Improved Outcomes in Patients with 22q11.2 Deletion Syndrome and Diagnosis of Interrupted Aortic Arch Prior to Birth Hospital Discharge, a Retrospective Study

Interruption of the aortic arch (IAA) is a rare but life-threatening congenital heart defect if not corrected in the neonatal period. IAA type B is highly correlated with 22q11.2 deletion syndrome (22q11.2DS); approximately 50% of patients with IAA type B also have 22q11.2DS (Peyvandi et al.; Goldmuntz et al.). Early identification and repair of IAA can prevent severe morbidity and death. However, IAA is challenging to identify prenatally, or even in the neonatal period. In this study, we examined infants with IAA, diagnosed during pregnancy and prior to discharge (PPTD) from the birth hospital vs. those diagnosed following discharge (FD) from the newborn nursery. Our goals were to determine: (1) if early diagnosis improved outcomes; and (2) if patients with IAA and without 22q11.2DS had similar outcomes. In total, 135 patients with a diagnosis of 22q11.2DS and IAA were ascertained through the 22q and You Center at the Children’s Hospital of Philadelphia (CHOP). The examined outcomes included: timing of diagnosis; age at diagnosis (days); hospital length of stay (LOS); duration of intensive care unit (ICU) stay; mechanical ventilation (days); duration of inotrope administration (days); year of surgical intervention; birth hospital trauma level; and overall morbidity. These outcomes were then compared with 40 CHOP patients with IAA but without 22q11.2DS. The results revealed that the PPTD neonates had fewer days of intubation, inotrope administration, and hospital LOS when compared to the FD group. The outcomes between deleted and non-deleted individuals with IAA differed significantly, in terms of the LOS (40 vs. 39 days) and time in ICU (28 vs. 24 days), respectively. These results support the early detection of 22q11.2DS via prenatal screening/diagnostics/newborn screening, as IAA can evade routine prenatal ultrasound and postnatal pulse oximetry. However, as previously reported in patients with 22q11.2DS and congenital heart disease (CHD), patients with 22q11.2DS tend to fare poorer compared to non-deleted neonates with IAA.

[1]  A. Bassett,et al.  Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening , 2021, CMAJ open.

[2]  E. Zackai,et al.  What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia , 2018, American journal of medical genetics. Part A.

[3]  Peter J. Scambler,et al.  22q11.2 deletion syndrome. , 2015, Nature reviews. Disease primers.

[4]  R. Jonas Management of Interrupted Aortic Arch. , 2015, Seminars in thoracic and cardiovascular surgery.

[5]  S. Gilboa,et al.  Estimated Number of Infants Detected and Missed by Critical Congenital Heart Defect Screening , 2015, Pediatrics.

[6]  E. Goldmuntz,et al.  22q11.2 Deletion syndrome is associated with increased perioperative events and more complicated postoperative course in infants undergoing infant operative correction of truncus arteriosus communis or interrupted aortic arch. , 2014, The Journal of thoracic and cardiovascular surgery.

[7]  B. Emanuel,et al.  22q11.2 Deletions in Patients with Conotruncal Defects: Data from 1,610 Consecutive Cases , 2013, Pediatric Cardiology.

[8]  E. Rosenthal Coarctation of the Aorta and Interrupted Aortic Arch , 2012 .

[9]  R. Axt‐Fliedner,et al.  Fetal and Neonatal Diagnosis of Interrupted Aortic Arch: Associations and Outcomes , 2011, Fetal Diagnosis and Therapy.

[10]  Gaël Varoquaux,et al.  Scikit-learn: Machine Learning in Python , 2011, J. Mach. Learn. Res..

[11]  S. Colan,et al.  Fetal diagnosis of interrupted aortic arch. , 2010, The American journal of cardiology.

[12]  F. Sebening,et al.  Interrupted aortic arch: Natural history and operative results , 2006, Pediatric Cardiology.

[13]  P. Volpe,et al.  Prenatal diagnosis of interruption of the aortic arch and its association with deletion of chromosome 22q11 , 2002, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[14]  E. Zackai,et al.  Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: Cast a wide FISHing net! , 2001, Genetics in Medicine.

[15]  M. Nagatsu,et al.  Interruption of the aortic arch at the isthmus with DiGeorge syndrome and 22q11.2 deletion , 1999, Cardiology in the Young.

[16]  E. Zackai,et al.  Frequency of 22q11 deletions in patients with conotruncal defects. , 1998, Journal of the American College of Cardiology.

[17]  R. Kucherlapati,et al.  Velo-cardio-facial syndrome: frequency and extent of 22q11 deletions. , 1995, American journal of medical genetics.

[18]  E. Zackai,et al.  Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. , 1992, American journal of medical genetics.

[19]  P. Scambler,et al.  Microdeletions within 22q11 associated with sporadic and familial DiGeorge syndrome. , 1991, Genomics.

[20]  H. Meire Ultrasound in Pregnancy , 1987, International Journal of Technology Assessment in Health Care.

[21]  F. Mortensen [Complete interruption of the aortic arch]. , 1983, Ugeskrift for laeger.

[22]  C. Higgins,et al.  Interruption of the aortic arch: preoperative and postoperative clinical, hemodynamic and angiographic features. , 1977, The American journal of cardiology.

[23]  S. Yorifuji,et al.  The congenital cardiovascular anomalies of the interruption of the aorta--Steidele's complex. , 1972, American heart journal.

[24]  Lawrence T. Post,et al.  American College of Surgeons , 2020, Definitions.