Annie J. Rohan, MSN, RNC, NNP/PNP, and Sergio G. Golombek, MD, MPH, FAAP 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 . 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- / 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, , 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 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 intrapartum asphyxia. There term newborn is sepsis. The clinical signs of is a possibility that IVH in the term infant is clinically are nonspecific and often camouflaged or associated with silent and underdiagnosed, and is the cause of later deficits other neonatal diseases such as respiratory distress syndrome, or hydrocephalus. Where symptoms exist, seizures are metabolic disorders, intracranial hemorrhage, and asphyxia. common. Ultrasonographic or CT imaging provides rapid As such, infection is considered and empirically treated with and accurate diagnosis. nearly all unexpected events of hypoxia in the term newborn. Significant subarachnoid hemorrhage can occur with in- Eighty-five percent of newborns with early-onset infection trapartum hypoxia, or can result from delivery trauma present within 24 hours, 5% present at 24 to 48 hours, and alone. It can be isolated or related to subdural and a smaller percentage of patients present between 48 hours cerebral contusion, depending on the degree of trauma. Pre- and 6 days of life (Anderson-Berry & Belig, 2006). sentation is highly variable but generally includes periods of The newborn sepsis syndrome is associated with acquisi- alternating CNS depression and irritability, and seizures, all tion of microorganisms from the mother. Transplacental commonly with ventilatory disturbance and hypoxia. Diag- infection or an ascending infection from the cervix may be nosis often occurs when a lumbar puncture is performed as caused by organisms that colonize in the mother’s geni- a more complete evaluation for suspected sepsis or menin- tourinary tract, with acquisition of the microbe by passage gitis, and demonstrates the presence of red blood cells. through a colonized birth canal at delivery. The microorganisms

July/August 2009 MCN 227 Table 2. Risk Factors for the Development of Neonatal Sepsis in the Term Newborn

MATERNAL FACTORS INTRAPARTUM FACTORS NEONATAL FACTORS

Low parity Increased duration of internal Low Apgar score (<6 at 1 or 5 monitoring minutes)

Recent urinary tract infection Increased duration of ruptured Low birth weight membranes

Poor prenatal care Increased number of vaginal 36 to 37 weeks examinations

Low socioeconomic status Greater duration of labor Asphyxia

Substance abuse Maternal fever >38º C

Chorioamnionitis

Difficult delivery

Meconium staining

most commonly associated with early-onset infection in- Hypotension and shock secondary to sepsis and other clude group B Streptococcus (GBS), Escherichia coli, causes—cardiogenic, neurogenic, hypovolemic—all present Haemophilus influenzae, and Listeria monocytogenes (An- with a similar cascade of events, and in all cases, the under- derson-Berry & Belig, 2006). lying cause must be addressed while treatment is given to Risk factors implicated in neonatal sepsis reflect stress on support the infants’ circulation and blood pressure (Stebor, the fetus during the intrapartum period, as well as the 2005; Vanhaesebrouck, 1987). If treatment is delayed, or problematical uterine environment surrounding the fetus the condition is prone to rapid deterioration, such as in ful- before delivery (Soper, 1989). Factors associated with early- minant sepsis, myocarditis, or asphyxia with multiorgan onset neonatal sepsis are summarized in Table 2. failure, neonatal shock will enter a final and irreversible The etiology of cyanosis and hypoxia in sepsis, with or phase, in which cellular damage leading to complete organ without CNS infection, is multifactorial. While apnea is a failure dominates the clinical picture, and death occurs hallmark of seizure as a result of CNS infection, apnea with invariably (Figueroa et al., 2005). resultant intermittent hypoxia is also common in both CNS Given the nonspecific nature of the signs of infection, and non-CNS infections without seizure, as is , providing treatment for suspected neonatal sepsis, while hypoventilation, and cardiovascular instability. excluding other disease processes, is prudent. Treatment An early phase of the cardiovascular instability with appropriate broad-spectrum antibiotics is standard (“shock”) of sepsis is typically a compensated phase, char- at the time of suspicion and prior to laboratory confirma- acterized by pulmonary hypertension, decreased cardiac tion of infection. Supportive care may include supplemen- output, and hypoxemia. Vital organ function is maintained tal oxygen administration or mechanical ventilation, by compensatory mechanisms that keep organ blood flow intravenous fluids, inotropic agents for hypotension, and primarily to the heart, brain, and adrenal glands, and nitric oxide for infection-associated pulmonary hyperten- away from the “nonvital” organs (the “diving seal re- sion. The mortality from infections has decreased over flex”). Without recognition and treatment, the infant may time with more aggressive intrapartum administration of later manifest with hypotension, pallor, poor capillary per- antibiotics to high-risk women and advances in neonatal fusion, and edema, as there is failure of the compensatory intensive care. mechanisms. It is at this point that the infant manifests with hypoxia and cyanosis. These late signs of shock are Hematologic Disorders indicative of severe compromise and are highly associated Another category of disorders with a possible manifestation with long-term morbidity (Noori, Friedlich, & Seri, 2004; as hypoxia in the term newborn are hematologic disorders, Seri & Evans, 2001). although these are significantly less common. As with many

228 VOLUME 34 | NUMBER 4 July/August 2009 other body systems in the neonate, the hematologic system instead is related to congenital absence of methemoglobin is immature at birth. As a result, newborns may be at an reductase. increased risk for various problems. Bleeding disorders in an infant can be viewed in two categories: inherited or ac- Metabolic Abnormalities quired. Inherited disorders include factor deficiencies such The clinical symptoms of metabolic disorders in the as hemophilia, von Willebrand disease, and both autoim- neonate, including those of drug withdrawal, are nonspe- mune and alloimmune thrombocytopenias. The most cific and usually not possible to distinguish from other commonly acquired disorders are and disorders without laboratory testing. Nearly all of these disseminated intravascular coagulation (DIC) secondary to disorders, however, can present with apnea and hypoxic some underlying cause. episodes in the term newborn, and as such, need to be DIC is a disorder of hemostasis that may occur in the considered by the clinician when called to evaluate an in- neonatal period as a complication of various other disease fant who has cyanosis or suboptimal oxygen saturation processes. Its effects on the newborn—typically an other- findings. wise sick infant—can be particularly devastating. The clini- The effect of maternal substance abuse during pregnan- cal manifestations of DIC and their time of onset can be cy on a neonate’s behavior and adaptation has long been variable. The infant will first show signs of the underlying acknowledged. Well-recognized signs of withdrawal in- disease process and then may progress to subtle clues or clude clonus, high-pitched and excessive crying, and diar- major signs of DIC. Bleeding is typically an initial presenta- rhea, but also can include hypoxia secondary to metabolic tion. An infant who continues to bleed after lab draws or derangement, apnea, or nasal congestion. There is also venipuncture should raise suspicion. Hem- orrhage can range from oozing of a wound to frank blood in the mouth, nose, or oro- gastric or endotracheal tube indicating a major gastrointestinal or pulmonary bleed, Methemoglobinemia is a the latter almost always associated with some degree of hypotension or shock. rare but great Hematologic disorders—whether inborn or acquired—may present as well with pe- impersonator of hypoxia techiae, purpura, ecchymoses, or hematomas. Ischemic damage related to in the newborn. thrombosis could manifest as cyanosis, as well as specific organ failure, depending on the site of the clot. As previously noted, hematologic disorders can also present with internal hemorrhage—especially intracranial hemorrhage. evidence that neurological alterations occur during with- Significant internal hemorrhage is often marked by a sud- drawal that prevent normal autonomic functions. New- den deterioration, hypovolemia, hypotension, cardiovascu- borns, in particular, depend on their reflexive suck and lar instability, and resultant hypoxia. While the internal swallow ability, which may be affected significantly by hemorrhage may not always be initially evident to the clini- intrauterine drug exposure. As such, poor feeding, unto cian, signs and symptoms will indicate shock with red itself, can start a cascade of other diagnoses. The vasocon- blood count or platelet abnormalities. strictive properties of cocaine have also been implicated as Methemoglobinemia is the rare but great impersonator a cause for intrauterine hypoxia with poor fetal growth in the evaluation of cyanosis of the newborn, and worth and persistent pulmonary hypertension (Bauer, 2005; Levy mentioning at this juncture. Methemoglobinemia causes & Koren, 1990). reduced blood-oxygen carrying capacity due to abnormal Electrolyte derangements, most commonly hypo- hemoglobin or enzyme deficiency. Examination generally glycemia but also abnormalities of calcium, phosphorus, reveals a markedly cyanotic infant without respiratory dis- magnesium, and potassium, can cause an array of nonspe- tress, who has an arterial PaO2 that is normal, although cific clinical symptoms in the neonate, with hypoxia com- the infant will have low oxygen saturation values. Arterial mon to all. The occurrence of these symptoms is different blood obtained from such an infant is often described as in individual infants and there is a lack of a universal “chocolate” in color. In the general population, methemo- threshold below or above which symptoms can be expect- globinemia is caused by ingestion of toxic agents such as ed. Cardiac rhythm disorders are also found as potassium nitrites, but in the term newborn, methemoglobinemia and calcium become increasingly out of range, and

July/August 2009 MCN 229 hypoxemia secondary to impaired cardiac output can be been used with success, while supportive measures are in observed in these cases. Hypermagnesemia—usually sec- place, and newer medical therapies such as inhaled nitric ondary to maternal administration of magnesium—can re- oxide are now improving upon those successes (Golombek, sult in hypoventilation or apnea in the newborn, with re- 2000; Verklan, 2006; Williams, 2004). sultant hypoxia and cyanosis. Given the often vague signs of , which Diagnosis of electrolyte derangement is made by blood includes hypoxia of various etiologies, evaluating for suspect- chemistry evaluation, and treatment often involves replacing ed sepsis while excluding other disease processes, is uniformly or withholding the offending electrolyte. In many cases, the prudent for the clinician. Treatment with appropriate broad- metabolic derangement is part of a larger syndrome, such as spectrum antibiotics is standard at the time of suspicion and hypoglycemia in Beckwith-Wiedemann syndrome and in the prior to laboratory confirmation of infection. infant of a diabetic mother, or in the case of hypocalcemia in Where cyanosis is secondary to poor cardiovascular func- hypoparathyroidism and in DiGeorge syndrome. tion in any form of shock, volume expanders and inotropic agents are important at maintaining adequate tissue oxygenation. Red blood cell transfu- sion to support oxygen-carrying capacity and The differentiation between metabolic and electrolyte management to cardiac, respiratory, optimize cardiac function are fundamental. For emergency conditions, such as pneu- metabolic, neurologic, and mothorax, evacuation by the bedside clinician is often warranted, even before specialized other causes of hypoxia in neonatal care. Obstructive lesions may also require urgent bedside palliation prior to the newborn nursery is a definitive treatment (i.e., oral airway for common difficulty. choanal atresia or Pierre Robin Sequence, tracheal intubation, and gastrointestinal evacuation for diaphragmatic hernia). Where gastroesophageal reflux is identi- Other metabolic disorders, although rare, have been fied, medical management with H2 blockers is often effective, implicated in hypoxia and include: as well as other pharmacologic remedies and formula • mitochondrial disorders thickening, for the management of events that cause hypoxia. • inborn errors of metabolism Unusual conditions, such as methemoglobinemia, are • peroxisomal disorders (adrenoleukodystrophy, cerebro- treated more uniquely under the guidance of subspecialists, hepatorenal syndrome) and after further targeted diagnostic tests are interpreted. • acid maltase deficiency (Pompe disease) Similarly, the treatment of hypoventilation as a function of • phosphofructokinase deficiency metabolic or neuromuscular disorder, while initially • phosphorylase deficiency supported by oxygen administration and ventilation, may • carnitine deficiency. require more specialized therapies. The workup and treatment for these listed disorders is complex and generally requires the consultation of a genetic Outcomes or metabolic specialist. During normal development, cardiovascular and circulatory functions progress from fetal life through transition at Management birth, and the fetus and newborn are clearly able to thrive In summary, treatment of the hypoxic infant depends on despite their “hypoxic” environment. Moreover, due to accurate diagnosis. Initially, however, respiratory support adaptive responses of the cardiovascular, metabolic and en- with oxygen, CPAP (continuous positive airway pressure), docrine systems, relatively severe intrauterine stress may be or mechanical ventilation is indicated in most cases. In tolerated and still permit the fetus to have relatively normal congenital heart disease, medication used to maintain the growth and development. However, hypoxic stress in patency of the PDA (patent ductus arteriosus) may be nec- utero—both acute and chronic—can be severe enough to essary to maintain tissue perfusion until surgical correction cause compromised circulation, organ dysfunction, and can be achieved. In PPHN (persistent pulmonary hyperten- threaten survival—or intact survival. At the time of transi- sion), the goal of the therapy is to lower the pulmonary-to- tion to extrauterine life, signs of a depressed circulatory sys- systemic vascular resistance ratio and thus reduce shunting. tem from in-utero hypoxia may become suddenly apparent ECMO (extracorporeal membrane oxygenation) and has because of the increased metabolic demands at birth, and

230 VOLUME 34 | NUMBER 4 July/August 2009 Table 3. Differentiating Between the Many Etiologies for Newborn Hypoxia: Typical History and Clinical Findings

LABOR AND RESPIRATORY RADIOLOGICAL CATEGORY DELIVERY PHYSICAL EXAM HISTORY SIGNS AND LAB DATA HISTORY

Congenital May have Unremarkable None or mild Significant Low PaO2 cardiac defects abnormal fetal murmur despite high sup- and disease echocardiogram, plemental oxy- maternal gen, abnormal diabetes cardiac silhouette on X-ray

Pulmonary Often Often with Mild to severe Variable, Low PaO2 hypertension unremarkable evidence fetal respiratory depending on despite (usually associat- stress/distress distress associated supplemental ed with a second category oxygen category)

Primary Often Often Mild to severe Often Abnormal pulmonary unremarkable, unremarkable, respiratory unremarkable bilateral lung disease sometimes but may have distress fields on X-ray gestational evidence fetal diabetes stress/distress, history cesarean birth, or delivery at 36-37 weeks

Airway May have Unremarkable Moderate to Notable or Abnormal obstruction abnormal fetal severe palpable neck/chest X-ray sonogram respiratory obstruction or CT distress

Extrinsic May have Unremarkable Moderate to Chest asymmetry Lesion on chest compression of abnormal fetal severe X-ray or CT the lungs sonogram respiratory distress

Central nervous May have Malpresentation Apnea Hypotonia Abnormal CT, system/ abnormal fetal common seizures, EEG, or neuromuscular sonogram, may nerve/muscle diseases— have evidence studies congenital abnormal fetal disorder movement

Central nervous Often Often with Apnea CNS depression Abnormal head system/ unremarkable, evidence fetal or irritability, CT neuromuscular sometimes LGA stress/distress seizures, diseases—injury increased ICP, anemia

Sepsis and Often Often with Apnea, mild to Hypotension, Abnormal CBC, hypotension unremarkable, evidence fetal severe poor perfusion, elevated CRP may have history stress/distress respiratory hypotonia UTI, poor distress prenatal care

CNS = central nervous system. CT = computed tomography. CRP = C-reactive protein. (continued)

July/August 2009 MCN 231 Table 3. Differentiating Between the Many Etiologies for Newborn Hypoxia: Typical History and Clinical Findings (continued)

LABOR AND PREGNANCY RESPIRATORY RADIOLOGICAL CATEGORY DELIVERY PHYSICAL EXAM HISTORY SIGNS AND LAB DATA HISTORY

Hematologic Unremarkable, or Often None, or mild if Petechiae, Abnormal disorders— may have family unremarkable if developing purpura, clotting studies, inherited and history inherited hypovolemia ecchymoses, anemia acquired disorder hematomas, (acquired prolonged disorders usually bleeding with associated with a heelstick second category)

Metabolic Often Unremarkable Apnea (associat- Hypotonia, Metabolic abnormalities unremarkable, ed with seizures) tremors acidosis, but may have electrolyte family history of abnormalities, metabolic positive disorder, or may toxicology screen have history of drug use

loss of placental gas exchange (Anderson, Kleinman, Lister, At some point, repetitive episodes of severe hypoxia & Talner, 2004). cause global neuronal, cortical, midbrain, and cerebellar damage, even to the “spared” CNS. Damage is typically to Acute Hypoxia the watershed areas of the cerebral cortex, an event closely Acute hypoxemia produces various circulatory adaptations correlated to and developmental disabilities in the fetus that enhances fetal survival, including the de- in later life. The human fetus may experience these episodes velopment of bradycardia, hypertension, redistribution of during a high-risk pregnancy, well before birth, with recov- blood flow toward the brain, myocardium and adrenals, ery of biochemical markers of distress, such as metabolic and depression of fetal breathing and skeletal muscle activ- acidosis (Bloom, 2006). ity. The fetal heart also has a greater capacity for anaero- If myocardial contractility is impaired following severe bic metabolism than the adult heart (Jensen, 1991; or sustained hypoxia, the resultant reduction in cardiac out- Philipps, 2004). put may further compromise cerebral blood flow and other Ischemia is a reduction of blood flow to an organ that organ perfusion. Again, depending on degree of insult, this either causes hypoxia by compromising oxygen and sub- can be associated with acute myocardial dilatation and re- strate delivery to an organ, or is caused by hypoxia when sultant tricuspid regurgitation, myocardial ischemia, and increasing hypoxic acidosis has a depressant effect on car- hypotension. Such hypotension is usually resistant to vol- diovascular function. While in theory, the diving seal reflex ume resuscitation—dopamine has been shown to be more maintains blood flow to vital organs during an acute hy- effective in restoring blood pressure in these infants. poxic event, in practice, any organ system may become Renal impairment is commonly reported following compromised after insult because of ischemia (Anderson et hypoxic-ischemic insult at birth. Again, depending on de- al., 2004; Jensen, 1991). gree of insult, impairment can take the form of mild olig- The neonatal brain is in some ways more resistant to uria with minor electrolyte abnormality and minimally el- acute hypoxia than the brain of an older child or adult. evated creatinine, to full-blown renal failure requiring Nevertheless, hypoxia occurring in the fetus or newborn is dialysis. a major cause of acute mortality and chronic neurologic Elevated liver enzymes are also common following acute disability in survivors. The outcome of infants sustaining hypoxia, but irreversible liver damage is very rare. Liver en- and ischemia is influenced by many fac- zymes levels are often telling in identifying the existence of tors, including the duration and severity of the event, and a perinatal insult. Similarly, coagulation impairment should associated infectious, traumatic, or metabolic (especially hy- also be anticipated in severely affected newborns; however, poglycemic) derangements (Bloom, 2006). treatment is supportive and resolution is the norm.

232 VOLUME 34 | NUMBER 4 July/August 2009 The full-term infant, while more likely to survive a severe The authors have disclosed that they have no financial hypoxic-ischemic insult at birth than a preterm infant (ap- relationships related to this article. proximately 70% vs. 30%), is also more likely to have sig- References nificant long-term morbidity than the preterm counterpart Anderson, P., Kleinman, C., Lister, G., & Talner, N. (2004). Cardiovascular (Gressens & Huppi, 2006). function during development and response to hypoxia. In: R. Polin, W. Fox, & S. Abman (Eds.), Fetal and neonatal physiology (pp. 635-669). Philadelphia, PA: Saunders. Chronic Hypoxia Anderson-Berry, A. L., & Belig, L. L. (2006). Neonatal sepsis. Retrieved May 28, 2009, from www.emedicine.com/ped/topic2630.htm Fetal cardiovascular and endocrine response may be al- Bauer, C. R. (2005). Acute neonatal effects of cocaine exposure during preg- tered not only in acute hypoxia but also in chronic hypox- nancy. Archives of Pediatric and Adolescent Medicine, 159, 824-834. Bloom, R. (2006). Resuscitation of the newborn. In: A. A. Fanaroff, & R. J. ia. This is important because recurrence of mild hypoxic Martin (Eds.), Neonatal-Perinatal Medicine (pp. 483–511). St Louis, insults may not be infrequent in human , MO: Mosby. Castrodale, V. (2003). The hypotonic infant: Case study of central core dis- where blood flow to the , , and fetus is ease. Neonatal Network, 22, 53-59. repeatedly compromised by many physiologic and environ- Figueroa, R., Khabbaz, A., & Quirk, G. (2005). Identification and manage- ment of the fetus at risk for acidosis. In: A. Spitzer (Ed.), Intensive Care mental influences. In states of considerable chronic hypox- of the Fetus and Neonate (pp. 91-110). Philadelphia, PA: Mosby. ia, such as may occur in a variety of clinical situations, fetal Golombek, S. G. (2000). The use of inhaled nitric oxide in newborn medi- cine. Heart Disease, 2, 342-347. growth retardation is not uncommon. Depression of Gressens, P., & Huppi, P. S. (2006). The central nervous system: Hypoxic is- growth factors during hypoxic states has an important chemic encephalopathy. In: R. J. Martin, A. A. Fanaroff, & M. C. Walsh (Eds.), Neonatal-perinatal medicine. St Louis, MO: Mosby. protective effect by conserving fetal substrate for energy as Hofmeyr, G. J., & Hannah, M. E. (2003). Planned caesarean section for opposed to growth needs (Noori et al., 2004; Seri & term breech delivery. Cochrane Database Review, 3, CD000166. Jensen, A. (1991). Effects of reducing uterine blood flow on fetal blood Evans, 2001). flow distribution and oxygen delivery. Journal of Developmental Physiology, 15, 309. Summary Levy, K., & Koren, G. (1990). Obstetric and neonatal effects of drug abuse. Emergency Medicine Clinics of North America, 8, 633. Possibly the most common approach for the pediatric clini- Noori, S., Friedlich, P., & Seri, I. (2004). Pathophysiology of shock in the fe- tus and newborn. In R. Polin, W. Fox, & S. Abman (Eds.), Fetal and cian involves the evaluation of the hypoxic infant during neonatal physiology (pp. 772-781). Philadelphia, PA: Saunders. this transitional period. Differentiating between the many Painter, M. J., & Gaus, L. M. (1993). Neonatal seizures. In: K. M. Pellock, & E. C. Myer (Eds.), Neurologic emergencies in infancy and childhood etiologies for newborn hypoxia is undoubtedly an incredi- (pp. 24-41). Boston: Butterworth-Heinemann. ble challenge for the pediatric specialist in the newborn Philipps, A. (2004). Oxygen consumption and general carbohydrate metabolism of the fetus. In R. Polin, W. Fox & S. Abman (Eds.), Fetal nursery. While there are several common causes for new- and neonatal physiology (pp. 465-478). Philadelphia, PA: Saunders. born cyanosis—primary pulmonary disease and sepsis—a Plessis, A. J. (2005). and hypoxic-ischemic brain injury. In A. Spitzer (Ed.), Intensive care of the fetus and neonate (pp. 775- myriad of disorders spanning all organ systems exist as pos- 802). Philadelphia, PA: Mosby. sibilities. It was the intention of this series to supply the Rohan, A., & Golombek, S. (2009a). Hypoxia in the term neonate: Part 1. MCN: The American Journal of Maternal Child Nursing, 34 (2). practitioner with a basic knowledge of the breadth of these Rohan, A., & Golombek, S. (2009b). Hypoxia in the term neonate: Part 2. possibilities, as well as a systematic approach to the assess- MCN: The American Journal of Maternal Child Nursing, 34 (3). Schwartz, J. F., Ahmann, P. A., Dykes, F. D., & Brann, A. F. (1993). Neonatal ment of these term newborns to assure accurate diagnosis, intracranial hemorrhage and hypoxia. In: K. M. Pellock, E. C. Myer treatment, and referral. (Eds.), Neurologic Emergencies in Infancy and Childhood (pp. 1-23). Boston: Butterworth-Heinemann. A summary of these categories of disorders, along with Seri, I., & Evans, J. (2001). Controversies in the diagnosis and manage- characteristic history and typical physical, laboratory, and ment of hypotension in the newborn infant. Current Opinions in Pedi- ✜ atrics, 13, 116. radiologic findings can be found in Table 3. Soper, D. E., Mayhall, C. G., & Dalton, H. P. (1989). Risk factors for intraam- niotic infection: A prospective epidemiologic study. American Journal of Obstetrics and Gynecology, 161, 562. Annie J. Rohan is a Senior Nurse Practitioner, Stony Brook Stebor, A. (2005). Basic principles of noninvasive blood pressure meas- Hospital, Stony Brook, New York, and Jonas Nursing urement in newborns. Advances in Neonatal Care, 5(5), 252-261. Vanhaesebrouck, P. (1987). Tight and neonatal hypovolemic Scholar, Columbia University School of Nursing, PhD Pro- shock. Archives of Diseases in Children, 62, 1276. gram, New York, NY. She can be reached via e-mail at Verklan, M. T. (2006). Persistent pulmonary hypertension of the newborn: Not a honeymoon anymore. Journal of Neonatal and Perinatal Nurs- [email protected] ing, 20, 98-112. Sergio G. Golombek is an Associate Professor of Pedi- Volpe, J. J. (2001a). Hypoxic-ischemic encephalopathy: Clinical aspects. In: Neurology of the newborn (pp. 331-394). Philadelphia, PA: Saunders. atrics and Clinical Public Health, New York Medical Col- Volpe, J. J. (2001b). Neonatal seizures. In: Neurology of the newborn (pp. lege, New York, NY, and an Attending Neonatologist, 178-214). Philadelphia, PA: Saunders. Williams, L. J., Shaffer, T. H., & Greenspan, J. S. (2004). Inhaled nitric oxide Maria Fareri Children’s Hospital of Westchester Medical therapy in the near-term or term neonate with hypoxic respiratory fail- Center, Valhalla, New York. ure. Neonatal Network, 23, 5-13.

For more than 27 additional continuing nursing education articles related to neonatal topics, go to www.nursingcenter.com/ce

July/August 2009 MCN 233