A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies.

Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018-2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.

Factors associated with high hospital resource use in a population-based study of children with orofacial clefts.

BACKGROUND: Little is known about population-based maternal, child, and system characteristics associated with high hospital resource use for children with orofacial clefts (OFC) in the US. METHODS: This was a statewide, population-based, retrospective observational study of children with OFC born between 1998 and 2006, identified by the Florida Birth Defects Registry whose records were linked with longitudinal hospital discharge records. We stratified the descriptive results by cleft type [cleft lip with cleft palate, cleft lip, and cleft palate] and by isolated versus nonisolated OFC (accompanied by other coded major birth defects). We used Poisson regression to analyze associations between selected characteristics and high hospital resource use (≥90th percentile of estimated hospitalized days and inpatient costs) for birth, postbirth, and total hospitalizations initiated before age 2 years. RESULTS: Our analysis included 2,129 children with OFC. Infants who were born low birth weight (<2500 grams) were significantly more likely to have high birth hospitalization costs for CLP (adjusted prevalence ratio: 1.6 [95% confidence interval: 1.0-2.7]), CL (adjusted prevalence ratio: 3.0 [95% confidence interval: 1.1-8.1]), and CP (adjusted prevalence ratio: 2.3 [95% confidence interval: 1.3-4.0]). Presence of multiple birth defects was significantly associated with a three- to eleven-fold and a three- to nine-fold increase in the prevalence of high costs and number of hospitalized days, respectively; at birth, postbirth before age 2 years and overall hospitalizations. CONCLUSION: Children with cleft palate had the greatest hospital resources use. Additionally, the presence of multiple birth defects contributed to greater inpatient days and costs for children with OFC.

[Life expectancy of extremely preterm infants]. / Extrém alacsony gesztációs korú koraszülöttek életkilátásai.

Extremely preterm infants [gestational age (GA) between 24-28 weeks] should be delivered optimally in an institute where neonatal intensive care unit (NICU) is available and their short- and long-term care is ensured. At the Department of Obstetrics and Gynecology, Medical School, University of Pécs, 7499 infants were born between 1st of January, 2000 and 31st of December, 2004. During this period the rate of preterm deliveries was 20% (1499/7499). Among preterm infants the incidence of extremely preterm babies (GA 28 weeks or less) was 18% (272/1499), the rate of profoundly preterm infants (GA less than 25 weeks) was 3.2% (48/1499). Advancing with gestational age the survival rate is increasing. At the department, the rate of handicapped infants among extremely premature babies was 15.3%. The majority of the handicapped infants were profoundly preterm, meanwhile, more than 50% of infants born at the 26 gestational weeks were free of symptoms influencing social activities. It is important to stress the prognostic value of the screening for hearing loss (otoacoustic emission), visual problems, and intracranial bleeding for the early detection and cure of the possible complications of prematurity.

Impacto economico de la prematurez y las malformaciones congénitas sobre el costo de la atención neonatal

Objetivos: Calcular los costos de la atención neonatal de recién nacidos prematuros y en portadores de malformaciones congénitas mayores compatibles con la vida. Pacientes y Método: Estudio retrospectivo efectuado en el Departamento de Ginecología y Obstetricia del Hospital Clínico de la Universidad de Chile, en 82 recién nacidos menores de 34 semanas de gestación y en 14 con malformaciones congénitas mayores, de más de 37 semanas de gestación, compatibles con la vida, atendidos entre enero y diciembre de 2004. Resultados evaluados son los costos de la atención neonatal subdivididos en componentes. Resultados: El costo promedio de la atención neonatal en recién nacidos menores de 34 semanas fue igual a $2.519.508, en menores de 32 semanas igual a $3.766.999, en menores de 1500 gramos igual a $12.017.650 y en portadores de malformaciones congénitas mayores compatibles con la vida de $30.967.180. El día cama representa el componente más significativo dentro cada paquete con más del 60 por ciento del costo promedio. Conclusiones: El costo de la atención neonatal de prematuros menores de 34 semanas o portadores de malformaciones congénitas mayores compatibles con la vida es mayor al contemplado en los paquetes de prestaciones a todo evento, representando el día cama su componente más significativo.

Objective: To calculate the cost involved in the neonatal care of premature or live born babies carriers of mayor congenital abnormalities compatible with life. Patients and method: Retrospective study who analyzed 82 premature live born of less than 34 weeks and 14 live born carriers of mayor congenital abnormalities compatible with life, from January to December 2004, at the Maternity Ward from the University of Chile Clinical Hospital. The outcome measures were the neonatal care average cost package subdivided by components. The cost was expressed in chilean currency. Results: Neonatal care average cost was $2.519.508 in live born of less than 34 weeks, $3.766.999 in less than 32 weeks, $12.017.650 in less than 1500 grams babies and $30.967.180 in carriers of mayor congenital abnormalities. In bed day cost represents the most significant component from the package, representing more than 60 percent of its total cost. Conclusions: Neonatal care cost of premature live born of less than 34 weeks or carriers of mayor congenital abnormalities compatible with life is higher than the maximum cost considered in the every-event health packages, representing in bed day its most significant component.

Windows on other worlds: the rise and fall of sideshow alley.

This article explores the world of Sideshow Alley, which emerged from the ancient fair culture of Britain and took root in the agricultural show movement of Australia by the 1880s. There it flourished until the 1950s, when modernity and respectability caused its demise. The article also argues that Sideshow Alley was a place of power that helped to shape the identities of many Australians through the display of difference and that it also provided a site of agency for those displaying themselves.

Cost-effectiveness of echocardiography for evaluation of children with murmurs.

Echocardiography is widely accepted as an accurate diagnostic test to evaluate heart murmurs in children, however its costs, and the ubiquity of murmurs in children, discourage its universal application. The purpose of this article is to identify some clinical circumstances in which the cost of echocardiography is justified for the evaluation of heart murmurs in infants and children. Eight common clinical problems were selected in which a heart murmur is present and a diagnosis is called for. Effectiveness of echocardiography and less costly clinical diagnostic methods in these settings were compared. In some circumstances, echocardiography is worth the cost, because clinical evaluation is unacceptably insensitive to important disease (the premature infant with a murmur which might represent a patent ductus arteriosus, the infant with a dysmorphic syndrome and a murmur). In others, the expert clinical examination is highly accurate (the asymptomatic child with a heart murmur) and is preferred over the echocardiogram as the initial diagnostic approach on the grounds of cost. When the expert clinical examination suggests minor structural heart disease, a continuum of echocardiographic cost-effectiveness relative to the expert clinical examination exists between these extremes depending on the working diagnosis. A threshold has not yet been defined at any point on this continuum above which the public will demand the greater diagnostic detail available echocardiographically, and below which the public will refuse to accept its greater cost. Quantitative formal cost-effectiveness analysis of echocardiography for evaluation of heart murmur in infants and children is not yet feasible because the benefits of echocardiography are indirect, dependent upon the as yet unmeasured benefits of correct management of congenital heart defects. To go beyond simple comparison of efficacy of echocardiography with less costly methods, further work is required in outcomes research in congenital heart disease.

Predicting hospital charge and length of stay for congenital heart disease surgery.

Three hundred twenty-two consecutive operations between December 1985 and December 1989 for 10 types of low-risk congenital cardiac malformations were reviewed to determine the hospital charge and postoperative length of stay. Multiple regression analysis of variance was used to predict the influence of the primary diagnosis and various preoperative parameters. The average hospital charge was $27,262 +/- $20,644 and the postoperative length of stay was 9.3 +/- 8.3 days. Age at operation alone did not influence the dependent variables. The diagnosis of atrial septal defect (p = 0.002) or coarctation of the aorta (p = 0.002) decreased the mean charge, whereas the 8 other primary diagnoses did not significantly influence the mean charge. Other preoperative factors found to be predictive of increased hospital charge were: the date of operation (p < 0.001), cyanosis (p = 0.008), previous thoracic surgery (p = 0.02), failure to thrive (p < 0.001), associated major extra cardiac anomalies (p < 0.001), oxygen requirement (p = 0.02), and distance > 100 miles from home to hospital (p = 0.05). A primary diagnosis of atrial septal defect decreased the mean postoperative length of stay by 3.1 days (p < 0.001). Other preoperative conditions increased the mean postoperative length of stay: major extracardiac malformation (p < 0.001), failure to thrive (p < 0.001), and oxygen requirement (p = 0.003). Charge and length of stay equations were generated which may assist in the prediction of resource utilization in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Baby Doe decisions: a hospital manager's perspective.

Profound changes have taken place in the treatment of seriously handicapped infants in hospitals. These changes are examined from the perspective of the hospital manager, looking at hospitals' response to the new challenges of handling "Baby Doe" types of cases, including the formation of Infant Care Review Committees in many hospitals.

The multihandicapped child with congenital rubella: impact on family and community.

In 1967, a hospital-based education program was created to provide services to multihandicapped children with congenital rubella syndrome (CRS). Since then 214 children have been enrolled, including 126 (59%) with laboratory-documented congenital rubella infection. An assessment of the ongoing training and life needs of those children with CRS enrolled in the program and the concomitant impact on families and community facilities has documented the general failure of the children to progress toward independence in spite of extensive educational programs and support services. The human and economic costs of these severe rubella-caused disabilities already have been enormous and will continue to be so for many years because even in adulthood these victims will require 24-hr supervision and care. The extensive rubella-vaccination effort made since 1969 has resulted in a progressive decline in the percentage of children requiring enrollment in this program whose disabilities are due to congenital rubella. The last such enrollee was born in 1981.