Hypoxia, Poor Lower Extremity Perfusion, and Metabolic Acidosis in the First Day of Life

A female infant is born at 35 + 6 weeks gestation secondary to preterm labor with a birth weight of 2505 g. In the delivery room, she requires positive pressure ventilation and is transferred to the neonatal intensive care unit on continuous positive airway pressure for presumed respiratory distress syndrome.An initial capillary blood gas is notable for polycythemia with hematocrit of 69. She is given a 10 mL/kg normal saline (NS) bolus and started on dextrose-containing intravenous fluids at 100 mL/kg per day. A venous complete blood count shows rapid normalization of the hematocrit to 55, and all subsequent hematocrit values are within normal limits.Around 12 hours of life, the infant develops increased irritability, increased need for supplemental oxygen, and decreased perfusion to her bilateral lower extremities. At 14 hours of life, her hypoxia worsens, and her abdomen and lower extremities are mottled with delayed capillary refill. Chest radiograph shows signs of mild respiratory distress syndrome without evidence of pneumothorax or other significant anomaly. She is intubated, given surfactant, and supported with 100% oxygen and nitric oxide (iNO) at 20 ppm. With initiation of iNO, her saturations improve from 40% to 90%. An umbilical venous catheter is placed, a blood culture is obtained, and she is started on ampicillin and gentamicin. Her oxygen saturations become undetectable. She is tachycardic to the 200s with a murmur noted. Her lower extremities are purple with capillary refill of 6–8 seconds, and her lower extremity pulses are weak. She is given another 10 mL/kg NS bolus and started on prostaglandins before transferring to the region’s level IV children’s hospital.The differential diagnosis for this neonate presenting in shock includes congenital heart disease, genetic and metabolic etiologies of cardiomyopathy and heart failure, pulmonary hypertensive crisis, tension pneumothorax, cardiac tamponade, thrombosis, and sepsis. Although initial capillary hematocrit was elevated, there was no evidence of polycythemia on venous samples, and thus polycythemia hyperviscosity syndrome is considered unlikely. With evidence of poor perfusion in the lower extremities, the team prioritizes an echocardiogram to evaluate for congenital heart disease, with leading suspicion of coarctation of the aorta.Upon arrival at the level IV neonatal intensive care unit, the infant is in extremis with severe metabolic acidosis and respiratory failure. She is hypertensive in the upper extremities with undetectable blood pressures in the lower extremities. Echocardiogram shows normal cardiac anatomy without aortic coarctation but diminished biventricular function. Further evaluation for obstruction is pursued with abdominal ultrasound, which demonstrates tapering/narrowing of the abdominal aorta distal to the origin of the superior mesenteric artery, suggesting possible midaortic syndrome, vasculitis, or neonatal thrombus. CT angiography of the abdomen is recommended for further radiologic evaluation, but the neonate is too unstable to obtain this imaging. Her metabolic acidosis, hypoxemia, and lower extremity perfusion continue to worsen despite maximal medical therapy, and she is cannulated onto venoarterial extracorporeal membrane oxygenation (ECMO) at approximately 24 hours of life. Following initiation of ECMO, she is emergently taken to the cardiac catheterization and is diagnosed with a large obstructive thrombus of the descending aorta with extension into the bilateral iliac vessels and evidence of prominent collateral circulation (Figure 1).Neonatal aortic thrombosis is a rare diagnosis, making up only 2.5% of all neonatal thromboses. The incidence reported in the literature is between 0.1 and 1.1 per 100 000 liveborn neonates.1,2 Nearly 80% of these cases are provoked and associated with umbilical arterial catheterization. This neonate did not undergo any catheterization of the umbilical arteries, suggesting a spontaneous aortic thrombosis. Prothrombotic conditions (hereditary thrombophilia [eg, antithrombin III deficiency, protein C or S deficiencies, factor V Leiden] and acquired thrombophilia [eg, congenital nephrotic syndrome]), sepsis, and coarctation of the aorta have been identified as causes of spontaneous aortic thrombosis in some cases, but in nearly half of cases the underlying cause remains unknown.3Clinical presentation varies depending on the location and extent of the thrombus. Mild presentations may include irritability, poor feeding, or lower extremity edema; severe presentations can be limb- or life-threatening with hypotension, respiratory failure, and end-organ dysfunction (necrotizing enterocolitis, renal failure).Mortality of this condition has dramatically decreased over recent decades (83% in the 1960s–1970s; 23% after 2000).3Management of neonatal aortic thrombosis depends on the severity of obstruction. For the least severe thromboses, anticoagulation alone may be appropriate in some cases. When not life- or limb-threatening, the preferred first line treatment is thrombolytic therapy (ie, tissue plasminogen activator). However, when the presentation is life-threatening, catheter-based treatment is becoming increasingly common at capable centers.4While on ECMO and in the catheterization lab, following identification of the large aortic thrombosis, the neonate undergoes cardiac complex mechanical suction thrombectomy with near resolution of her thrombus and achievement of vessel patency (Figure 2). Thrombotic workup does not reveal another underlying cause, and whole exome sequencing does not find any pathogenic variants associated with her presentation. She remains critically ill on ECMO and, within 2 days, develops evidence of a catastrophic intracranial hemorrhage in her cerebellum. With this finding, the parents elect to redirect care with support of the care team, and she dies surrounded by family.Aortic thrombosis should be included in the differential diagnosis for an infant with distal cyanosis or poor end-organ perfusion.When obstructive etiology of shock is suspected but echocardiogram does not reveal the cause, evaluation for obstructive thrombosis at other levels of the great vessels should be considered.Management options for major thromboses include thrombolysis, anticoagulation, and surgical/catheter-based thrombectomy.American Board of Pediatrics Neonatal-Perinatal Content SpecificationRecognize the clinical features of a neonate with an arterial vascular abnormality.Recognize the laboratory, imaging, and other diagnostic features of a neonate with an arterial vascular abnormality.Formulate a differential diagnosis for a neonate with an arterial vascular abnormality.Know the evaluation and medical and/or surgical management and associated potential complications or adverse effects of such management for a neonate with an arterial vascular abnormality.Know the evaluation and medical and/or surgical management and associated potential complications or adverse effects of such management for a neonate with a left-sided cardiac obstructive lesion.Recognize the clinical features of a neonate with a left-sided cardiac obstructive lesion.Formulate a differential diagnosis of a neonate with a left-sided cardiac obstructive lesion.