Epidemiology

The incidence of preterm birth continues to rise in the United States, with 12.7% of infants born before 37 weeks’ estimated gestational age (EGA), representing an almost 20% increase over the past 15 years.¹ Preterm infants are stratified by birth weight or EGA, or both. For classification purposes, the EGA of preterm infants is not rounded up. For example, an infant born at weeks is classified as a 26-week EGA infant.² The survival of all preterm cohorts has risen dramatically over the past few decades owing to improvements in perinatal medicine, but many of these infants remain at risk for neurodevelopmental deficits. According to the 2007 report from the Institute of Medicine’s Committee on Understanding Preterm Birth, preterm infants account for 64% to 75% of infant mortality, 42% to 47% of children with cerebral palsy, 27% of children with cognitive deficits, 37% of children with visual impairments, and 23% of those with hearing impairments.³ Neurodevelopmental outcomes are discussed in more detail later.

The prevalence of IVH varies, depending on the availability and quality of neonatal intensive care, and only a small subset of patients requires neurosurgical intervention. The incidence of IVH increases inversely with decreasing birth weight or EGA.⁴ In a study of infants born in the mid-1990s weighing less than 1500 g, 22% had IVH, and one fourth of those infants had progressive ventricular dilation.⁵ Among survivors with progressive ventricular dilation, one third required surgical intervention.⁵ Although infants born more recently continue to suffer IVH, fewer require surgical intervention. A recent collaborative study from the National Institutes of Health (NIH) Neonatal Research Network following more than 6000 preterm infants born at less than 1000 g between 1993 and 2002 showed that one third suffered IVH, and one third of those with IVH developed progressive ventricular dilation.⁶ Ten percent of those with IVH (3% of the total weighing <1000 g) required shunt insertion for symptomatic PHH, a decrease from 15% in older studies.⁶ IVH is graded on Papile’s scale from I to IV (Table 187-1).⁷ Although only 1% of infants with grade I or II IVH in this recent NIH study required shunt insertion, 18% of infants with grade III and 29% with grade IV IVH required a shunt.⁶ As perinatal care continues to improve, the proportion of preterm neonates who require shunt insertion will likely continue to decline.

TABLE 187-1 Papile’s Classification of Preterm Intraventricular Hemorrhage on Ultrasonography

Because less than 10% of infants with IVH develop PHH and require a shunt, strong collaboration between the neurosurgical team and the neonatology team is required to obtain neurosurgical consultation in a timely manner and to avoid unnecessary nonsurgical consults. Intravenous access in cranial veins should be avoided in any preterm infants who might develop hydrocephalus.

Pathophysiology of Germinal Matrix Hemorrhage and Posthemorrhagic Infarction

The germinal matrix is a transient structure in the subependyma of the ventricular walls that generates neural cell progenitors for the overlying cortex, primarily from 8 to 28 weeks’ EGA. The germinal matrix typically completes involution by 32 weeks’ EGA. The proliferative germinal matrix is a metabolically active area with friable, immature vessels prone to hemorrhage.⁸ Hemorrhage can be limited to within the germinal matrix (grade I), but about 80% of germinal matrix hemorrhages rupture through the ventricular wall into the ventricle (grade II, III, or IV; see Table 187-1). Grade IV is also called periventricular hemorrhagic infarction.⁹ Venous infarction is believed to result from the germinal matrix hemorrhage rather than direct expansion of the hemorrhage into the parenchyma.

Multiple factors contribute to the germinal matrix’s propensity to hemorrhage, and the pathophysiology is incompletely understood. Because of their immaturity, preterm infants have impaired cerebral autoregulation. Systemic fluctuations in blood volume, flow, and pressure that commonly occur in preterm infants are thus transferred to the friable germinal matrix without the buffer of cerebral autoregulation. In addition, the germinal matrix has lower levels of fibronectin and other extracellular matrix components than do other areas of the late-gestation brain, and this likely contributes to the propensity to hemorrhage.¹⁰ An experimental study suggests that prenatal betamethasone treatment may enhance fibronectin levels and thus decrease the risk of hemorrhage. This correlates with the decreased risk of IVH observed clinically with prenatal betamethasone treatment.¹¹ Although neonatologists have worked aggressively with obstetricians to minimize stress to preterm infants during the peripartum, the risk for IVH most likely reflects a combination of genetic and environmental factors. After IVH occurs, the absorption of cerebrospinal fluid (CSF) is impaired, likely caused by a combination of decreased absorption across the arachnoid villi into veins and from ependyma into parenchyma.⁸

IVH can occur in association with periventricular leukomalacia (PVL), injury to the developing white matter. PVL can occur as both deep cystic white matter lesions and diffuse noncystic loss of oligodendrocytes with associated astrocyte gliosis.¹² Cystic PVL is visible on cranial ultrasonography (US), and most attention has focused on the white matter injury. Observations during the past decade from magnetic resonance imaging (MRI) and autopsy studies have shown that injury to the developing central nervous system affects both white and gray matter.¹³ The combined injury has been designated encephalopathy of prematurity, which more accurately reflects the widespread nature of the injury not only to the cerebral gray and white matter but also to the diencephalon, brainstem, and cerebellum.¹⁴ PVL is about 10-fold more common than IVH among infants weighing less than 1500 g at birth. At least half of these infants have imaging signs of PVL, but only 5% have IVH.¹⁴

Clinical Presentation and Diagnostic Evaluation

Most IVH occurs within the first 72 hours of life, when most preterm newborns are quite unstable (Fig. 187-1). IVH is readily diagnosed by bedside cranial US. Transport to obtain computed tomography (CT) or MRI can cause additional stress and potential injury in these very fragile patients. CT scans also involve radiation, and repeated exposure of the preterm brain to radiation should be minimized if possible. In general, CT scans should be reserved for the evaluation of diffuse, life-threatening cerebral hemorrhages when MRI is not feasible. US provides a reliable means of identifying ventricular dilation and IVH. If possible, all preterm newborns weighing less than 1500 g should have a cranial ultrasound examination within the first 48 hours of life, and then weekly or biweekly as needed. PVL can also be assessed by US. Although the interreader reliability for grades III and IV IVH is excellent, the reliability for grades I and II IVH and for PVL is less.¹⁵ These limitations of cranial US rarely present a problem for neurosurgical management (Fig. 187-2).

FIGURE 187-1 Typical imaging findings in posthemorrhagic hydrocephalus from germinal matrix hemorrhage after preterm birth at 27 weeks’ gestation. Cranial ultrasonography (US) in the coronal (A) and axial (B) planes at 12 hours of life shows minimal abnormalities. Repeat US 2 days later reveals bilateral grade IV intraventricular hemorrhage (C and D), also termed periventricular hemorrhagic infarction. The patient did not develop signs of symptomatic hydrocephalus as a neonate. At term equivalent, magnetic resonance imaging shows a paucity of white matter, suggesting the diffuse form of periventricular leukomalacia (E). Also note the small cerebellum, a typical finding among former preterm infants (F). At 8 months of age he developed symptomatic hydrocephalus, with an enlarging head circumference and dilated ventricles observed on CT (G). Several months later, a baseline CT scan shows well-decompressed ventricles, but the paucity of white matter remains (H, arrow).

FIGURE 187-2 Progressive ventricular dilation on cranial ultrasonography (US) in the neonatal period. Initial US of this infant born at 27 weeks’ gestation shows bilateral grade II intraventricular hemorrhage (IVH) (A). Although distinguishing between the lower grades of IVH on cranial US may be difficult for the average observer, the progressive ventricular dilation, with retraction of the germinal matrix clot, at 2 weeks (B) and 3 weeks (C) is readily apparent. After B, serial lumbar punctures were initiated for an enlarging head circumference with splayed sutures, but they failed to control the hydrocephalus. After C, a ventriculosubgaleal shunt was inserted.

Most preterm infants develop symptomatic hydrocephalus over several days, with a gradual shift in their clinical course. Infants with IVH should be observed closely with daily measurement of the occipitofrontal circumference. An increase of 0.5 to 1 cm/day for 2 to 3 consecutive days often suggests symptomatic hydrocephalus. The anterior fontanelle in very small infants is often quite large; usually the shift from a soft, slightly bulging fontanelle to a tense, full one can be appreciated. Widening of the space between the bone edges along the sagittal and coronal sutures (splayed sutures) is often a reliable finding on daily examination to assess the development of symptomatic hydrocephalus. Preterm infants with symptomatic hydrocephalus can have episodes of spontaneous apnea or bradycardia. Other symptoms and signs of increased intracranial pressure include refractory seizures, lethargy, and impaired upward gaze (“sunset” phenomenon). In addition to the daily clinical examination, serial ultrasound studies every few days are useful to assess for additional hemorrhage or the development of ventricular dilation. Rarely, preterm infants experience acute clinical deterioration due to a rapid onset of increased intracranial pressure. In these patients, more extensive and severe intracerebral hemorrhage may have occurred, often in association with other systemic problems such as sepsis and coagulopathy. Urgent interventions may be needed to sustain these infants, but the heroic nature and poor long-term outcome of these interventions should be discussed with the parents.

Hydrocephalus ex vacuo refers to ventricular dilation without increased intracranial pressure. In the mid-1990s, 24% of surviving infants with IVH had ventricular dilation without progression.⁵ Hydrocephalus ex vacuo reflects encephalomalacia, or a lack of adequate parenchymal brain growth; the implications for developmental outcomes are discussed later. Infants can have transient symptomatic hydrocephalus that spontaneously resolves. Distinguishing hydrocephalus ex vacuo from symptomatic hydrocephalus can be challenging. With continued observation, the type of hydrocephalus typically declares itself.

Treatment

Preterm infants are challenging patients. Their relatively poor nutrition, immature immune system, and other comorbidities make them less than ideal surgical candidates. For example, many preterm infants have anemia of prematurity treated with erythropoietin, red blood cell, and platelet transfusions. Even with scrupulous attention to minimizing blood loss during surgery, a preterm neonate may require a transfusion after a surgical procedure. Because grades III and IV IVH tend to occur in the smallest and sickest infants, they are more likely to have other confounding illnesses. Interventions for symptomatic hydrocephalus are offered in a stepwise progression to identify patients in whom permanent CSF diversion is not required. This process allows surgery to be avoided in all but the few who definitely need it. It also shows the family that every reasonable nonsurgical measure has been tried. This is important because neither CSF shunts nor endoscopic third ventriculostomy offers highly effective lifelong treatment without complications.