RESUMO
OBJECTIVE: To evaluate genetic testing utilization and diagnostic yield in infants with esophageal atresia (EA)/tracheoesophageal fistula (TEF) over the past 12 years to inform future practices and individualize prognostication and management. STUDY DESIGN: A retrospective cohort study was performed for all infants with EA or EA/TEF hospitalized between January 2011 and January 2023 at a quaternary children's hospital. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed. RESULTS: There were 212 infants who were classified as follows: 1) complex/syndromic with EA/TEF plus an additional major anatomic anomaly (n = 114, of which 74 met VACTERL criteria); 2) isolated/nonsyndromic EA/TEF (n = 88) and 3) isolated/nonsyndromic EA (n = 10). A range of genetic tests were sent with varying diagnostic rates including karyotype analysis in 12 (all with complex/syndromic phenotypes and all positive), chromosomal microarray analysis in 189 (114 of whom were complex/syndromic with an overall diagnostic rate of 3/189), single gene testing for CHD7 in 18 (4 positive), and exome analysis in 37 complex/syndromic patients (8 positive). CONCLUSIONS: EA/TEF with and without additional anomalies is genetically heterogeneous with a broad range of associated phenotypes. While the genetic etiology of EA/TEF with or without VACTERL remains largely unknown, genome wide testing (exome or genome) including copy number analysis is recommended over chromosomal microarray testing. We anticipate that expanded genetic/genomic testing modalities such as RNA sequencing and tissue specific molecular testing are needed in this cohort to improve our understanding of the genomic contributors to EA/TEF.
Assuntos
Atresia Esofágica , Testes Genéticos , Fístula Traqueoesofágica , Humanos , Fístula Traqueoesofágica/genética , Fístula Traqueoesofágica/diagnóstico , Atresia Esofágica/genética , Atresia Esofágica/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Recém-Nascido , Lactente , GenômicaRESUMO
OBJECTIVE: To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers. STUDY DESIGN: The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge. RESULTS: Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both). CONCLUSIONS: Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.
Assuntos
Obstrução das Vias Respiratórias , Fissura Palatina , Micrognatismo , Lactente , Criança , Humanos , Recém-Nascido , Micrognatismo/epidemiologia , Micrognatismo/cirurgia , Fissura Palatina/epidemiologia , Fissura Palatina/cirurgia , Obstrução das Vias Respiratórias/cirurgia , Unidades de Terapia Intensiva , América do Norte , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate genetic testing use in infants with congenital diaphragmatic hernia (CDH) over the past decade to better inform future practices and individualize prognostication and management. STUDY DESIGN: A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children's Hospital of Philadelphia, born between January 2011 and February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed. RESULTS: The charts of 411 infants were analyzed. Overall, 22% (n = 89) were complex/syndromic and 78% (n = 322) were isolated/nonsyndromic. Mortality was significantly higher in complex/syndromic infants (P < .001) and in infants with diagnostic genetic testing (P < .001). Microarray was diagnostic in 9% (n = 34/399) and exome sequencing was diagnostic in 38% (n = 15/39). Genetic testing was diagnostic in 57% (n = 51/89) of complex/syndromic infants, but in only 2% of isolated/nonsyndromic infants (n = 8/322). Overall, genetic testing was diagnostic in 14% (n = 56). CONCLUSIONS: The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/nonsyndromic infants do not have a genetic etiology identified. This finding underscores the need for additional genetic and genomic studies (eg, whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH.