PL is associated with infection and inflammation. Zupan and colleagues (1996) studied 753 infants born between 24 and 32 weeks, 9 percent of whom developed PVL. Those born before 28 weeks, those who had inflammatory events during the last days to weeks before delivery, and those who had both were at highest risk. In another study, PVL was strongly associated with prolonged membrane rupture, chorioamnionitis, and neonatal hypotension (Perlman, 1996). Bailis and coworkers (2008) reported that chronic-and not acute-placental inlammation was associated with PVL.
Fetal infection may be a key element in the pathway between preterm birth and CP (Burd, 2012; Leviton, 2010). As discussed in Chapter 42 (p. 810), chorioamnionitis is a major cause of spontaneous preterm delivery. In the pathway proposed in Figure 34-2, antenatal reproductive tract infection evokes the production of cytokines such as tumor necrosis factor and interleukins-1, -6, and -8. hese in turn stimulate prostaglandin production and preterm labor. Preterm fetal intracranial blood vessels are susceptible to rupture and damage, and the cytokines that stimulate preterm labor also have direct toxic efects on oligodendrocytes and myelin. Vessel rupture, tissue hypoxia, and cytokine-mediated damage result in massive neuronal cell death. Glutamate is released, stimulating membrane receptors to allow excess calcium to enter the neurons. High intracellular calcium levels are toxic to white matter, and glutamate may be directly toxic to oligodendrocytes (hwaja, 2008).
Many studies have shown that infection and cytokines can directly damage the immature brain (Chau, 2014; Yoon, 1997a). Tumor necrosis factor and interleukin-6 were more frequently found in the brains of infants who died with PVL (Yoon, 1997b). Cytokines are strongly linked to white matter lesions even when organisms cannot be demonstrated (Y oon, 2000).
FIGURE 34-2 Schematic representation of the hypothesized pathway between maternal or intrauterine infection and preterm birth or periventricular leukomalacia. Both potentially lead to cerebral palsy. LPS = lipopolysaccharide; PG = prostaglandin.
Andrews and colleagues (2008) provided data that raise questions regarding a higher incidence of adverse neurodevelopmental outcomes related to exposure to chorioamnionitis. In a cohort born between 23 and 32 weeks, they studied several surrogate indicators and direct markers of in utero inflammation. These included clinical findings, cytokine levels, histological findings, and microbial culture results. Infants undergoing comprehensive psychoneurological testing had similar incidences of CP, intelligence quotient (IQ) scores <70, or both, regardless of these markers. The researchers interpreted their findings to support current practices that employ eforts to delay delivery with preterm pregnancies in the absence of overt intrauterine infection. Importantly, this does not apply to preterm pregnancy in which clinical chorioamnionitis is diagnosed. Of 3094 singletons born before 33 weeks' gestation, 15 percent had evidence of clinical chorioamnionitis (Soraisham, 2009). Compared with noninfected infants, cases complicated by infection had significantly higher rates of early-onset sepsis-4.8 versus 0.9 percent-and ofaIH-22 versus 12 percent.