Fetal Cardiovascular Malformations Research Articles

Chromosomal Microarray Analysis in Fetuses Detected with Isolated Cardiovascular Malformation: A Multicenter Study, Systematic Review of the Literature and Meta-Analysis.

Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate investigation with fetal echocardiography and the assessment through genetic counseling and testing. In particular, chromosomal microarray analysis (CMA) allows the identification of copy number variations. We performed a systematic review and meta-analysis of the literature, studying the incremental diagnostic yield of CMA in fetal isolated CVM, scoring yields for each category of heart disease, with the aim of guiding genetic counseling and prenatal management. At the same time, we report 59 fetuses with isolated CVM with normal karyotype who underwent CMA. The incremental CMA diagnostic yield in fetuses with isolated CVM was 5.79% (CI 5.54–6.04), with conotruncal malformations showing the higher detection rate (15.93%). The yields for ventricular septal defects and aberrant right subclavian artery were the lowest (2.64% and 0.66%). Other CVM ranged from 4.42% to 6.67%. In the retrospective cohort, the diagnostic yield was consistent with literature data, with an overall CMA diagnostic yield of 3.38%. CMA in the prenatal setting was confirmed as a valuable tool for investigating the causes of fetal cardiovascular malformations.

Description of misdiagnosis and missed diagnosis of fetal complex heart malformations by prenatal echocardiography combined with postnatal cardiovascular casting.

To compare prenatal echocardiography with postnatal cardiovascular casting for detection of fetal cardiovascular malformations, and to discuss the causes of prenatal misdiagnosis and missed diagnosis. We retrospectively identified patients from 2013 to 2018 at our Maternal-Fetal Medicine Center who were reported to have a fetal diagnosis of severe congenital heart malformations (CHMs). Subjects had postnatal confirmation of CHMs. Prenatal and postnatal medical records, including ultrasound results and casting findings, were reviewed and analyzed. Postnatal casting showed that all 35 fetuses had complex CHMs. In these 35 cases, 90 cardiovascular malformations were found by postnatal casting, and 69 were detected by prenatal echocardiography. Among the other 21 cardiovascular malformations, 7 were misdiagnosed and 14 diagnoses were missed by prenatal ultrasound. Prenatal echocardiography may lead to misdiagnosis and missed diagnoses, especially in cases with great arterial branching anomalies. Postnatal casting can demonstrate the configuration of the great vessels and smaller branches directly. Thus, understanding of such malformations via postnatal casting may help to improve prenatal diagnostic accuracy.

Clinical analysis of prenatal ultrasound diagnosis of fetal cardiovascular malformations in the first and second trimesters of pregnancy: A CARE-compliant article.

Fetal cardiovascular malformations is widely focused and screened, but the accuracy of screening is not satisfactory. In this study, we compared the types of congenital heart malformation, accompanying diseases and fetal outcomes in the first and second trimesters of pregnancy to clarify the advantage of early screening.From January 2013 to June 2018, 230 fetuses were diagnosed with congenital heart malformations using ultrasound method in Qilu Hospital of Shandong University, and divided into 2 groups:the first trimester fetuses (group A) and the second trimester fetuses (group B). In addition, we collected and organized medical data of 347 cases diagnosed with congenital heart disease during 1998 to 2005 (group C). We compared the spectrum of congenital heart disease, associated comorbidities and outcome of fetuses diagnosed with congenital heart disease.There were differences in the types and incidence of cardiac malformations between the first and second trimesters of pregnancy. The number of cases of non-cardiac malformation, congenital heart disease with single ventricular circulation, fetal intrauterine death and premature pregnancy termination was significantly lower in the late stage (group A and group B) than that in the early stage (group C). More patients were screened for trisomy 21, 18, 13 syndromes and Turner syndrome in group A than group B (P <.001). More fetuses with a 22q11 deletion were screened in group B than group C.Early pregnancy screening using ultrasound diagnosis is very important for fetuses with congenital heart disease.

Effects of Prenatal PM10 Exposure on Fetal Cardiovascular Malformations in Fuzhou, China: A Retrospective Case-Control Study.

Background:Maternal exposure to ambient air pollution has been associated with an increased risk of congenital heart defects in offspring; however, the results are inconsistent.Objectives:We investigated whether there is an association between prenatal exposure to particulate matter with diameter () during early pregnancy and fetal cardiovascular malformations.Methods:The gravidae from a hospital-based case–control study in Fuzhou, China, during 2007–2013 were assigned 10-d or 1-mo averages of daily using an air monitor–based inverse distance weighting method during early pregnancy. A total of 662 live-birth or selectively terminated cases and 3,972 live-birth controls were enrolled. The exposure was considered as a categorical variable. A multivariable logistic regression model was constructed to quantify the adjusted odds ratios (aORs) of the exposure to and the risks of fetal cardiovascular malformations.Results: levels were positively associated with the risks of atrial septal defect (aORs ranging from 1.29 to 2.17), patent ductus arteriosus [, 1.63; 95% confidence intervals (CIs): 1.17, 2.23; 1.06, 3.24], overall fetal cardiovascular malformations (; 95% CI: 1.03, 1.61), ventricular septal defect (; 95% CI: 1.00, 1.43), and tetralogy of Fallot (; 95% CI: 1.01, 2.19) in the various observed periods scaled by 10 d or 1 mo in the first and second gestation months. The strongest associations were observed for exposure to in the second quartile, whereas the associations were attenuated when higher concentrations of in the third and fourth quartiles of the exposure were evaluated. No correlations of levels with these cardiovascular malformations in the other time periods of gestation were observed.Conclusions:Our findings suggest some positive associations between maternal exposure to ambient during the first two months of pregnancy and fetal cardiovascular malformations. https://doi.org/10.1289/EHP289

The clinical value of prenatal ultrasound in fetal cardiovascular malformations

Objective To study the diagnostic value of prenatal ultrasound in fetal cardiovascular malformations.Methods 4 152 cases of pregnant women received prenatal ultrasound were slected in the study.The accuracy of prenatal ultrasound diagnosis was confirmed by follow-up.Results In 4 152 cases of pregnant women,24 cases of fetal cardiovascular malformations were detected,incidence rate of 5.78 per thousand,the follow-up confirmed 19 cases,3 cases refused an autopsy,2 cases were lost.The diagnostic accuracy reached 79.17％.Conclusion Prenatal ultrasound for diagnosis fetal cardiovascular malformations has high diagnostic accuracy,which may achieve clinical early diagnosis and early intervention,help control birth defects. Key words: Ultrasonography, prenatal ; Fetus ; Abnormalities ; Diagnosis

Pregnancy outcome after gestational exposure to erythromycin - a population-based register study from Norway.

Erythromycin is a macrolide antibiotic indicated for respiratory tract infections, genital chlamydia and skin infections. It has recently been suggested that erythromycin use in the first trimester of pregnancy can increase the risk of congenital cardiovascular malformations. This study aimed to determine whether erythromycin exposure in the first trimester is associated with cardiovascular or other malformations. We studied 180 120 women in Norway who were pregnant during 2004-2007. Data on all live births stillbirths and induced abortions after 12 gestational weeks from The Medical Birth Registry of Norway (MBRN) were linked to information from the Norwegian prescription database (NorPD). We compared the pregnancy outcomes of women who had taken erythromycin (n= 1786, 1.0%), penicillin V (n= 4921, 2.7%) or amoxicillin (n= 1599, 0.9%) in their first trimester with outcomes of women who had not taken any systemic antibiotics (n= 163 653, 90.9%) during this period. The risk of cardiovascular malformations was not significantly different with or without exposure to erythromycin in the first trimester (adjusted OR = 1.2 [95% CI 0.8, 1.8]) or in the most vulnerable period of heart formation (adjusted OR = 1.6 [95% CI 0.9-3.0]). Sub-analyses showed that the risk for any specific malformations was not increased with erythromycin, macrolides, penicillin V or amoxicillin compared with no antibiotic use in first trimester. This large, population-based register study did not find that exposure to erythromycin or macrolides in the first trimester of pregnancy was associated with fetal cardiovascular or other malformations. These results suggest that the risk of erythromycin use during early pregnancy, if any, is low.

Added value of three‐/four‐dimensional ultrasound in offline analysis and diagnosis of congenital heart disease

Many published studies have shown that application of three-dimensional (3D) and real-time 3D (4D) ultrasound modalities can improve certain aspects of fetal echocardiography, but have left open the question of whether these modalities improved the accuracy of prenatal detection of anatomical fetal cardiovascular malformations. We aimed to determine whether 3D/4D ultrasound improved diagnostic ability in cases of congenital heart disease (CHD). Women who attended for early- or midtrimester targeted organ scans had complete fetal echocardiography according to our five-planes protocol, as well as examination of the ductus venosus and longitudinal aortic arch planes, performed with 2D ultrasound combined with 2D color Doppler, spatiotemporal image correlation (STIC), STIC with color Doppler, and STIC with B-flow. Ultrasound data of cases of CHD were stored in a dedicated archive. Stored cases were anonymized and the list order was randomized. Stored 2D ultrasound cineloops and 4D ultrasound volumes were reviewed separately according to a standardized table of 23 specified structures on five required planes of visualization: the upper abdomen, four-chamber view, five-chamber view, pulmonary artery bifurcation view, and three vessels and trachea plane. Separate diagnoses were recorded and finally compared. Diagnoses were confirmed by pathological examination or neonatal echocardiography. During the study period, 13 101 examinations were performed; 181 diagnoses of CHD were made. In 12 of these, 3D/4D ultrasound added to the accuracy of our diagnosis: one right aortic arch with anomalous branching; one transposition of the great arteries with pulmonary atresia diagnosed with tomographic ultrasound imaging (TUI); one segmental interrupted aortic arch diagnosed with TUI; one right ventricle aneurysm diagnosed with B-flow; two agenesis of ductus venosus to the coronary sinus diagnosed by multiplanar reconstruction (MPR) and B-flow; two total anomalous pulmonary venous connection diagnosed with MPR; and four ventricular septal defect (VSD) diagnosed with the aid of virtual planes. There were 12 missed diagnoses and no false-positive results. 3D/4D ultrasound modalities may have advantages in some aspects of fetal cardiovascular evaluation, however, overall 3D/4D ultrasound modalities had added value in only about 6% of cases of fetal anatomical cardiovascular anomalies.

Population screening of fetal cardiac abnormalities through prenatal echocardiography in low-risk pregnancies in the municipality of Porto Alegre.

To study the morphological and functional abnormalities of the fetal cardiovascular system detectable through ultrasonography. The study comprised 3,980 fetuses of pregnant women with no obstetrical or cardiological risk in the municipality of Porto Alegre, who, from July 1996 to November 2000, underwent echocardiography for screening fetal cardiovascular malformations. The examinations consisted of 4-chamber and right and left ventricular outflow tract echocardiographic views. One hundred and three diagnoses of fetal cardiovascular abnormalities were established, corresponding to 2.58% (103/3,980) of the population studied, or 25.8/1000, of which 47 represented morphological and functional changes in the fetal heart with an overall prevalence of 11.8/1000 (47/3,980), and 56 showed changes in refringence (golf ball). Three false negative and no false positive results increased the overall prevalence to 12.5/1000 (50/3,980), or 26.6/1000 (106/3,980), when the refringence changes were also included. The detection of cardiovascular malformations still in the intrauterine period, aiming at perinatal planning, is possible, which confirms the international experience. Implantation of cardiovascular malformation screening into the routine care network of obstetrical ultrasonography is suggested.

Epilepsy and pregnancy: an obstetric perspective

ObjectiveThe purpose of this study was to determine the obstetric and neonatal outcomes of women with prepregnancy diagnoses of epilepsy. Study designThis was a cohort study of women with epilepsy (n=414 women) who were delivered in a tertiary referral center (1978-2000). Outcomes were compared with women who did not have epilepsy (n=81,759 women) who were delivered during the same period, with the use of t tests or contingency table analyses. ResultsComparison showed increased rates of nonproteinuric hypertension (P<.05), induction of labor (P<.001), and fetal cardiovascular malformations (P<.001) among women with epilepsy. Rates of other antenatal, intrapartum, and neonatal complications and congenital malformations were similar to those of control subjects. There were fewer instrumental vaginal deliveries. There were no live births with neural tube defects. The occurrence of major antepartum seizures did not increase the rate of adverse outcomes significantly. Major congenital malformations increased in proportion to the number of anticonvulsants that were prescribed. ConclusionWomen with epilepsy are not at increased risk for obstetric complications, provided that appropriate care is available during preconception, pregnancy, labor, delivery, and after delivery.

603 Integration of pediatric cardiology with perinatal obstetrics: A model for increased detection of fetal cardiovascular malformations

603 Integration of pediatric cardiology with perinatal obstetrics: A model for increased detection of fetal cardiovascular malformations

Prenatal diagnosis and management of fetal cardiovascular malformations

Screening for fetal cardiovascular malformations is widely performed. Its accuracy is not yet satisfactory, but better training of ultrasonographers and extension from the four-chamber view to the study of the outflow tract are probably clues to an improvement. The main impact of prenatal diagnosis is still the termination of pregnancy for severe malformations and for those associated with chromosomal or extracardiac anomalies. There is now evidence that prenatal diagnosis improves perinatal morbidity or mortality for some malformations. New information about the molecular genetic basis of congenital heart disease will help in management and counselling.

Fetal cardiovascular physiology and therapy.

The ability to diagnose fetal cardiovascular malformations prenatally has been established during the past 14 years. This has naturally led to an increased interest in the possibility of providing timely therapy in the neonatal period and has raised the prospects for prenatal intervention. Before medical, catheter, and/or surgical interventions are performed, however, it is important to understand the normal and abnormal physiology of the fetal cardiovascular system. Significant insights have been gained into human fetal cardiovascular physiology utilizing data previously gleaned from fetal lamb models and correlating anatomic, pulsed Doppler, and color flow Doppler observations that have been made echocardiographically during the second and third trimesters of human fetal cardiac development. Regional blood flow distribution studies in the human have demonstrated a relative right-ventricular volume dominance in the human fetus of a somewhat lesser magnitude than previously described in the lamb. Observations of ventricular filling characteristics suggest a relative paucity of diastolic 'reserve' in the human fetal heart implying a relative sensitivity to acute volume overloading. The human fetal heart, like that of the fetal lamb, also appears to have a relatively modest amount of 'systolic reserve', making the heart particularly susceptible to acute ventricular afterload. Further studies have demonstrated the ability to recognize altered intrauterine shunt flow across the fetal ductus arteriosus and foramen ovale. As predicted in fetal lamb models, alterations in shunt flow accompany major malformation complexes including ventricular hypoplasia. Studies to date suggest that attempts at surgical intervention should be made very cautiously due to the inability to ascertain whether altered shunt flow patterns precede (cause?) or follow the development of structural abnormalities.