 months, although the ultrasound scan does not show any other associated alterations.     

Antenatal sonographic detection of single umbilical artery.

The absence of one umbilical artery of single umbilical artery (SUA) is one of the most common congenital malformations in man. This vascular anomaly of the umbilical cord is frequently associated with other congenital malformations as well as some adverse perinatal events such as intrauterine growth retardation (IUGR), premature delivery, and increased perinatal mortality. Five cases of SUA detected prenatally by ultrasound are reported here in detail, including the first reported case in a twin gestation. None of the 5 affected infants had associated anomalies, but 2 cases of intrauterine growth retardation (IUGR) and 1 stillborn infant were noted in this series. An umbilical vein/umbilical artery ratio less than 2 was invariably found in all cases, making this observation another useful sonographic characteristic to use in the antenatal detection of SUA. Since the umbilical cord can be easily seen prenatally by ultrasound, and SUA is recognized as an important index for detecting congenital malformations, examination of the umbilical cord for the absence of one umbilical artery is an extremely valuable tool in prenatal diagnosis. The prenatal detection of SUA demands an extensive search for associated anomalies and a close surveillance of fetal well-being, since these fetuses have a high risk of fetal death or IUGR. Sonologists and sonographers should be aware of the possibility of SUA, especially in those cases associated with congenital malformations or IUGR.     

Fetal magnetic resonance imaging: a review

PURPOSE OF REVIEW: To describe advances in magnetic resonance technology and the current indications and advantages of magnetic resonance imaging that have led to increased utilization in fetal medicine. RECENT FINDINGS: The article covers the most common uses of magnetic resonance imaging in fetal medicine. The advantages of magnetic resonance imaging for the diagnosis of fetal malformations are described, in particular the advantages of magnetic resonance imaging in central nervous system malformations not optimally diagnosed by ultrasound are described. These cases include malformations of migration, malformations of development, such as agenesis of the corpus callosum, and destructive lesions. Noncentral nervous system lesions include chest abnormalities, abdominal wall defects, gastrointestinal and genitourinary abnormalities and fetal neoplasms. Abnormalities of placentation and other maternal factors affecting pregnancy are shown. SUMMARY: Recent studies have shown that magnetic resonance imaging can add significantly to the prenatal diagnosis and management of congenital abnormalities. In addition, placental abnormalities have been diagnosed with greater accuracy.     

Fast-scan magnetic resonance imaging of fetal anomalies.

OBJECTIVE--To identify those congenital fetal anomalies, previously identified by ultrasound scanning, in which fast-scan magnetic resonance imaging (F-SMRI) would give additional information for the perinatal management of the infants. DESIGN--Observational clinical study. SETTING--Hospital Department of Obstetrics and Gynaecology/Resonance Research Centre. SUBJECTS--Seven women carrying eight fetuses in whom congenital abnormalities had been identified using ultrasound scans. The duration of the pregnancies was 28 to 39 weeks gestation. INTERVENTIONS--Fast-scan magnetic resonance imaging at between 28 and 39 weeks gestation. MAIN OUTCOME MEASURES--Identification of fetal abnormalities. RESULTS AND CONCLUSIONS--F-SMRI was of limited value in the diagnosis of further assessment of fetuses with abnormalities of accumulation of tissue fluid. Renal anomalies were poorly identified unless associated with cystic formation of the kidney. Further study is required in the imaging of fetal central nervous system anomalies. Until echoplanar imaging is more widely available, MRI does not contribute to the diagnosis of cardiac anomalies. F-SMRI appears to be most useful in the diagnosis and management of soft tissue gastro intestinal abnormalities.     

Ultrasound screening for fetal urinary tract malformations: a prospective study in general population

Routine ultrasound examination at a first level ultrasound unit was performed on 4586 fetuses in general pregnant population at 18 and 34 weeks, to detect urinary tract malformations. Suspected renal abnormality was confirmed by postnatal investigations. Infants were followed up to 2-4 years to detect any renal malformations missed in screening. Urinary tract abnormalities were observed antenatally in 27 fetuses, eight cases at 18 weeks, and 19 cases at 34 weeks. An anteroposterior diameter of renal pelvis of 1 cm or more was the criterion for fetal hydronephrosis, which was the main ultrasound finding in 18 fetuses showing 24 hydronephrotic kidneys. In five cases, slight hydronephrosis disappeared spontaneously after birth, explaining the five 'false positive' cases of the study. Four children had renal abnormalities that were missed antenatally. The incidence of true urinary tract malformations detected by screening antenatally was 0.48%, and the overall incidence after 2-4 years follow-up was 0.57%, which is much higher than reported earlier in series without routine ultrasound screening. The antenatal screening showed a sensitivity of 84.6%, a specificity of 99.9%, a positive predictive value of 81.5%, and a negative predictive value of 99.9%. The main differential diagnostic problems occurred in two fields: in differentiating (1) functional hydronephrosis from obstructive uropathy, and (2) multicystic renal dysplasia of Potter's type IV from severe hydronephrosis. The prenatal diagnosis in cases with definitive renal abnormality corresponded to the postnatal diagnosis in 19/22 (86.4%) of the cases. 68% of the infants with urinary tract anomaly survived, 60% of them undergoing postnatal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

What does fetal autopsy unmask in oligohydramnios?

Objective: We aimed to determine the value of autopsy in fetuses with antenatally diagnosed oligohydramnios.

Patients and methods: We evaluated all fetal losses over a period of 6.5 years. Those with oligohydramnios on antenatal scan were critically analyzed. Oligohydramnios was defined as amniotic fluid index of less than five objectively or as an obvious lack of liquor at subjective assessment. A detailed postmortem examination was carried out in all the fetuses after obtaining an informed consent.

Results: Fetal autopsy was conducted in 255 cases. Fifty-five (21.5%) fetuses were diagnosed to have oligohydramnios on antenatal ultrasonography. On analysis of antenatal causes of oligohydramnios, maternal/placental factors were noted in 18%, ultrasound findings known to affect amniotic fluid in 27% while cause remained unidentified in 54.5% of cases. On autopsy, fetal malformations were noted in 61.8% cases, intrauterine growth retardation in 21.8% fetuses and no obvious malformations in 16.3% fetuses. Renal anomalies were noted in 40% cases and non-renal malformations in 21.8% cases.

Conclusion: The postmortem examination helped us to identify the cause of fetal loss in 46 (83.6%) fetuses with antenatal oligohydramnios. A working diagnosis could not have been established without autopsy in 19 (34.5%) cases.     

Comparison of ultrasound and magnetic resonance imaging in 100 singleton pregnancies with suspected brain abnormalities

OBJECTIVE: To compare the diagnostic accuracy of the current reference standard-ultrasound with in utero magnetic resonance imaging, in a selected group of patients. DESIGN: Prospective study. SETTING: Five fetal maternal tertiary referral centres and an academic radiology unit. SAMPLE: One hundred cases of fetuses with central nervous system abnormalities where there has been diagnostic difficulties on ultrasound. In 48 cases the women were less than 24 weeks of gestation and in 52 cases later in pregnancy. METHODS: All women were imaged on a 1.5 T clinical system using a single shot fast spin echo technique. The results of antenatal ultrasound and in utero magnetic resonance were compared. MAIN OUTCOME MEASURES: The definitive diagnosis was made either at autopsy or by postmortem magnetic resonance imaging, in cases that went to termination of pregnancy, or a combination of postnatal imaging and clinical follow up in the others. RESULTS: In 52 of cases, ultrasound and magnetic resonance gave identical results and in a further 12, magnetic resonance provided extra information that was judged not to have had direct effects on management. In 35 of cases, magnetic resonance either changed the diagnosis (29) or gave extra information that could have altered management (6). In 11 of the 30 cases where magnetic resonance changed the diagnosis, the brain was described as normal on magnetic resonance. CONCLUSIONS: In utero magnetic resonance imaging is a powerful tool in investigating fetal brain abnormalities. Our results suggest that in selected cases of brain abnormalities, detected by ultrasound, antenatal magnetic resonance may provide additional, clinically useful information that may alter management.     

产前超声诊断单脐动脉与胎儿异常的相关性研究

目的探讨超声检测胎儿脐带血管数目预测胎儿先天异常的价值。方法2000年1月至2006年10月在中山大学附属第一医院采用超声检测胎儿脐血管数目，对单脐动脉胎儿行产前超声系统筛查及胎儿染色体检查；分析单脐动脉合并畸形类型，与染色体异常的关系及胎儿结局。结果产前超声诊断胎儿单脐动脉119例，包括左侧72例（60．5％），右侧47例（39．5％）。单纯性单脐动脉59例（49.6％）；合并其他结构畸形60例（50．4％），其中泌尿系统畸形25例（41．7％），心血管系统畸形17例（28.3％），中枢神经系统畸形15例（25.0％），下肢畸形9例（15．0％），前腹壁和消化道畸形各5例（各占8．3％），唇裂或唇腭裂畸形3例（5．0％），其他畸形3例（5．0％）。行胎儿染色体检查41例，发现染色体异常8例，包括18-三体综合征3例、13-三体综合征1例、21．三体综合征1例、染色体片段异常3例，均合并其他畸形。结论胎儿单脐动脉左侧发生率高于右侧，约50％合并其他畸形；合并畸形时，染色体异常发生率较高；大部分单纯性单脐动脉胎儿结局良好。     

Antenatal evaluation and management of ultrasonically detected fetal anomalies

With the advent of improved ultrasound imaging, it is now possible to make an intrauterine diagnosis of many fetal anomalies. The key to an accurate antenatal diagnosis is careful scanning of the fetus and knowledge of the abnormalities that may be associated with a particular anomaly. In the presence of fetal anomalies known to be associated with increased frequency of chromosome abnormalities, fetal karyotyping is indicated, using either amniocentesis or fetal blood sampling, depending upon the urgency of the diagnosis. Fetal echocardiography is mandatory when the ultrasonically detected fetal anomaly is one that is known to be associated frequently with cardiac disease. Based on the antenatal findings, the parents should receive appropriate genetic and perinatal counseling. The management plan should always take into consideration the parents' wishes. Management plans for the most common ultrasonically detected fetal anomalies are presented, based upon review of the literature and authors' experience.     

Prenatal diagnosis and outcome of lymphangiomas and its relationship with fetal chromosomal abnormalities

Objectives: Our aim was to evaluate ultrasound findings and perinatal outcome after prenatal diagnosis of lymphangioma.

Methods: This was a retrospective case series study. We searched the archives of our ultrasound database at our center for cases with the prenatal diagnosis of the lymphangioma in the period between January 2008 and November 2014. We described maternal, fetal and perinatal variables for all cases.

Results: Nine fetuses with lymphangioma were identified. All cases were diagnosed during the second and third trimesters with the average gestational age of 22.6?±?3.9 weeks. The average diameter of lymphangioma was 55.4?±?20.1?mm at the time of diagnosis. Five fetuses (55.6%) had lymphangioma on the neck, and four fetuses (44.4%) had lymphangioma on other localizations. Normal fetal karyotype was detected in all cases. There were a total of six live births, one intrauterine death and two medical terminations of pregnancy following the diagnosis of lymphangioma. No abnormal Doppler finding or hydrops were detected in the antenatal follow-up of remaining six cases.

Conclusion: The risk of chromosomal abnormalities is very low in pregnancies with isolated lymphangioma. The outcome of pregnancies with lymphangioma is generally favorable and prognosis depends on their locations and size.     

Comparison of ultrasound and autopsy findings in pregnancies terminated due to fetal anomalies

OBJECTIVE: To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. DESIGN: Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. SETTING: Cases were identified through fetal autopsy reports. SUBJECTS: Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. MAIN OUTCOME MEASURES: The findings at the last ultrasound examination were compared with the autopsy reports. RESULTS: In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. CONCLUSION: Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.     

Antenatal Depiction of the Fetal Ear With Three-Dimensional Ultrasonography

Objective: To evaluate the feasibility of examining the fetal ear with three-dimensional ultrasound.Methods: In 125 pregnancies between 19 and 38 weeks of gestation, fetal ears were evaluated by three-dimensional ultrasound. The volume images with surface rendering were analyzed to depict the morphology, lying axis, orientation, and cranial location of the fetal ears.Results: Three-dimensional images of one or both ears were successfully reconstructed in 105 fetuses. Among them, 18 fetuses had anomalous ears. The anomalous ears, including microtia, low-set ear with slope axis, abnormal ear orientation, and edematous ear, were confirmed after delivery. Three-dimensional ultrasound consistently displayed fetal ear abnormalities with greater accuracy and clarity.Conclusion: Because anomalous ears may be a part of complex fetal malformations, it is important to recognize ear abnormalities. Due to the complexity of the fetal ear, three-dimensional ultrasound offers more important information than two-dimensional ultrasound, which simply gives auricular geometry. We suggest that three-dimensional ultrasound can be used better to examine the fetal ear and may prove to be useful for prenatal diagnosis and genetic counseling.     

Omphalocele and gastroschisis: prenatal diagnosis and peripartal management. A case analysis of the years 1989-1997 at the Department of Obstetrics and Gynecology, University of Homburg/Saar

OBJECTIVE: The article presents a retrospective analysis (1989-1997) of the prenatal diagnosis, the course and completion of pregnancy of 26 fetuses with omphalocele and 18 fetuses with gastroschisis. SUBJECTS: 44 pregnancies with anterior fetal wall defect diagnosed by prenatal ultrasound, clinical or patho-anatomic examination between 1989 and 1997 at the Department of Obstetrics and Gynecology, University of Homburg/Saar. RESULTS: In 40 of 44 pregnancies (91%) the fetal ventral abdominal wall defect could be detected antenatally with ultrasound. Associated malformations in fetuses with omphalocele were seen in 18 cases (69%), whereas only five fetuses with gastroschisis (28%) had an associated malformation. Nineteen of 26 fetuses (73%) with omphalocele had a normal karyotype. Seven of 26 fetuses (27%) with omphalocele had an abnormal karyotype. Eleven fetuses with omphalocele were live born, three of them with minor anomalies. Ten babies with omphalocele survived. No chromosomal anomalies were detected in fetuses with gastroschisis. There were four gastrointestinal malformations and one lethal associated malformation in fetuses with gastroschisis. There were 15 live born babies with gastroschisis, all of whom have survived. In 20 of 44 cases (45%) with ventral abdominal wall defect oligohydramnios could be detected by ultrasound. In 28 of 44 cases (64%) we found fetal growth retardation <10th percentile for gestational age. CONCLUSION: In case of a fetal ventral abdominal wall defect, the detection and appropriate classification of associated fetal anomalies is of great importance for the further course of pregnancy. Fetal karyotyping should be offered in case of a fetal abdominal wall defect. Early and close prenatal consultation of the neonatologist and the pediatric surgeon will favorably influence the perinatal outcome.     

Abnormal pregnancy sonogram: selective indication for fetal karyotype

The inability to make a definitive diagnosis in the fetus with a sonographically identified abnormality often results in parental and physician uncertainty. An antenatal chromosome evaluation could resolve this uncertainty. Forty-one fetuses with an abnormal ultrasound examination were tested for karyotypic abnormality using a variety of specimens. Nearly one-third (13 of 41) of these fetuses had various chromosome abnormalities. There were only seven survivors in this series, underscoring the often poor prognosis when a significant ultrasound defect is detected antenatally. Knowledge of the fetal chromosome constitution in the setting of an abnormal ultrasound has important epidemiologic, cost-benefit, counseling, and pregnancy management implications.