Prenatal diagnosis of genetic renal diseases: breaking the code.
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Biomedical subjects
Publications and source records attributed to Y Ville.
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OBJECTIVE: To evaluate the contribution of new imaging techniques in the prenatal diagnosis of skeletal dysplasia. METHODS: Between May and October 2003, a prospective study was conducted in a single referral center. Three-dimensional ultrasound (3D-US) and three-dimensional helical computer tomography (3D-HCT) were performed after two-dimensional ultrasound (2D-US) in six cases of skeletal dysplasia. Diagnostic accuracy and detailed findings with each of the three techniques were compared with postnatal radiological findings. RESULTS: There were three cases of achondroplasia, two cases of osteogenesis imperfecta type II and one case of chondrodysplasia punctata. Termination of pregnancy was performed in five cases and one fetus with osteogenesis imperfecta type II was delivered at term by Cesarean section. 2D-US made the correct diagnosis in four cases. 3D-US and 3D-HCT achieved an accurate diagnosis in all six cases. 3D-HCT and 3D-US identified significantly more abnormalities than did 2D-US (3D-HCT: 94.3% (33/35); 3D-US: 77.1% (27/35); 2D-US: 51.4% (18/35); P < 0.01). The diagnosis was made between 27 and 36 weeks' gestation in all cases. The advantage of 3D-HCT over 3D-US was the possibility of imaging the entire fetus. CONCLUSION: 3D-US and 3D-HCT seem to be useful complementary methods to 2D-US, and may improve accuracy of the prenatal diagnosis of skeletal disorders. These new imaging technologies may have a role in the prenatal multidisciplinary approach to the diagnosis of skeletal dysplasias.
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OBJECTIVE: To investigate whether pathological changes in the umbilical artery (UA), ductus venosus (DV) and short-term fetal heart variation are related to perinatal outcome in severe, early intrauterine growth restriction (IUGR). METHODS: This multicenter, prospective, longitudinal, observational study was carried out in the Departments of Fetal Medicine and Obstetrics in Hamburg, Amsterdam, Utrecht and London. In 70 singleton pregnancies with IUGR fetuses, delivered at 26-33 weeks of gestation because of antepartum fetal distress, short-term variation (STV) of fetal heart rate, pulsatility index of the fetal UA (UA PI) and DV pulsatility index for veins (DV PIV) were assessed at least weekly. The final measurement was performed within 24 h of delivery. Standard cut-off levels (2 SD or 3 SD, absent flow or reversed flow) were used and new cut-off levels were calculated by means of receiver-operating characteristics analysis. Adverse outcome was defined as perinatal death, cerebral hemorrhage (> or = Grade II) or bronchopulmonary dysplasia before discharge. The predictive value for adverse outcome was calculated for different cut-off levels of the monitoring parameters, adjusted for gestational age (GA), by multivariate logistic regression analysis. Data were analyzed separately for three different time blocks, namely 8-14, 2-7 and 0-1 days before delivery. RESULTS: Adverse perinatal outcome occurred in 18/70 (26%) infants. During the last 24 h before delivery DV PIV and UA PI were significantly higher and STV lower in the adverse outcome group, while 2-7 days before delivery only DV PIV was significantly higher. Adverse perinatal outcome could be predicted at 0-1 days before delivery by DV PIV at a cut-off of three multiples of the SD (odds ratio (OR) 11.3; 95% CI 2.3-57) and GA (OR 0.4; 95% CI 0.3-0.8), at 2-7 days by DV PIV at 2 SD (OR 3.0; 95% CI 0.8-12) and GA (OR 0.5; 95% CI 0.3-0.8) and at 8-14 days by DV PIV at 2 SD (OR 3.9; 95% CI 0.8-20) and GA (OR 0.5; 95% CI 0.3-0.8). Other parameters did not contribute to the multivariate model. CONCLUSIONS: DV PIV measurement is the best predictor of perinatal outcome. This measurement may be useful in timing the delivery of early IUGR fetuses and in improving perinatal outcome, even when delivery may be indicated at an earlier GA. However, as GA was also an important factor influencing outcome, with poorer outcome at earlier gestation at delivery, this hypothesis needs to be tested in a multicenter, prospective, randomized trial.
OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all gestational ages. The purpose of this study was to compare female and male fetuses in terms of intrauterine ultrasound growth measurements and to develop gestational-age-related charts based on a computerized perinatal database. METHODS: This was a retrospective study of unselected women in the second and third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data analysis was performed using measurements obtained from a mixed-race population of 4234 women, who underwent 5198 ultrasound examinations. The scans were performed by four trained sonographers, according to a standardized protocol. Routine measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The main end-points were sex- and race-specific differences in fetal biometry, which were also used to estimate fetal weight. RESULTS: The base-line demographic characteristics and risk factors were comparable in female and male fetuses. Significant differences in fetal BPD, HC, AC and estimated fetal weight, but not FL, were seen between male and female fetuses. Centile charts for each of these variables were constructed for both male and female fetuses. CONCLUSIONS: This study suggests that small but consistent sex-related differences in prenatal BPD, HC and AC measurements are established by as early as 15 weeks of gestation. The use of sex-specific nomograms may improve the prenatal assessment of fetal growth as well as the diagnosis of structural abnormalities.
OBJECTIVE: To evaluate mid term results, tolerance and efficiency of interposition of a tension-free polypropylene monofilament mesh by vaginal approach for the repair of cystoceles. PATIENTS AND METHODS: Fourty consecutive women underwent this new procedure between March 2001 and September 2002. After complete dissection of the cystocele, the polypropylene mesh (Gynemesh), Gynecare, Ethicon, Johnson & Johnson, France), proper cut-out was positioned under the bladder without any fixation. The lateral extensions of the mesh where introduced in the para-vesical spaces in contact with the arcus tendinus fascia pelvis. RESULTS: Before surgery all patients had cystocele of more or equal than grade II according to the POP-Q classification. Eight had grade II cystocele (20%) and 32 had grade III cystocele (80%). Thirty women had associated posterior or median prolapse (82.5%). Thirty women had urinary incontinence (75%). Mean age was 63.9 years (51-78). The procedure was performed without any difficulty in all cases. Duration of a cystocele cure procedure was 20 min +/- 2.2 (16-24). Mean follow-up is 16.4 months +/- 4.7 (12-24). The early complication rate was 7.5% (two vaginal erosions and one complete exposition of the mesh which requires secondary ablation). There was no mesh infection. The success rate was 95%. The satisfaction index overpasses 80% in 95% of our patients 6 months after the cystocele repair. DISCUSSION AND CONCLUSIONS: The interposition of a sub-vesical transversal tension-free polypropylene mesh by the vaginal route seems to be an excellent procedure in the definitive surgical treatment of grades II and III anterior vaginal wall prolapse. This new procedure is simple, mini-invasive, reproducible and efficient with low morbidity and good tolerance.
Uterine artery embolization is a recent technique intended for treating uterine fibroids, as an alternative to hysterectomy. The possible side effects putting at stake the prognosis of fertility after embolization are considered as a brake to its use for the treatment of infertility associated with myoma. Secondary hysterectomy and permanent amenorrhea are the two main risks. But they are not so frequent and can be prevented. To date, the experience in the field of fertility and pregnancy after arterial embolization for fibroids is quite limited. However, first results are encouraging and not very different from those observed after surgical myomectomy. A therapeutic trial using arterial embolization for the management of fibroids within a context of infertility can be devised in the presence of submucosal or intramural myomas responsible for metromenorrhagia and with no major infertility factors associated. It is likely that uterine artery embolization should provide results equivalent or superior to those of surgical myomectomy in case of numerous and intramural fibroids with no prevailing myoma. Arterial embolization could be also interesting in case of recurrent myoma after laparotomic myomectomy.
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Successive development of different methods to screen down syndrome (DS) have had unexpected effects, leading to an inflation in the number of karyotypes ordered and the number of induced abortions. In our district (Yvelines, France), DS screening leads to perform 16% karyotypes rate. Rapid progress in biology and ultrasonography has enabled us to correct this overprescription by conducting an early screening program using a combination of ultrasound graphic and new biochemical markers (Pregnancy-associated plasma protein A and the free fraction of ss-hCG) which allow an overall evaluation of risk. This method has high sensitivity (85%) and leads to a false positive rate karyotypes in about 5% of pregnancies. The purpose of the study conducted between January 1, 2001 and December 31, 2002 in the Yvelines was to confirm the validity of this method and determine its reproducibility in routine practice. Five partners contributed to the study: the Regional delegation for clinical research of the Paris-public assistance hospitals (AP-HP), the district health insurance fund (CPAM 78), the Yvelines maternity network which includes all ten maternity wards in the district, and the Echo 78 association which includes all ultrasoundgraphists working in the district who accepted to participate as investigators, as well as five biology laboratories where DS screening was performed.
OBJECTIVE: To analyze the indications and the results of invasive testing for fetal karyotyping for ultrasound abnormality in the third trimester of pregnancy, when first- and second-trimester screening tests were negative. METHODS: Retrospective study of 171 consecutive pregnancies that underwent invasive testing after 28 weeks of gestation in 2 institutions between January 1999 and December 2001. Forty-one patients did not have any form of screening for fetal aneuploidy beforehand. One hundred and thirty of them had a normal first-trimester scan and a low risk of fetal aneuploidy by nuchal translucency and/or maternal serum screening and were included in the statistical analysis. RESULTS: Mean maternal age, gestational age at diagnosis and at invasive testing were 30.5 years; 29.3 weeks and 32.5 weeks respectively. Amniocentesis and fetal blood sampling were performed in 97 and 33 cases respectively. The most frequent indications for invasive testing in the third trimester were major fetal malformations (51%) and intrauterine growth restriction (19%) detected on routine second- or third-trimester ultrasound examination. Ultrasound markers of aneuploidy and polyhydramnios accounted for 17 and 11% of the indications respectively. Fetal karyotype was normal in 121/130 cases. A gene mutation was found in one case. The karyotype was abnormal in nine cases, including seven cases of aneuploidy (one Turner syndrome, three trisomy 18, and three trisomy 21) and two cases of structural chromosomal abnormalities (46,XX, del 4 p16.1 and 46,XX, dup1). One hundred cases resulted in the delivery of a normal baby. Thirty cases led to termination of pregnancy or intrauterine death due to major fetal malformations (N = 25), abnormal karyotype in six of these, and severe IUGR (N = 5) with normal karyotype. Fetal US markers of aneuploidy and isolated polyhydramnios were associated with a favorable outcome in all cases.A significant increase in the risk of chromosomal anomaly was seen when two or more anomalies were found, rising from 2% with one anomaly to 21% when two or more anomalies were present. CONCLUSION: In low risk patients, fetal karyotyping in the third trimester may be justified when the diagnosis of fetal malformation is made in the third trimester of pregnancy. Two or more anomalies increase the risk of fetal aneuploidy even with a negative-screening test in the first and second trimester of pregnancy.
INTRODUCTION: Although advances in ultrasound have facilitated the diagnosis of fetal abnormalities in the first trimester, fetal biometry at this stage of pregnancy remains underused in prenatal diagnosis. We hypothesized that charts which directly correlate measurements to crown-rump length (CRL) could be more accurate than those based on gestational age (GA) derived from CRL measurement. The aim of this study was to construct CRL-based biometric charts. METHODS: Measurements of biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC) were prospectively collected from 939 normal singleton fetuses. Charts and predictive equations were constructed from data obtained from pregnancies in which the CRL was between 45 and 84 mm and for which the outcome was normal. RESULTS: Measurements of BPD, HC and AC from 880 fetuses who met the criteria were correlated with CRL and used to construct charts and predictive equations. The standard error of estimates using CRL was significantly lower than that using GA in all cases. DISCUSSION: First-trimester growth charts and predictive equations based on CRL instead of GA are more accurate. They might have a role in quality control of first-trimester ultrasound examination and may help in the diagnosis of fetal conditions that involve early growth abnormalities.
OBJECTIVE: To compare nasal bone assessment by ultrasound examination at 11-14 weeks' gestation and postmortem X-ray examination in fetuses with trisomy 21. METHODS: Twenty-one fetuses with trisomy 21 which had undergone sonographic examination at 11-14 weeks for measurement of nuchal translucency thickness and assessment of the nasal bones were examined by postmortem X-ray following termination of pregnancy. RESULTS: The nasal bones were absent in 11/21 (52.4%) fetuses on ultrasound examination at 11-14 weeks and in 10/21 (47.6%) fetuses on X-ray examination at 14 to 25 + 5 weeks. Ultrasound and X-ray findings were discordant in 9/21 (42.9%) cases. Eight of 11 (72.7%) fetuses with absent nasal bones on ultrasound examination had a nuchal translucency thickness > 95th centile. CONCLUSION: The high incidence of absent nasal bones in first-trimester fetuses with trisomy 21 is compatible with a developmental delay. Prior to inclusion of nasal bone assessment into risk calculation for trisomy 21, the independence of absence of nasal bones by ultrasound and increased nuchal translucency above the 95th centile at 11-14 weeks should be investigated more extensively.
OBJECTIVES: Examination of the fetal nasal bones by ultrasound between 11 and 14 weeks of gestation has been proposed as an additional tool in the detection of trisomy 21 in a high-risk population. However the variability in the identification of fetal nasal bones by ultrasound has not yet been investigated. The aim of this study was to assess the intraobserver and interobserver reproducibility of fetal nasal bone identification by ultrasound between 11 and 14 weeks of gestation. METHODS: A total of 1040 consecutive ultrasound examinations were performed at 11-14 weeks of gestation for nuchal translucency (NT) measurement and nasal bone identification by ultrasound. A total of 657 consecutive video-loops were assessed by three experienced operators. Each operator assigned cases to one of three categories, namely present, uncertain or absent nasal bones, and the results were compared between operators. To assess the intraoperator variability each operator reviewed 100 randomly selected videos out of the 657 loops and again used the same classification. Results were compared by pairwise unweighted and weighted Kappa index to evaluate the inter- and intraoperator variability. RESULTS: Among the 1040 fetuses, there were 51 (4.9%) with an NT measurement above the 95th centile. Nasal bones were identified by ultrasound in 948, not seen in eight and impossible to assess in 84 fetuses. Four fetuses had trisomy 21 including three with absent nasal bones and increased NT and one with present nasal bones and normal NT. The Kappa and weighted Kappa values for interoperator variability between the three operators were between 0.26 and 0.37 and 0.33 and 0.44, respectively. The Kappa and weighted Kappa values for intraoperator variability were between 0.35 and 0.48 and 0.43 and 0.55, respectively. CONCLUSION: The assessment of fetal nasal bones is only fairly reproducible. Although the performance of the test in fetuses at high risk for trisomy 21 has been reported to be good, its implementation as an additional screening technique in the general population must be accompanied by teaching and quality control programs.
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OBJECTIVE: Craniosynostosis is defined as the premature closure of the calvarial sutures. The prevalence of this heterogeneous condition is 1 in 2000 and approximately 100 different forms have been described with an established genetic transmission in half of them. Prenatal diagnosis of craniosynostosis relies mainly on identification of associated anomalies and molecular analysis of fetal DNA, which is only feasible in some syndromic forms and in well-documented families. The objective of this study was to investigate the value of prenatal ultrasound examination of cranial sutures in fetuses at risk for craniosynostosis. METHODS: Forty fetuses at risk for craniosynostosis on the basis of either a family history (Group 1, n = 16) or skull deformity suspected on a first-level fetal ultrasound examination (Group 2, n = 24) were retrospectively investigated. Craniosynostosis was suspected on the basis of skull deformities when present, however the diagnosis was only made in cases where there was a loss of hypoechogenicity of the normal sutures. All infants had both clinical and radiological investigations performed postnatally. RESULTS: In Group 1, serial ultrasound examination from 12 weeks' gestation onwards led to accurate prenatal diagnosis in all 16 cases. Dysmorphism and skull deformity preceded closure of the sutures by 4 to 16 weeks. In Group 2, prenatal diagnosis was correct in 23/24 cases. There were no false-negative results in either group. CONCLUSIONS: This series questions further the uncertain genetic determinism of craniosynostosis and seems to rule out the hypothesis of a deformation sequence following primary closure of the cranial sutures. It also suggests that ultrasound examination is useful to demonstrate closure of the sutures in the third trimester of pregnancy in most affected cases.
We present a case of recurrent primary developmental microcephaly of late onset, the prenatal diagnosis of which could not be achieved despite performing targeted serial ultrasound scans that revealed no obvious fetal abnormality. Serial scans for head measurements and detailed examination of the brain anatomy by both transabdominal and transvaginal sonography including color and power Doppler assessment revealed no obvious brain abnormality. Frontal lobe distance and thalamic frontal lobe distance at 36 weeks were on the 30th and 50th centiles, respectively. Growth velocity remained on the 50th centile up to 36 weeks; between 36 and 38 weeks measurements were between the 35th and 40th centiles. The infant was delivered by Cesarean section at 38 weeks on parental request. On examination after birth the head circumference was on the 9th centile, but the facies was that of a microcephalic child with a sloping forehead and neurologically he was severely abnormal. The adequacy of the normal reference ranges used is reviewed: the use of sex-specific growth charts at 38 weeks would have demonstrated the biparietal diameter and the head circumference to be on the 20th and 15th centiles, respectively, rather than just below the 40th centile. However, even sex-specific charts may not allow the recognition of a substantial number of affected fetuses.
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