Congenital Heart Defects Group Research Articles

Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.

Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects.

Study on the Potential Biomarkers of Maternal Urine Metabolomics for Fetus with Congenital Heart Diseases Based on Modified Gas Chromatograph-Mass Spectrometer.

Background There has been significant research on the genetic and environmental factors of congenital heart defects (CHDs), but few causes of teratogenicity, especially teratogenic mechanisms, can be clearly identified. Metabolomics has a potential advantage in researching the relationship between external factors and CHD. Objective To find and identify the urinary potential biomarkers of pregnancy (including in the second and third trimesters) for fetuses with CHD based on modified gas chromatograph-mass spectrometer (GC-MS), which could reveal the possibility of high-risk factors for CHD and lay the foundation for early intervention, treatment, and prevention. Methods Using a case-control design, we measured the urinary potential biomarkers of maternal urine metabolomics based on GC-MS in a population-based sample of women whose infants were diagnosed with CHD (70 case subjects) or were healthy (70 control subjects). SIMCA-P 13.0 software, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), Wilcoxon-Mann-Whitney test, and logistics regression were used to find significant potential biomarkers. Result The 3D score graph of the OPLS-DA showed that the CHD and control groups were fully separated. The fitting parameters were R2x=0.78 and R2y=0.69, and the forecast rate was Q2=0.61, indicating a high forecast ability. According to the ranking of VIPs from the OPLS-DA models, we found 34 potential metabolic markers with a VIP > 1, and after two pairwise rank sum tests, we found 20 significant potential biomarkers, which were further used in multifactor logistic regressions. Significant substances, including 4-hydroxybenzeneacetic acid (OR=4.74, 95% CI: 1.06-21.06), 5-trimethylsilyloxy-n-valeric acid (OR=15.78, 95% CI: 2.33-106.67), propanedioic acid (OR=5.37, 95% CI: 1.87-15.45), hydracrylic acid (OR=6.23, 95% CI: 1.07-36.21), and uric acid (OR=5.23, 95% CI: 1.23-22.32), were associated with CHD. Conclusion The major potential biomarkers in maternal urine associated with CHD were 4-hydroxybenzeneacetic acid, 5-trimethylsilyloxy-n-valeric acid, propanedioic acid, hydracrylic acid, and uric acid, respectively. These results indicated that the short chain fatty acids (SCFAs) and aromatic amino acid metabolism may be relevant with CHD.

Metal nickel exposure increase the risk of congenital heart defects occurrence in offspring: A case-control study in China.

Background:Previous studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between exposure to nickel and CHDs occurrence in offspring. The aim of this study was to analyze the association between nickel exposure in mothers and the risk of CHDs in offspring.Materials and methods:To explore the association of nickel exposure and occurrence of CHD, a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of nickel in hair of pregnant woman and fetal placental tissue were measured and used a logistic regression analysis to explore the relationship between nickel exposure and risk of CHD.Results:The median concentrations of nickel were 0.629 ng/mg, P < .05 (adjusted odds ratio [aOR], 1.326; 95% CI, 1.003–1.757) and 0.178 ng/mg, P < .05 (aOR, 2.204; 95% CI, 0.783–6.206), in maternal hair and in fetal placental tissue in the CHD group, respectively. Significant differences in the level of nickel in hair were also found in the different CHD subtypes including septal defects (P < .05), conotruncal defects (P < .05), right ventricular outflow tract obstruction (P < .01), and left ventricular outflow tract obstruction (P < .05). Dramatically different nickel concentrations in fetal placenta tissue were found in cases with other heart defects (P < .05).Conclusions:The finding suggested that the occurrence of CHDs may be associated with nickel exposure.

889: Utility of Noninvasive Prenatal Testing (NIPT) in evaluation of Congenital Heart Defects (CHD)

NIPT side steps many of the issues associated with invasive fetal testing, and has become a popular screening tool in assessing chromosome abnormalities when fetal anomalies are identified. Our clinical experience suggested NIPT has low yield in fetuses with heart defects. This study describes the utility of NIPT in specific classes of congenital heart disease. Retrospective chart analysis identified pregnancies with isolated (I) or non-isolated (NI) fetal CHD. Inclusion criteria: confirmed cardiac diagnosis, prenatal NIPT results known, abnormal postnatal chromosome results. CHDs were classified based on their embryological development: 1) hypoplastic left heart (HLH); 2) transposition of great arteries (TGA); 3) truncus arteriosus (TA); 4) conotruncal defects (CT); 5) atrioventricular septal defect (AVSD); 6) muscular septal defects (mVSD); 7) right aortic arch (RAA); 8) coarctation of aorta (CoA)/interrupted aortic arch (IAA); and, 9) right sided defects. Utility of NIPT was defined as the chance NIPT could provide a causative diagnosis for the CHD ( T21, T18, T13, 45,X, triploidy, del22q11.2) to the patient to supplant invasive testing in confirmed (I) and (NI) CHD groups Eighty two babies with abnormal chromosomes were studied, 57 with isolated defects and 25 with both cardiac and extracardiac abnormality. Table 1 shows the percentage of cases predicted accurately by NIPT, ordered by CHD class. The highest utility of NIPT in (I) and (NI) cases was in cases with TA or AVSD, 100% and 94.4%, respectively. NIPT gave no valuable information in isolated HPLH, TGA, or RAA. Overall yield of NIPT was 64% for isolated CHD, 70.7% for non-isolated cases. Genetic conditions not identified by NIPT in NI CHD cases include microarray abnormalities and single gene conditions (Noonan syndrome). Two cases of aortic coarctation were diagnosed with mosaic Turner syndrome; the technology of NIPT may be limited in mosaic cases. NIPT has satisfactory (although not complete) utility in AVSD and CT abnormalities more often associated with standard aneuploidies. A low-risk result from NIPT does not eliminate microarray abnormality for all other types of CHD and is not reliable enough to substitute for invasive fetal testing. Invasive procedures have modest associated risks, but the additional information they provide may be key for families and healthcare providers. The CHD category is an important factor to consider if NIPT is offered as an option.

A Comparison of Developmental Outcomes of Adolescent Neonatal Intensive Care Unit Survivors Born with a Congenital Heart Defect or Born Preterm

To compare cognitive, motor, behavioral, and functional outcomes of adolescents born with a congenital heart defect (CHD) and adolescents born preterm. Adolescents (11-19 years old) born with a CHD requiring open-heart surgery during infancy (n = 80) or born preterm ≤29 weeks of gestational age (n = 128) between 1991 and 1999 underwent a cross-sectional evaluation of cognitive (Leiter International Performance Scale-Revised), motor (Movement Assessment Battery for Children-II), behavioral (Strengths and Difficulties Questionnaire), and functional (Vineland Adaptive Behavior Scale-II) outcomes. Independent samples t tests and Pearson χ2 or Fisher exact tests were used to compare mean scores and proportions of impairment, respectively, between groups. Adolescents born with a CHD and adolescents born preterm had similar cognitive, motor, behavioral, and functional outcomes. Cognitive deficits were detected in 14.3% of adolescents born with a CHD and 11.8% of adolescents born preterm. Motor difficulties were detected in 43.5% of adolescents born with a CHD and 50% of adolescents born preterm. Behavioral problems were found in 23.7% of adolescents in the CHD group and 22.9% in the preterm group. Functional limitations were detected in 12% of adolescents born with a CHD and 7.3% of adolescents born preterm. Adolescents born with a CHD or born preterm have similar profiles of developmental deficits. These findings highlight the importance of providing long-term surveillance to both populations and guide the provision of appropriate educational and rehabilitation services to better ameliorate long-term developmental difficulties.

Impaired placental perfusion and major fetal cardiac defects.

To investigate the relationship between fetal congenital heart defects (CHD) and placental perfusion assessed by uterine artery pulsatility index (UtA-PI), in relation to development of pre-eclampsia (PE). This was a prospective screening study of singleton pregnancies at 19-24 weeks' gestation. Transvaginal ultrasound was used to measure UtA-PI and the values were converted into multiples of the normal median (MoM). Median MoM values in pregnancies with a fetus with isolated major CHD were compared to those without CHD, in relation to development of PE. The 91 407 singleton pregnancies fulfilling the entry criteria included 206 (0.23%) with isolated major fetal CHD and 91 201 without CHD. The prevalence of PE was 4.4% in pregnancies with fetal CHD and 2.7% in those without CHD (relative risk (RR), 1.6 (95% CI, 0.84-3.04); P= 0.150); the respective values for preterm PE with delivery at < 37 weeks' gestation were 2.4% and 0.7% (RR, 3.4 (95% CI, 1.42-8.09); P= 0.006). In the total population, median UtA-PI MoM was significantly higher in those that developed PE compared to those without PE (1.22 (interquartile range (IQR), 0.94-1.57) vs 1.00 (IQR, 0.84-1.19); P< 0.0001) and, in the PE group, the median UtA-PI MoM was inversely related to gestational age at delivery (r= -0.458; P< 0.0001). The same pattern of inverse relationship between UtA-PI MoM and gestational age at delivery with PE was observed in pregnancies with and those without CHD, but, in the CHD group, compared to those without CHD, UtA-PI was significantly higher both in pregnancies with and in those without PE. In pregnancies both with and without fetal CHD that develop PE, impedance to flow in the UtAs is increased and this increase is particularly marked in those with preterm PE. The prevalence of preterm PE is more than three times higher in pregnancies with than those without fetal major CHD, and the prevalence of major CHD in pregnancies with preterm PE is also more than three times higher than in those without PE. However, > 97% of pregnancies with fetal CHD do not develop preterm PE and > 99% of pregnancies with preterm PE are not associated with fetal CHD. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Expression profile of maternal circulating microRNAs as non-invasive biomarkers for prenatal diagnosis of congenital heart defects

ObjectiveThe discovery of cell free fetal microRNAs (miRNAs) in maternal circulation has opened up novel probabilities for non-invasive prenatal diagnosis. This study aims to investigate circulating miRNAs as potential biomarkers in the serum of pregnant women with congenital heart defect (CHD) fetuses. MethodA total of 110 pregnant women including 50 CHD cases and 60 healthy controls were included in this study. miRNA microarray followed by real-time PCR was used to explore miRNA expression. Receiver operating characteristic (ROC) curves were calculated to assess the diagnostic capability of miRNAs for fetal CHDs. Results38 Serum miRNAs were revealed to be differentially expressed in the CHD group as compared to control group via microarray. Among these, nine down-regulated and three up-regulated miRNAs were validated by real-time PCR. Ten of these miRNAs were rapidly reduced in the normal maternal serum after delivery as compared to before delivery. In particular, we identified a biomarker panel consisting of four miRNAs (miR-142-5p, miR-1275, miR-4666a-3p and miR-3664-3p) capable of distinguishing CHDs from controls (area under the ROC curve (AUC), 0.920; p < 0.0001). ConclusionThe discovery of these dysregulated pregnancy-associated miRNAs in maternal serum may be potential biomarkers for non-invasive prenatal diagnosis of fetal CHDs.

Preliminary Evaluation of Fetal Congenital Heart Defects Changes on Fetal-Maternal Heart Rate Coupling Strength.

Monitoring fetal heart rate in an important aspect in evaluating fetal well being. Maternal-fetal interaction has shown evolution during fetal maturation. In this work, we studied maternal-fetal heart rate synchronization in early and late gestation fetuses. We also evaluated variations in the synchronization due to congenital heart defect (CHD). Maternal-fetal heart rate synchronization for 22 early gestation (Age < 32 weeks), $late gestation (Age >32 weeks) and 7 CHD fetuses (5 of them with gestational age < 32 weeks). The synchronization ratio between the mother and the fetus was more localized at certain fetus heart rate in the early gestation group while it was spreading over more fetal heart rate for the late group. For example, for maternal primary cycle of 3 beat- to-beat (m=3), the synchronization ratio of 5 fetus beats (n=5) contributed 60±30% of the whole coupling ratios for the early group while it contributed 30°30% for the late group (p< 0.01). On the other hand, the coupling ratio of m:n=3:7 contributed 4±17% of the early group and 13±24% for the late group (p< 0.05). The standard deviation of the phase coherence index $(\lambda_{-\mathrm{S}\mathrm{D}})$ for both the late and the CHD groups were significantly higher than the early group at different values. For example, $\lambda -\mathrm{S}\mathrm{D} was 0.006\pm 0.004$ for the early group while it was 0.009±0.008 for the late group (p< 0.01) and 0.01± 0.002 for the CHD group (p< 0.01) for m=3. The variation between the early and late normal groups might indicate a healthy development of the autonomic nervous system while the higher variation in the CHD group could be a good marker for impairment of the cardiac autonomic activity. Further coupling analysis with more abnormal cases is needed to verify these findings.

Decreased tissue oxygenation in newborns with congenital heart defects: a case-control study.

AimTo compare regional tissue oxygenation (rSO2) in the brain, intestine, and kidney between newborns with and without congenital heart defects (CHD).MethodsThis observational case-control study was conducted at the Neonatal Deparetment of Children's Hospital Ljubljana between December 2012 and April 2014. It included 35 newborns with CHD and 30 healthy age- and sex-matched controls. CHD were assessed echocardiographically and divided into acyanotic and cyanotic group. RSO2 in the brain, intestine, and kidney was measured using near-infrared spectroscopy (NIRS). Simultaneously, heart rate (HR), breathing frequency (BF), mean arterial blood pressure (MAP), and arterial oxygen saturation (Sao2) were recorded.ResultsNewborns with CHD had significantly lower rSO2 in the left brain hemisphere (67 ± 11% vs 76 ± 8%, P = 0.004), right brain hemisphere (68 ± 11% vs 77 ± 8%, P < 0.001), and the kidney (68 ± 13% vs 77 ± 10%, P = 0.015). RSO2 in the intestine did not significantly differ between the groups. HR, MAP, and Sao2 also did not differ between the groups, whereas BF was significantly higher in the CHD group (57 ± 12 vs 39 ± 10 breaths/min, P < 0.001). Between cyanotic and acyanotic group, we found no significant differences in rSO2 of any tissue.ConclusionsMonitoring tissue oxygenation by NIRS could enable a timely detection of hemodynamically important CHD.

CONGENITAL HEART DEFECTS: CURRENT STATE AND PRESENT ISSUES

Congenital heart defects are found with the frequency of 6-8 cases per 1000 childbirth. They are most threatening the child's life in the period after birth, especially in case by their characteristics they refer to the so-called critical defects: coarctation of the aorta, hypoplastic syndrome of the left heart, critical pulmonary artery stenosis, aortic stenosis, pulmonary artery atresia with intact interventricular septum. Coarctation of the aorta is one of the most common cardiac and vascular defects, accounting for about 8% of birth defects among the born alive neonates. This is a disorder of the normal development of the aorta in the projection of its isthmus up to complete interruption. The frequency of the hypoplastic syndrome of the left heart is 1-8% of all birth defects in the heart. With this pathology, 72% of newborns die during the first week of life. Critical pulmonary artery stenosis is approximately 11% of all birth defects in the heart; it can be compared by the occurrence with ventricular or atrial septum defects, characterized by the presence of obstacles that slow down the overall flow of blood in the area of the pulmonary trunk valve. Aortic stenosis is a group of congenital heart defects characterized by disorders of the blood flow from the left ventricle to the aorta. The following types of stenosis are differentiated: subvalvular (20-25%), supravalvular (5-10%), and valvular (50-70%). Atresia of the pulmonary artery with an intact interventricular septum is a rare congenital heart disease, in 25% of cases atresia is formed due to muscular obliteration of the right ventricle arterial cone.

Phospholipids and L-Carnitine Screening in Children with Congenital Heart Diseases Undergoing Surgical Correction

Objectives: Congenital heart defect (CHD) represents almost 33% of all major congenital deformities, representing a worldwide health problem. The aim of the study is to identify the value of lecithin, cephalin, sphingomyelin & other phospholipids screening in the pathogenesis and prognosis of CHDs and consequently improve their management. Methods: A total of 89 child with CHDs were included [35 atrial septal defect (ASD), 27 ventricular septal defect (VSD) and 27 patent ductus arteriosus (PDA)] and 34 child as a control group. Biochemical analysis of the plasma levels of total and different component of phospholipids for both CHD and control group were done by colorimetry and two-dimensional thin layer chromatography. Assay of plasma L-carnitine level was done by ELISA for both patients and control group. Results:The overall results of the present study revealed a significant reduction in the total phospholipids among CHD patients in comparison to the control group; also, a significant change in the phospholipid profile. A significant lower plasma L-carnitine levels in the CHDs group when compared with the control group (p < 0. 001). Conclusions: Disturbed total and differential types of phospholipids &plasma L-carnitine levels occurs in children with CHDs. Moreover, cell-specific targeting of L-carnitine and phospholipid biosynthetic pathways might serve as a possible strategy for helping favorable outcome in management of CHDs.

Barium exposure increases the risk of congenital heart defects occurrence in offspring

Context: Several studies have investigated the association between heavy metal exposure and congenital heart defects (CHDs). However, there are limited data regarding the relationship between barium exposure and the occurrence of CHDs. The objective of this study was to analyze the association between barium exposure in mothers and the risk of CHD in offspring.Materials and methods: We developed a case-control study with 399 cases and 490 controls with normal live births in China. The concentrations of barium in hair of pregnant woman and fetal placenta were measured. We used a logistic regression analysis to explore the association between barium exposure and the risk of CHD.Results: Logistic regression analysis indicated that the median concentration of barium in maternal hair in the CHD group was 4.180 ng/mg (adjusted odds ratio [aOR], 1.230; 95% confidence interval [CI], 1.146–1.321; p < .001), which was significantly higher than that in the control group (2.740 ng/mg). Furthermore, the median concentration of barium in fetal placental tissue in the CHD group was 0.617 ng/mg, while that in the control group was 0.447 ng/mg (aOR, 1.392; 95% CI, 1.074–1.659; p = .003). Significant differences in the concentration of barium in hair were also found between the different CHD subtypes and the controls. These differences were found in cases with septal defects (p < .001), conotruncal defects (p < .001), right ventricular outflow track obstruction (p < .001), left ventricular outflow track obstruction (p < .001), and anomalous pulmonary venous return (p = .010). Significantly different barium concentrations in fetal tissue were only found in cases with septal defects (p = .010).Conclusions: Maternal barium exposure was dose-dependently related to the risk of CHD in the offspring. Our findings suggest that the occurrence of some subtypes of CHD is associated with barium exposure.

Association Between Preeclampsia and Congenital Heart Defects [38L

INTRODUCTION: Emerging research supports a common dysfunctional angiogenic mechanism that manifests in mothers as preeclampsia (PE) and in fetuses as congenital heart defects (CHD). METHODS: CHD fetuses came from patients assessed by UMMC's Fetal Heart Program. Controls were identified retrospectively from our ultrasound database, and those with known chromosomal or non-CHD anomalies were excluded. PE was diagnosed by the American College of Obstetricians and Gynecologists’ 2013 guidelines and categorized as early (delivery &lt; 34 weeks) or late. Contributors to early and late PE were assessed and compared with controls using binary logistics regression and Chi-square analysis. RESULTS: Of 2856 meeting inclusion criteria, 215 (7.5%) had CHD. PE occurred in 182 (6.4%) cases, early PE in 28 (1%) and late PE in 153 (5.4%). CHD cases had no increased risk for early PE (OR:2.07 CI:0.71-6.01) or late PE (OR:0.85 CI:0.44-1.64) compared to controls. In the CHD group, developing late PE was significantly increased by diabetes (OR:7 (1.9-26) p=0.0005), or chronic hypertension (CHT) (OR:15 (3.7-63) p&lt; 0.0001). In the CHD group, CHT was the major determinant of late PE (Logistic regression R2=0.23 p &lt; 0.0001). In patients with CHT, CHD significantly determined late PE (OR:3.43 CI:1.3-9.1 p=0.001.) In those without CHD, late PE was not increased by diabetes (OR:1.4 CI: 0.93-2.11 p=0.11) or CHT (OR: 1.4 CI: 0.79-2.32 p=0.26). No maternal characteristics significantly correlated with early PE in either cohort. CONCLUSION: Fetal CHD did not solely predict an increased risk of PE. However, in women with CHT, fetal CHD increases risk of PE. Enhanced surveillance and treatment appear warranted in these women.

Ten-Year Clinical Experience with the Lumenless, Catheter-Delivered, 4.1-Fr Diameter Pacing Lead in Patients with and without Congenital Heart.

Patients with congenital heart defects (CHD) often present more challenges to pacing therapy due to anatomy than those without CHD. The lumenless, 4.1Fr diameter M3830 pacing lead (Medtronic, Inc., Minneapolis, MN, USA), approved for use in 2005, has, to date, reported to have excellent short-term (<6 years) lead performance. Unfortunately, very long-term performance is unknown, especially among CHD patients and with implants at alternate pacing (AP) sites. This study reports a 10-year clinical experience with the M3830 lead. Records of patients who received the M3830 lead were reviewed: patient demographics, implant techniques and locations, sensing and pacing characteristics, impedances (Imp), and any complications at implant and follow-up. From 2005 to 2015, 141 patients (ages 2-50, mean 20.1 years, 57% males) received 212 leads: atrial 115; ventricle 97. CHD was present in 62% of patients. Leads were inserted at AP sites in 96% of patients. Postimplant follow-up was from 3 months to 10 years (mean 56.3 months). Comparative implant versus follow-up values (mean ± standard deviation) were available on 196 leads (92.5%), showing persistently low (<1 v @ 0.4-0.5 ms) pacing thresholds (P = 0.57). Sensing was also comparable (atrial leads, P = 0.41; ventricular leads, P = 0.9). Impedances differed (P < 0.05) but remained within the normal range. Two A leads became dislodged and one was repositioned while two other leads (1 A, 1 V) were extracted. There are no differences observed in the pacing characteristics between the CHD and non-CHD groups on follow-up. The 4.1Fr lumenless pacing lead shows ease of implant regardless of CHD or AP site, excellent very long-term (10 years) stability, and performance indices with a very low rate of complications.

Conotruncal Heart Defects

Conotruncal anomalies comprise a diverse group of congenital heart defects involving the outflow tracts of the heart and the great .They are a leading cause symptomatic cyanotic cardiac disease diagnosed in utero. Conotruncal anomalies can be diagnosed by prenatal echocardiography with a high degree of accuracy. The overall prognosis for fetuses with a conotruncal anomaly is poor

Presence of Aggregatibacter actinomycetemcomitans in saliva and cardiac tissue samples of children with congenital heart disease.

The purpose of this study was to analyze the presence of Aggregatibacter actinomycetemcomitans in saliva and cardiac tissue samples of children requiring cardiac surgery in Istanbul, Turkey. Twenty-five patients (mean age: 6.24 ± 2.93) undergoing surgery for congenital heart defects (CHDs) and an age/gender-matched control group of 25 healthy children were enrolled in the study. Saliva samples were collected from all children; plaque index (PI) and gingival index (GI) were also determined. In CHD group, cardiac tissue samples were received during surgery. All samples were evaluated for the presence of A. actinomycetemcomitans and its highly leukotoxic JP2 clonal strains using polymerase chain reaction. The findings were analyzed by Mann-Whitney U, Chi-square, and Fisher's exact tests. No significant differences were found in PI and GI values between the groups. A. actinomycetemcomitans was not detected in cardiac tissue samples. A. actinomycetemcomitans in saliva was detected in 2 (8%) of the CHD and 5 (20%) of the control children (p > 0.05). A. actinomycetemcomitans JP2 clonal strains were determined from 1 (4%) of the control group while it was not determined from the samples of the CHD group. Early colonization of A. actinomycetemcomitans in oral cavities could be assessed as a risk marker for periodontal disease. Periodontal pathogens may enter bloodstream through bacteremia; thus, the presence of periodontal pathogens in the oral cavity of children should be assessed as a risk marker for cardiac diseases in older ages.

The Spectrum of Congenital Heart Defects in Infants with Down’S Syndrome, Khartoum, Sudan

The aim of this study was to determine the prevalence and the types of congenital heart defects (CHD). In children with Down’s syndrome (DS); and to assess the impact of CHD on nutritional status. This was a prospective cohort study of infants with DS over a six month period starting Sept 2011. CHD occurred in 43.1% of 109 children with DS. Atrioventricular Septal defect (AVSD) was found in 32%, Ventricular Septal defect (VSD) in 26%, Patent Ductus Arteriosus (PDA) in 17% and Atrial Septal Defect (ASD) in 15% of the affected infants. Over all under-nutrition was found in 62 (56.9 %) infants; 87.2% were in the CHD group and 33.9% in the group with normal hearts. The presence of CHD in children with DS had an influence on their nutritional status. Early recognition of the cardiac condition of neonates with DS by screening is justified.

Impact of introduction of 20-week ultrasound scan on prevalence and fetal and neonatal outcomes in cases of selected severe congenital heart defects in The Netherlands

To evaluate in a population-based cohort the effect of the introduction of the 20-week ultrasound scan in 2007 on the time of diagnosis, pregnancy outcome and total prevalence and liveborn prevalence of cases with selected congenital heart defects (CHDs) in The Netherlands. We included children and fetuses diagnosed with selected severe CHD, born in the 11-year period from 2001 to 2011. Two groups of CHD were defined: those associated with an abnormal four-chamber view at ultrasound (Group 1), and those associated with a normal four-chamber view at ultrasound (Group 2). The time of diagnosis, pregnancy outcome and total liveborn prevalence were compared for both groups over two 5-year periods, before and after the introduction of the 20-week ultrasound scan. Trends in total and liveborn prevalence were examined over 2001 to 2011. Information was collected on 269 children and fetuses. After the introduction of the 20-week ultrasound scan, the prenatal detection rate of CHDs increased in both groups (Group 1, 34.6% in 2001-2005 vs 84.8% in 2007-2011 (P < 0.001); Group 2, 14.3% in 2001-2005 vs 29.6% in 2007-2011 (P = 0.037)). The rate of termination of pregnancy (TOP) increased significantly only for Group 1 (15.4% vs 51.5% (P < 0.001)). The total prevalence of CHD in Group 1 increased over time from 2.9 per 10 000 births in 2001 to 6.4 per 10 000 births in 2011 (P = 0.016). The liveborn prevalence did not show a trend over time. For Group 2, no trends in total or liveborn prevalence could be detected over time. Since the implementation of the routine 20-week ultrasound scan in The Netherlands, prenatal detection rate of selected severe CHDs increased significantly. Improved prenatal detection was accompanied by a more than three-fold increase in TOP, although only in those CHDs with an abnormal four-chamber view at prenatal ultrasound.

Prenatal diagnosis of congenital heart defect by genome-wide high-resolution SNP array

This study aimed to detect genomic imbalances in fetuses with congenital heart defect (CHD) by high-resolution single-nucleotide polymorphism (SNP) array. A total of 99 fetuses with CHDs with or without other ultrasound anomalies (including structural anomalies and soft markers) but normal karyotypes were investigated using Affymetrix CytoScan HD array. Clinical significant copy number variations (CNVs) were detected in 19 fetuses (19.2%). The proportion for variants of unknown significance was 3% after parental analysis. Five known microdeletion/microduplication syndromes were identified. The detection rate in CHD plus structural anomaly (27.8%) or soft marker (25%) group was higher than but not statistically different from isolated CHD group (15.9%). There was no significant difference between the detection rates in simple and complex CHD groups (20.7% vs. 16.7%). The detection rate in fetuses with CHD and neurologic defect was significantly higher than those with other types of structural anomaly (75% vs. 14.3%, P < 0.05). Our results demonstrated the value of high-resolution SNP arrays in prenatal diagnosis of CHD; it should become an integral aspect in clinically molecular diagnosis and genetic counseling. The complexity of the cardiac defect was not related to the frequency of clinical significant CNV, but the presence of neurologic defect was related.

The presence of extensive atrial scars hinders the differential diagnosis of focal or macroreentrant atrial tachycardias in patients with complex congenital heart disease

Atrial tachycardias (ATs) frequently develop in patients with congenital heart defects (CHDs). This study aimed to evaluate the effects of extensive atrial scar formation on the total atrial activation time (TAAT) and its relation to the tachycardia cycle length (CL) to classify AT. Seventy-one patients were included and divided into two groups: patients without CHD (Group I, 35 patients) and with CHD (Group II, 36 patients). All patients underwent CARTO electroanatomical activation mapping. Two subgroups were created: centrifugal (CAT) or macroreentrant AT (MRAT). Total atrial activation time, CL, and mean bipolar signal amplitude (BiSA) were analysed. In Group I, 18 patients (51.4%) had CAT and 17 (48.6%) MRAT. The mean BiSA for Group I was 1.30 ± 0.32 mV. Total atrial activation time/CL ratios were different between CAT and MRAT (28.4 ± 16.9 vs. 66.6 ± 14.3%, P < 0.001). In Group II, 18 patients (50%) had CAT and 18 patients (50%) MRAT. The mean BiSA was 0.94 ± 0.50 mV and was not different for CAT and MRAT subgroups (1.04 ± 0.64 vs. 0.85 ± 0.29, P = 0.243). Total atrial activation time/CL ratios were comparable between CAT and MRAT patients (69.0 ± 40.4 vs. 83.6 ± 8.3%, P = 0.243). A significant lower BiSA was found for CAT with TAAT/CL ratios above 40% (0.62 ± 0.11 vs. 1.90 ± 0.18 mV, P < 0.001). A strong negative correlation was identified between the BiSA and the TAAT/CL ratio in patients with CAT in Group II (-0.742; P < 0.001). Low mean BiSA values in CHD patients are associated with altered impulse propagation, making TAAT- and CL-based diagnostic tools inaccurate. Further diagnostic tests are needed to determine the correct mechanism of ATs.