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.     

Are isolated facial cleft lip and palate associated with increased perinatal mortality? A cohort study from the West Midlands Region, 1995-1997.

OBJECTIVE: To investigate the association between cleft lip and/or palate and perinatal mortality. METHODS: A retrospective review was performed of cases of cleft lip/palate born to West Midlands residents from 1995 to 1997. Perinatal mortality for identified cases was compared with all births from 1995 to 1997. RESULTS: 347 cases of cleft lip and/or cleft palate were delivered from 1995 to 1997. Thirty-six pregnancies were terminated due to parental wishes--2 were registerable births. There were 310 spontaneous registerable births (stillbirths/livebirths) with cleft lip and/or palate and 1 further late fetal loss. In 220 (70.5%), the lesion was isolated. Of these, there were 7 perinatal deaths, 5 had post mortems and no additional anomalies were identified. In 92 (29.5%) cases other abnormalities were identified. The overall perinatal mortality rate (PNMR) in the West Midlands, was 10.0/1000 total births. The overall PNMR for babies with facial clefts was 89.7/1000 total births. The PNMR for those with associated anomalies was 228.3/1000 live/still births. The PNMR for isolated facial clefts was 31.8/1000 live/still births, significantly higher than the background population (OR 3.3, 95% CI: 1.5-7.0). CONCLUSION: Consideration should be given to screening the fetus at 20-24 weeks for facial deformity. This has implications for detection both of fetal anomalies and of a population at risk for adverse outcome.     

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.     

Evaluation of a rapid optical immunoassay-based test for group B streptococcus colonization in intrapartum patients

Objective.?To investigate the association between cleft lip and/or palate and perinatal mortality.

Methods.?A retrospective review was performed of cases of cleft lip/palate born to West Midlands residents from 1995 to 1997. Perinatal mortality for identified cases was compared with all births from 1995 to 1997.

Results.?347 cases of cleft lip and/or cleft palate were delivered from 1995 to 1997. Thirty-six pregnancies were terminated due to parental wishes - 2 were registerable births. There were 310 spontaneous registerable births (stillbirths/livebirths) with cleft lip and/or palate and 1 further late fetal loss. In 220 (70.5%), the lesion was isolated. Of these, there were 7 perinatal deaths, 5 had post mortems and no additional anomalies were identified. In 92 (29.5%) cases other abnormalities were identified. The overall perinatal mortality rate (PNMR) in the West Midlands, was 10.0/1000 total births. The overall PNMR for babies with facial clefts was 89.7/1000 total births. The PNMR for those with associated anomalies was 228.3/1000 live/still births. The PNMR for isolated facial clefts was 31.8/1000 live/still births, significantly higher than the background population (OR 3.3, 95% CI: 1.5–7.0).

Conclusion.?Consideration should be given to screening the fetus at 20–24 weeks for facial deformity. This has implications for detection both of fetal anomalies and of a population at risk for adverse outcome.     

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.     

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.     

Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation,cleft lip and cleft palate,cardiovascular abnormalities

ObjectiveTrisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality.Case reportThe first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch.ConclusionComplete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy.     

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.     

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。     

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.     

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.     

First-trimester nuchal translucency measurement and echocardiography at 16 to 18 weeks of gestation in prenatal detection for trisomy 18

BACKGROUND: Trisomy 18, the second most common autosomal trisomy, has the highest incidence of congenital heart disease of all chromosomal abnormalities. This study assessed the use of nuchal translucency (NT) measurement and fetal echocardiography at 16 to 18 weeks of gestation in prenatal detection for trisomy 18. METHODS: Screening for chromosomal aneuploidy using fetal NT measurement was performed at 10 to 14 weeks of gestation. Detailed fetal echocardiography was performed at 16 to 18 weeks of gestation immediately before genetic amniocentesis for fetal karyotyping in singleton pregnancies with increased fetal NT thickness. RESULTS: Of the 3151 singleton pregnancies included in our study, 171 cases (5.4%) of increased (> or =3.0 mm) NT were noted. Fetal chromosomal abnormalities were identified in 22 (12.9%) of these pregnancies, including 9 with trisomy 21, 5 with trisomy 18, 4 with 45,X and 4 with unbalanced structural abnormalities. Major defects of the heart and the great arteries were identified in 13 (7.6%) of these pregnancies with increased NT. These included eight pregnancies that also had the diagnosis of chromosomal aneuploidy. Among the 22 fetuses with confirmed aneuploidy, all 5 fetuses with trisomy 18, 1 of the 4 fetuses with 45,X and 2 of the 9 fetuses with trisomy 21 had increased fetal NT thickness associated with abnormal fetal echocardiography findings. CONCLUSIONS: Screening for Down syndrome and cardiac defects using first-trimester fetal NT measurement in combination with fetal echocardiography at 16 to 18 weeks of gestation is a feasible and sensitive procedure for the prenatal detection of trisomy 18.     

Bilateral cleft lip and palate associated with increased nuchal translucency and maternal cocaine abuse at 14 weeks of gestation

A case of bilateral cleft lip and palate associated with increased fetal nuchal translucency detected at 14 weeks of gestation in a cocaine abusing pregnant woman is presented. There were no other associated structural or chromosomal abnormalities. We propose that systematic examination in both the sagittal and parasagittal plane of the fetal profile and recognition of the characteristic ultrasound appearance of a premaxillary protruding echogenic mass should make detection of this type of cleft relatively easy at the moment of the first trimester scan. First trimester diagnosis of cleft lip and palate can facilitate the parental decision-making process on continuing or terminating the pregnancy and should open the perspective of fetal surgery.     

Alpha-tocopherol levels in mothers of children with cleft lip or with cleft lip and palate

OBJECTIVES: Environmental factors may play equally critical role as genes in facial embryogenesis. It was suggested that cleft palate occurring in association with cleft lip may result from environmental factors that affect development of both the lip and the palate. Cleft lip forms from the third through seventh week of embryonic development. During these period fetal nutrition is histotrophic, pressure of oxygen is low, genes for antioxidant enzymes are supressed and alpha-tocopherol play an essential role in the fetal tissues antioxidant capacity. Cleft palate forms from the fifth through twelfth weeks of gestation, when hemonutrition and antioxidant enzymes are developing, and hypothetical deficiency of tocopherol is not so crucial. AIM: The goal of the study was to investigate concentrations of alpha-tocopherol in women who gave birth to a child with cleft lip and mothers of children with cleft lip and palate. MATERIAL AND METHODS: Blood samples from 31 healthy mothers of children with isolated cleft lip (CL) and 29 healthy mothers of children with isolated cleft lip and palate (CLP) were collected. Fasting plasma alpha-tocopherol concentrations were measured by the high performance liquid chromatography. Kolmologorov-Smirnov test with Lilefors correction and k-means cluster analysis were applied to determine differences between the groups of women. RESULTS: We found that alpha-tocopherol concentrations were lower in CL compared to CLP, but the difference did not achieve level of statistical significantly (medians: 15.8 micromol/L vs. 20.0 micromol/L; p = 0.066). There were identified three clusters of alpha-tocopherol concentrations: 14.0 micromol/L (19CL+8CLP), 19.6 micromol/L (8CL+13CLP), and 21.1 micromol/L (4CL+8CLP). The distribution of results to the clusters was dependent on type of the orofacial cleft (chi squared = 6.95 with 2 degrees of freedom, p = 0,031). CONCLUSIONS: Analysis for environmental risk factors should be performed separately for cleft lip and cleft lip and palate because these two conditions appear to be etiologically distinct. The role of a higher periconceptional intake of alpha-tocopherol in reduction of risk of giving birth to a child with cleft lip requires further research.     

Single umbilical artery and its siding in the second trimester of pregnancy: relation to chromosomal defects

OBJECTIVES: To determine the possible association between single umbilical artery (SUA) in the second trimester of pregnancy and the incidence of chromosomal abnormalities. To determine whether the presence of chromosomal defects in fetuses with SUA is related to the side of the missing artery. METHODS: Color flow imaging of the fetal pelvis was used to determine the number of umbilical arteries in 2147 fetuses immediately before amniocentesis for karyotyping in the second trimester of pregnancy. RESULTS: SUA was diagnosed in 102/2147 (4.8%) cases. The left umbilical artery was absent in 60/102 (58.8%) fetuses, compared with the 42/102 (41.2%) for the right artery. The rate of chromosome abnormalities was significantly higher among fetuses with SUA than among those with 2 umbilical arteries (19/102 or 18.6% versus 109/2045 or 5.3%; OR = 4.1, 95% CI 2.3-7.1, p < 0.0001). Among fetuses with SUA, there was no significant difference in the rate of chromosome abnormalities between those with absence of the left versus the right artery (11/60 or 18.3% versus 8/42 or 19.0%, p = 0.93). There was an SUA in 5/39 (12.8%) cases with trisomy 21, 8/16 (50%) with trisomy 18, 1/4 (25%) with trisomy 13 and 5/69 (7.2%) with other chromosomal defects. There were no chromosome abnormalities in fetuses where a single umbilical artery was an isolated sonographic finding. All fetuses with SUA and chromosomal defects had associated abnormalities detected by ultrasound. CONCLUSION: A single umbilical artery (SUA) in the second trimester of pregnancy has a high association with trisomy 18, 13, 21 and other chromosomal defects, but all chromosomally abnormal fetuses had associated malformations detected by ultrasound. The absence of the left artery is more frequent than the absence of the right artery. The association with chromosomal abnormalities seems to be equal on each side.     

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。     

产前诊断唇腭裂308例回顾性研究

目的:探讨胎儿唇腭裂与染色体异常的关系,为该疾病的临床咨询及预后评估提供依据。方法:回顾性分析我院2008年1月至2016年12月所有超声诊断为唇裂/腭裂/唇腭裂的308例孕妇的产前诊断情况,比较不同类型唇腭裂的超声表型特征及染色体异常的发生率。结果:(1)超声诊断结果显示,在308例唇腭裂胎儿中非综合征型唇腭裂258例(83.77%),综合征型唇腭裂50例(16.23%),其中单纯唇裂40例(12.99%),唇裂合并腭裂266例(86.36%),单纯腭裂2例(0.65%)。(2)同意进行产前诊断137例(44.48%),染色体异常共22例(16.06%),其中23例综合征型唇腭裂中发现染色体异常共12例(52.17%),分别为13-三体8例(66.67%),18-三体2例(16.67%),三倍体2例(16.67%);而在114例非综合征型唇腭裂中发现染色体异常10例(8.77%),分别为18-三体1例,21-三体1例,标记染色体1例,发现基因微缺失微重复等遗传综合征4例(B超检查均无任何软指标及除唇腭裂外的其他结构异常),臂间倒位等染色体多态性3例。染色体基因芯片分析(CMA)检测的染色体异常检出率为16.16%(16/99),染色体核型分析异常检出率为15.79%(6/38)。(3)随访到204例患者,186例患者选择引产,18例患者出生后进行手术干预治疗。结论:唇腭裂胎儿染色体异常发生率较高,建议对所有类型唇腭裂均进行产前诊断;CMA检测可以发现除非整倍体外的拷贝数变异,建议对唇腭裂胎儿优选基因芯片进行产前诊断。     

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.     

Chromosomal abnormalities in fetuses with ultrasonographically detected neural tube defects

We analyzed the karyotype of fetuses with ultrasonographically detected neural tube defects (NTDs). In our study, we included a total of 194 fetuses with NTDs. We analyzed the type of NTD, the karyotype, maternal age, fetal gestational age at diagnosis, and fetal sex. Of the 194 fetuses with NTDs, 87 were anencephalic and 107 had other, nonanencephalic, NTDs. A total of 12 fetuses were shown to have chromosomal abnormalities. Three of 87 anencephalic fetuses (3.45%) had chromosomal abnormalities. The sex ratio for anencephalic fetuses was 65.5% : 34.5% for female and male fetuses. Nine of 107 fetuses with other NTDs (8.41%) had chromosomal abnormalities. Seven fetuses had isolated NTDs and a further seven fetuses had additional ultrasonographic anomalies. Two of the latter had abnormal karyotypes. The sex ratio of all other NTD cases was 67.3% : 32.7% for female and male fetuses. The high number of chromosomal abnormalities justifies prenatal karyotyping in all fetuses with ultrasonographically diagnosed NTDs.     

Fetal lateral cerebral ventriculomegaly: associated malformations and chromosomal defects

In 267 consecutive cases of fetal lateral cerebral ventriculomegaly, additional fetal malformations were detected by ultrasonography in 209 (78%) of the cases. On the basis of the ultrasound findings, the patients were subdivided into three groups: (i) isolated ventriculomegaly (n = 58), (ii) ventriculomegaly and open spina bifida only (n = 172), and (iii) ventriculomegaly and other malformations (n = 37) with or without spina bifida. Antenatal karyotyping was performed in 64 cases from groups (i) and (iii), and 11 (18%) of the fetuses had chromosomal abnormalities. The incidence of chromosomal abnormalities was strongly related to the presence of multisystem malformations. Thus, only 3% of fetuses with isolated ventriculomegaly as opposed to 36% of those with additional malformations had chromosomal defects. Furthermore, the degree of ventriculomegaly in the chromosomally abnormal fetuses was relatively mild. In the chromosomally normal fetuses, mild, static ventriculomegaly was associated with apparently normal subsequent mental development.