Characteristics and outcomes of fetuses with laterality defects are the current outcomes better? A single center study.

Objective: To analyze the more recent outcomes of fetuses with different laterality defects.Material and methods: Out of 1508 fetuses with congenital heart disease (CHD) diagnosed by echocardiography between January 1995 and December 2015, 94 (6.3%) presented abnormal visceroatrial situs: 42 till December 2002 (group 1, analyzed retrospectively) and 52 since then until December 2015 (group 2, analyzed prospectively). Twenty-one had left isomerism (Lisom), 22 right isomerism (Risom), 16 situs inversus- dextrocardia (SVI-dx), 5 situs inversus- levocardia (SVI-levo), and 30 situs solitus-dextrocardia (SSol-dx).Results: Seventy-six cases (81%) had CHD, more frequently complex atrioventricular defect. Eighteen cases showed normal heart: half of subgroups SVI-dx and SVI-levo, a third of SSol-dx. Postoperative mortality in continuing pregnancy in group 2 was 43.7 versus 40% in group 1, lower in SVs-dx (0 versus 50%) and Lisom (33.3 versus 66.7%), worse in Risom (71.4 versus 25%). Total mortality in group 2 was 48.3 versus 55% in group 1, better in Ssol-dx (37.5 versus 50%) and in Lisom (27.4 versus 71.4%). In isolated forms all but one case are alive.Conclusions: Our fetal cases presented a relevant mortality in both periods. The outcomes were slightly better in a more recent era in SSol and Lisom.What is known about this topic?Out of laterality defects, the heterotaxies (i.e. left and right isomerism) are known to be associated to a relevant mortality in fetal and neonatal cases.Heterotaxies have a variable position of the heart, but some authors evaluated only those with dextrocardia in their studies on different laterality defects.Controversial data are presented in the literature for the outcomes of fetuses with laterality defects. Many large studies analyzed the data of a very long time period in which it is opinable to compare the results of the treatment, because of a recent improved management and surgical techniques.What does this study add?Our study presents an experience of a single center with cases of different types of laterality defects observed during a routine fetal echocardiography, not only heterotaxies.The knowledge of different laterality defects and of their characteristics (association with cardiac and extracardiac anomalies or with normal heart) is useful for the prenatal counseling.We compare the postoperative and total mortality in more recent period (since 2003) with respect to the previous era (1995-2002).

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.

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.

Norman-Roberts syndrome: characterization of the phenotype in early fetal life.

PURPOSE: Our purpose is to describe the prenatal manifestation of Norman-Roberts syndrome and to expand the knowledge of the fetal phenotype of this rare condition. The recurrence in two sibs might contribute to the hypothesis of a recessive condition. METHODS: Three cases are presented in which the diagnosis was suggested by a prenatal ultrasound examination and confirmed by pathology of the fetuses, after termination of pregnancy. The major sign was the ultrasound detection of microcephaly at the 22nd and 23rd week of gestation. Fetal Magnetic Nuclear Resonance, the pathological examination with histological studies, was applied to arrive at the diagnosis of Norman-Roberts syndrome. CONCLUSION: To the best of our knowledge, this is the second description of prenatal cases of Norman-Roberts syndrome. The combined clinical and pathological data is a contribution that might help to increase the identification of this rare condition and to correctly define the risk of its recurrence.

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.