Neonatal infection is indeed linked to cerebral palsy (CP), a group of permanent movement disorders caused by abnormal brain development or damage to the developing brain. The connection between infections occurring around the time of birth and the risk of cerebral palsy has been extensively studied, revealing complex biological mechanisms involving inflammation and immune responses.
One of the primary pathways through which neonatal infection may contribute to cerebral palsy is **inflammation in the placenta and fetal brain**. Conditions such as chorioamnionitis, an infection and inflammation of the fetal membranes (chorion and amnion), are strongly implicated. Chorioamnionitis triggers a robust immune response characterized by the infiltration of neutrophils—white blood cells that act as the first line of defense—at the maternal-fetal interface. These neutrophils, along with other innate immune cells like monocytes and macrophages, release cytokines and chemokines (signaling molecules) such as interleukin-1 (IL-1), interleukin-8 (IL-8), and granulocyte colony-stimulating factor (G-CSF). This inflammatory cascade can cross the placental barrier, leading to neuroinflammation in the fetus, which disrupts normal brain development, including myelin formation critical for nerve signal transmission[1].
The severity and timing of chorioamnionitis appear to influence the risk of cerebral palsy. Research indicates that **early-stage and mild chorioamnionitis may paradoxically be associated with a reduced risk of CP**, possibly due to a priming effect on the fetal immune system. However, **advanced-stage and severe chorioamnionitis significantly increase the risk** of cerebral palsy, especially in preterm infants[2]. This suggests that the extent of inflammation and infection plays a crucial role in determining neurological outcomes.
Another related condition, **funisitis**, which is inflammation of the umbilical cord, has been shown to increase the risk of death or cerebral palsy in extremely preterm infants. Funisitis represents a fetal inflammatory response and is often a marker of severe intrauterine infection. The presence of funisitis correlates with worse neurodevelopmental outcomes, reinforcing the link between fetal infection, inflammation, and brain injury[3].
The mechanisms by which infection leads to cerebral palsy involve **damage to the developing brain through inflammatory mediators**. Cytokines and other inflammatory molecules can cause direct injury to brain cells, disrupt the formation of myelin (the protective sheath around nerve fibers), and induce oxidative stress. These processes can result in white matter injury, a common pathological finding in cerebral palsy. The placenta acts as a critical window into these processes, as placental inflammation reflects the intrauterine environment and fetal exposure to infection and inflammation[1].
Infections at birth, including those acquired during delivery or shortly after, also contribute to neonatal infections that may increase CP risk. Factors such as inadequate hand hygiene, improperly sterilized medical equipment, and contaminated surfaces in the delivery environment can lead to newborn infections. These infections can cause systemic inflammation and sepsis, further increasing the risk of brain injury and subsequent cerebral palsy[4].
In summary, neonatal infection—particularly intrauterine infections like chorioamnionitis and funisitis—is strongly tied to cerebral palsy through inflammatory pathways that damage the developing brain. The degree and timing of infection and inflammation are critica
