Etiology

Intracranial hemorrhage usually develops spontaneously; less commonly, it may be due to trauma or asphyxia, and rarely, it occurs from a primary hemorrhagic disturbance or congenital vascular anomaly. Intracranial hemorrhage often involves the ventricles (intraventricular hemorrhage [IVH]) of premature infants delivered spontaneously without apparent trauma. Primary hemorrhagic disturbances and vascular malformations are rare and usually give rise to subarachnoid or intracerebral hemorrhage. In utero hemorrhage associated with maternal idiopathic or, more often, fetal alloimmune thrombocytopenia may occur as severe cerebral hemorrhage or a porencephalic cyst after resolution of a fetal cortical hemorrhage. Intracranial bleeding may be associated with disseminated intravascular coagulopathy, isoimmune thrombocytopenia, and neonatal vitamin K deficiency, especially in infants born to mothers receiving phenobarbital or phenytoin.

Epidemiology

The overall incidence of IVH has decreased over the past decades as a result of improved perinatal care and increased use of antenatal corticosteroids, surfactant to treat respiratory distress syndrome (RDS), and, possibly, prophylactic indomethacin; however, it continues to be an important cause of morbidity in preterm infants. Approximately 30% of premature infants <1,500 g have IVH. The risk is inversely related to gestational age and birthweight, with the smallest and most immature infants being at the highest risk; 7% of infants 1,001-1,500 g have a severe IVH (grade III or IV), compared with 14% of infants 751-1,000 g and 24% of infants ≤750 g. In 3% of infants <1,000 g, periventricular leukomalacia (PVL) develops.

Pathogenesis

The major neuropathologic lesions associated with VLBW infants are IVH and PVL. IVH in premature infants occurs in the gelatinous subependymal germinal matrix. This periventricular area is the site of origin for embryonal neurons and fetal glial cells, which migrate outwardly to the cortex. Immature blood vessels in this highly vascular region of the developing brain combined with poor tissue vascular support predispose premature infants to hemorrhage. The germinal matrix involutes as the infant approaches full-term gestation and the tissue’s vascular integrity improves; therefore IVH is much less common in the term infant. Periventricular hemorrhagic infarction often develops after a grade IV IVH owing to venous congestion. Predisposing factors for IVH include prematurity, respiratory distress syndrome, hypoxic-ischemic or hypotensive injury, reperfusion injury of damaged vessels, increased or decreased cerebral blood flow, reduced vascular integrity, increased venous pressure, pneumothorax, thrombocytopenia, hypervolemia, and hypertension.

Understanding of the pathogenesis of PVL is evolving, and it appears to involve both intrauterine and postnatal events. A complex interaction exists between the development of the cerebral vasculature and the regulation of cerebral blood flow (both of which are gestational age dependent), disturbances in the oligodendrocyte precursors required for myelination, and maternal/fetal infection and/or inflammation. Similar factors (hypoxia-ischemia), venous obstruction from an IVH, or undetected fetal stress may result in decreased perfusion to the brain, leading in turn to periventricular hemorrhage and necrosis. PVL is characterized by focal necrotic lesions in the periventricular white matter and/or more diffuse white matter damage. The risk for PVL increases in infants with severe IVH and/or ventriculomegaly. The corticospinal tracts descend through the periventricular white matter, hence the association between cerebral white matter injury/PVL and motor abnormalities, including cerebral palsy.

Clinical Manifestations

The majority of patients with IVH, including some with moderate to severe hemorrhages, have no clinical symptoms. Some premature infants in whom severe IVH develops may have acute deterioration on the 2nd or 3rd day of life. Hypotension, apnea, pallor, or cyanosis; poor suck; abnormal eye signs; a high-pitched, shrill cry; convulsions, or decreased muscle tone; metabolic acidosis; shock; and a decreased hematocrit or failure of the hematocrit to increase after transfusion may be the 1st clinical indications. IVH may rarely manifest at birth; 50% of cases are diagnosed within the 1st day of life, and up to 75% within the 1st 3 days. A small percentage of infants have late hemorrhage, between days 14 and 30. IVH as a primary event is rare after the 1st month of life.

PVL is usually clinically asymptomatic until the neurologic sequelae of white matter damage become apparent in later infancy as spastic motor deficits. PVL may be present at birth but usually occurs later as an early echodense phase (3-10 days of life), followed by the typical echolucent (cystic) phase (14-20 days of life).

The severity of hemorrhage may be defined on CT scans by the location and degree of ventricular dilatation. In a grade I hemorrhage, bleeding is isolated to the subependymal area. In Grade II hemorrhage, there is bleeding within the ventricle but without evidence of ventricular dilatation. Grade III hemorrhage consists of IVH with ventricular dilatation. In Grade IV hemorrhage, there is intraventricular and parenchymal hemorrhage. Another grading system describes 3 levels of increasing severity of IVH detected on ultrasound: In grade I, bleeding is confined to the germinal matrix–subependymal region or to <10% of the ventricle (≈35% of IVH cases); grade II is defined as intraventricular bleeding with 10-50% filling of the ventricle (≈40% of IVH cases) and in grade III, more than 50% of the ventricle is involved, with dilated ventricles (Fig. 93-3). Ventriculomegaly is defined as mild (0.5-1 cm), moderate (1.0-1.5 cm), or severe (>1.5 cm).

Figure 93-3 Grading the severity of germinal matrix intraventricular hemorrhage with parasagittal ultrasound scans. A, Grade I: Note the echogenic blood in the germinal matrix (arrowheads) just anterior to the anterior tip of the choroid plexus, which (normally) is also echogenic. B, Grade II: Note the echogenic blood (arrowheads) filling <50% of the ventricular area. C, Grade III: Note the large blood clot nearly completely filling and distending the entire lateral ventricle.

(From Intracranial hemorrhage: germinal matrix-intraventricular hemorrhage of the premature infant. In Volpe JJ: Neurology of the newborn, ed 4, Philadelphia, 2001, WB Saunders.)

Diagnosis

Intracranial hemorrhage is suspected on the basis of the history, clinical manifestations, and knowledge of the birthweight-specific risks for IVH. The associated clinical signs of IVH are typically nonspecific or absent; therefore, it is recommended that premature infants <32 wk of gestation be evaluated with routine real-time cranial ultrasonography through the anterior fontanel to screen for IVH. Infants <1,000 g are at highest risk and should undergo cranial ultrasonography within the 1st 3-7 days of age, when approximately 75% of lesions will be detectable. Ultrasonography is the preferred imaging technique for screening because it is noninvasive, portable, reproducible, and sensitive and specific for detection of IVH. All at-risk infants should undergo follow-up ultrasonography at 36-40 wk of postmenstrual age to evaluate adequately for PVL, because cystic changes related to perinatal injury may not be visible for at least 2-4 wk. In one study, 29% of LBW infants who later experienced cerebral palsy did not have radiographic evidence of PVL until after 28 days of age. Ultrasonography also detects the precystic and cystic symmetric lesions of PVL and the asymmetric intraparenchymal echogenic lesions of cortical hemorrhagic infarction. Furthermore, the delayed development of cortical atrophy, porencephaly, and the severity, progression, or regression of posthemorrhagic hydrocephalus can be determined by serial ultrasonographic examinations.

Approximately 3-5% of VLBW infants have posthemorrhagic hydrocephalus and require ventriculoperitoneal shunt insertion; if the initial ultrasonography findings are abnormal, additional interval ultrasonographic studies are indicated to monitor for the development of hydrocephalus.

IVH represents only one facet of brain injury in the term or preterm infant. MRI is a more sensitive tool for evaluation of extensive periventricular injury and may be more predictive of adverse long-term outcome. CT or, more reliably, diffusion-weighted MRI is indicated for term infants in whom brain injury or stroke is suspected, because ultrasonography may not reveal edema or intraparenchymal hemorrhage and infarction.

Prognosis

The degree of IVH and the presence of PVL are strongly linked to neurodevelopmental impairment. For infants with birthweight <1,000 g, the incidences of severe neurologic impairment (defined as mental developmental index <70, psychomotor development index <70, cerebral palsy, blindness, or deafness) are about 50%, 55%, and 70% for infants with grade II, grade III, and grade IV IVH, respectively (Table 93-1). In contrast, the rate of neurodevelopmental impairment is approximately 40% in infants without IVH and those with grade I IVH. PVL, cystic PVL, and progressive hydrocephalus requiring shunt insertion are each independently associated with a poorer prognosis.

Table 93-1 PERCENTAGE OF INFANTS WITH EACH NEUROLOGIC OUTCOME AT 18 TO 22 MONTHS CORRECTED AGE BY HEAD ULTRASOUND FINDINGS*

Most infants with IVH and acute ventricular distention do not have posthemorrhagic hydrocephalus (PHH). Ten percent to 15% of LBW neonates with IVH demonstrate hydrocephalus, which may initially be present without clinical signs, such as an enlarging head circumference, lethargy, a bulging fontanel or widely split sutures, apnea, and bradycardia. In infants in whom symptomatic hydrocephalus develops, clinical signs may be delayed 2-4 wk despite progressive ventricular distention with compression and thinning of the cerebral cortex. Many infants with PHH have spontaneous regression; 3-5% of VLBW infants with PHH require shunt insertion. Infants with PHH requiring shunt insertion have lower cognitive and psychomotor performance at 18-22 mo.

Prevention

Improved perinatal care is imperative to minimize traumatic brain injury and decrease the risk of preterm delivery. The incidence of traumatic intracranial hemorrhage may be reduced by judicious management of cephalopelvic disproportion and operative (forceps, vacuum) delivery. Fetal or neonatal hemorrhage caused by maternal idiopathic thrombocytopenic purpura or alloimmune thrombocytopenia may be reduced by maternal treatment with steroids, intravenous immunoglobulin, fetal platelet transfusion, or cesarean section. Tenacious care of the LBW infant’s respiratory status and fluid and electrolyte management—including avoidance of acidosis, hypocarbia, hypoxia, hypotension, wide fluctuations in neonatal blood pressure or PCO₂, and pneumothorax—are important factors that may affect the risk for development of IVH and PVL.

A single course of antenatal corticosteroids is recommended in pregnancies 24-34 wk of gestation that are at risk for preterm delivery. Antenatal steroids decrease the risk of death, grade III and IV IVH, and PVL in the neonate. The prophylactic administration of low-dose indomethacin (0.1 mg/kg/day for 3 days) to VLBW preterm infants reduces the incidence of severe IVH.

Treatment

Although no treatment is available for IVH, it may be associated with other complications that require therapy. Seizures should be treated with anticonvulsant drugs. Anemia and coagulopathy require transfusion with packed red blood cells or fresh frozen plasma. Shock and acidosis are treated with the judicious and slow administration of sodium bicarbonate and fluid resuscitation.

Insertion of a ventriculoperitoneal shunt is the preferred method to treat progressive and symptomatic posthemorrhagic hydrocephalus; some infants require temporary cerebrospinal fluid diversion before a permanent shunt can be safety inserted. Diuretics and acetazolamide are not effective. Serial lumbar punctures, ventricular taps or reservoirs, and externalized ventricular drains are potential temporizing interventions; they have an associated risk of infection and of “puncture porencephaly” owing to injury to the surrounding parenchyma. A ventriculosubgaleal shunt inserted from the ventricle into a surgically created subgaleal pocket provides a closed system for constant ventricular decompression without these additional risk factors. Decompression is regulated by the pressure gradient between the ventricle and the subgaleal pocket.

Etiology

Most neonatal encephalopathic or seizure disorders, in the absence of major congenital malformations or syndromes, appear to be due to perinatal events. Brain MRI or autopsy findings in full-term neonates with encephalopathy demonstrate that 80% have acute injuries, <1% have prenatal injuries, and 3% have non–hypoxic-ischemic diagnoses. Fetal hypoxia may be caused by various disorders in the mother, including (1) inadequate oxygenation of maternal blood from hypoventilation during anesthesia, cyanotic heart disease, respiratory failure, or carbon monoxide poisoning; (2) low maternal blood pressure from acute blood loss, spinal anesthesia, or compression of the vena cava and aorta by the gravid uterus; (3) inadequate relaxation of the uterus to permit placental filling as a result of uterine tetany caused by the administration of excessive oxytocin; (4) premature separation of the placenta; (5) impedance to the circulation of blood through the umbilical cord as a result of compression or knotting of the cord; and (6) placental insufficiency from toxemia or postmaturity.

Placental insufficiency often remains undetected on clinical assessment. Intrauterine growth restriction may develop in chronically hypoxic fetuses without the traditional signs of fetal distress. Doppler umbilical waveform velocimetry (demonstrating increased fetal vascular resistance) and cordocentesis (demonstrating fetal hypoxia and lactic acidosis) identify a chronically hypoxic infant (Chapter 90). Uterine contractions may further reduce umbilical oxygenation, depressing the fetal cardiovascular system and CNS and resulting in low Apgar scores and respiratory depression at birth.

After birth, hypoxia may be caused by (1) failure of oxygenation as a result of severe forms of cyanotic congenital heart disease or severe pulmonary disease; (2) severe anemia (severe hemorrhage, hemolytic disease); (3) or shock severe enough to interfere with the transport of oxygen to vital organs from overwhelming sepsis, massive blood loss, and intracranial or adrenal hemorrhage.

Pathophysiology and Pathology

The topography of injury typically correlates with areas of decreased cerebral blood flow. After an episode of hypoxia and ischemia, anaerobic metabolism occurs and generates increased amounts of lactate and inorganic phosphates. Excitatory and toxic amino acids, particularly glutamate, accumulate in the damaged tissue. Increased amounts of intracellular sodium and calcium may result in tissue swelling and cerebral edema. There is also increased production of free radicals and nitric oxide in these tissues. The initial circulatory response of the fetus is increased shunting through the ductus venosus, ductus arteriosus, and foramen ovale, with transient maintenance of perfusion of the brain, heart, and adrenals in preference to the lungs, liver, kidneys, and intestine.

The pathology of hypoxia-ischemia depends on the affected organ and the severity of the injury. Early congestion, fluid leak from increased capillary permeability, and endothelial cell swelling may then lead to signs of coagulation necrosis and cell death. Congestion and petechiae are seen in the pericardium, pleura, thymus, heart, adrenals, and meninges. Prolonged intrauterine hypoxia may result in inadequate perfusion of the periventricular white matter, resulting, in turn, in PVL. Pulmonary arteriole smooth muscle hyperplasia may develop, which predisposes the infant to pulmonary hypertension (Chapter 95.7). If fetal distress produces gasping, the amniotic fluid contents (meconium, squames, lanugo) are aspirated into the trachea or lungs.

The combination of chronic fetal hypoxia and acute hypoxic-ischemic injury around the time of birth results in gestational age–specific neuropathology (Table 93-3). Term infants demonstrate neuronal necrosis of the cortex (later, cortical atrophy) and parasagittal ischemic injury. Preterm infants demonstrate PVL (later, spastic diplegia), status marmoratus of the basal ganglia, and IVH. Term more often than preterm infants have focal or multifocal cortical infarcts that manifest clinically as focal seizures and hemiplegia.

Table 93-3 TOPOGRAPHY OF BRAIN INJURY IN TERM INFANTS WITH HYPOXIC-ISCHEMIC ENCEPHALOPATHY AND CLINICAL CORRELATES

Clinical Manifestations

Intrauterine growth restriction with increased vascular resistance may be the 1st indication of fetal hypoxia. During labor, the fetal heart rate slows and beat-to-beat variability declines. Continuous heart rate recording may reveal a variable or late deceleration pattern (see Fig. 90-4). Particularly in infants near term, these signs should lead to the administration of high concentrations of oxygen to the mother and consideration of immediate delivery to avoid fetal death and CNS damage.

At delivery, the presence of meconium-stained amniotic fluid is evidence that fetal distress has occurred. At birth, affected infants may be depressed and may fail to breathe spontaneously. During the ensuing hours, they may remain hypotonic or change from a hypotonic to a hypertonic state, or their tone may appear normal (Tables 93-4 and 93-5). Pallor, cyanosis, apnea, a slow heart rate, and unresponsiveness to stimulation are also signs of HIE. Cerebral edema may develop during the next 24 hr and result in profound brainstem depression. During this time, seizure activity may occur; it may be severe and refractory to the usual doses of anticonvulsants. Though most often a result of the HIE, seizures in asphyxiated newborns may also be due to hypocalcemia, hypoglycemia, or infection.

Table 93-4 PREDICTOR VARIABLES, ODDS RATIOS, AND SCORES ASSIGNED TO EACH VARIABLE FOR DEATH/DISABILITY SCORING IN INFANTS WITH HYPOXIC-ISCHEMIC ENCEPHALOPATHY

Table 93-5 HYPOXIC-ISCHEMIC ENCEPHALOPATHY IN TERM INFANTS

In addition to CNS dysfunction, heart failure and cardiogenic shock, persistent pulmonary hypertension, respiratory distress syndrome, gastrointestinal perforation, hematuria, and acute tubular necrosis are associated with perinatal asphyxia secondary to inadequate perfusion (see Table 93-2).

The severity of neonatal encephalopathy depends on the duration and timing of injury. Symptoms develop over a series of days, making it important to perform serial neurologic examinations (see Tables 93-4 and 93-5). During the initial hours after an insult, infants have a depressed level of consciousness. Periodic breathing with apnea or bradycardia is present, but cranial nerve functions are often spared with intact pupillary responses and spontaneous eye movement. Seizures are common with extensive injury. Hypotonia is also common as an early manifestation.

Diagnosis

Diffusion-weighted MRI is the preferred imaging modality in neonates with HIE because of its increased sensitivity and specificity early in the process and its ability to outline the topography of the lesion (Figs. 93-5 to 93-8). CT scans are helpful in identifying focal hemorrhagic lesions, diffuse cortical injury, and damage to the basal ganglia; CT has limited ability to identify cortical injury during the 1st few days of life. Ultrasonography has limited utility in evaluation of hypoxic injury in the term infant; it is the preferred modality in evaluation of the preterm infant.

Figure 93-5 MR images of selective neuronal injury. The infant experienced intrapartum asphyxia and had seizures on the 1st postnatal day. MRI was performed on the 5th postnatal day. A, An axial, fluid-attenuated inversion recovery image shows increased signal in the putamen bilaterally (arrows) but no definite abnormality in the cerebral cortex. B, By contrast, a diffusion-weighted image shows striking increased signal intensity (i.e., decreased diffusion) in the frontal cortex (in addition to a more pronounced basal ganglia abnormality).

(From Volpe JJ, editor: Neurology of the newborn, ed 5, Philadelphia, 2008, Saunders/Elsevier, p 420.)

Figure 93-6 MR images of hypoxic-ischemic injury to basal ganglia and thalamus. MRI was performed in a 5-day-old infant who experienced severe perinatal asphyxia. A, Note, in this parasagittal T1-weighted image, the markedly increased signal intensity in the basal ganglia, especially the putamen (arrowheads) and the thalamus (arrow). B, An axial proton density image also demonstrates the injury well in the same distribution.

(From Volpe JJ, editor: Neurology of the newborn, ed 5, Philadelphia, 2008, Saunders/Elsevier, p 420.)

Figure 93-7 MR image of a parasagittal cerebral injury. A coronal T1-weighted image, obtained on the 5th postnatal day in an asphyxiated term infant, shows striking triangular lesions in the parasagittal areas bilaterally; increased signal intensity is also apparent in the basal ganglia and thalamus bilaterally.

(From Volpe JJ, editor: Neurology of the newborn, ed 5, Philadelphia, 2008, Saunders/Elsevier, p 421.)

Figure 93-8 MR images of focal ischemic cerebral injury. MRI was performed on the 3rd postnatal day. A, An axial T2-weighted image shows a lesion in the distribution of the main branch of the left middle cerebral artery. B, A diffusion-weighted image demonstrates the lesion more strikingly.

(From Volpe JJ, editor: Neurology of the newborn, ed 5, Philadelphia, 2008, Saunders/Elsevier, p 422.)

Amplitude-integrated electroencephalography (aEEG) may help to determine which infants are at highest risk for long-term brain injury. A single-channel tracing is generated from 2 electrodes placed in the biparietal area. A filter is used to filter and attenuate the signal between 2 Hz and 15 Hz. This technique is simple to perform and correlates with standard EEG. It has good reliability, a positive predictive value of 85%, and a negative predictive value of 91-96% for infants who will have adverse neurodevelopmental outcome. The technique provides information quickly within the window during which intervention is most likely to be useful. Also, aEEG is able to detect seizure activity, which is common in patients with HIE. Continuous aEEG monitoring detects subclinical seizure activity during the subacute phase.

Treatment

Selective cerebral or whole body (systemic) therapeutic hypothermia reduces mortality or major neurodevelopmental impairment in term and near-term infants with HIE. Hypothermia decreases the rate of apoptosis and suppresses production of mediators known to be neurotoxic, including extracellular glutamate, free radicals, nitric oxide, and lactate. The neuroprotective effects are thought to be secondary to downregulation of the secondary mediators of injury resulting from cerebral edema, accumulation of cytokines, and seizures. Animal data suggest that the intervention is most effective when implemented within 6 hr of the event.

Several clinical trials and a meta-analysis demonstrate that either isolated cerebral cooling or systemic hypothermia to a core temperature of 33.5°C within the 1st 6 hr after birth reduces mortality and major neurodevelopmental impairment at 18 mo of age. Systemic hypothermia may result in more uniform cooling of the brain and deeper CNS structures. Infants treated with systemic hypothermia have a lower incidence of cortical neuronal injury on MRI.

Phenobarbital, the drug of choice for seizures, is given with an intravenous loading dose (20 mg/kg); additional doses of 5-10 mg/kg (up to 40-50 mg/kg total) may be needed. Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may be needed for refractory seizures. Phenobarbital levels should be monitored 24 hr after the loading dose has been given and maintenance therapy (5 mg/kg/24hr) is begun. Therapeutic phenobarbital levels are 20-40 µg/mL. There is some clinical evidence that high-dose prophylactic phenobarbital may decrease neurodevelopmental impairment in infants with HIE.

Additional therapy for infants with HIE includes supportive care directed at management of organ system dysfunction. Hyperthermia has been found to be associated with impaired neurodevelopment, so it is important to prevent hyperthermia before initiation of hypothermia. Careful attention to ventilatory status and adequate oxygenation, blood pressure, hemodynamic status, acid-base balance, and possible infection is important. Secondary hypoxia or hypotension due to complications of HIE must be prevented. Aggressive treatment of seizures is critical and may necessitate continuous EEG monitoring.

Prognosis

The outcome of HIE, which correlates with the timing and severity of the insult, ranges from complete recovery to death. The prognosis varies depending on the severity of the insult and the treatment. Infants with initial cord or initial blood pH <6.7 have a 90% risk for death or severe neurodevelopmental impairment at 18 mo of age. In addition, infants with Apgar scores of 0-3 at 5 min, high base deficit (>20-25 mmol/L), decerebrate posture, and lack of spontaneous activity are also at increased risk for death or impairment. These predictor variables can be combined to determine a score that helps with prognosis (see Table 93-4). Infants with the highest risk are likely to die or have severe disability despite aggressive treatment including hypothermia. Those with intermediate scores are likely to benefit from treatment. In general, severe encephalopathy, characterized by flaccid coma, apnea, absence of oculocephalic reflexes, and refractory seizures, is associated with a poor prognosis (see Table 93-5). A low Apgar score at 20 min, absence of spontaneous respirations at 20 min of age, and persistence of abnormal neurologic signs at 2 wk of age also predict death or severe cognitive and motor deficits. The combined use of early EEG and MRI is useful in predicting outcome in term infants with HIE. Normal MRI and EEG findings are associated with a good recovery, whereas severe MRI and EEG abnormalities predict a poor outcome. Microcephaly and poor head growth during the 1st year of life also correlate with injury to the basal ganglia and white matter and adverse developmental outcome at 12 mo. All survivors of moderate to severe encephalopathy require comprehensive high-risk medical and developmental follow-up. Early identification of neurodevelopmental problems allows prompt referral for developmental, rehabilitative, neurologic care, and early intervention services so that the best possible outcome can be achieved.

Brain death after neonatal HIE is diagnosed from the clinical findings of coma unresponsive to pain, auditory, or visual stimulation; apnea with PCO₂ rising from 40 to >60 mm Hg without ventilatory support; and absence of brainstem reflexes (pupillary, oculocephalic, oculovestibular, corneal, gag, sucking) (Chapter 63.1). These findings must occur in the absence of hypothermia, hypotension, and elevations of depressant drugs (phenobarbital). An absence of cerebral blood flow on radionuclide scans and of electrical activity on EEG (electrocerebral silence) is inconsistently observed in clinically brain-dead neonatal infants. Persistence of the clinical criteria for 2 days in term infants and 3 days in preterm infants predicts brain death in most asphyxiated newborns. Nonetheless, no universal agreement has been reached regarding the definition of neonatal brain death. Consideration of withdrawal of life support should include discussions with the family, the health care team, and, if there is disagreement, an ethics committee. The best interest of the infant involves judgments about the benefits and harm of continuing therapy or avoiding ongoing futile therapy.

Brachial Palsy

Brachial plexus injury is a common problem, with an incidence of 0.6-4.6/1,000 live births. Injury to the brachial plexus may cause paralysis of the upper part of the arm with or without paralysis of the forearm or hand or, more commonly, paralysis of the entire arm. These injuries occur in macrosomic infants and when lateral traction is exerted on the head and neck during delivery of the shoulder in a vertex presentation, when the arms are extended over the head in a breech presentation, or when excessive traction is placed on the shoulders. Approximately 45% of brachial plexus injuries are associated with shoulder dystocia. In Erb-Duchenne paralysis, the injury is limited to the 5th and 6th cervical nerves. The infant loses the power to abduct the arm from the shoulder, rotate the arm externally, and supinate the forearm. The characteristic position consists of adduction and internal rotation of the arm with pronation of the forearm. Power to extend the forearm is retained, but the biceps reflex is absent; the Moro reflex is absent on the affected side (Fig. 93-9). The outer aspect of the arm may have some sensory impairment. Power in the forearm and hand grasps is preserved unless the lower part of the plexus is also injured; the presence of hand grasp is a favorable prognostic sign. When the injury includes the phrenic nerve, alteration in diaphragmatic excursion may be observed with ultrasonography or fluoroscopy. Klumpke paralysis is a rare form of brachial palsy, in which injury to the 7th and 8th cervical nerves and the 1st thoracic nerve produces a paralyzed hand and ipsilateral ptosis and miosis (Horner syndrome) if the sympathetic fibers of the 1st thoracic root are also injured. Mild cases may not be detected immediately after birth. Differentiation must be made from cerebral injury; from fracture, dislocation, or epiphyseal separation of the humerus; and from fracture of the clavicle. MRI demonstrates nerve root rupture or avulsion.

Figure 93-9 Brachial palsy of the left arm (asymmetric Moro reflex).

Full recovery occurs in most patients; prognosis depends on whether the nerve was merely injured or was lacerated. If the paralysis was due to edema and hemorrhage about the nerve fibers, function should return within a few months; if it was due to laceration, permanent damage may result. Involvement of the deltoid is usually the most serious problem and may result in shoulder drop secondary to muscle atrophy. In general, paralysis of the upper part of the arm has a better prognosis than paralysis of the lower part.

Treatment consists of initial conservative management with monthly follow-up and a decision for surgical intervention by three months if function has not improved. Partial immobilization and appropriate positioning are used to prevent the development of contractures. In upper arm paralysis, the arm should be abducted 90 degrees with external rotation at the shoulder, full supination of the forearm, and slight extension at the wrist with the palm turned toward the face. This position may be achieved with a brace or splint during the 1st 1-2 wk. Immobilization should be intermittent throughout the day while the infant is asleep and between feedings. In lower arm or hand paralysis, the wrist should be splinted in a neutral position, and padding placed in the fist. When the entire arm is paralyzed, the same treatment principles should be followed. Gentle massage and range-of-motion exercises may be started by 7-10 days of age. Infants should be closely monitored with active and passive corrective exercises. If the paralysis persists without improvement for 3 months, neuroplasty, neurolysis, end-to-end anastomosis, and nerve grafting offer hope for partial recovery.

The type of treatment and the prognosis depend on the mechanism of injury and the number of nerve roots involved. The mildest injury to a peripheral nerve (neurapraxia) is due to edema and heals spontaneously within a few weeks. Axonotmesis is more severe and is due to nerve fiber disruption with an intact myelin sheath; function usually returns in a few months. Total disruption of nerves (neurotmesis) or root avulsion is the most severe, especially if it involves C5-T1; microsurgical repair may be indicated. Fortunately, most (75%) injuries are at the root level C5-C6, involve neurapraxia and axonotmesis, and should heal spontaneously. Botulism toxin may be used to treat biceps-triceps co-contractions.

Phrenic Nerve Paralysis

Phrenic nerve injury (3rd, 4th, 5th cervical nerves) with diaphragmatic paralysis must be considered when cyanosis and irregular and labored respirations develop. Such injuries, usually unilateral, are associated with ipsilateral upper brachial palsy. Because breathing is thoracic in type, the abdomen does not bulge with inspiration. Breath sounds are diminished on the affected side. The thrust of the diaphragm, which may often be felt just under the costal margin on the normal side, is absent on the affected side. The diagnosis is established by ultrasonographic or fluoroscopic examination, which reveals elevation of the diaphragm on the paralyzed side and seesaw movements of the 2 sides of the diaphragm during respiration.

No specific treatment is available; infants should be placed on the involved side and given oxygen if necessary. Initially, intravenous feedings may be needed; later, progressive gavage or oral feeding may be started, depending on the infant’s condition. Pulmonary infections are a serious complication. Recovery usually occurs spontaneously by 1-3 mo; rarely, surgical plication of the diaphragm may be indicated.

Facial Nerve Palsy

Facial palsy is usually a peripheral paralysis that results from pressure over the facial nerve in utero, from efforts during labor, or from forceps use during delivery. Rarely, it may result from nuclear agenesis of the facial nerve. Peripheral paralysis is flaccid and, when complete, involves the entire side of the face, including the forehead. When the infant cries, movement occurs only on the nonparalyzed side of the face, and the mouth is drawn to that side. On the affected side the forehead is smooth, the eye cannot be closed, the nasolabial fold is absent, and the corner of the mouth droops. The forehead wrinkles on the affected side with central paralysis because only the lower of the face is involved. The infant also usually has other manifestations of intracranial injury, most commonly 6th nerve palsy. The prognosis depends on whether the nerve was injured by pressure or the nerve fibers were torn. Improvement occurs within a few weeks in the former instance. Care of the exposed eye is essential. Neuroplasty may be indicated when the paralysis is persistent. Facial palsy may be confused with absence of the depressor muscles of the mouth, which is a benign problem.

Other peripheral nerves are seldom injured in utero or at birth except when they are involved in fractures or hemorrhage.