Cerebral palsy and fetal inflammatory response syndrome: a review

Abstract

Cerebral palsy (CP) is the most common cause of severe physical disability in childhood. The precise etiological factor for the development of the majority of cases of CP has not been identified, however, prematurity is considered to be the leading identifiable risk factor. During the last decade, intrauterine infection/inflammation has been identified as the most common cause of preterm delivery and neonatal complications. When microorganisms or their products gain access to the fetus they stimulate the production of cytokines and a systemic response termed FIRS (Fetal Inflammatory Response Syndrome). Subsequently, FIRS was implicated as a cause of fetal or neonatal injury that leads to CP and chronic lung disease. Several authors found an increase in the risk for CP in infants born to mothers with clinical chorioamnionitis, especially in preterm neonates. A relationship between CP and intra-amniotic inflammation was demonstrated, intrauterine infection may lead to activation of the cytokine network which in turn can cause white matter brain damage and preterm delivery, as well as the future development of CP. This white matter insult is identified clinically as periventricular leucomalacia (PVL) which is associated with the subsequent development of impaired neurological outcomes of variable severity including CP.

The preterm parturition syndrome and its implications for understanding the biology, risk assessment, diagnosis, treatment and prevention of preterm birth

“…The risk of death of a preterm neonate is 120 times greater than that of an infant born at term [6,[12][13][14][15][16]. Moreover, survivors are at risk of short-term morbidity (respiratory distress syndrome, intraventricular haemorrhage, necrotizing enterocolitis, sepsis, retinopathy of prematurity) [17][18][19][20][21][22][23][24][25][26][27][28][29], and long-term morbidity [30,31] such as cerebral palsy [32][33][34][35][36] learning disabilities [23,37,38], blindness [39,40] and crippling respiratory disease [41][42][43][44][45][46][47][48]. Recent evidence suggests that preterm neonates may also be at risk for altered metabolic states in adult life [49][50][51][52].…”

TLR-4-Dependent and -Independent Mechanisms of Fetal Brain Injury in the Setting of Preterm Birth

“…[5][6][7][8][9] Epidemiological data have demonstrated an association between prenatal inflammation and the subsequent development of cerebral palsy. [10][11][12][13][14][15] Despite the emphasis of cerebral palsy as the main adverse outcome of interest in ex-preterm children, an emerging body of evidence demonstrates that prenatal inflammation is also associated with a spectrum of neurobehavioral disorders. 10,12,[16][17][18][19][20][21][22] In fact, recent studies demonstrate that ex-preterm infants have high screen positive rates for autism spectrum disorders (ASDs) and that chorioamnionitis and preterm birth are specific risk factors for ASD.…”

Increased sTREM-1 in pregnant women with premature rupture of membranes and subclinical chorioamnionitis

“…Subclinical chorioamnionitis poses a serious threat to the safety of mother and child by causing puerperal infection, sepsis and other infectious diseases in infants (10). In order to identify sensitive and specific markers of infection, Ohlsson and Wang evaluated 23 relevant indicators and proposed that certain laboratory indicators such as WBC count, erythrocyte sedimentation rate and CRP have varying specificity and positive predictive value for the monitoring of intrauterine infection, but lack sufficient sensitivity and negative predictive value (11).…”