Congenital heart defects in IVF/ICSI pregnancy: systematic review and meta-analysis.

OBJECTIVE: There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. METHODS: A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: 'IVF', 'IVF/ICSI', 'ART pregnancy', 'assisted conception', 'birth defect', 'congenital heart defects' and 'congenital malformation or abnormalities'. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. RESULTS: Forty-one studies were identified for review including six case-control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20-1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21-1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03-1.60; P = 0.02; I2 = 0%; P = 0.43). CONCLUSION: Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Postmortem microcomputed tomography (micro-CT) of small fetuses and hearts.

OBJECTIVE: To assess the feasibility and utility of contrast-enhanced microcomputed tomography (micro-CT) for identifying structural anomalies in ex-vivo first- and second-trimester human fetuses and isolated fetal hearts. METHODS: Radiopaque iodine staining and micro-CT scanning protocols were first developed in rodent studies and then used to examine routinely fixed whole human fetuses (n = 7, weight 0.1-90 g, gestational age, 7-17 weeks) and isolated fetal hearts (n = 14, weight 0.1-5.2 g, gestational age, 11-22 weeks). Samples were scanned using an isotropic resolution of 18 (and, if necessary, 9 or 35) µm and findings were interpreted jointly by four fetal pathologists, a fetal cardiologist and a radiologist. Samples with gestational ages ≥ 13 weeks also underwent conventional autopsy or dissection. RESULTS: Micro-CT identified all anatomical structures and abnormalities documented by the macroscopic examination. In all seven cases involving fetuses ≤ 13 weeks (four fetuses, three isolated hearts), micro-CT excluded the presence of structural anomalies. In the remaining 14 cases, it provided all the information obtained with invasive autopsy or dissection and in seven of the 14 (two fetuses, five isolated hearts) it furnished additional diagnostic details. CONCLUSIONS: This pilot study confirms the feasibility of postmortem contrast-enhanced micro-CT assessment of structural anomalies in whole small fetuses and fetal hearts. Further study is needed to confirm our findings, particularly in whole fetuses, and to define the extent to which this virtual examination might be used instead of conventional invasive autopsy.

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.

Reliability of the first-trimester cardiac scan by ultrasound-trained obstetricians with high-frequency transabdominal probes in fetuses with increased nuchal translucency.

OBJECTIVE: To examine prospectively the reliability of ultrasound-trained obstetricians performing a first-trimester fetal cardiac scan with high-frequency transabdominal probes, by confirming normal or abnormal heart anatomy, in pregnancies referred for increased nuchal translucency thickness (NT). METHODS: Trained obstetric operators assessed the fetal heart in 133 fetuses with increased NT (> 95th centile) at 11-14 weeks of gestation. A high-frequency transabdominal probe was used to confirm or refute normal cardiac anatomy rather than to establish a specific diagnosis. Following this preliminary screening by the ultrasound-trained obstetrician, specialized fetal echocardiographers rescanned the fetal heart in order to confirm the accuracy of the obstetric operators' findings and to establish a diagnosis in abnormal cases. Fetal cardiologists repeated the examinations at 20 and 32 weeks of pregnancy. Postnatal follow-up lasted 2 years. Twelve fetuses with normal karyotype and normal anatomy were lost to follow-up. RESULTS: A total of 121 fetuses with increased NT between 11 and 14 weeks' gestation were studied. Congenital heart disease (CHD) was detected in 20/121 (16.5%) fetuses. In addition, there were three with mild ventricular disproportion, the right ventricle being larger than the left, considered as a minor non-specific cardiac abnormality. CHD was associated with chromosomal anomalies in 12/20 (60%) cases. Among the 121 fetuses, there was agreement between ultrasound-trained obstetricians and fetal cardiologists in 116 (95.9%) of the cases, and the ultrasound-trained obstetricians correctly identified 18 cases with major cardiac defects. However, there was disagreement in five cases: two with small ventricular septal defects and three with ventricular disproportion. CONCLUSIONS: Our results provide evidence that obstetricians, trained to study the heart in the second trimester, can also differentiate reliably between normal and abnormal heart findings in the first trimester, when using a high-frequency transabdominal ultrasound probe.

Clinical characteristics and cardiac outcome of acute rheumatic fever in Italy in the last 15 years.

OBJECTIVE: To analyze clinical characteristics, cardiac outcome and response to therapy of an Italian pediatric population affected with acute rheumatic fever (ARF) in the last 15 years. METHODS: 135 patients with ARF (aged 2-14.9 years, mean 8.4+/-2.5 years) diagnosed from 1992 to 2006 at the Pediatric Rheumatology Centre of the University of Milan (Italy) were retrospectively reviewed. All patients underwent physical examination, laboratory evaluation, electrocardiogram and echocardiography. Patients were divided into 2 groups: group 1 - patients with complete adherence to updated Jones criteria (107 patients), and group 2 - exceptions (28 patients). Echocardiographic criteria were used to confirm the presence of carditis and to evaluate severity of mitral (MR) and aortic regurgitation (AR) at diagnosis and after treatment with steroids or acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: We observed a persistence of ARF in the last 15 years (mean 9 new cases/year with a peak of 19 cases in 2000). Carditis and arthritis were the main major criteria observed (102/135 and 71/135 patients respectively), then chorea (29/135), erythema marginatum (8/135) and subcutaneous nodules (1/135). Arthritis and chorea resolved completely with various therapies. At the last follow-up (> or =5 years) in group 1, loss of MR was observed in 46% steroid-treated (26/56 cases) and in 39% ASA/NSAID-treated (7/18 cases) patients and loss of AR in 59% steroid-treated (22/38) and 2/7 ASA/NSAID-treated patients (p>0.05). CONCLUSION: Incidence of ARF is clinically important currently in the area of northern Italy. Non-suppurative complications of streptococcal pharyngitis should be considered when deciding therapy in a pediatric patient that presents with sore throat.

[Patency of foramen ovale in fullterm and preterm neonates. A follow-up study]. / Pervietà del foramen ovale nei neonati a termine e nei prematuri. Uno studio di follow-up.

The aim of our study was evaluate the clinical outcome of PFO without associated congenital heart disease, in the 1st year of life, in a consecutive series of preterm vs term infants. Out of 178 infants, 83 F/94 M, 49% born preterm, with echo diagnosis of PFO (< 5 mm) by 1 month of age, 122 were controlled at 3 mo, 67 at 6 mo and 30 at 12 mo distance. 23 (12%) had an associated PDA, 11 preterm (6 G.A. <32 w). Closure at f-u GA > 38 > 32 < 38 < 32 3mo 38/122 31% 24/66 35% 11/42 26% 3/14 22% 6mo 38/67 57% 20/35 57% 13/25 52% 5/7 71% 12 m 11/30 37% 5/13 38% 5/15 33% 1/2 50% PFO diameter slightly increased in 2 out of 122 (ga. > 38 w), remained so in 6, and decreased in 108. Only 3/33 children whose PFO was closed at 3rd month control were. <32 wGA. No one was hemodynamically significant. In all right ventricular prevalence both at ECG and Echo normalized by 3 mo of age: 21/23 PDA spontaneously closed by the following control before PFO closure. Our data show that: (1) PFO has no clinical relevance even in the WLGA newborn; (2) Inverse correlation between GA and early closure; (3) PDA was'nt predictive for early closure; (4) Spontaneous closure of ductus was always earlier the the FOP's one. Our data support that even in preterm infants PFO is benign and there is no need for an emotionally expensive and time losing follow-up.

Cardiovascular function in a chronic peritoneal dialysis pediatric population on recombinant human erythropoietin treatment.

Anemia, through a hyperkinetic state, is an important contributor to myocardial function impairment. To determine the cardiovascular effects of recombinant human erythropoietin (rHuEPO) therapy, 10 chronic peritoneal dialysis (CPD)-treated anemic children were studied before and during 18 months of treatment. The following parameters were recorded: hemoglobin (Hb) [percent of target level (TL) = x-2 standard deviations of normal Hb values for age and sex], heart rate (HR, beats/minute), mean arterial pressure (MAP, mmHg), end-diastolic left ventricular diameter (EDLVD, mm/sm BSA), shortening fraction (SF, percent), and interventricular septal thickness (IVS, mm/sm BSA). Student's t-test for paired data showed (vs time before treatment, T0) a progressive increase in Hb, a progressive decrease in HR, and a progressive increase in MAP. EDLVD progressively decreased, while SF and IVS remained unchanged throughout the study. Regression analysis showed a close correlation between anemia correction and decrease of HR (p < 0.01), while no correlation was found between Hb and EDLVD or SF, IVS, or MAP. Our data indicate that anemia correction in these patients is mainly associated with a decrease in hyperkinetic state (HR reduction with SF unvaried), while left ventricular function and dimensions remain normal, despite an increase in MAP.

Long-term clinical outcome of patients with tricuspid atresia. I. "Natural history".

The clinical course and outcome of 111 patients with tricuspid atresia, seen during 1972-1982, were reviewed. All clinical and investigation data, progress and management were analysed. The mean age at presentation was 21.9 +/- 8.8 days. Patients with reduced pulmonary blood flow presented earlier. Patients with normal or increased pulmonary blood flow usually presented in heart failure. "True" natural history was observed in 13 unoperated patients. Six of these died at the age of 7 days to 8 months (mean 32.2 days). Seven patients survived without surgery for 11 months to 24 years, the older ones developing pulmonary vascular obstructive disease. The overall mortality in the whole series was 32.4% (36/111), the mean age at death was 3.1 years (range 3 days-48 years). The mortality rate within the first year of life was 22.5%. The mean age of survivors at follow-up was 10.7 +/- 0.9 years (range 11 months-27 years).

The long-term clinical outcome of patients with tricuspid atresia. II. Influence of surgical procedures.

One-hundred and eleven patients with tricuspid atresia were seen during 1972-1982 and thirteen of these were not operated upon. The remaining 98 patients have undergone at least one operation. Those with low pulmonary blood flow had 1-4 shunt procedures; in 15 patients with high pulmonary blood flow the pulmonary artery was banded. The mortality rate after the first shunt was 10% (8/82), 9% after the second shunt (3/32) and 12% after the third and fourth shunts. Three out of 15 (20%) patients died after pulmonary artery banding. Twenty three patients underwent a Fontan operation and five died (22%); eighteen survivors are clinically well (after 1-7 years). One patient required a pacemaker implantation and revision of his Fontan procedure. The survivors of the palliative operations and the unoperated patients were more restricted, the older ones having developed pulmonary vascular obstructive disease, chronic heart failure or arrhythmias.

Prenatal diagnosis and management of congenital heart disease.

Thirty-two fetuses were diagnosed as having congenital heart disease (CHD). The major indications for level II echocardiography other than suspected cardiac abnormalities were fetal malformations, nonimmune hydrops and cardiac arrhythmia. Only three patients had a previous history of fetal CHD. No false-abnormal diagnosis of severe CHD was made. Aortic arch anomalies represented the major diagnostic problem among the six correct but incomplete diagnoses. Sixty-one percent of the fetuses were growth retarded, thus confirming the severity of their CHD. Chromosomal anomalies and extracardiac malformations were associated in 19% and 44% of the fetuses, respectively. Obstetric management and fetal prognosis in cases of extracardiac malformations were greatly influenced by the diagnosis of CHD. The poorest perinatal outcome was associated with heart failure. The only intrauterine deaths occurred in that group, and only one neonate survived. The outcome was more favorable in neonates without other malformations or heart failure. Four of ten (40%) of those neonates survived, while the overall perinatal survival rate was 24%.

Autoptic and echocardiographic findings in seven foetuses with congenital heart anomalies, lung lobation defects and normal visceroatrial arrangement.

OBJECTIVES: Congenital heart defects may be associated with various extracardiac and chromosomal anomalies, and complex cardiac defects may occur in the presence of heterotaxy syndromes, in which both lungs are bilobate, in left isomerism, or both trilobate, in right isomerism. Lung lobation defects are otherwise very rare. Lung lobation is recognisable only at autopsy; however, its definition is fundamental for evaluation of the visceroatrial arrangement, together with other characteristic signs. METHOD: We report seven cases of congenital heart defects diagnosed prenatally at 14-31 weeks of gestation (wg), 5 females and 2 males, in which autopsy revealed lung lobation defects in the presence of normal visceroatrial arrangement, in association with other extracardiac anomalies or dysmorphism. RESULTS: Three foetuses had hypoplastic left heart syndrome, one had corrected transposition of great arteries, one had tricuspid atresia, one Ebstein's anomaly and one had ventricular septal defect in trisomy 21. In six cases, pregnancy had been terminated, while the foetus with Ebstein's anomaly died in utero at 32 wg for supraventricular tachycardia. Monolobate, bilobate, trilobate and quadrilobate lungs were found in these foetuses, together with other minor extracardiac anomalies or dysmorphism. CONCLUSIONS: Autoptic analysis in cases with prenatal diagnosis is needed to confirm echographic findings and reveal other minor anomalies, undetectable by ultrasound imaging that may complete the malformation pattern, which is useful to the couple for genetic counselling.

Fetal echocardiography at the time of the nuchal translucency scan.

OBJECTIVE: The fetal heart is not studied routinely in the first trimester because of technical and time limitations. Our aim was to assess the feasibility of performing a fetal cardiac study in pregnancies referred for nuchal translucency (NT) screening, using high-frequency linear transabdominal transducers with a specific ultrasound preset. METHODS: A single trained operator assessed the fetal heart in pregnancies with a fetal crown-rump length (CRL) of 60-84 mm that had been referred for NT screening. A 15- or 6-MHz transabdominal linear transducer with a specific preset suitable mainly for color-flow mapping was used to confirm or refute normal cardiac anatomy rather than to establish a specific diagnosis. Fetuses having an increased risk for congenital heart disease were referred to a tertiary center for a further examination within 1 week. This group consisted of all fetuses with NT > 95(th) centile and those in which a family history or the initial heart scan increased the risk. RESULTS: A total of 608 fetuses with a median CRL of 65 mm was examined between 2003 and 2005. A cardiac scan was performed successfully in 456 (75%) using a 15-MHz linear transducer alone, and the additional use of a 6-MHz transducer allowed diagnostic images to be obtained in a further 152. Normal cardiac anatomy was assessed confidently within 10 min in 517/608 (85%) pregnancies; in 85 (14%) a longer time was needed and six patients were rescheduled within 2 weeks because of non-diagnostic images at the initial scan. In 571/608 (94%) the risk for congenital heart disease (CHD) was not increased and the heart was considered normal at initial echocardiography; this was confirmed by later scans and at postnatal follow-up. In 37/608 (6%) fetuses the risk for CHD was increased (35 for NT > 95(th) centile and two for family history). In this group normal heart anatomy was described in 34 fetuses and confirmed by subsequent specialist echocardiography. Cardiac defects were suspected in three fetuses (all with increased NT) and confirmed by a fetal cardiologist in each case. CONCLUSIONS: A trained operator can perform a fetal heart study during the NT screening test using transabdominal high-resolution transducers in an acceptable length of time.

Fetal hydrops due to a tachyarrhythmia progressing to organic pulmonary stenosis.

We discovered supraventricular tachycardia with advanced hydrops in the setting of normal cardiac anatomy at 26 weeks of gestation which resolved successfully following administration of digoxin and flecainide to the mother. A female baby was born after a premature rupture of the membranes at 30.6 weeks. The neonate was in sinus rhythm, showed a progressive regression of right ventricular insufficiency, but developed signs of acquired pulmonary valvar and subvalvar stenosis at 2 months of age.

Evolution of left ventricular diseasein the fetus. Case report.

A fetal case is described that showed a rapid progression from the features of initial left ventricular fibroelastosis at 20 weeks of gestation to a more marked dilation at 22 weeks and finally to a hypoplastic left ventricle with aortic stenosis at 24 weeks of gestation. This case confirms the evolutive character of left ventricular disease during fetal life.

Evolution and long term outcome in cases with fetal diagnosis of congenital heart disease: Italian multicentre study. Fetal Cardiology Study Group of the Italian Society of Pediatric Cardiology.

OBJECTIVES: To analyse the evolution and outcome in utero and after birth of infants with a fetal diagnosis of congenital heart disease. DESIGN: Inclusion criteria were the fetal diagnosis of congenital heart disease, confirmed postnatally or postmortem, and a complete follow up in utero and after birth. SETTING: 20 centres operating prenatal echocardiographic screening. PATIENTS: 847 cases were included in the study. Gestational age at diagnosis ranged from 15-39 weeks; in 370 cases (43.7%) the diagnosis was made before 24 weeks' gestation. RESULTS: 245/847 cases (28.9%) were terminated during pregnancy, 227 following early diagnosis; 128/245 cases (52. 2%) had associated anomalies and 117/245 (47.8%) had serious congenital heart disease. Of the remaining 602 cases that continued the pregnancy, 72 (11.9%) died in utero, 259 (43%) died postnatally (83 after surgery or invasive procedures), and 271 infants (45%) survived and presently range in age from 18 months to 13 years old. The mortality rate was higher in cases with associated extracardiac or chromosomal anomalies (68% and 74% of cases continuing pregnancy, respectively), and in cases with heart failure and complex cardiac defects. CONCLUSIONS: The data confirm a relevant fetal and postnatal loss in cases with complex congenital heart disease, and major clinical use of prenatal diagnosis in the management of ductus dependent anomalies. Negative prognostic factors for the outcome were associated anomalies and heart failure.

Fetal hydrops due to right ventricular and tricuspid valve dysplasia. A case report.

We report a case of fetal hydrops at 32 weeks of gestation, diagnosed prenatally due to an unusual form of non-Ebstein dysplasia of the tricuspid valve and of the right ventricle, different from the classification used in the literature. Digoxin therapy, administered for two weeks in utero and then after the premature delivery, did not improve the massive right heart failure due to the tricuspid insufficiency, and the baby died at 4 days of life.

[Cardiovascular abnormalities in Kawasaki disease. An Italian prospective study]. / Complicanze cardiovascolari in una popolazione pediatrica con malattia di Kawasaki. Uno studio prospettico.

We report a prospective study performed over a 9 year period in 96 children with Kawasaki disease (mean age 35 +/- 29 months), 84 of whom < 5 years of age. The male/female ratio was 1.5 (57/39). A total of 38 patients had cardiac involvement, including flattened T waves in the ECG (10 patients), pericardial effusion (6 patients), myocarditis (1 patient), and coronary artery aneurysms (25 patients; frequency of aneurysms: 26%). All patients were evaluated during the acute phase (first month) of the illness. The first echocardiographic examination was performed 15 days (range 4.30 days) from the appearance of fever, and coronary aneurysms were observed in 23 patients; in 2 patients, however, aneurysms appeared later (2 and 6 months). Aneurysms were small (< or = 4.5 mm) in 12, medium (4.5-7 mm) in 11, and large (> 7 mm) in 12 patients. Male sex (p = 0.02), age < 12 months (p = 0.005), ESR (p = 0.001), platelet count (p = 0.009), and pericardial effusion (p = 0.02) were significantly related to the presence of aneurysm. Among females, incidence of aneurysms was significantly higher in infants < 12 months than in older patients (60 vs 6%, p < 0.001). Intravenous immunoglobulin treatment was started early (within 10 days) in 61 patients and late (> 10 days) in 22. Compared to late treatment, early i.v. immunoglobulin treatment was associated with smaller aneurysms and higher regression rate (67 vs 28%, p < 0.05). No difference was observed concerning frequency and number of dilated vessels as related to therapeutical regimens. Total i.v. immunoglobulin dose (2 g/kg) was administered over 1-2 days in 26 patients (scheme I) or over 4-5 days in 58 (scheme II). Frequency of aneurysms was significantly lower in patients treated early (p = 0.02). No myocardial infarctions or deaths occurred at short- or long-term follow-up.