Maternal transmission of interstitial 8p23.1 deletion detected during prenatal diagnosis.

We report on the first prenatally diagnosed interstitial 8p23.1 maternally inherited deletion. At 20 weeks of gestation (WG) the fetus was diagnosed with a complete atrioventricular canal. In infancy, the mother underwent a two-step cardiac surgery for an interrupted aortic arch type A associated to an inlet ventricular septal defect (VSD). A straddling of the tricuspid valve type B was confirmed during surgery. The outcome showed no cardiac failure or conduction anomalies. However, she presented with moderate intellectual disability. Classical and molecular cytogenetic studies on amniotic and maternal lymphocytes cells showed a nearly identical interstitial deletion of the 8p23.1 region encompassing the GATA4 gene locus (Mother: nt 6,913,337-12,580,828, fetus: nt 7,074,449-12,580,828) with no modification of the telomeric region. The relevance of our report is not only the maternal syndromic interstitial 8p23.1 deletion, but also maternal transmission which has never been reported before. The maternal and fetal phenotypes were not identical, however, even though they had the same cellular and molecular background: an alteration of the epithelial mesenchymal transition of the atrioventricular valvulo-septal complex where GATA4 plays a positive role in the regulation. We reviewed all cases of interstitial 8p23.1 deletions diagnosed either prenatally or postnatally.

[Prognosis of atrioventricular canal in euploid foetus without abnormality of atrial situs]. / Pronostic des canaux atrioventriculaires chez les foetus euploïdes sans anomalie du situs atrial.

Atrioventricular septal defects are commonly diagnosed during fetal life. Postnatal prognosis of atrioventricular septal defects associated with trisomy 21 and with heterotaxia sequences are relatively well known. However, predicting postnatal outcome in fetus with atrioventricular septal defects and normal chromosome and normal atrial situs remains a challenge. In a series of 141 fetal atrioventricular septal defects, we analyzed 80 fetuses with normal karyotype. Twenty-seven had an abnormal atrial situs. One fetus was lost for follow-up. Finally, 52 fetuses were included in the study. Termination of pregnancy was performed in 18 cases (34%). Six fetuses died in utero (18% of ongoing pregnancies). Twenty eight infants were born alive, 2 of them were lost for follow-up right after birth and 3 live born infants died postanatally (11%). Postoperative mortality was 3/15 (20%). Complete repair was proceed for 13 infants, palliative repair for 2; and 8 infants didn't have surgery at the end of follow-up because of partial or intermediate atrioventricular septal defect. The only factor significantly associated with poor outcome was the small size of the left ventricle. Isolated atrioventricular septal defects are of poor cardiac prognosis particularly when associated with left heart obstructions.

[Ductus venosus agenesis]. / Agénésie du canal d'Arantius.

OBJECTIVE: Congenital absence of the ductus venosus is a rare anomaly in the fetus. The aim of our study was to evaluate the clinical and ultrasonographic features and outcome of the fetuses with ductus venosus agenesis. STUDY DESIGN: We describe 12 cases in the period between 1992 and 2004. The umbilical vein drained either into the right atrium directly (2 cases) or by the coronary sinus (1 case), or in the inferior vena cava (5 cases), or in the azygos vein (1 case), or in the portal vein (3 cases). Our data where analyzed with the cases published in the literature. Two groups of anastomoses where defined on the basis of the hemodynamic consequences: the group of extrahepatic anastomoses (53 cases) and the group of intrahepatic anastomoses (22 cases). RESULTS: In the group of extra hepatic anastomoses, cardiomegaly was the most common antenatal finding (39%), while in the intra hepatic group hydrops fetalis occurred most frequently (23%). Malformation rate was high in both groups (56% and 45%) and chromosomal anomalies where present in 9% of cases. CONCLUSION: Careful assessment of the umbilical venous return and the ductus venosus should be a part of examination of every fetus with cardiomegaly, polyhydramnios, ascites or hydrops. In case of absence of the ductus venosus a referral scan, a fetal echocardiography and a karyotype should be performed.

Echocardiographic ventricular shape analysis in congenital heart disease with right ventricular volume or pressure overload.

In this 2-dimensional (2-D) echocardiographic study, a computerized Fourier analysis technique refined from one that allows quantification of changes in septal shapes in normal fetuses, newborns and infants allowed analysis of left ventricular (LV) shapes in 14 patients with right ventricular (RV) volume overload (atrial septal defects), 5 with volume and pressure overload (total anomalous pulmonary venous connection), and 10 with pressure overload (complete transposition of the great arteries [TGA] with intact ventricular septum). Diastolic shape factors in the 3 groups were significantly different from those of normal subjects (p less than 0.01). Highest diastolic values were found in patients with TGA (mean 4.59 +/- 1.28). Systolic shape factors were similar in patients with atrial septal defect and normal subjects. Significant differences existed between normal subjects and patients with total anomalous pulmonary venous connection, with the greatest differences in systolic shape factor being 5.61 for TGA vs 1.87 (p less than 0.005) for normal subjects. Shape factor correlated well with hemodynamic data for RV/LV systolic pressure ratios (r = 0.93, p less than 0.001) for normalized interventricular pressure differences (r = -0.95, p less than 0.001). The lower the normalized systolic pressure difference or the higher the RV/LV ratio, the more the septum encroached into the LV cavity. Significant but weaker correlations were noted for values during diastole. Quantitative application of Fourier shape factor analysis to LV shapes allows numerical expression of visually interpreted distortions over a wide range of geometric alterations.

Congenital diaphragmatic hernia: antenatal prognostic factors. Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia?

UNLABELLED: Despite regular progress in neonatal intensive care, congenital diaphragmatic hernia (CDH) diagnosed antenatally is still associated with up to 80% mortality. It is impossible to predict which fetus with CDH will survive or not. OBJECTIVE: To identify reliable antenatal predictors of outcome and of pulmonary hypoplasia (PH) in fetuses with CDH. DESIGN: Retrospective study. SETTING: Paediatric intensive care unit of a university children's hospital. PATIENTS AND METHODS: Antenatal parameters and presence of left ventricular hypoplasia in utero were compared retrospectively to outcome and to presence of PH in 32 consecutive newborn infants with antenatally diagnosed CDH. Antenatal parameters included: gestational age at diagnosis, herniated organs, associated malformations and presence of polyhydramnios. Size of the cardiac ventricles, the aorta (Ao) and the pulmonary artery (PA) were obtained by fetal echocardiography, from which we calculated a cardioventricular index (left ventricle/right ventricle, LV/RV) and a cardiovascular index (Ao/PA). Delivery was planned in order to provide ventilatory and hemodynamic management. In case of death, PH was assessed according to the following criteria: the lung weight/body weight index and the radial alveolar count. For statistical comparisons, patients were separated into two groups: the hypoplasia group (H) and the non-hypoplasia group (NH). RESULTS: Thirty-two pregnancies were delivered. Twenty-six newborns died (81%), 6 survived (19%). When comparing non-survivors to survivors, predictors of poor outcome were: mean gestational age at diagnosis (23 vs 28 weeks, p = 0.002), intrathoracic stomach (20 vs 1 s, p = 0.01) and associated malformations (6 vs 0). Cardiac ventricular disproportion, expressed by the LV/RV ratio, appeared to correlate well with a poor outcome (0.63 in non-survivors vs 0.93 in survivors, p = 0.03) and with PH (0.63 in the H group vs 0.95 in the NH group, p = 0.03). CONCLUSIONS: Our study confirmed the factors for a poor prognosis associated with CDH previously described in the literature, but none with a consistent demonstration of accuracy. LV hypoplasia may be a more accurate predictor of outcome and of PH but it has to be assessed by prospective studies with larger samples. Further basic science and Doppler-flow studies may be helpful to understand the natural history and pathophysiology of LV hypoplasia in CDH.

Congenital diaphragmatic hernia: antenatal prognostic factors : Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia?

UNLABELLED: Despite regular progress in neonatal intensive care, congenital diaphragmatic hernia (CDH) diagnosed antenatally is still associated with up to 80 % mortality. It is impossible to predict which fetus with CDH will survive or not. OBJECTIVE: To identify reliable antenatal predictors of outcome and of pulmonary hypoplasia (PH) in fetuses with CDH. DESIGN: Retrospective study. SETTING: Paediatric intensive care unit of a university children's hospital. PATIENTS AND METHODS: Antenatal parameters and presence of left ventricular hypoplasia in utero were compared retrospectively to outcome and to presence of PH in 32 consecutive newborn infants with antenatally diagnosed CDH. Antenatal parameters included: gestational age at diagnosis, herniated organs, associated malformations and presence of polyhydramnios. Size of the cardiac ventricles, the aorta (Ao) and the pulmonary artery (PA) were obtained by fetal echocardiography, from which we calculated a cardioventricular index (left ventricle/right ventricle, LV/RV) and a cardiovascular index (Ao/PA). Delivery was planned in order to provide ventilatory and hemodynamic management. In case of death, PH was assessed according to the following criteria: the lung weight/body weight index and the radial alveolar count. For statistical comparisons, patients were separated into two groups: the hypoplasia group (H) and the non-hypoplasia group (NH). RESULTS: Thirty-two pregnancies were delivered. Twenty-six newborns died (81 %), 6 survived (19 %). When comparing non-survivors to survivors, predictors of poor outcome were: mean gestational age at diagnosis (23 vs 28 weeks, p = 0.002), intrathoracic stomach (20 vs 1 s, p = 0.01) and associated malformations (6 vs 0). Cardiac ventricular disproportion, expressed by the LV/RV ratio, appeared to correlate well with a poor outcome (0.63 in non-survivors vs 0.93 in survivors, p = 0.03) and with PH (0.63 in the H group vs 0.95 in the NH group, p = 0.03). CONCLUSIONS: Our study confirmed the factors for a poor prognosis associated with CDH previously described in the literature, but none with a consistent demonstration of accuracy. LV hypoplasia may be a more accurate predictor of outcome and of PH but it has to be assessed by prospective studies with larger samples. Further basic science and Doppler-flow studies may be helpful to understand the natural history and pathophysiology of LV hypoplasia in CDH.

Clinical biological features of Ballantyne syndrome and the role of placental hydrops.

Ballantyne syndrome was first described in association with severe hydrops fetalis caused by rhesus isoimmunization, and lately, in association with diverse etiologies of nonimmunological severe fetal hydrops. This report is a case of typical Ballantyne syndrome in association with lethal hydrops fetalis caused by Ebstein's anomaly. It is likely that any severe fetal hydrops with massive placental hydrops may produce Ballantyne syndrome. Hemodilution could be the main biological feature, differentiating Ballantyne syndrome from usual preeclamptic syndromes. Pathophysiological hypotheses are discussed.

[Clinical spectrum of prenatal tetralogy of Fallot]. / Spectre clinique de la tétralogie de Fallot anténatale.

The aim of this study of 44 cases of tetralogy of Fallot was to assess the echocardiographic aspects and the prognosis with respect to associated abnormalities and the potential evolution in utero. Group I, tetralogy of Fallot with other abnormalities (N = 27: 2 valvular agenesis, 26.5 5.3 weeks), had genetic anomalies in 18 of the foetus (10 trisomies including 5 trisomy 21, 5 structural abnormalities including 2 micro-deletions 22q11 in the two cases of valvular agenesis, and one deletion of chromosome 8p23.1, 3 mendelian syndromes) and other abnormalities in 9 cases. Hypoplasia of the pulmonary artery was present in 60% of cases with a non-dilated aorta in 72%, infundibular hypertrophy in 33% and 2 evolutions to pulmonary atresia. Aspect of "isolated" ventricular septal defect were observed in 20% of cases. Survival was 10%. In Group II, tetralogy of Fallot was isolated (N = 17, including 2 pulmonary valve agenesis, 31 +/- 6 weeks) (p < 0.01 versus Group I). Pulmonary artery hypoplasia was observed in 50% of cases with dilatation of the aorta and infundibular hypertrophy in all and in one a postnatal progression towards pulmonary atresia. A correlation between growth of the pulmonary artery and gestational age was found in 5 foetus out of 9 studied sequentially (p between 0.03 and 0.007) and between age at first surgery and size of the pulmonary artery (r = 0.80, p = 0.001). Survival was 84%. The risk of malformation (61%) and the prenatal potential evolution of this disease justifies continuous follow-up of all cases of tetralogy of Fallot, high resolution karyotyping and postnatal evaluation in a specialized centre.

[Bundle of His tachycardia and chronic reciprocating rhythm: rare forms of prenatal tachycardia]. / Tachycardie hissienne et rythme réciproque chronique. Formes rares de tachycardie anténatale.

In cases of permanent tachycardia, ante-natal diagnosis of chronic reciprocating rhythms with long RP' intervals or His bundle tachycardias is difficult. The authors report two cases of permanent foetal tachycardia with 1/1 atrioventricular conduction. In one case, the tachycardia rate was 170/min with anasarca treated by amiodarone in view of a family history of His bundle tachycardia. In the other case, the tachycardia rate was 200/min but with no signs of cardiac failure and was, therefore, not treated. The ECG at birth confirmed the diagnosis of His bundle tachycardia in the first case and identified a chronic reciprocating rhythm in the other.

[Antenatal diagnosis of congenital left ventricular aneurysm]. / Diagnostic anténatal d'un anévrisme congénital du ventricule gauche.

Congenital aneurysm of the left ventricle is a rare condition of unknown origin, the main differential diagnosis of which is the diverticulum. The natural history of this pathology is well known in adults and adolescents, contrary to those forms diagnosed by foetal echocardiography. Based on a case of congenital left ventricular aneurysm diagnosed ante-natally and a review of the literature, the authors propose echocardiographic prognostic factors useful for prenatal management. Thus, early antenatal diagnosis, size and progression of the aneurysm, signs of antenatal cardiac failure, are poor prognostic factors and should be discussed during parent counselling.

[Antenatal atrial tachycardia. Two case reports]. / Tachycardies atriales anténatales. A propos de 2 cas.

The authors report two cases of foetal supraventricular tachycardia in healthy hearts with 1/1 atrioventricular conduction which turned out to be atrial tachycardias in the postnatal period. The first foetus had permanent tachycardia at 190/minute at 34 weeks' amenorrhea with left ventricular dysfunction at 36 weeks. In the postnatal period, treatment with digoxine and amiodarone restored sinus rhythm and normal left ventricular function. Permanent foetal tachycardia, even at a rate of less than 200 beats/minute, should suggest an arrhythmia and may lead to left ventricular dysfunction in utero. The other foetus had an aneurysm of the foramen ovale with paroxysmal tachycardias at 220/minute without cardiac dysfunction. A Holter at 1 month showed paroxysmalatrial tachycardia. Postnatal rhythm monitoring is necessary in paroxysmal foetus tachycardia, especially with prenatal aneurysm of the foramen ovale.

[Has prenatal diagnosis of transposition of great vessels changed its prognosis?]. / Le diagnostic anténatal de la transposition des gros vaisseaux a-t-il modifié son pronostic?

Neonatal anatomical correction of transposition of the great arteries (TGA) has transformed the prognosis of this condition but the diagnosis must be made rapidly. The aim of this retrospective study was to evaluate the benefits of antenatal diagnosis on the outcome of TGA. The cases of 50 consecutive neonates with TGA with or without ventricular septal defect hospitalised between 1989 and 1996 were reviewed. All these children underwent anatomical correction of their malformation in the neonatal period. In seventeen of the children the diagnosis was made in the antenatal period at a gestational age of 28.7 +/- 5 weeks of amenorrhea and the other 33 had a postnatal diagnosis at 6.2 +/- 13 days. The clinical and echographic features were identical in the two groups. The risk factors of mortality for the whole population were a Yacoub type B or C coronary disposition, an intramural coronary course, difficulties in reimplantation of the coronary arteries and/or peroperative haemodynamic failure. In the authors' experience, the time of diagnosis (antenatal or postnatal) did not had on the management and prognosis of TGA. Studies with larger population groups are probably necessary to demonstrate the possible benefits of antenatal diagnosis.

[Interrupted aortic arch. A series of 15 patients]. / Interruption de l'arche aortique. Une série de 15 patients.

Between 1983 and 1989, 15 children underwent surgical repair of interrupted aortic arch at 1 to 20 days of age. The anatomical form was a Celoria and Patton type B in all patients with an associated perimembranous ventricular septal defect in all but one who had multiple ventricular septal defects, and patent ductus arteriosus. Six children had a retro-esophageal right subclavian artery, two had subaortic stenosis and two had a right-sided descending thoracic aorta. In two children with severe hypoplasia of the ascending aorta the repair was performed in one stage with two deaths due to left ventricular failure. In the other B cases, a two-stage repair was carried out. The reconstruction of the aortic arch varied according to the individual case. All children had pulmonary artery banding. Seven children survived longer than 30 days. Six of them later underwent a complete repair. The only survivors were those patients in whom the neo-aortic arch grew harmoniously. The authors conclude that: a two-stage repair gave disappointing results in this series of consecutive patients, mainly because of the poor quality of the reconstruction of the aortic arch by thoracotomy.

Unraveling changes in myocardial contractility during human fetal growth: a finite element analysis based on in vivo ultrasound measurements.

Knowledge of normal fetal heart (FH) performance and development is crucial for evaluating and understanding how various congenital heart lesions may modify heart contractility during the gestational period. However, since biomechanical models of FH are still lacking, structural approaches proposed to describe the mechanical behavior of the adult human heart cannot be used to model the evolution of the FH. In this paper, a finite element model of the healthy FH wall is developed to quantify its mechanical properties during the gestational period. An idealized thick-walled ellipsoidal shape was used to model the left ventricle (LV). The diastolic LV geometry was reconstructed from in vivo ultrasound measurements performed on 24 normal FHs between 20 and 37 weeks of gestation. An anisotropic hyperelastic constitutive law describing the mechanical properties of the passive and active myocardium was used. The evolution of the mechanical properties of the normal LV myocardium during fetal growth was obtained by successfully fitting the ejection fraction predicted by the model to in vivo measurements. We found that only the active tension varies significantly during the gestational period, increasing linearly from 20 kPa (at 20 weeks) to 40 kPa (at 37 weeks of gestation). We propose a possible explanation of the increasing force-generating ability of the myocardial tissue during fetal heart development based on a combination of myocyte enlargement, differentiation, and proliferation kinetics.

Prenatal Marfan syndrome: report of one case and review of the literature.

OBJECTIVES: Our objective was to describe the features of prenatal Marfan syndrome. METHODS: Doppler fetal echocardiograms were performed. The morphology and rhythm of the fetal heart were examined sequentially. RESULTS: The case was referred because of cardiomegaly and dilated great vessels. Sequential Doppler echocardiographic evaluation led to the diagnosis of prenatal Marfan syndrome. The main features are cardiomegaly, dysplastic atrioventricular valves with tricuspid regurgitation and dilated great vessels, which can be aneurysmal at their origin. The fetus died in utero at 39 weeks of gestation because of cardiac failure. Pathological study confirmed the Marfan habitus and complications. Molecular genetic study showed a de novo point mutation in exon 26 of the FBN1 gene. CONCLUSION: We report a case of prenatal Marfan syndrome diagnosed by sequential evaluation of the cardiac signs, which are essential for prenatal diagnosis. The prognosis seems as poor as the neonatal one. The prenatal diagnosis is essential for adequate counselling.

Fetal dextrocardia: diagnosis and outcome in two tertiary centres.

OBJECTIVE: To evaluate the incidence of fetal dextrocardia, associated cardiac and extracardiac malformations, and outcome. DESIGN: Retrospective echocardiographic study. SETTING: Two tertiary centres for fetal cardiology. PATIENTS: 81 consecutive fetuses with a fetal dextrocardia presenting at Guy's Hospital, London, between 1983 and 2003 and at Hôpital Robert Debré, Paris, between 1988 and 2003. Fetal dextrocardia was defined as a condition in which the major axis of the heart points to the right. RESULTS: The incidence was 0.22%. There were 38 fetuses (47%) with situs solitus (SS), 24 (30%) with situs ambiguus (SA), and 19 (23%) with situs inversus (SI). Structural cardiac malformations were found in 25 cases (66%) of SS, 23 cases (96%) of SA, and 12 cases (63%) of SI. Extracardiac malformations were identified in 12 cases (31%) of SS, in five cases (21%) of SA, and in two cases (10%) of SI. Of the 81 cases of fetal dextrocardia, there were 27 interrupted pregnancies (15 of 24 SA, 10 of 38 SS, and 2 of 19 SI), six intrauterine deaths (3 of 38 SS, 2 of 24 SA, and 1 of 19 SI), and five neonatal deaths (3 of 24 SA, 1 of 19 SI, and 1 of 38 SS). There were 43 survivors (24 of 38 SS, 15 of 19 SI, and 4 of 24 SA). CONCLUSION: The majority of fetuses with dextrocardia referred for fetal echocardiography have associated congenital heart disease. There is a broad spectrum of cardiac malformation and the incidence varies according to the atrial situs. Fetal echocardiography enables detection of complex congenital heart disease so that parents can be appropriately counselled.

Unusual evolution of a pericardial mass diagnosed by fetal echocardiography.

An intrapericardial mass with a pericardial effusion was diagnosed by ultrasound examination in the fetus of a 29-year-old gravida 1 para 0 woman at 32 weeks' gestation. Serial in utero examinations showed disappearance of the pericardial effusion at 35.5 weeks' gestation, while the mass remained unchanged. Vaginal delivery ensued at 39 weeks. Clinical and echocardiographic examination of the newborn revealed normal cardiac anatomy with no abnormal mass or pericardial effusion. Follow-up examinations confirmed these normal data.