Infection in pregnancy and cerebral palsy

Infections in pregnancy, including the most common congenital infections (TORCH: toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus), are known causes of long-term neurodevelopmental disabilities, although the proportion of children with specific disabilities attributable to TORCH infections appears to be 5% to 10% or less. Intrauterine infection, especially subclinical infection of the kind associated with preterm birth, is under investigation as a cause of neurodevelopmental disability. These studies have focused almost exclusively on cerebral palsy. Summary estimates from a published meta-analysis suggest that chorioamnionitis is associated with a twofold increased risk of cerebral palsy in preterm and a fivefold increased risk in term children. In some studies, cytokine levels in amniotic fluid or newborn blood have also been found to be significantly elevated in preterm and term children with cerebral palsy compared to controls. These data suggest that factors related to the fetal inflammatory response, including cytokines, may be causal agents in brain damage and neurodevelopmental disability associated with intrauterine infection. We need to greatly improve both our understanding of and our ability to measure the relevant exposures related to infection and inflammation, to further understand differences in the association between intrauterine infection and cerebral palsy relative to gestational age, and to investigate a broad range of neurodevelopmental outcomes as potential adverse effects of intrauterine infection.