Identifying birth defects in automated data sources in the Vaccine Safety Datalink.

PURPOSE: The Vaccine Safety Datalink (VSD), a collaboration between the Centers for Disease Control and Prevention and several large healthcare organizations, aims to monitor safety of vaccines administered in the USA. We present definitions and prevalence estimates for major structural birth defects to be used in studies of maternal vaccine safety. METHODS: In this observational study, we created and refined algorithms for identifying major structural birth defects from electronic healthcare data, conducted formal chart reviews for severe cardiac defects, and conducted limited chart validation for other defects. We estimated prevalence for selected defects by VSD site and birth year and compared these estimates to those in a US and European surveillance system. RESULTS: We developed algorithms to enumerate >50 major structural birth defects from standardized administrative and healthcare data based on utilization patterns and expert opinion, applying criteria for number, timing, and setting of diagnoses. Our birth cohort included 497 894 infants across seven sites. The period prevalence for all selected major birth defects in the VSD from 2004 to 2013 was 1.7 per 100 live births. Cardiac defects were most common (65.4 per 10 000 live births), with one-fourth classified as severe, requiring emergent intervention. For most major structural birth defects, prevalence estimates were stable over time and across sites and similar to those reported in other population-based surveillance systems. CONCLUSIONS: Our algorithms can efficiently identify many major structural birth defects in large healthcare datasets and can be used in studies evaluating the safety of vaccines administered to pregnant women. Copyright © 2017 John Wiley & Sons, Ltd.

Uhl's anomaly: perspective of fetal echocardiography and histopathological correlation.

We report a case of Uhl's anomaly imaged at 19 weeks of gestation by fetal echocardiography with pathological confirmation by anatomical gross heart specimen and tissue histology. Uhl's anomaly of the right ventricle is a rare cardiac disorder with isolated right ventricular enlargement with almost complete absence of the right ventricular myocardium.

Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18 months to 10 years, mean follow-up 60 months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed.

Right Ventricular Enlargement In Utero: Is It Coarctation?

Antenatal diagnosis of right heart enlargement has a wide spectrum of differential diagnosis from maternal, placental and fetal causes, and outcomes of all are not known. Coarctation of the aorta is in the differential diagnosis of right heart enlargement. In our study, we focused to measure multiple cardiac dimensions in fetuses with right heart enlargement to identify the fetus with coarctation of the aorta utilizing echocardiographic measurements. Ten cardiovascular dimensions were measured from fetal studies between 20- and 34-week gestation, and six were measured on postnatal echocardiograms. Z-scores for the cardiac dimensions were calculated, and each variable for fetuses and infants was tested using a two-sample t test between patients with and without coarctation. We excluded fetuses with TAPVR, Shone complex, interrupted aortic arch, Ebstein anomaly or HLHS. Of the 31 fetuses with in utero right heart enlargement, 11 had coarctation postnatally and 20 did not have coarctation. We compared the fetal and newborn cardiac dimensions between the groups. The mean fetal carotid-subclavian index (CS Index) was 0.7 mm with coarctation compared with 1.1 mm without coarctation (p < 0.0001). The mean difference in diameter z-scores for fetal aortic isthmus (p < 0.0001), mitral valve (<0.001) and aortic valve (p < 0.009) was also significantly different. Similar significant differences were noted postnatally in the diameters of the cardiac dimensions between the coarctation and no-coarctation group: CS index (p < 0.0001), aortic isthmus (p < 0.0002) and aortic valve annulus (p < 0.007). A spectrum of diagnoses was found postnatally in fetuses with right heart enlargement, including a normal heart. The likelihood of identifying fetuses with coarctation of the aorta and planning for postnatal management can be refined by noninvasive screening measurements. A smaller CS index and smaller diameters of the aortic isthmus, mitral valve and aortic valve were significantly associated prenatally (p < 0.05) with coarctation of the aorta versus without coarctation and might be useful in prenatally diagnosing coarctation of the aorta. Postnatally, these measurements are reproducible. This is the first study utilizing these specific measurements to diagnose coarctation prenatally.

Pathology of the aortic arch in hypoplastic left heart syndrome: surgical implications.

Aortic arch reconstruction plays an important role in the success of the Norwood procedure (NP) for hypoplastic left heart syndrome (HLHS). This study investigated the cardiac specimens to determine the etiology of distal aortic arch obstruction after the NP for HLHS and to locate coarctation of the aorta in HLHS untreated by surgery. This study examined 17 cardiac specimens: 9 that had NP and 8 not treated by surgery. The findings after NP showed frequent failure to resect the coarctation segment completely and failure to extend the augmentation patch into the descending aorta. Five (62.5%) of the eight hearts not treated by surgery had significant periductal coarctation of the aorta. After NP for nine patients, three (33%) had residual coarctation of the aorta. To minimize the risk of recurrent or persistent aortic arch obstruction after NP and to improve the long- and short-term outcome, the ductal tissue and the coarctation segment encircling the aortic lumen should be resected. The distal wall incision should be extended at least 5 mm beyond the distal aspect of the ductal tissue. These steps could avoid major aortic arch obstruction, promote growth of the native aortic tissue, and avoid ventricular dysfunction.

Polyhydramnios with bidirectional fetal ductus arteriosus flow in a fetus with congenital diaphragmatic hernia: case report.

The etiology of polyhydramnios may be attributed to either increased production of amniotic fluid (fetal polyuria or high-output cardiac failure) or decreased fetal swallowing (obstruction or neurological impairment). Although idiopathic polyhydramnios occurs in nearly half of all cases, it is often associated with fetal abnormalities. Fetal ductus arteriosus flow is normally from right to left. We report a case of antenatally detected bidirectional fetal ductus arteriosus flow diagnosed concomitantly with polyhydramnios. Amnioreduction was performed due to severe maternal symptoms, which resulted in correction of the fetal ductus arteriosus flow. Postnatal diagnosis of a Morgagni diaphragmatic hernia indicates that our sonographic findings collectively may have been a diagnostic clue.

Effect of dexmedetomidine on pulmonary artery pressure in children with congenital heart disease and pulmonary hypertension.

Background: This study was undertaken to determine the effects of dexmedetomidine on pulmonary artery pressure (PAP) in children with congenital heart disease (CHD) and pulmonary hypertension (PH) undergoing cardiac catheterization with and without a planned intervention during monitored anesthetic care using midazolam and ketamine. Materials and Methods: Children (<18 years) with known CHD and PH who were scheduled for cardiac catheterization and interventional procedures were included in the study. The procedures were performed under monitored anesthesia. After obtaining baseline PAPs, an intravenous (IV) infusion of dexmedetomidine (1 µg/kg) was given for over 10 min. During infusion, heart rate (HR), blood pressure (BP), respiratory rate (RR), and peripheral arterial oxygen saturation (SPO2) were recorded every 2 min until completion of dexmedetomidine infusion, 15 min later, and when the procedure was completed. In addition, pulmonary artery systolic and diastolic pressures, and mean pulmonary artery pressure (MPAP) were recorded and the pulmonary artery systolic pressure (PASP)/systolic blood pressure (BP) ratio was calculated. Results: All children tolerated the procedure without adverse events. The HR decreased significantly over time during dexmedetomidine infusion. The changes in systemic systolic BP and PAPs were not significantly different from the baseline value at all points of measurement as was the ratio between the systolic pulmonary artery and systolic systemic BPs. Conclusions: Administration of dexmedetomidine in a dose of 1 µg/kg over 10 min did not significantly alter the PAP in children with CHD and PH. There was a decrease in the HR that was not clinically significant. The children tolerated dexmedetomidine without adverse events.

Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors.

BACKGROUND: Childhood cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance. OBJECTIVES: To assess the timing of changes in serial echocardiographic parameters in pediatric age childhood cancer survivors and to evaluate their associations with cardiomyopathy development. METHODS: We performed a multi-center retrospective case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening (FS) ≤28% or ejection fraction (EF) ≤50% on ≥2 occasions) were matched to controls (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core lab, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2D, M-mode, pulsed wave Doppler and tissue Doppler imaging derived parameters across time between cases and controls. RESULTS: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n=181; controls, n=231) determined that indices of LV systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and LV size (end diastolic dimension z-scores) were significantly different between cases and controls, even four years prior to the development of cardiomyopathy. CONCLUSIONS: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric age childhood cancer survivors and are associated with the development of cardiomyopathy.

Relation of increase in adiposity to increase in left ventricular mass from childhood to young adulthood.

This study evaluated the influence of adiposity on the progression of left ventricular (LV) mass from childhood to adulthood and the relation of LV mass to insulin resistance in young adulthood. One hundred thirty-two healthy children recruited into a longitudinal study at a mean age of 13 years and reevaluated at 27 years, at which time insulin resistance studies were also performed, were studied. Echocardiographic assessment of LV mass was made and indexed for height. Body mass index (BMI) at 13 years was highly correlated with BMI at 27 years, as was LV mass index at 13 and 27 years. The cross-sectional correlation of LV mass index and BMI at 13 years (r = 0.38, p < 0.0001) had strengthened considerably by 27 years (r = 0.55, p < 0.0001). A BMI increase > or = 5.5 kg/m2 from 13 to 27 years was associated with a significantly greater increase in the LV mass index (p < 0.0001) than a BMI change < 5.5 kg/m2, and this relation was similar in children who were thin and heavy at baseline. In young adulthood, the relation of LV mass index to lean mass was weaker than that of LV mass index to fat mass. The association of LV mass with insulin resistance was dependent on adiposity. In conclusion, adiposity and LV mass are related in childhood, and this association tracks and becomes stronger in young adulthood. Moreover, the increase in LV mass from childhood to young adulthood is related to the degree of increase in BMI, independent of BMI at 13 years, suggesting that an excessive increase in LV mass could be limited by controlling gain in body fat during adolescence.

Intraoperative transesophageal echocardiographic assessment of left ventricular Tei index in congenital heart disease.

BACKGROUND: Use of the Tei index has not been described to assess myocardial function before or after surgery in pediatric patients. This study was designed to evaluate the left ventricular (LV) function using the Tei index pre- and post-cardiopulmonary bypass in patients with lesion that result in a volume loaded right ventricle (RV). METHODS: Retrospective data on 55 patients who underwent repair of a cardiac defect were analyzed. Patients with volume overload RV (n = 15) were compared to patients without volume overload but with other cardiac defects (n = 40). We reviewed pre- and post-operative LV myocardial performance index (Tei index). Tei index was obtained from transesophageal Doppler echocardiogram. RESULTS: Patients with right heart volume overload, the mean preoperative Tei index was 0.6, with a postoperative mean decrease of 0.207 (P = 0.014). Patients without right heart volume overload, the mean preoperative Tei was 0.48 with no significant postoperative change (P = 0.82). CONCLUSION: Pre- and post-operative transesophageal echocardiogram assessment provides an easy and quick way of evaluating LV function intra-operatively using LV Tei index. Preoperative LV Tei index was greater in the RV volume overload defects indicating diminished LV global function. This normalized in the immediate postoperative period, implying an immediate improvement in LV function. In patients without right heart volume load, consist of other cardiac defects, demonstrated no changes in the pre- and post-operative LV Tei. This implies that LV function was similar after the surgery.

A case of fetal diagnosis of noncompaction cardiomyopathy and coarctation of the aorta.

Background Left ventricular noncompaction (LVNC) cardiomyopathy is a rare form of cardiomyopathy. It is difficult to diagnose prenatally and therefore not well described in the fetal population. There have been a few reports in the literature detailing isolated cases of fetal and neonatal LVNC cardiomyopathy. Case Report We present a case of LVNC cardiomyopathy and coarctation of the aorta detected prenatally at 29 + 6 weeks of gestation with survival in infancy. This is the first case report in the literature describing the fetal diagnosis of noncompaction cardiomyopathy and associated coarctation of the aorta; a rare combination. Conclusion With a high index of suspicion, the antenatal diagnosis of noncompaction cardiomyopathy may improve neonatal morbidity and mortality.

Evaluation of traditional and novel measures of cardiac function to detect anthracycline-induced cardiotoxicity in survivors of childhood cancer.

PURPOSE: Cardiovascular disease is the leading noncancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function, but newer imaging modalities may provide additional information about preclinical disease. This study aimed to evaluate these modalities in detection of anthracycline-induced cardiac toxicity. METHODS: We compared mean radial displacement, EF, and FS among 17 adult survivors of childhood cancer exposed to ≥ 300 mg/m(2) of anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a history of cardiac-directed radiation, diabetes, or heart disease were excluded. RESULTS: Survivors (35% male), mostly with history of treatment for a solid tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m(2). FS (35.5 vs. 39.6%, p < 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02) were significantly lower in survivors compared to controls, respectively. Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7%), it was not statistically significant (p = 0.057). All echocardiographic measures were inversely associated with anthracycline dose, though radial displacement was no longer significantly correlated with anthracycline dose after controlling for survival time (p = 0.07), while EF remained correlated (p = 0.003). IMPLICATIONS FOR CANCER SURVIVORS: Radial displacement, EF, and FS are lower in childhood cancer survivors compared to controls. In this study, radial displacement added no new information beyond the traditional measures, but clinical utility remains undetermined and requires further longitudinal study.

Fetal complete common atrioventricular canal defect: spontaneous closure of the ventricular septal defect--in utero anatomic evolution and postnatal outcomes.

BACKGROUND: We describe in utero anatomic evolution and postnatal outcome of complete common atrioventricular canal defect (CCAVCD). METHODS: Retrospective data on 31 fetuses with CCAVCD were analyzed. We reviewed prenatal and postnatal echocardiograms, karyotype, and postnatal outcomes. RESULTS: A total of 20 fetuses had complete data, 18 with serial fetal echocardiograms and postnatal data and 2 terminations. At initial examination, isolated CCAVCD was seen in 12 (67%) fetuses while 6 (33%) were associated with heterotaxy syndrome. On follow-up, 4 fetuses (22%) had spontaneous closure of the inlet ventricular septal defect (VSD) component of the CCAVCD, seen both at 30 to 35 weeks of gestation and on postnatal echocardiograms. These 4 fetuses had previously demonstrated CCAVCD between 18 and 25 weeks of gestation. A total of 15 (83%) patients underwent operative correction, 10 with isolated complete atrioventricular septal defect and 5 with heterotaxy had surgical repair. Four infants in whom spontaneous intrauterine closure of the VSD component was observed had no VSD noted at surgery and underwent closure of primum atrial septal defect and repair of the left atrioventricular (AV) valve cleft. CONCLUSIONS: Our data demonstrate that CCAVCD diagnosed during fetal life is not a static anomaly. In our series, an inlet VSD less than 4 mm and Rastelli type A anatomy (AV valve attachment to septal crest) during second trimester may evolve during third trimester by formation of AV sulcus pouch and spontaneous closure of the VSD. To the best of our knowledge, this is the first study to report such anatomic evolution of CCAVCD in the fetus. This information is vital for appropriate counseling for expectant parents.

"Vanishing" pulmonary valve stenosis.

OBJECTIVE: Both spontaneous resolution and progression of mild pulmonary valve stenosis (PS) have been reported. We reviewed characteristics of the pulmonary valve (PV) to determine factors that could influence resolution of mild PS. METHODS: Fifteen asymptomatic pediatric patients with spontaneous resolution of isolated mild PS were retrospectively reviewed. RESULTS: There was no correlation between the PV gradient, clinical presentation, age at diagnosis, or PV morphology. The PV annulus was small at initial presentation, which normalized at follow up. When corrected for the body surface area (z-score), the PV annulus was normal in all patients, including at initial evaluation. CONCLUSIONS: Based on our observation, neither age at diagnosis, nor PV-morphology-influenced resolution of mild PS. The variable clinical presentation makes it difficult to categorize and observe mild PS by auscultation alone. The PV annulus z-score could be a useful adjunct to determine the course and serial observation of mild PS.

Fetal diagnosis of left ventricular aneurysm: a case report.

Congenital left ventricular aneurysm is a rare but potentially lethal condition. We describe a case of isolated congenital left ventricular aneurysm diagnosed at 28 weeks' gestation. In addition to standard imaging, we utilized color-coded transthoracic tissue Doppler techniques to further evaluate the aneurysm postnatally.

Prenatal diagnosis and outcome of fetuses with double-inlet left ventricle.

The aim of this study is to characterize the in utero presentation of the subtype of double-inlet left ventricle (DILV), a rare congenital heart disease, and assess the postnatal outcome. We retrospectively studied fetuses diagnosed prenatally with DILV between 2007 and 2011. We reviewed the prenatal and postnatal echocardiograms, clinical presentations, karyotypes, and the postnatal outcomes. There were eight fetuses diagnosed with DILV with L-transposition of the great vessels (S, L, L). Mean gestational age at diagnosis was 24.7 weeks. Of these, four fetuses (50%) had pulmonary atresia. One fetus (12.5%) also had tricuspid atresia and coarctation of the aorta and died at 17 months of age. Complete heart block and long QT syndrome was present in one fetus (12.5%), who died shortly after birth. There were no extracardiac or karyotypic abnormalities. Six (75%) infants are alive and doing well. Double-inlet left ventricle with varied presentation can be accurately diagnosed prenatally. The outcome of fetuses is good in the absence of associated rhythm abnormalities with surgically staged procedures leading to a Fontan circulation.

A trileaflet "mitral valve" with three papillary muscles: brand new echocardiographic finding.

Congenital mitral valve malformations are rare, but are well known and described entities. Mitral valve malformations involve mitral valve apparatuses (leaflets and annulus) and subvalvar apparatuses (chordae and papillary muscle). Case reports of accessory mitral leaflets were already described, but were usually an appendix of the normal valve. We describe here a case report and present the images of a trileaflet mitral valve sustained by three papillary muscles in a young girl with subaortic stenosis.

Fetal goiter mimicking anomalous pulmonary venous connection.

Fetal thyroid dysfunction is a well-recognized cause of secondary cardiac disease, including arrhythmias and hydrops fetalis, but has not previously been reported to mimic structural heart disease. We describe a case of fetal goiter presenting as suspected anomalous pulmonary venous connection and highlight lessons for the obstetrician and pediatric cardiologist with regard to imaging as well as communication.

Prenatal diagnosis of conotruncal malformations: diagnostic accuracy, outcome, chromosomal abnormalities, and extracardiac anomalies.

The purpose of this study was to determine whether continuing experience in prenatal diagnosis of conotruncal malformations (CTMs) has resulted in improved diagnostic accuracy and outcome. Previous reports have demonstrated particular difficulty with ascertainment of the spatial relationship of the great arteries in patients with CTM. The prognosis for fetuses with CTM was poor. Medical records of 113 consecutive fetuses in whom a CTM (tetralogy of Fallot [TOF], double-outlet right ventricle [DORV], type B aortic arch interruption, transposition of the great arteries [TGA], and persistent truncus arteriosus [TA]) was diagnosed antenatally between 1994 and 2003 were reviewed. The diagnosis of the 91 fetuses with CTM included TOF (n = 32), TGA (n = 29), DORV (n = 22), and TA (n = 8). The great arterial spatial relationship was diagnosed accurately in 84 of the 91 (92%) live-born infants. In the other seven infants with DORV, the great arterial spatial relationship was identified inaccurately. The overall survival to 30 days was 85 of 91 (93%). Twenty-three of 91 (25%) patients had extracardiac anomalies. Genetic diagnosis (amniocentesis) was obtained in 63 of 94 patients; 11 (17%) had chromosomal abnormalities. Maternal glucose tolerance results were obtained in 65 of the 91 patients and were abnormal in 25 of 65 (38%). Prenatal diagnostic accuracy of conotruncal malformations is excellent; the arterial spatial relationship of DORV remains problematic. The populations of fetuses with CTMs who continue to develop to term have an excellent prognosis.