Chiara Boschetto

Spectrum and outcome of atrioventricular septal defect in fetal life

OBJECTIVES OF THE STUDY to analyse the features and outcomes of different types of atrioventricular septal defects, detected during fetal life, as compared to postnatal data. MATERIAL AND METHODS We analysed retrospectively the data concerning 82 fetuses with atrioventricular septal defect, diagnosed from 19 through 37 weeks gestation with a median of 26 weeks. In 46 cases (56.1%), the diagnosis has been made before the age of 24 weeks. RESULTS Characteristics of the series--in 44 fetuses the atrioventricular septal defect was not associated with other cardiac anomalies, while 38 fetuses had a more complex form. Chromosomal anomalies were present in 33 of the fetuses (40.2%), more frequently in cases without associated intracardiac defects (56.8%). Trisomy 21 occurred in just over one quarter the series, and in 43.2% of cases without associated defects. In addition, 11% of fetuses had trisomy 18, and one had trisomy 13. Extracardiac anomalies were present in 12 of the fetuses (14.6%), more frequently in cases without associated abnormalities. Of fetuses with more complex defects, 46.4% had hypoplasia of the left ventricle and aorta. Complete atrioventricular block was present in 10 of the fetuses (12.2%), mainly in fetuses with other malformations, and particularly with left isomerism. Recurrence of congenital heart disease was observed in 5 of the fetuses (6.1%). OUTCOME In 25 instances (30.5%) the parents opted for termination of pregnancy. Of 57 cases that continued through pregnancy, 9 fetuses died prior to term (15.8%), 32 died postnatally (56.13%) and only 16 fetuses (28.1%) survived. Overall, the mortality was higher in cases with associated malformations, in those with heart failure or those with atrioventricular block. Cardiac surgery was performed in 19 infants, with 5 dying postoperatively, and one late. CONCLUSIONS Our data show a high prevalence of atrioventricular septal defect associated with other malformations when diagnosed during fetal life. This combination is less frequently associated with chromosomal and extracardiac anomalies, but more often with obstructive lesions of the left heart and with atrioventricular block. The association results in a less favourable outcome.

Prenatal/neonatal pathology in two cases of Cornelia de Lange syndrome harboring novel mutations of NIPBL

Purpose: This study reviews prenatal findings in two cases with a suspected diagnosis of Cornelia de Lange Syndrome, a multisystem disorder characterized by somatic defects and mental retardation, that were later confirmed by postmortem examination and molecular testing. Although the correlation between the Cornelia de Lange Syndrome genotype and phenotype is still unclear, preliminary data indicate several severe phenotypic features that are likely to be detected prenatally in NIPBL-mutated patients.Methods: We report on two prenatal/neonatal cases with unusual pathologic findings indicating Cornelia de Lange Syndrome. The first, with suspected Cornelia de Lange Syndrome after a set of typical dysmorphisms was noted by prenatal ultrasound, was confirmed by a physical examination after termination of the pregnancy. The second was diagnosed neonatally on the basis of typical clinical signs. Medical complications led to death within the first month of life.Results: Molecular analysis of NIPBL, the gene that codes for delangin (a component of the cohesin complex), performed postnatally detected two de novo mutations: a missense change (P2056L) in a highly conserved residue and a nonsense alteration (S2490 replaced by a stop codon).Conclusion: We suggest that early diagnosis of Cornelia de Lange Syndrome would be made much easier by the assemblage of a set of prenatal diagnostic features and criteria in Cornelia de Lange Syndrome cases that have been confirmed by direct physical and molecular examinations. We also suggest that Cornelia de Lange Syndrome genotype–phenotype correlations need to be extended to prenatal cases.

Changed outcomes of fetuses with congenital heart disease: new Italian Multicentre study.

Objectives To analyse the outcomes of fetuses with congenital heart disease between 2000 and 2005 in comparison to a previous multicentre study regarding the period 1983–1996. Participants and methods Data of seven centres were prospectively collected, the inclusion criteria being a confirmed fetal diagnosis after birth or at autopsy and a known follow-up, for at least 6 months after birth. Data of 649 fetuses, median age at diagnosis 24 weeks’ gestation (15–37), 340/649 (52.4%) diagnosed before 24 weeks, were analysed. Results Sixty seven and 59 cases had chromosomal or extracardiac anomalies (10.3 and 9.1%). Termination of pregnancy was chosen in 21.6% of cases versus 28.9% in the previous study, being significantly lower in cases with early diagnosis (P <0.001). Out of 509 fetuses continuing pregnancy, 23 died in utero (4.5%) and 110 (21.1%) postnatally, versus 43% in the previous study (P <0.0017). Total surgical/postprocedure death occurred in 20.6% (59/287 infants) versus 37% previously (P <0.003), 67 infants being premature and 35 with associated chromosomal or extracardiac anomalies. The current overall mortality rate was higher in cases with chromosomal or extracardiac anomalies (59.5 and 51.35%, respectively, whereas it was 20.1% in isolated congenital heart disease). Overall current survival was 376 of 509 (73.9%) versus 45% in the previous study (P <0.0001). Conclusion Our data show a reduced overall and surgical mortality, with respect to our previous study, resulting from resulting from an improved perinatal management and treatment of affected fetuses in the more recent era.

Unusual Aortic Valve Anomaly in the Fetus: A Case Report

Aortic valve anomalies in fetal life usually concern aortic valve stenosis, in severe forms associated to left ventricular impairment – endocardial fibroelastosis and mitral valve insufficiency. Isolated aortic regurgitation in utero is infrequent and is usually considered to be due to a rare anomaly: aorto-left ventricular tunnel. We describe an unusual case of fetal aortic valve anomaly with severe dysplasia, with a marked regurgitant flow through the aortic valve, passing in a retrograde way from the duct, associated with a marked left ventricular endocardial fibroelastosis and dysfunction, resulting in the fatal outcome of the case.

Swallowing, Sucking, and Handedness as Inferred from Fetal Thumb Sucking

Wide-ranging theories have flourished around fetal nutrition for centuries. The Greeks were somehow more accurate in their intuitions than many of those who followed them. Democritus and Epicurus thought that the unformed fetus ate and drank ‘per os’, through the mouth [1]. Hippocrates rightly assumed that the maternal blood flow nourished the embryo and even respiration emerged from the cord. Subsequently an almost ‘agricultural’ view of nutrition prevailed. Fetuses were regarded as passive creatures which simply absorbed nutrients from their mothers, who were equated to the earth and its fertile soil. Albertus Magnus thought that embryos absorbed nutrients ‘like a sponge’. Others, like Hildegard of Bingen, believed that retained menstrual blood was the primary source of fetal nourishment [1]. Menstruation ceased in the pregnant woman, and this was taken as a sign that menstrual blood was the fetus’s main food. Still others imagined the fetus branching out many vessels into the placenta, the socalled matrix, through which the nourishment was sucked in as from a fertile terrain.

Fetal Breathing Movements

Although aerial respiration only begins at birth, it is currently widely recognized that breathing has a long preparatory history during the 9 months preceding parturition. In describing the changes occurring at birth, most authors purposely omit the idiomatic expression ‘first breath’ and talk instead about a shift from periodic to continuous respiration.

Rest-activity Cycles, Clusters and the Ontogeny of Sleep

Sleep is a very widespread, almost ubiquitous phenomenon. Mammals, birds, most reptiles, amphibians, and fishes sleep. Sleep has different characteristics throughout the animal kingdom [1, 2], but common ground can be found in the near-total inactivity, the decreased capacity to react to environmental stimuli, and the cyclic quality of sleep. Even insects and molluscs display prolonged sleep-like periods of inactivity.

Twin Fetuses and Twin Myths

Since time immemorial twin births have been perceived as an extraordinary, often disquieting phenomenon. Many legends and myths flourished around their origins. Twins were thought to be the result of adultery, considered as the incarnation of evil spirits and ancestors, or, as in the myth of Castor and Pollux, one was regarded as having godly origins and the other not.

SERIAL AMNIOCENTESES IN THE MANAGEMENT OF TWIN-TWIN TRANSFUSION SYNDROME :WHEN IS IT VALUABLE ?

Serial decompressive amniocenteses were performed at 18-23 weeks of gestation in 23 pregnancies referred due to echographic signs typical of twin-twin transfusion syndrome. The procedures were repeated until delivery or permanent normalization of the amniotic fluid volume both in the donor and the recipient twin sac. The overall survival rate was 57%, but in only 39% of the pregnancies did both twins survive without handicaps. The absence of end diastolic flow in the umbilical artery of the donor twin was associated with poor chances of survival for both fetuses; in contrast, the presence of hydrops or ascites in the recipient twin did not worsen the prognosis. A policy of aggressive amniotic fluid decompression may achieve permanent resolution of the fluid in over 50% of the pregnancies complicated by twin-twin transfusion syndrome.