Evaluation of prenatal diagnosis of cleft lip with or without cleft palate and cleft palate by ultrasound: experience from 20 European registries. EUROSCAN study group

Ultrasound scans in the mid-trimester of pregnancy are now a routine part of antenatal care in most European countries. Using data from registries of congenital anomalies a study was undertaken in Europe. The objective of the study was to evaluate prenatal detection of cleft lip with or without cleft palate (CL(P)) and cleft palate (CP). All CL(P) and CPs suspected prenatally and identified at birth in the period 1996-98 were registered from 20 Congenital Malformation Registers from the following European countries: Austria, Croatia, Denmark, France, Germany, Italy, Lithuania, Spain, Switzerland, The Netherlands, UK, Ukraine. These registries followed the same methodology. A total of 709,027 births were covered; 7758 cases with congenital malformations were registered. Included in the study were 751 cases reported with facial clefts: 553 CL(P) and 198 CP. The prenatal diagnosis by transabdominal ultrasound of CL(P) was made in 65/366 cases with an isolated malformation, in 32/62 cases with chromosomal anomaly, in 30/89 cases with multiple malformations and in 21/36 syndromic cases. The prenatal diagnosis of CP was made in 13/198 cases. One hundred pregnancies were terminated (13%); in 97 of these the cleft was associated with other malformations.     

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 cleft palate by 3D ultrasound

A case of a fetus seen at 33.2 weeks of gestation who was diagnosed with cleft lip in the third quarter by routine ultrasound. Describes the sequential steps that led to a multidisciplinary support the diagnosis of cleft palate by three-dimensional image reconstruction, which were originally obtained to demonstrate the fetal face surface. Birth confirmed the prenatal findings and established the diagnosis of cleft lip and cleft hard and soft palate. It has been reported that the diagnosis of facial clefts can be done with relative ease prenatally, but the detection rate of facial clefts in routine tests is only 20%. Until recently the diagnosis of cleft palate is not considered possible, however in recent years advances in three-dimensional technology has made possible the development of techniques for the assessment of the palate and various authors have reported promising results of ingenious applications that make think that in the near future will approach the palate a fact. We discuss the advantages and disadvantages of these methods are relatively new and highlights how valuable this information is for parents of the affected creature.     

Prenatal sonographic diagnosis of Malpuech syndrome

Malpuech syndrome (MS) is a rare autosomal recessive syndrome featuring pre- and post-natal growth deficiency, mental retardation, facial dysmorphism, cleft lip and palate (typically midline or bilateral), caudal appendage, renal malformations and male genital abnormalities. A prenatal diagnosis of MS was made in this fetus based on the family history and a combination of conventional and 3D prenatal ultrasound findings. The family were consanguineous with an affected first child. Prenatal ultrasound in the second pregnancy demonstrated bilateral cleft lip and palate in association with intrauterine growth retardation on serial prenatal ultrasound scans. Dysmorphic facial features and a small penis consistent with the diagnosis were confirmed on 3D scanning. Post-natal examination of the neonate confirmed the diagnosis of MS. To the best of our knowledge, this is the first prenatal diagnosis of this syndrome.     

Obesity and the risk and detection of fetal malformations

The incidence of obesity in pregnancy has increased over the past 2 decades, with nearly 50% of U.S. women aged 15-49 years classified as overweight or obese. Obesity (independent of diabetes) among gravidae poses unique risks that extend toward the fetus, with several large population-based analyses demonstrating independent increased risks for fetal malformations including neural tube defects, cardiac anomalies, and orofacial clefts, as well as stillbirth and macrosomia. Unfortunately, several lines of evidence also suggest that the quality of the prenatal fetal anatomic survey and certain aspects of prenatal diagnostic screening programs are significantly limited. The net effect is that among obese gravidae, the increased risk of fetal anomalies is further offset by a concomitant diminished ability to sonographically detect such malformations in the prenatal interval. The purpose of this summary review is to systematically examine the evidence suggesting an increased risk of fetal malformations in obese gravidae, the contributing role of diabetes, and the limitations of prenatal diagnostic and sonographic screening among this at-risk population.     

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.     

Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts

In utero diagnosis of de novo distal 11q deletion associated with renal and orofacial malformations has not been previously described. We present a 35-year-old pregnant woman with prenatal sonographic findings of a unilateral duplex renal system, pyelectasis and orofacial clefts at 20 weeks' gestation. Both genetic amniocentesis and postnatal cytogenetic analysis revealed de novo 46,XX,del(11)(q23). After birth, the fetus manifested a dysmorphic phenotype correlated with del(11q) syndrome. Genetic marker analysis showed a paternally derived distal deletion of chromosome 11q and a breakpoint centromeric to D11S1341. The present case represents the earliest prenatal diagnosis of a duplex renal system, pyelectasis and an additional feature of orofacial clefts associated with distal 11q deletion. Prenatal sonographic detection of a duplex renal system, pyelectasis and orofacial clefts should warrant a careful assessment of fetal anatomy and prompt cytogenetic analysis looking for chromosomal aberrations.     

A case of lateral facial clefts with Fallot tetralogy, duodenal stenosis and intestinal malrotation: a new multiple congenital anomaly syndrome?

Multiple congenital malformations in a Caucasian female infant are described which include lateral facial clefts, malformed external ears, cleft palate, Fallot tetralogy, duodenal stenosis and intestinal malrotation. There were no associated limb or spinal anomalies. This case appears to be an example of a new multiple congenital anomaly syndrome.     

Evaluation of routine ultrasound examination for the prenatal diagnosis of malformation

In 1986, a retrospective survey was undertaken in the southern part of the province of Hainaut, Belgium, in order to measure the frequency of ultrasound examinations during pregnancy and to evaluate the effectiveness of the routine practice of echography screening for the detection of congenital malformations in an unselected population. The reference populations comprised 8316 pregnancies covered by the EUROCAT Registry of Hainaut. In 1986, 190 congenital malformations cases were registered. For each of the 190 cases, one control ending in the birth of a non-malformed infant was retrospectively selected. The analysis showed that an average of four ultrasound examinations were performed during pregnancy. When all malformations are considered, the sensitivity of the screening is 14% (27/190). Sensitivity of detection varied from 100% for gross malformations such as anencephaly to 0% for defects of a minor size such as facial clefts. In these 27 cases, obstetrical interventions following prenatal diagnosis were termination of pregnancy in 14 cases and induction of labor in 3 cases. Antenatal care was planned in 8 cases, 5 of which had early surgical repair. In the control group, a malformation was suspected in 3 of the 144 pregnancies (specificity of detection, 98%).     

Factors determining occurrence of cleft lip and cleft palate.

The modern care of newborn infants with oral clefts renders their survival possible. Since they will eventually reproduce, a slight increase in the incidence may be expected and genetic counseling will be requested on occasion. The cleft lip with or without cleft palate has a different genetic inclination from isolated cleft palate and the risk of recurrence is different. Drugs, such as antiepileptics, salicylates, benzodiazepines and cortisone, have a role in causing oral clefts. When an oral cleft is a part of a syndrome, the genetics of the particular syndrome must be outlined and genetic counseling is given accordingly. Oral clefts alone are usually multifactorial.     

Prenatal evaluation of facial clefts with two-dimensional and adjunctive three-dimensional ultrasonography: a prospective trial

OBJECTIVE: The purpose of this study was to compare the prenatal diagnostic capabilities of two-dimensional ultrasonography versus adjunctive three-dimensional ultrasonography for fetal cleft lip and palate. STUDY DESIGN: Fetuses that were suspected of a facial cleft were then examined sequentially with two-dimensional ultrasonography then with a targeted scan of the fetal face with three-dimensional ultrasonography. The images were coded as cleft, no cleft, or equivocal for lip and palate. Postnatal outcome follow-up was obtained. RESULTS: Fifty-three of 57 fetuses had outcome results available. The diagnostic accuracy (true positive + true negative) of adjunct three-dimensional ultrasonography versus two-dimensional ultrasonography alone were improved for cleft lip (100% [53/53 fetuses] vs 91% [48/53 fetuses], P <.05) and cleft palate (89% [47/53 fetuses] vs 57% [30/53 fetuses], P <.05) CONCLUSION: There is significant improvement in diagnostic accuracy with two-dimensional ultrasonography with adjunctive three-dimensional ultrasonography compared with two-dimensional ultrasonography alone for the prenatal evaluation of facial clefts.     

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。     

Unusual case of a fetus with congenital cystic adenomatoid malformation of the lung associated with trisomy 13

Congenital cystic adenomatoid malformation of the lung can be detected with antenatal ultrasound as hyperechogenic areas in the fetal chest. Associated extrapulmonary malformations as well as chromosomal aberrations are described as very rare. We present a case report of a fetus in the 23rd week of gestation who showed in the course of a routine ultrasound screening a large number of malformations: holoprosencephaly, arrhinencephaly, cleft palate, CCAM type III of the right inferior pulmonary lobe, ventricular septal defect and bilateral clubfeet. Chromosome analysis confirmed the suspicion of trisomy 13. The present case shows how important it is-even with malformations that are rarely accompanied by associated anomalies and which have a very good prognosis-to carry out a directed diagnosis including a fetal karyotyping.     

Fetale Heterotaxie-Syndrome

The spectrum of conditions associated with heterotaxy syndromes includes a wide variety of cardiovascular and visceral anomalies that are differently distributed amongst the two clinical variants, left and right isomerism, and which determine the intrauterine as well as the postnatal course and outcome. An exact prenatal diagnosis is therefore warranted. Important sonographic markers in heterotaxy syndromes are the associated anomalies of the situs and cardiac defects. Prenatal differentiation of the two clinical variants can be based on the anomalies, the course of the inferior vena cava and the presence of a heart block.In left isomerism, mortality is highest in the prenatal period due to frequent association with a complete heart block and subsequent intrauterine heart failure. In the postnatal period, the outcome depends mainly on the associated cardiac malformations and their ability to be corrected.In contrast, in right isomerism the mortality is highest in the postnatal period. This is mainly due to the more complex type of associated cardiac malformations.     

胎儿期唇裂的诊断和治疗

文章概述了胎儿期唇腭裂的发生、相关因素、诊断和治疗。介绍了胎儿唇腭裂与染色体异常发生率的关系。随着产前诊断技术(超声、MR I等)的提高,越来越多的胎儿唇腭裂得到诊断。胎儿镜等技术促进了胎儿宫内治疗的发展,唇腭裂的宫内治疗亦是一个趋势,但目前大量的研究仍然是局限在动物模型。     

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.     

A population-based study of the prenatal diagnosis of congenital malformation over 16 years

OBJECTIVE: A population-based study of the trends in accuracy over time of prenatal diagnosis of congenital malformations. DESIGN: A prospective study of all congenital malformations. SETTING: The counties of Cleveland, Durham, North Cumbria, Northumberland and Tyne and Wear. POPULATION: All 573,471 babies born to residents at 24 weeks of gestation or more, and all terminations for fetal abnormality, occurring between 1985 and 2000. METHODS: An analysis of all congenital anomalies whether antenatally detected or diagnosed before one year of age to examine the accuracy of prenatal diagnosis and its trends over four consecutive four-year periods. MAIN OUTCOME MEASURES: The proportion of cases where a diagnosis before birth was correctly made, wrongly made or not made in a range of important structural malformations. RESULTS: There was a substantial improvement in the accuracy of prenatal diagnosis of all conditions reported here. However, the extent to which different conditions were diagnosed varied widely. It now exceeds 90% for anencephaly and for abdominal wall defects but is still less than 70% for diaphragmatic hernia, bladder outlet obstruction and many major skeletal defects. Termination of pregnancy for fetal malformation rose from 23 to 47 per 10,000 registrable births. CONCLUSION: This large prospective study provides data on the accuracy of prenatal diagnosis of a number of malformations in a geographically defined population under service conditions. Diagnostic accuracy has improved over time but may well be lower than many clinicians assume for some important conditions and may not match public expectations.     

Prenatal diagnosis and management of fetal cardiovascular malformations

Screening for fetal cardiovascular malformations is widely performed. Its accuracy is not yet satisfactory, but better training of ultrasonographers and extension from the four-chamber view to the study of the outflow tract are probably clues to an improvement. The main impact of prenatal diagnosis is still the termination of pregnancy for severe malformations and for those associated with chromosomal or extracardiac anomalies. There is now evidence that prenatal diagnosis improves perinatal morbidity or mortality for some malformations. New information about the molecular genetic basis of congenital heart disease will help in management and counselling.     

Fetal echocardiography. I: Methods, limitations and indications

The prenatal detection of congenital heart disease is rather seldom, compared with other fetal malformations. The paper considers the necessity of the development of fetal echocardiography and presents therefore an introduction for the prenatal sonographer. The fetal cardiac characteristics are first analysed, before considering the possibilities and frontiers of the investigation. The different available sonographic methods like the real-time, M-mode, pulsed Doppler and color Doppler are discussed and the importance of each one is emphasized. The indications for fetal echocardiography are further enumerated, as well as the possible consequences resulting from the diagnosis of a heart abnormality. Because of the sophisticated ultrasound devices needed for a precise diagnosis as well as the optimal postnatal care, suspected fetuses have to be referred to centers specialised in perinatal medicine.     

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.