Chorioamnionitis and brain injury
Section snippets
Chorioamnionitis
Amniotic fluid is normally sterile, so finding organisms in that fluid has been used to define the presence of intrauterine infection (IUI). Twice as many infections occur in the maternal decidua as in the amniotic sac, however [9]. Of agents identified in amniotic fluid, the most common are genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis), the anaerobes including Fusobacterium, Bacteroides, and Peptostreptococcus, and the aerobes Garnerella vaginalis, group B streptococci,
Manifestations of brain injury examined
The neurologic outcome in the infant that has been linked most often with chorioamnionitis is CP. CP can be defined as a chronic disability of central nervous system origin, characterized by aberrant control of movement or posture, appearing early in life, and not the result of a progressive disease. Clinical phenotypes include spastic quadriparesis, hemiplegia, diplegia, mixed forms, and minor ataxic and athetoid variants. Associated neurologic conditions include seizure disorder and cognitive
Association of chorioamnionitis with cerebral palsy in term infants
Few studies have examined the association of infectious antecedents with CP in term infants. Where studied, C-chorio, H-chorio, and neonatal sepsis syndrome were associated with later diagnosis of CP [18], [43], [44]. When C-chorio or H-chorio were associated with CP, neonatal sepsis syndrome was seldom an intermediary [43], [44]. Relatively high concentrations of inflammatory cytokines have been observed postnatally in the blood of many term infants with a subsequent diagnosis of CP [45], [46].
CP in premature infants
There are more studies of infectious antecedents of CP in low birth weight and prematurely born infants. Gestational age is the major predictor of CP in VLBW infants, so gestational age needs excruciating control and was not comparable or defined comparably across studies. Some argue that prematurity is in the causal pathway, and that infection, believed causal of most premature births, may be causal of CP [11], [47]. As we discuss more fully below, few infants born prematurely with antecedents
Suspected developmental delay
The association of chorioamnionitis with poor performance on standardized developmental tests or with aggregate adverse neurological outcomes is weak; most report no association in univariate analyses [2], [3], [5], [51]. In animal models, gray matter necrosis such as might be the basis for cognitive impairment is potentiated by interactions between by-products of bacterial infection and asphyxia [52].
Neonatal encephalopathy
Six recent studies call attention to the association of maternal fever or chorioamnionitis with neonatal encephalopathy in term infants, and two additional studies reported an association with C- or H-chorio (Table 2). Epidural analgesia was associated with maternal fevers [53] and is also associated with neonatal depression when variables associated with H-chorio were controlled for [54], [55]. Epidurals may contribute to maternal fever beyond any increase in H-chorio resulting from prolonged
Action at a distance
It has been mentioned that although neonatal sepsis and meningitis in the neonate can cause CP, such infections are uncommon in the term neonate [44] and common in very premature neonates with or without CP [4], [60]. The majority of neonates who subsequently develop CP or cognitive insults have no clear antecedent infectious syndrome [2], [3], [4], [5], [43], [51], [58], [59]. We find it notable that M-chorio, the obvious “smoking gun”, is less well associated with adverse neurologic outcome
Susceptibility during development
The clinical syndromes of CP, quadriplegia, hemiplegia, and diplegia are shared between infants born prematurely and at term, although the relative frequency of the syndromes varies by gestational age. Epidemiologically, the age-specific prevalences of intrauterine infection, placental inflammation and CP change in strikingly parallel fashion across human gestation. It is therefore tempting to consider infection, inflammation, and outcome of CP as a single continuous process across gestation.
Why this baby?
The prevalence of infection among extremely premature infants, measured by amniotic fluid microbiology or placental histology, approximates 40% to 80% [16], [84]. Despite this high rate of exposure to infection, only 5% to 13% of extremely premature infants develop CP [3], [21], [35], [36], [83]. CP and cognitive defects occur independently in the same populations, so there are likely to be additional causes of brain injury contributing differentially to these relatively infrequent outcomes.
What can we do?
The process associated with infection and CP in term infants may be discoverable by measurement of cytokine concentrations during the postnatal period and may be amenable to intervention; howver, there are several limitations that temper the authors' desire to apply what has been learned to clinical practice at this time [97].
Why not start screening now? Cytokine induction is not specific to infection. Furthermore, much more information is needed about specificity and sensitivity of cytokine
Summary
The limited available evidence supports a strong association of chorioamnionitis with neonatal encephalopathy and CP in the term infant. The association of chorioamnionitis with depressed Apgar scores or neonatal seizures and with CP is equivocal in the preterm infant. Different study results may be related to differences in study populations, perhaps specifically to differences in susceptibility by stages of neurologic development as well as differences in gene frequencies associated with
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Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia Presented in poster format at the annual meeting of the Pediatric Academic Societies, Vancouver, British Columbia, Canada, May 3-6, 2014.
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