Neonatal intracranial hemorrhage refers to a common condition in newborns, particularly preterm infants. It is also a significant form of severe brain injury. The condition has a high mortality rate, and severe cases often result in neurological sequelae.
Etiology and Pathogenesis
Preterm Birth
This condition is more frequently observed in preterm infants born before 32 weeks of gestation. The mechanisms include the following:
- Brain blood flow lacks autoregulatory function, leading to pressure-passive cerebral circulation.
- The germinal matrix (GM) consists of an immature capillary network, with vessel walls composed of only a single layer of endothelial cells, lacking collagen and elastic fibers for support, making them prone to rupture.
- Endothelial cells in GM vessels are rich in mitochondria and have high oxygen consumption, rendering them highly sensitive to hypoxia and acidosis.
- Small veins in this region converge in a U-shaped pattern into the vein of Galen. This unique vascular configuration increases the likelihood of slowed or stagnant blood flow, elevated capillary bed pressure, and subsequent hemorrhage.
- Increased fibrinolytic protein activity is present. Beyond 32 weeks of gestation, the GM gradually regresses and is replaced by glial cells, which form the foundation of cerebral white matter postnatally.
Hypoxia and Ischemia
Hypoxia or hypercapnia during asphyxia impairs the autoregulatory function of cerebral blood flow, resulting in pressure-passive cerebral circulation and cerebral vasodilation. These changes can increase vascular pressure, leading to capillary rupture or cause venous stasis, thrombosis, and rupture of cerebral venous vessels. This mechanism affects both preterm and term infants.
Trauma
Traumatic injury, primarily resulting from birth trauma, represents another cause. Instances include abnormal fetal position, macrosomia, precipitous labor, prolonged labor, or the use of mechanical interventions such as high-forceps delivery, vacuum extraction, or breech traction, which can lead to tears in the tentorium cerebelli, cerebral falx, or rupture of superficial cerebral veins, causing subdural or intracranial hemorrhage. These cases are more commonly observed in term infants.
Hematologic Disorders
Coagulation abnormalities or thrombocytopenia, whether primary or secondary, serve as risk factors. Potential causes include congenital coagulation factor deficiencies, congenital thrombocytopenia, or secondary factors such as hypoxia and ischemia, septicemia, shock, necrotizing enterocolitis in newborns, hepatic dysfunction, or immune thrombocytopenia.
Other Factors
Administration of hypertonic solutions such as calcium gluconate, mannitol, or sodium bicarbonate may result in capillary rupture. The narrow range of autoregulation in preterm infants' vasculature makes them vulnerable to hemorrhage when blood pressure undergoes significant sudden changes. Such changes may occur as a result of frequent procedures like venipuncture, suctioning, or endotracheal intubation, as well as improper ventilator settings during mechanical ventilation or significant left-to-right shunting in the presence of a patent ductus arteriosus (PDA). These scenarios can lead to abrupt hemodynamic changes or loss of autoregulatory function, resulting in capillary rupture and subsequent hemorrhage.
Clinical Manifestations
The clinical manifestations primarily depend on the location and volume of hemorrhage. Mild cases may be asymptomatic, while significant hemorrhages can lead to rapid deterioration and death within a short time. Common symptoms and signs include:
- Altered consciousness, presenting as irritability, lethargy, or coma.
- Respiratory changes, such as increased or decreased respiratory rate, irregular breathing, or severe apnea.
- Increased intracranial pressure (ICP), manifesting as bulging of the anterior fontanelle, elevated blood pressure, seizures, opisthotonus, or a high-pitched cerebral cry.
- Ocular signs, including fixed gaze, strabismus, or nystagmus.
- Pupillary abnormalities, such as unequal pupil sizes or lack of response to light.
- Abnormal muscle tone, which may be increased, decreased, or absent.
- Other findings, such as unexplained metabolic acidosis, pallor, anemia, and jaundice.
Based on the location of the intracranial hemorrhage, the clinical condition is classified into the following types:
Periventricular-Intraventricular Hemorrhage (PVH-IVH)
This condition primarily occurs in premature infants with a gestational age below 32 weeks and a birth weight under 1,500 grams. Its incidence increases with decreasing gestational age. Among preterm infants weighing less than 1,500 grams, the incidence of PVH-IVH is approximately 17.5%. Additionally, 2%-3% of PVH-IVH cases can occur in full-term infants, primarily originating from the choroid plexus due to trauma or asphyxia.
PVH-IVH is classified into four grades based on cranial imaging:
- Grade I: Hemorrhage confined to the subependymal germinal matrix.
- Grade II: Intraventricular hemorrhage involving less than 50% of the ventricular volume, with no ventricular enlargement.
- Grade III: Intraventricular hemorrhage involving more than 50% of the ventricular size or accompanied by ventricular enlargement.
- Grade IV: Ventricular enlargement with periventricular white matter damage or hemorrhagic infarction of terminal veins in the periventricular region.
Fifty percent of cases occur within the first 24 hours after birth, and 90% occur within the first 72 hours, with only a small proportion developing later. Post-hemorrhagic hydrocephalus occurs in 25%-35% of cases, predominantly in infants with Grade III–IV PVH-IVH, usually developing 2 to 6 weeks after the initial hemorrhage.
Primary Subarachnoid Hemorrhage (SAH)
This type of hemorrhage is confined to the subarachnoid space, excluding hemorrhages from other sites such as the subdural space, ventricles, or cerebellum that later extend into the subarachnoid space. SAH is relatively common in neonates, especially in premature infants, and is associated with factors such as hypoxia, acidosis, or birth trauma.
In most cases, the volume of bleeding is small, with no clinical symptoms, and the prognosis is favorable. In some typical cases, seizures may occur on the second postnatal day, with normal intervals between episodes. Rare cases involving large-volume hemorrhages may present with recurrent central apnea, convulsions, or coma and may result in death within a short period. The main sequelae include communicating or obstructive hydrocephalus.
Intraparenchymal Hemorrhage (IPH)
This type is more commonly observed in full-term infants and usually results from small venous thrombosis causing an increase in capillary pressure and subsequent rupture. Clinical manifestations vary significantly depending on the location and volume of the hemorrhage:
- Small, patchy hemorrhages may not produce noticeable symptoms.
- Brainstem hemorrhages in the early stages may manifest with pupillary abnormalities, irregular respiration, or bradycardia, while tension in the anterior fontanelle may remain normal.
Liquefaction of the hemorrhaged area may result in a cyst that communicates with the ventricles, forming a porencephalic cyst. The main sequelae include cerebral palsy, epilepsy, and delayed intellectual or motor development. Motor impairments of the lower limbs are more common due to the proximity of the neural tracts for lower-limb control to the lateral ventricles, compared to the neural tracts for the torso, upper limbs, and facial muscles, which are located further away.
Subdural Hemorrhage (SH)
This type is typically caused by trauma that leads to rupture of the subdural venous sinuses or their adjacent blood vessels. It represents the most common type of intracranial hemorrhage resulting from birth trauma and is more frequently observed in full-term macrosomic infants, breech deliveries with abnormalities, or those delivered via high-forceps assistance.
Small-volume hemorrhages may be asymptomatic. Larger hemorrhages generally present within 24 hours after birth with neurological symptoms such as seizures, hemiplegia, and strabismus. Severe cases with rupture of the tentorium cerebelli, falx cerebri, or superficial cerebral veins may lead to posterior fossa hemorrhage, resulting in brainstem compression and death within hours of birth. In some cases, symptoms in the neonatal period may remain subtle, with chronic subdural effusions developing months later.
Cerebellar Hemorrhage (CH)
Cerebellar hemorrhage includes four types: primary cerebellar hemorrhage, hemorrhage from the ventricles or subarachnoid space extending into the cerebellum, venous hemorrhagic infarction, and trauma-induced cerebellar tears. This condition is frequently observed in premature infants with a gestational age below 32 weeks or a birth weight under 1,500 grams, as well as full-term infants with a history of birth trauma. Clinical manifestations vary depending on the underlying cause and the volume of hemorrhage. Severe cases may present with general neurological symptoms alongside brainstem compression, often leading to rapid death. The prognosis is generally poor, particularly in preterm infants.
Diagnosis
A detailed medical history, symptoms, and clinical signs provide diagnostic clues; however, a definitive diagnosis relies on cranial imaging. Cranial ultrasound, which offers high resolution for midline brain lesions and can be conducted at the bedside, is the preferred diagnostic method for PVH-IVH.
The American Academy of Neurology recommends routine cranial ultrasound for preterm infants with a gestational age of ≤30 weeks within the first week of life. Infants with intraventricular hemorrhage require weekly follow-up scans, while preterm infants without intraventricular hemorrhage should undergo a follow-up scan at a corrected gestational age of 34–36 weeks.
Cranial ultrasound is limited in detecting hemorrhages in the subarachnoid space, posterior fossa, or epidural space, requiring further evaluation using CT or MRI. MRI is the most sensitive modality for diagnosing intracranial hemorrhages and assessing prognosis. In rare cases, cerebrospinal fluid analysis may be necessary to distinguish this condition from other central nervous system diseases.
Treatment
Supportive Therapy
Maintaining a calm environment for the affected infant and minimizing handling or stimulus can help stabilize the condition. Efforts are typically focused on maintaining normal and stable levels of PaO2, PaCO2, pH, osmotic pressure, perfusion pressure, and blood pressure in order to prevent further deterioration. Keeping the infant's head in a midline position promotes unobstructed jugular venous flow, reducing the risk of jugular venous congestion and subsequent intracranial hemorrhage.
Hemostasis
Hemostatic agents, such as vitamin K1, batroxobin injection, or prothrombin complex, may be used to control bleeding. Fresh frozen plasma can also be administered based on clinical judgment.
Seizure Control
Reduction of Intracranial Pressure
For infants presenting with symptoms of elevated intracranial pressure, furosemide at a dose of 0.5–1 mg/kg can be administered intravenously 2–3 times per day. In cases of central respiratory failure, mannitol at a dose of 0.25–0.5 g/kg may also be given intravenously every 6–8 hours.
Serial Lumbar Punctures
Although the effectiveness of this technique remains controversial, it is primarily considered for cases of Grade III or higher intraventricular hemorrhage where imaging confirms the presence of obstructive hydrocephalus with progressively enlarging lateral ventricles displaying high tension. The volume of fluid removed during each procedure is generally limited to 8–10 ml, with a maximum of 14 ml. Punctures are typically performed every other day. If there is no improvement after three attempts, alternative treatments should be considered.
Surgical Intervention
For large hematomas posing a life-threatening risk, such as severe subdural hematomas, subarachnoid hemorrhage, intraparenchymal hemorrhage, and cerebellar hemorrhage that may cause symptoms of brainstem compression, urgent neurosurgical management is required to save the infant's life.
Treatment of Hydrocephalus
Acetazolamide may be used to reduce the production of cerebrospinal fluid, administered orally at a dose of 10–30 mg/(kg·d) divided into 2–3 doses per day, with a treatment duration not exceeding two weeks. However, this drug has shown poor long-term efficacy and is now rarely used. For infants with Grade III or higher PVH-IVH, obstructive hydrocephalus, or progressive enlargement of the lateral ventricles, external ventricular drainage may be performed once the condition stabilizes (typically around two weeks after birth). Common techniques include placement of an Ommaya reservoir beneath the parietal galea aponeurotica for periodic fluid aspiration, or ventriculoperitoneal shunt surgery to relieve ventricular pressure.
Prognosis
Prognosis is influenced by multiple factors, including the volume and location of the hemorrhage, gestational age, and perinatal complications. Poor outcomes are associated with prematurity, bilateral hemorrhages, Grade III and IV PVH-IVH, or intraparenchymal hemorrhagic infarction. The mortality rate for severe intracranial hemorrhages is as high as 27%–50%. Survivors often experience varying degrees of neurological sequelae, such as cerebral palsy, epilepsy, sensory or motor dysfunction, as well as cognitive, behavioral, or developmental impairments.
Prevention
Perinatal Prevention
Proper perinatal care is essential, including enhanced health care for pregnant women to prevent preterm birth, advanced obstetric techniques to reduce perinatal asphyxia and birth trauma, and timely treatment of maternal bleeding disorders.
Appropriate Medical and Nursing Measures
Improved medical and nursing care aims to eliminate factors that could lead to iatrogenic intracranial hemorrhage. Emphasis is placed on maintaining relatively stable intracranial pressure and cerebral blood flow, avoiding significant fluctuations. Preservation of cardiac function and normal systemic circulation is particularly critical, especially during treatments involving mechanical ventilation or specialized drugs. Rapid infusion of hypertonic fluids or large volumes of fluid should be avoided. Nursing interventions emphasize gentle handling, adequate warmth, maintaining a quiet environment, and minimizing disturbances to reduce excessive crying or agitation. Elevating the head to an angle of 15°–30° has been shown to effectively reduce the risk of neonatal intracranial hemorrhage.
Pharmacological Prevention
The use of certain drugs, such as phenobarbital or indomethacin, has been explored, but their efficacy remains subject to ongoing debate.