Clinical course and outcome of antenatally detected atrioventricular block: experience of a single tertiary centre and review of the literature.

OBJECTIVE: The objective is to study the course and outcome of fetuses with congenital atrioventricular block (AVB) in a single centre. METHODS: Retrospective analysis of cases diagnosed prenatally with second and third degree AVB. The clinical characteristics and outcome of fetal AVB were evaluated including in utero treatment. RESULTS: Sixty-two cases were studied. AVB was associated with a congenital heart defect (CHD-AVB) in 17 cases (27%), whereas it was isolated (i-AVB) in 45 (73%), 42 of which were associated with maternal antibodies. There were nine (52.9%) live births in the CHD-AVB group, five of which (55%) resulted in infant deaths. In the i-AVB group, there were 40/45 (88.9%) live births and 1/40 (2.5%) infant death; 36 (90%) babies required a permanent pacemaker. The only factor predictive of postnatal death was the presence of CHD (5/9 vs 1/39 or 48.7 [3.6; 1457.7], p < 0.001). Nineteen fetuses (40.5%) with i-AVB received steroids in utero. No difference in outcome was found between the AVB treated in utero versus the no-treatment group in terms of permanent pacemaker placement, postnatal death or development of dilated cardiomyopathy. CONCLUSION: The most important prognostic factor for congenital AVB is the association with CHD. In utero treatment remains questionable.

[Fetal taking in some particular circumstances]. / Prélèvements fœtaux : à propos de quelques situations problématiques.

Fetal takings still concern about 6 to 7% of the pregnancies. If, in the majority of the cases, the taking does not present difficulty for a trained operator, particular circumstances related to maternal context (anticoagulating treatment, vaginal bleeding, fever…) may make the taking become more difficult. From a questionnaire sent to the French multidisciplinary centers for prenatal diagnosis and a review of the literature, we establish guidelines for fetal taking in these circumstances.

Three-dimensional helical computed tomography in prenatal diagnosis of fetal skeletal dysplasia.

OBJECTIVES: (1) To study the use and diagnostic value, as a complement to ultrasound, of helical computed tomography (helical CT) to differentiate normal fetuses from cases of skeletal dysplasia; (2) to define the most relevant indications for helical CT; and (3) to evaluate its diagnostic performance with respect to radiological criteria considered discriminatory. METHODS: This was a retrospective study from 2005 to 2008 in 67 pregnant women who underwent helical CT after 26 weeks of gestation for suspected fetal skeletal dysplasia due to fetal shortened long bones on ultrasound (≤ 10(th) percentile), either alone or associated with other bone abnormalities. The results were compared with pediatric examinations in 41 cases and with fetal autopsy findings after elective termination of pregnancy in the others. RESULTS: Helical CT had a sensitivity of 82%, specificity of 91% and positive and negative predictive values of 90% and 83%, respectively, for diagnosis of fetal skeletal dysplasia. An etiological diagnosis that had not been suspected at ultrasound was specified in 15% of cases and diagnoses suspected at ultrasound were confirmed in 24% and discounted in 43% of cases. The prevalence of skeletal dysplasia was increased in cases of micromelia < 3(rd) percentile or if there was a combination of bone signs. Helical CT showed 69% sensitivity in identifying individual predefined pathological bone signs which were confirmed on fetal autopsy findings. CONCLUSION: Helical CT is a key examination, in combination with ultrasound, in the diagnosis of fetal skeletal dysplasia from 26 weeks of gestation. It should be reserved for cases with severe micromelia below the 3(rd) percentile and for those with micromelia ≤ 10(th) percentile associated with another bone sign. A checklist of discriminatory signs is proposed.

The value of daily fetal heart rate home monitoring in addition to serial ultrasound examinations in pregnancies complicated by fetal gastroschisis.

OBJECTIVES: To audit the practice of daily fetal heart rate home monitoring (FHM) in pregnancies complicated by fetal gastroschisis (GS). METHODS: Prenatal records and pregnancy outcome were reviewed of all cases with fetal GS between 1999 and 2010, managed with a consistent protocol, which included weekly fetal cardiotocography and ultrasound examinations after 30 weeks, and option of daily FHM. Data were collected including gestational age (GA) at FHM and the presence of fetal heart rate anomaly. Follow-up included fetal growth, amniotic fluid volume, gastrointestinal appearance and cardiotocography findings. RESULTS: One hundred five cases of GS were identified. Stillbirth rate was 1.9% (2/105). FHM was performed in 97/105 (92.4%) cases. Abnormal FHM was recorded in 24 cases. Fetuses with abnormal versus normal FHM were more likely to have C-section for fetal heart rate anomaly (50% vs 24%, p=0.025) at an earlier gestational age (34.9 ± 1.7 vs 35.8 ± 1.4 weeks, p=0.016). There was no difference in Apgar score or umbilical artery pH at birth. CONCLUSION: Fetal heart rate abnormalities are frequent in fetuses with GS. FHM appears useful in detecting fetal distress necessitating expedited delivery. However, the impact of a daily FHM policy on neonatal outcome should be evaluated in a randomized study.

Hidden mortality of prenatally diagnosed vein of Galen aneurysmal malformation: retrospective study and review of the literature.

OBJECTIVE: To evaluate the prognosis of prenatally diagnosed vein of Galen aneurysmal malformation (VGAM) in a large cohort with this condition and to review the literature on prenatally diagnosed VGAM. METHODS: This was a retrospective study of all cases of prenatally diagnosed VGAM managed in our referral center during a 12-year period. VGAM was categorized as being either isolated or associated with any other abnormality, based on fetal ultrasound and magnetic resonance imaging findings. Poor outcomes comprised termination of pregnancy with confirmation of antenatal findings, perinatal death and severe cardiac and/or neurological impairment in survivors. The literature was also reviewed for similar cases. RESULTS: Twenty-one cases of prenatally diagnosed VGAM were managed in our center. Four (19.0%) cases were isolated and 17 (81.0%) were associated with other anomalies. There were nine terminations (42.9%) and six neonatal deaths (28.6%). Six children (28.6%) were still alive at last follow-up, of whom three had abnormal neurological development. VGAM associated with other anomalies was strongly associated with a poor outcome compared with isolated forms (P < 0.0001). One hundred and nine cases from the literature were also reviewed. CONCLUSION: Fetuses with prenatally diagnosed VGAM have unexpectedly poor outcomes in the presence of cardiac or cerebral anomalies, while those with strictly isolated VGAM tend to have more favorable outcomes. Our literature review corroborates these findings.

Is complex gastroschisis predictable by prenatal ultrasound?

OBJECTIVE: To establish a correlation between prenatal ultrasound findings and postnatal outcome in neonates with gastroschisis (GS). DESIGN: Retrospective case-control study. SETTING: Prenatal ultrasound reports, labour and neonatal intensive care unit notes, and paediatric surgical clinic records were reviewed. POPULATION: Neonates with an antenatal diagnosis of isolated GS. METHODS: The neonates were divided into two groups: one with associated bowel complications including intestinal atresia, perforation, necrosis or volvulus ('complex' GS), and the second without bowel complication ('simple' GS). Prenatal ultrasound markers: small-for-gestational-age, intra-abdominal and extra-abdominal bowel dilatation (>6 mm), thickened intestinal wall and stomach dilatation were correlated with outcome. MAIN OUTCOME MEASURES: Fetal or neonatal death in complex versus simple GS. Time on parenteral nutrition and duration of hospital stay were also noted. RESULTS: In all, 105 cases were eligible for analysis. Survival rate was 101/105 (96.2%). None of the ultrasound markers was predictive of fetal or neonatal death. Fourteen of 103 live-born babies (14.6%) had complex GS, which was associated with longer time on parenteral nutrition [8.0 (51.5-390) versus 33.5 (25.3-53.3) days, P<0.001] and longer duration of hospital stay [85.3 (55.5-210) versus 41.5 (33.0-64.8) days, P<0.001]. Infants with complex GS were more likely to require bowel resection and stoma placement (P<0.05). Intra-abdominal bowel dilatation was the only predictive ultrasound marker of complex GS (odds ratio 4.13, 95% CI 1.32-12.90; P=0.018). Receiver operating characteristic curve for observed/expected bowel diameter yielded 6 as the cutoff value for predicting complex GS (odds ratio 7.9, 95% CI 2.3-27.3; P=0.001) with 54% and 88% for sensibility and specificity, respectively. CONCLUSIONS: Intra-abdominal bowel dilatation is the only ultrasound marker predictive of complex GS but it is a strong marker.

[Prenatal diagnosis and management of foetal lung lesions]. / Malformations pulmonaires congénitales : diagnostic et prise en charge anténataux.

INTRODUCTION: Foetal lung lesions are uncommon (<1/1000 deliveries). Prenatal ultrasound can distinguish echogenic and cystic lesions. BACKGROUND: The most frequently diagnosed abnormalities are congenital cystic adenomatoid malformation (echogenic and/or cystic), pulmonary sequestration (echogenic), congenital lobar emphysema (echogenic) and bronchogenic cyst (cystic). Most of them carry a good prognosis but complications, including foetal hydrops, may occur and should be looked for regularly prenatally. Congenital upper airway obstruction syndromes are very rare and carry a very poor prognosis. VIEWPOINT: The follow-up of these pregnancies should be undertaken in a tertiary centre and information regarding postnatal management should be given prenatally by the doctors who will care for the infant after birth. Serial ultrasound examinations are required to evaluate the natural history and detect complications. Spontaneous regression may occur. The occurrence of foetal hydrops is usually fatal in the absence of treatment and should be managed as an emergency. CONCLUSIONS: Congenital malformations of the lung are rare and usually carry a good prognosis. Careful follow-up and delivery should be performed in a tertiary centre and postnatal investigation should include clinical and radiological evaluation.

Factors associated with partial and complete regression of fetal lung lesions.

OBJECTIVE: A decrease in the volume of congenital pulmonary malformations (CPM) can be observed on prenatal ultrasonography, but the underlying mechanism for this phenomenon is unknown. Our objective was to identify factors associated with the prenatal reduction in size of cystic and/or hyperechoic lung lesions. METHODS: This was a retrospective study of cases with a prenatal diagnosis of hyperechoic and/or cystic lung lesion. The extent of reduction in lesion size was calculated from ultrasound measurements. Clinical, ultrasound, radiological and histological data were tested for their relationship with prenatal CPM reduction. RESULTS: In a 4-year period, 36 patients were referred with a cystic and/or hyperechoic fetal lung lesion diagnosed at a mean gestational age of 23.4 weeks. The lesions were cystic in 16 cases (44%), hyperechoic in 12 (33%) and both in eight (22%). The malformation was no longer visible before birth (apparent disappearance) in nine cases (25%), shrank by 18-90% in 15 (42%) and did not reduce in 12 (33%). Findings on postnatal computed tomography were always abnormal. Isolated hyperechoic lesions were significantly more likely to shrink in utero. The mean reductions were 79%, 35% and 19%, for isolated hyperechoic, cystic and mixed lesions, respectively (P=0.001). Only 8% of hyperechoic lesions demonstrated no volume reduction, as compared to 50% and 42% of cystic and mixed lesions, respectively (P=0.03). Greater gestational age at birth was also associated with a decrease in the incidence of malformations (P=0.02). In cases that underwent surgery, hyperechoic lesions were linked to a variety of pathological diagnoses, whereas cystic lesions were all described histologically as congenital cystic adenomatoid malformations. CONCLUSIONS: Prenatal size reduction of fetal lung malformations is associated with isolated hyperechogenicity and greater gestational age at birth. This might result from the resumption of normal lung development after local disruption of lung growth.

Prenatal diagnosis of cardiac rhabdomyomas: incidence of associated cerebral lesions of tuberous sclerosis complex.

OBJECTIVES: To determine the prevalence of specific cerebral lesions of tuberous sclerosis complex (TSC) and neurological outcome in cases diagnosed prenatally with cardiac rhabdomyomas. METHODS: We reviewed all fetuses diagnosed prenatally with cardiac rhabdomyomas which had undergone detailed ultrasound evaluation and cerebral magnetic resonance imaging (MRI) and which were recorded in the database of a single institution covering the period January 1992 to December 2005. RESULTS: Fifty-one fetuses were included in the study. MRI was performed at a mean +/- SD gestational age of 30 +/- 3 gestational weeks and showed specific lesions of TSC in 49% of cases. Termination of pregnancy was chosen by the parents in 26 cases. Neurological development was studied in 20 cases, follow-up lasting 4.8 +/- 2.9 years. Neurodevelopmental events occurred during the follow-up period in 45% of cases. Neurological complications occurred in 67% of patients who had cerebral lesions at MRI and in 33% of patients with normal MRI results. There was no significant difference between the two groups of patients (P = 0.2). CONCLUSION: In fetuses with cardiac rhabdomyomas detailed ultrasound examination and third-trimester cerebral MRI are able to diagnose most TSC cerebral lesions, but fail to determine neurological outcome.

Keyhole sign: how specific is it for the diagnosis of posterior urethral valves?

OBJECTIVES: Posterior urethral valves (PUV) are the most common cause of renal impairment in boys during early childhood. Although antenatal suspicion of this pathology has become quite common in recent years, prenatal diagnosis remains challenging. The aim of this study was to evaluate the predictive value of different ultrasound criteria currently used to diagnose PUV. METHODS: We reviewed the antenatal and postnatal files of 54 male patients referred to our center from 2000 to 2006 after detection of fetal bilateral hydronephrosis. The following ultrasound criteria were evaluated in relation to the postnatal diagnosis of PUV: amniotic fluid volume, bladder wall thickness, bladder dilatation and the presence of the 'keyhole sign'. RESULTS: Forty-two fetuses (77.8%) were suspected to have PUV on prenatal examination. Out of these, 29 (69.0%) had PUV confirmed postnatally. The sensitivity and specificity of the antenatal diagnosis of PUV were 94% and 43%, respectively. Increased bladder wall thickness and bladder dilatation were highly associated with the diagnosis of PUV (P < 0.001). However, a thick-walled bladder was observed in 39.1% and a dilated bladder in 47.8% of the infants with a postnatal diagnosis other than PUV. The presence of the keyhole sign was not found to predict a diagnosis of PUV (P = 0.27). CONCLUSION: In this series the use of classical prenatal ultrasound signs to diagnose PUV showed high sensitivity but low specificity. The best diagnostic indicators were increased bladder wall thickness and dilatation of the bladder. The keyhole sign was not found to be a reliable predictor of PUV.

Stability of the m.8993T->G mtDNA mutation load during human embryofetal development has implications for the feasibility of prenatal diagnosis in NARP syndrome.

BACKGROUND: Mitochondrial DNA (mtDNA) mutations cause a wide range of serious genetic diseases with maternal inheritance. Because of the high transmission risk and the absence of therapy in these disorders, at-risk couples often ask for prenatal diagnosis (PND). However, because heteroplasmy load (coexistence of mutant and wild-type mtDNA) may vary among tissues and with time, the possibility that a single fetal sample may not reflect the whole neonate impedes prenatal diagnosis of mtDNA diseases. METHODS: We performed 13 prenatal diagnoses for the NARP (neurogenic weakness, ataxia, retinitis pigmentosa) m.8993T-->G mtDNA mutation (p.Leu156Arg) in the ATP synthase subunit 6 gene. Analyses were performed on chorionic villous (CVS) and/or amniocyte samples carried out at various stages of pregnancy, using a method enabling quantification of low DNA amounts. RESULTS: Maternal mutant loads ranged from 0 to 75% in blood and had no predictive value for the fetus status, except for women with no detectable mutant DNA, whose fetuses were consistently mutation-free. In 8/13 PND, mutant load was <30%. These children are healthy at 2-7 years of age. In 5/13 PND, mutant load ranged from 65 to 100%, and parents preferred to terminate the pregnancies (15-22 weeks of gestation). Single-cell analysis of 20 trophoblastic cells and 21 amniocytes isolated from two affected fetuses found an average mutant load close to the overall CVS and amniocyte mutant load, despite striking intercellular variation. The m.8993T-->G mutant loads, assessed in 7, 17, 11, and 5 different tissues from 4 terminations, respectively, were identical in all tissues from a given individual (mean (SD) 78 (1.2)%, 91 (0.7)%, 74 (2)%, and 63 (1.6)% for the 4 fetuses, respectively). CONCLUSIONS: Our results indicate that the placental/amniotic mutant loads do reflect the NARP mutant mtDNA load in the whole fetus, even when the sample amount is small, and suggest that heteroplasmy level remains stable during pregnancy, at least after 10 weeks of gestation. Although these data establish the feasibility of PND for this mutation, assessing more precisely the correlation between mutant load and disease severity should further help in interpreting PND results.

[Emergency thoraco amniotic shunting in cases with compressive pleural effusion with hydrops: A retrospective study of 60 cases]. / Drainage thoraco-amniotique en urgence en cas d'épanchement pleural compressif responsable d'anasarque foetale: une série rétrospective de 60 cas.

OBJECTIVES: To study perinatal outcome following thoraco-amniotic shunting for fetal pleural effusions with hydrops. MATERIALS AND METHODS: Retrospective study (1984-2004) to evaluate a policy of emergency thracoamniotic shunting in hydropic fetuses with suspected chylothorax, on the basis of the rationale that mediastinal compression could lead to acute fetal distress. RESULTS: Shunting was performed immediately following diagnosis, and was successful in all 60 cases attempted. There were 7 pregnancy terminations, 10 in utero deaths, and 43 live births, of which 7 children died in the neonatal period and 36 survived (33 without sequels). Among the liveborn, 26 were delivered preterm (72%), of which 7 (19%) had preterm premature rupture of membranes and 4 (11%) had chorioamnionitis. Perinatal death (24/60, 40%) was related to underlying anomalies (7 cases), pulmonary hypoplasia (5 cases), chorioamnionitis (2 cases), or treatment failure for unknown reasons (10 cases). All 36 survivors had chylothorax, 33 of which were primary, and 3 were secondary to right congenital diaphragmatic hernia, pulmonary sequestration, or Noonan syndrome. CONCLUSION: Following shunting, pleural effusion with hydrops has survival rate >50%, but still have a high rate of morbidity and mortality.

Predicting pulmonary hypoplasia using the sonographic fetal lung volume to body weight ratio--how precise and accurate is it?

OBJECTIVES: To determine the precision and accuracy of ultrasound in estimating the fetal lung to body weight ratio (FLB ratio) using two-dimensional (2D) and three-dimensional (3D) ultrasound by comparison with postmortem measurements, and to evaluate its potential to diagnose pulmonary hypoplasia. METHODS: Lung volumes were estimated by 3D ultrasound (rotational technique) and fetal weights were measured by 2D ultrasound (Hadlock equation) in 35 fetuses immediately before termination of pregnancy at 15-38 weeks. Sonographic estimates of FLB ratio were compared with postmortem values. Based on the pathological definition of pulmonary hypoplasia, the accuracy of sonographic estimation of the FLB ratio was analyzed. RESULTS: The mean gestational age at termination of pregnancy was 26.7 (range, 15-38) weeks. The mean FLB ratios were 0.018 (SD, 0.006) on ultrasound and 0.019 (SD, 0.007) at autopsy (P = 0.730). Bias and precision of sonographic FLB ratio were - 0.001 and 0.003 (absolute limits, - 0.007 to + 0.006), respectively. Pulmonary hypoplasia was diagnosed in 12 (34.3%) cases at autopsy. The sonographic FLB ratio was significantly lower in fetuses with pulmonary hypoplasia at autopsy (median, 0.011; range, 0.004-0.014) than it was in those without pulmonary hypoplasia (median, 0.022; range, 0.013-0.045, P < 0.001). The sensitivity and specificity of the sonographic FLB ratio for diagnosing pulmonary hypoplasia were 91.7% (11/12) and 91.3% (21/23), respectively, the positive and negative predictive values were 84.6% (11/13) and 95.5% (21/22), and the accuracy was 91.4% (32/35). CONCLUSION: FLB ratio can be estimated precisely on ultrasound examination, albeit with wide limits of agreement. The sonographically estimated FLB ratio may be useful in the prediction and diagnosis of pulmonary hypoplasia.

Rendering in fetal cardiac scanning: the intracardiac septa and the coronal atrioventricular valve planes.

OBJECTIVE: In this study we aimed to apply spatio-temporal image correlation (STIC) rendering to visualize the virtual planes of the interventricular and interatrial septa (IVS, IAS) as well as the atrioventricular (AV) annuli plane just distal to the semilunar valves (coronal atrioventricular (CAV) plane) in normal and pathological fetal hearts, to ascertain whether these planes add to fetal cardiac examination. METHODS: Unselected gravidae presenting for anatomy scan or patients referred for fetal echocardiography in the second and third trimesters of pregnancy with suspected or diagnosed cardiac malformation were scanned using the five planes technique with the STIC modality to obtain cardiac volume sets for each patient. Rendering capabilities were employed to obtain the 'virtual planes' to evaluate the IVS, IAS, AV annuli, and size and alignment of the great vessels. RESULTS: A total of 136 normal scans were performed to establish a learning curve for STIC acquisition and post-processing rendering and analysis. An additional 35 cases with cardiac anomalies were accrued. In 131/136 (96.3%) normal scans the IAS and IVS were visualized successfully, while in 127/136 (93.4%) normal fetuses the CAV plane was successfully visualized. In 13 anomalous cases the IVS plane improved ventricular septal defect (VSD) evaluation, and in four the IAS plane contributed to foramen ovale evaluation. The modality improved visualization of the septa and the assessment of the defects, as well as the foramen ovale flap and pattern of movement of the foramen ovale. In five cases the CAV plane improved evaluation of the alignment of the major vessels in relation to the AV annuli, and in three the evaluation of the semilunar valves, with or without malalignment of the great vessels. CONCLUSIONS: Rendering STIC technology allows the visualization of virtual planes (IAS, IVS, AV annuli-CAV plane), which can clarify our understanding of anatomical defects and may improve communication with the management team and family.

Prenatal diagnosis of some metabolic diseases using early amniotic fluid samples: report of a 15 years, experience.

BACKGROUND: In the present study, we report the results of 132 prenatal diagnoses performed on chorionic villi and cell-free amniotic fluid obtained simultaneously at 12-13 weeks of gestation. In addition, we report the result of 59 prenatal diagnoses performed at 12-13th week using amniotic fluid only. METHODS AND RESULTS: A total of one fetal loss (1/191) was observed when a sample of amniotic fluid was obtained at around 12-13 weeks, whereas three losses (3/82) were observed after midtrimester amniocentesis. We attribute this finding to the fact that only a very small volume of amniotic fluid was sampled using a very small needle. CONCLUSION: From these data it appears that when a couple is facing a high risk of recurrence of some metabolic diseases, the study of chorionic villus and amniotic fluid sampled simultaneously offers a safe and reliable method of early prenatal diagnosis.

Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development.

INTRODUCTION: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNA(leu) gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome. MATERIALS AND METHODS: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy. RESULTS: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months-3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months-6 years. CONCLUSION: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.

Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development.

BACKGROUND: The acronym CHARGE refers to a non-random cluster of malformations including coloboma, heart malformation, choanal atresia, retardation of growth and/or development, genital anomalies, and ear anomalies. This set of multiple congenital anomalies is frequent, despite rare patients with normal intelligence, and prognosis remains poor. Recently, CHD7 gene mutations have been identified in CHARGE patients; however, the function of CHD7 during development remains unknown. METHODS: We studied a series of 10 antenatal cases in whom the diagnosis of CHARGE syndrome was suspected, considering that a careful pathological description would shed light on the CHD7 function during development. CHD7 sequence analysis and in situ hybridisation were employed. RESULTS: The diagnosis of CHARGE syndrome was confirmed in all 10 fetuses by the identification of a CHD7 heterozygous truncating mutation. Interestingly, arhinencephaly and semi-circular canal agenesis were two constant features which are not included in formal diagnostic criteria so far. In situ hybridisation analysis of the CHD7 gene during early human development emphasised the role of CHD7 in the development of the central nervous system, internal ear, and neural crest of pharyngeal arches, and more generally showed a good correlation between specific CHD7 expression pattern and the developmental anomalies observed in CHARGE syndrome. CONCLUSIONS: These results allowed us to further refine the phenotypic spectrum of developmental anomalies resulting from CHD7 dysfunction.

Accuracy of fetal lung volume assessed by three-dimensional sonography.

OBJECTIVE: To determine the accuracy and precision of prenatal three-dimensional (3D) ultrasound in estimating fetal lung volume using the rotational multiplanar technique (VOCAL) by comparing it to postmortem volume measurements. METHODS: Fetal lung volume was measured during 3D ultrasound examination using a rotational multiplanar technique in eight cases of congenital diaphragmatic hernia (CDH) (six left and two right-sided) and in 25 controls without pulmonary malformation, immediately before termination. Prenatal 3D sonographic estimates of fetal lung volume were compared with postmortem measurement of fetal lung volume achieved by water displacement. RESULTS: The intraclass correlation coefficient of fetal lung volume estimated by 3D ultrasound and measured at postmortem examination was 0.95 in CDH cases and 0.99 in controls. Based on Bland-Altman analysis, the bias, precision and limits of agreement were, respectively, 0.35 cm(3), 1.46 cm(3) and between -2.51 and + 3.21 cm(3) in cases with CDH and 0.08 cm(3), 2.80 cm(3) and between -5.41 and + 5.57 cm(3) in controls. The mean relative error of 3D ultrasound fetal lung volume measurement was -7.19% (from -42.70% to + 18.11%) in CDH cases and -0.72% (from -30.25% to + 19.22%) in controls, while the mean absolute error of 3D ultrasound fetal lung volume measurement was 1.40 (range, 0.71-2.52) cm(3) and 2.12 (range, 0.05-4.98) cm(3), respectively. Accuracy of 3D ultrasound for measuring fetal lung volumes was 84.86 (range, 57.30-99.48)% in cases with CDH and 91.38 (range, 69.75-99.45)% in controls. The mean intraobserver variability for lung volume estimated by 3D ultrasound was 0.28 cm(3) in controls and 0.17 cm(3) in CDH cases. CONCLUSION: Prenatal 3D ultrasound can estimate accurately fetal lung volume using the rotational multiplanar technique for volume measurements (VOCAL), even in fetuses with very small lungs, such as cases with isolated CDH.

Correlation between ultrasound and anatomical findings in fetuses with lower urinary tract obstruction in the first half of pregnancy.

OBJECTIVE: The prognosis of fetal lower urinary tract obstruction (LUTO) depends upon renal function and also upon the underlying etiology. Precise identification of the latter remains a challenge antenatally. Our objective was to examine the underlying pathology in male fetuses with sonographic evidence of severe and isolated LUTO. METHODS: Detailed postmortem examination was carried out after termination of pregnancy in 24 male fetuses presenting before 25 weeks of gestation with ultrasound evidence of isolated severe LUTO. RESULTS: All fetuses had megacystis and hyperechogenic kidneys. There was anhydramnios/oligohydramnios and pelvicalyceal dilatation in 20 and 15 cases, respectively. Posterior urethral valves (PUV) were suspected antenatally in 20 cases and urethral atresia was not suspected antenatally. However, postmortem examination of the urethra demonstrated atresia in six cases, severe stenosis in eight cases, PUV in nine cases and an apparently normal urethra in one case. Renal dysplasia was found in all cases but one. Urethral atresia was the most common urethral anomaly at 12-17 weeks. Hydronephrosis was more frequent in cases with PUV (8/9) and urethral stenosis (6/8) than with urethral atresia (0/6). In LUTO presenting in the first and second trimester, hyperechogenic kidneys were predictive of renal dysplasia in 95% of cases. The association of a sagittal diameter of the bladder of at least 40 mm with hydronephrosis before 28 weeks was predictive of PUV with a positive (PPV) and negative (NPV) predictive value of 44.4% and 66.6%, respectively. Absence of hydronephrosis and a sagittal diameter of the bladder of less than 40 mm were predictive of urethral atresia or stenosis with a PPV and NPV of 100% and 47.6%, respectively. The absence of hydronephrosis was predictive of urethral atresia with a PPV and NPV of 66.6% and 100%, respectively. CONCLUSION: LUTO in a male fetus presenting with megacystis in the first or second trimester of pregnancy is as likely to reflect urethral atresia or stenosis as it is PUV. The size of the bladder and the presence of hydronephrosis should be considered in order to improve prenatal diagnosis and counseling.

Prenatal diagnosis of pulmonary sequestration using three-dimensional power Doppler ultrasound.

OBJECTIVE: To investigate the contribution of three-dimensional power Doppler ultrasound to the prenatal diagnosis of pulmonary sequestration. METHODS: Prenatal three-dimensional power Doppler ultrasound was used to screen for an abnormal pulmonary blood supply in eight fetuses with hyperechogenic lung lesions and to image the pulmonary blood supply in 50 normal controls. A comparison was made with postnatal findings. RESULTS: Postnatally the eight pulmonary lesions were found to be an isolated pulmonary sequestration (n = 3), a microcystic congenital adenomatoid malformation (n = 4), and a mixed (macrocystic and microcystic) congenital adenomatoid malformation (n = 1). Prenatal three-dimensional power Doppler ultrasound demonstrated an abnormal blood supply in all cases of pulmonary sequestration and in none of the other cases. Among the three cases that turned out to be pulmonary sequestrations, conventional two-dimensional ultrasound failed to identify the feeding vessel in one case and identified it at a later stage of gestation than did three-dimensional power Doppler in the other two. CONCLUSION: Prenatal three-dimensional power Doppler ultrasound may be useful in identifying the feeding vessel and thus establishing the diagnosis of pulmonary sequestration in the presence of a hyperechogenic pulmonary lesion, allowing its differentiation from congenital cystic adenomatoid malformation.