Intrauterine
infection induces an intra-amniotic inflammatory response involving the activation of a number of
cytokines and
chemokines which, in turn, may trigger preterm contractions, cervical ripening and
rupture of the membranes.
Infection and
cytokine-mediated
inflammation appear to play a prominent role in
preterm birth at early gestations (<30 weeks). The role of
infection/
inflammation in
preterm birth in Europe has been incompletely characterised. The rate of
preterm birth in Sweden is lower, and the rate of
chorioamnionitis,
bacterial vaginosis (BV),
neonatal sepsis, and
urinary tract infections during pregnancy is lower compared with the USA. In a Swedish population of women with preterm labour or
preterm premature rupture of the membranes (
PPROM) <34 weeks of gestation, microorganisms were detected in the amniotic fluid in 25% of women with
PPROM and in 16% of those in preterm labour. Nearly half of these women had intra-amniotic
inflammation defined as elevated
interleukin-6 (IL-6) and
IL-8, and there was a high degree of correlation between
cytokine levels and
preterm birth or the presence of microbial colonisation. These data do not support the hypothesis that
infection-related
preterm birth is less frequent in northern Europe than elsewhere. The intra-amniotic inflammatory response has also been associated with white matter injury and
cerebral palsy. We find that in experimental models, induction of a systemic inflammatory response using
lipopolysaccharide activates
toll-like receptors (TLRs), which produce either white matter lesions or increase brain susceptibility to secondary insults. Recently,
IL-18 in umbilical blood was shown to correlate with
brain injury in preterm infants and
IL-18 deficiency in mice decreases CNS vulnerability.