Annie J. Rohan, MSN, RNC, NNP/PNP, and Sergio G. Golombek, MD, MPH, FAAP HYPOXIA IN THE Term Newborn: PART THREE—SEPSIS AND HYPOTENSION, NEUROLOGIC, METABOLIC AND HEMATOLOGIC DISORDERS ABSTRACT Causes of hypoxia and cyanosis in the term newborn can be found within all physiologic systems and take the form of hundreds of specific diagnoses. In the first and second parts of this series, a wide range of cardiac and pulmonary caus- es for newborn hypoxia and cyanosis have been examined. Because they are familiar, cardiac and pulmonary diagnoses often represent our reactionary opinions—the options that we first entertain even before a proper systematic approach to the infant has been taken. In this final of a three part series, neurologic, hematologic and metabolic disorders are explored as a cause for abnormal oxygenation, as well as sepsis and hypotension. It is within these final categories that we find many of the obscure possibilities for neonatal hypoxia—the diagnoses that often require rigorous testing, or more sophisticated laboratory interpretation. Without consideration of these elusive entities, however, appropriate treatment and referral will be unnecessarily delayed. Key Words: Hypoxia; Metabolic; Neurologic; Newborn. 224 VOLUME 34 | NUMBER 4 July/August 2009 ewborn care providers need to meet the familiar suspected when neurologic examination is abnormal with- challenge of evaluating hypoxia in the term infant. out a perinatal course suggesting neurologic injury. In addi- NThe first article in this three-part series (Rohan & tion, history may suggest isolated lack of movement on Golombek, 2009a) discussed cardiopulmonary adaptation sonographic examination or reveal breech presentation of the term newborn, definitions and features of neonatal secondary to the fetus’ limited ability to shift in utero. hypoxia, cardiac causes for hypoxia in the newborn, and Almost any condition that affects the central or peripher- neonatal pulmonary hypertension. The second article (Ro- al nervous system of the newborn can be expressed with a han & Golombek, 2009b) described primary pulmonary reduction in tone, and can thus impact respiration. Respira- disease, airway obstruction, and lung or airway compres- tory failure, hypoxia, and cyanosis caused by significant sion as a cause for impaired oxygenation. In this final part, muscle weakness may be due to abnormalities of the nerv- neuromuscular, metabolic disorders, and hematologic disor- ous system, irregularity of the muscles, and sometimes ders will be explored as causes for hypoxia in the term in- concomitant deformity of the chest wall. fant, as well as sepsis and hypotension. When tone impacts the infant’s ability to sustain ade- quate ventilatory function, ventilatory assistance with con- Central Nervous System/ tinuous positive airway pressure or intermittent positive Neuromuscular Diseases pressure ventilation may be required until a definitive diag- Central nervous system (CNS) disorders and neuromuscular nosis and treatment plan is established. Because of the rari- diseases can cause altered control of respiration and result in ty of these disorders, however, when hypoventilation is a hypoxia in the term neonate.This compromised neurologic presenting feature, it is prudent for the on-call practitioner control of respiration can be a result of a congenital neuro- to consider the possibilities of infection or metabolic de- logic disorder, due to seizures or CNS infection, or as a re- rangement, and arrange an appropriate chemistry panel, sult of neurologic injury. A summary of these neurologic metabolic support, cultures, and antibiotics pending more causes can be found in Table 1. extensive neurologic investigation (Castrodale, 2003). Congenital Neurologic Disorder Seizures Congenital neurologic disorders as a cause of hypoxia in When apnea presents in the term infant, without other signs the term newborn infant are infrequent, and should be of respiratory distress, one must consider seizures as an July/August 2009 MCN 225 Table 1. Neurologic Conditions That Can Cause Respiratory Failure, Hypoxia, and Cyanosis CONGENITAL SEIZURES NEUROLOGIC INJURY CNS INFECTION NEUROLOGIC DISORDERS Mechanism of Reduction of tone: Epileptiform activity: Increased ICP, Can cause reduction in hypoxia decreased respiratory apnea Impaired circulation tone, seizures, effort brain structures: increased ICP, apnea multifaceted effect on respiratory control, can cause seizures/apnea Examples Congenital Seizures resulting Hypoxic-ischemic Bacterial Infection: hydrocephalus from congenital encephalopathy Group B neurologic disorder Streptococcus, or genetic syndrome Werdnig-Hoffman Intraventricular Escherichia coli, disease hemorrhage Listeria monocytogenes Seizures resulting from CNS injury Neurologic Subdural hemorrhage Viral infection: malformations Syphilis (i.e., Chiari malformation) Seizures resulting Subarachnoid toxoplasmosis, from infection hemorrhage Herpes simplex, Spinal muscle atrophy Rubella, Seizures resulting Hemorrhagic from metabolic infarction Cytomegalovirus Dejerine-Sottas disease derrangement Muscular dystrophy Intracerebellar hemorrhage Charcot Marie tooth disease Neurogenic arthrogryposis Phrenic nerve paralysis Congenital myasthenia Congenital myopathies Congenital neuropathies CNS malignancies CNS = central nervous system. ICP = intracranial pressure. etiology. Recognition of neonatal seizures is difficult, as gen- neurologic injury and hypoglycemia are common culprits; eralized clonic jerking is rare. Rather, clinical manifestations during days 5 to 7, hypocalcemia is seen, and at any time in are often minimal, with brief periods of posturing or tonic the first week, infectious and genetic causes can emerge. In extension, eye deviation, or apnea. Particularly when a almost all cases, evaluation by electroencephalography and seizure presents with apnea, the infant may become hypoxic anticonvulsant therapy for seizure control is indicated until and cyanotic as a first clinical sign (Volpe, 2001a, 2001b). differential diagnoses are assimilated and eliminated (Volpe, Fifty percent of neonatal seizures occur during the first 2001b, pp. 178-214; Painter, 1993). day of life, and 75% by day 3. Adding to diagnostic com- plexity, the most likely etiology of a neonatal seizure trans- Neurologic Injury forms over the first week of life: During the first 48 hours, There are two major categories of neurologic injury that 226 VOLUME 34 | NUMBER 4 July/August 2009 can be observed in the full-term infant—hypoxic-ischemic When subarachnoid hemorrhage is associated with other encephalopathy (HIE) and intracranial hemorrhage. These signs of physical injury caused by difficult delivery often injuries can occur separately, or in concert, and often can with mid or high forceps application, outcome is frequently be suggested by the perinatal history. In most clinically sig- poor (Schwartz et al., 1993). nificant cases, the infant exhibits periods of hypoxia and Clinically significant subdural hemorrhage, which is also cyanosis, the duration and degree of which is determined commonly associated with instrumented or difficult breech by the nature and extent of the injury. deliveries, has become a rarer disorder of the newborn An infant with a history of problems during labor and (Hofmeyr & Hannah, 2003). Such events produce exces- delivery, with severely depressed level of consciousness and sive molding of the infant’s skull or excessive extension of seizures, is likely to have sustained neurologic injury, or “hy- the infant’s neck, with relatively sudden tearing of venous poxic-ischemic encephalopathy.” Many clinical features of channels over the hemispheres, or of the venous sinus. In neonatal HIE are nonspecific, but low cord or scalp pH association with ventilatory disturbance, early manifesta- (<7.0), poor Apgar scores (<5 persisting beyond 5 minutes), tions of significant subdural hemorrhage usually include and early severe metabolic acidosis are common indicators signs of increased intracranial pressure, seizures, anemia, for early transfer to a neonatal intensive care unit (Plessis, and jaundice, and physical examination may reveal a 2005). Typically, these infants have a significant degree of bulging fontanelle and other neurologic deficits. CT scan- ventilatory depression (especially apnea and respiratory fail- ning is a more reliable method of diagnosis over cranial ure) and oxygen requirement at delivery that brings urgency ultrasound. to their bedside in the labor and delivery suite. More subtle cases, however, where blood gas testing is absent and Apgar Sepsis and Hypotension scoring is overly zealous, may transfer to the newborn nurs- Outside of primary pulmonary disease, perhaps the next ery with “cyanosis” as the first sign (Figueroa et al., 2005; most common abnormality presenting with hypoxia in the Volpe, 2001a, pp. 331-394). Intracranial hemorrhage in the full term infant occurs much less commonly than in the preterm infant, being seen with clinical symptoms in fewer than one in 100 births The etiology of (Schwartz, Ahmann, Dykes, & Brann, 1993). These hemorrhages can be intraven- cyanosis and hypoxia tricular, subarachnoid, subdural, or intra- cerebellar in origin. All, however, commonly in sepsis is present with ventilatory disturbance and hypoxia from a varying level of neurologic multifactorial. depression or disruption. Intraventricular hemorrhage (IVH) in the full-term infant most commonly origi- nates from the choroid plexus. Many of these infants have evidence of