Khattar Divya, Suhrie Kristen R
Department of Neonatal Perinatal Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
Department of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, USA.
Cureus. 2023 Feb 8;15(2):e34779. doi: 10.7759/cureus.34779. eCollection 2023 Feb.
Objective Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) has a reported incidence of 1 in 3500 live births and requires intensive care and surgery. To evaluate the prevalence of a molecularly confirmed genetic etiology of EA/TEF in a level IV neonatal intensive care unit (NICU), focusing on genetic evaluation, diagnostic yield, and clinical outcomes of these neonates. Study design A retrospective cohort study over a period of seven years was performed for all patients admitted with a diagnosis of EA/TEF. Automated data was extracted for demographic information and manual extraction was done to evaluate the frequency of associated anomalies, type of genetic evaluations and diagnoses, and outcomes at NICU discharge. Results Sixty-eight infants met the inclusion criteria. The majority were male (n=42; 62%), born at >37 weeks' gestation (n=36; 53%), and had EA with distal TEF (n=54; 79%). Most (n=53; 78%) had additional associated congenital anomalies, but only 47 (69%) patients had a genetics evaluation performed and genetic testing was sent for 44 (65%) of those patients. The most common genetic testing performed was chromosomal microarray analysis (n=40; 59%), followed by chromosome analysis (n=11; 16%), and whole exome/genome sequencing (n=7; 10%). Five unique genetic diagnoses including CHARGE Syndrome, Fanconi Syndrome, EFTUD2-related mandibulofacial dysostosis, and two different chromosomal deletion syndromes were made for a total of nine (13%) patients in our cohort. The cohort suffered a high rate of morbidity and mortality during their NICU stay with important differences noted in isolated vs non-isolated EA/TEF. Twelve infants (18%) died prior to NICU discharge. Of those surviving, 40 (71%) infants had a primary repair, 37 (66%) infants required G or GJ feedings at NICU discharge, and eight (14%) patients were discharged on some type of respiratory support. Conclusion In this high-risk cohort of EA/TEF patients cared for at a quaternary NICU, a majority were non-isolated and had some form of a genetic evaluation, but a minority underwent exome or genome sequencing. Given the high prevalence of associated anomalies, high mortality, and genetic disease prevalence in this cohort, we recommend standardization of phenotyping and genetic evaluation to allow for precision care and appropriate risk stratification.
目的 食管闭锁伴或不伴气管食管瘘（EA/TEF）的报道发病率为每3500例活产中有1例，需要重症监护和手术治疗。为评估在四级新生儿重症监护病房（NICU）中经分子确诊的EA/TEF遗传病因的患病率，重点关注这些新生儿的遗传评估、诊断率和临床结局。研究设计 对所有诊断为EA/TEF的住院患者进行了为期七年的回顾性队列研究。提取自动数据用于人口统计学信息，并进行人工提取以评估相关异常的频率、遗传评估和诊断的类型以及NICU出院时的结局。结果 68名婴儿符合纳入标准。大多数为男性（n = 42；62%），孕龄>37周出生（n = 36；53%），且为伴有远端TEF的EA（n = 54；79%）。大多数（n = 53；78%）有其他相关先天性异常，但只有47名（69%）患者进行了遗传学评估，其中44名（65%）患者接受了基因检测。最常进行的基因检测是染色体微阵列分析（n = 40；59%），其次是染色体分析（n = 11；16%）和全外显子组/基因组测序（n = 7；10%）。在我们的队列中，共对9名（13%）患者做出了5种独特的基因诊断，包括CHARGE综合征、范可尼综合征、EFTUD2相关的下颌面骨发育不全以及两种不同的染色体缺失综合征。该队列在NICU住院期间发病率和死亡率较高，孤立性与非孤立性EA/TEF之间存在显著差异。12名婴儿（18%）在NICU出院前死亡。在存活的婴儿中，40名（71%）进行了一期修复，37名（66%）婴儿在NICU出院时需要胃造口或胃空肠造口喂养，8名（14%）患者出院时仍需某种形式的呼吸支持。结论 在这家四级NICU护理的这一高危EA/TEF患者队列中，大多数为非孤立性，且进行了某种形式的遗传评估，但少数患者接受了外显子组或基因组测序。鉴于该队列中相关异常的高患病率、高死亡率和遗传疾病患病率，我们建议对表型分型和遗传评估进行标准化，以实现精准护理和适当的风险分层。
