What Causes Cerebral Palsy
Cerebral palsy results from non-progressive disturbances occurring in the developing fetal or infant brain, with prenatal factors accounting for 80-90% of cases, though the etiology is multifactorial and includes genetic, maternal, pregnancy-related, and early postnatal causes. 1, 2
Primary Etiologic Categories
Genetic Factors
- Recent evidence demonstrates that 14% of cases have a genetic component, representing a significant proportion previously attributed to other causes 1
- Whole exome sequencing has revealed that at least one-third of CP cases in term infants are genetic in origin and therefore not labor-related 3
- Abnormal genetic copy number variations are recognized preconception risk factors 1
Maternal and Preconception Factors
- Maternal thyroid disease is an important endocrine factor in neurologic development 1, 4
- Preeclampsia increases risk of CP 1
- Maternal infections during pregnancy contribute to CP development 1
- History of stillbirths, miscarriages, and low socioeconomic status are preconception risks 1
- Assisted reproduction technologies are associated with increased risk 1
Pregnancy Complications
- Intrauterine growth restriction is a significant prenatal risk factor 1
- Multiple gestation increases CP risk 1
- Prenatal factors account for the vast majority (80-90%) of CP cases, challenging historical assumptions about birth asphyxia 2
Prematurity and Low Birth Weight
- Premature delivery is the single most important antecedent of cerebral palsy 4
- In children born with body weight below 1500g, the frequency of CP is 70 times higher compared to those over 2500g at birth 5
- White matter injury patterns (cystic periventricular leukomalacia or periventricular hemorrhagic infarctions) account for 56% of MRI findings and are strongly associated with prematurity 1
Perinatal and Postnatal Causes
- Infections, trauma, stroke, and hypoxic events occurring in early infancy can cause CP 1
- Birth asphyxia plays a role in some cases, though associations do not always indicate causation, as some prenatally damaged infants manifest clinical signs suggestive of birth asphyxia perinatally 4
- Postnatal causes include untreated infections and postnatal intracranial hemorrhages 3
Neuroimaging Patterns Reflecting Etiology
The most predictive MRI patterns provide insight into timing and mechanism of injury:
- White matter injury (56%): Typically associated with prematurity and hypoxic-ischemic events 1
- Cortical and deep gray matter lesions (18%): Including basal ganglia/thalamus lesions, watershed injury, multicystic encephalomalacia, or stroke 1
- Brain maldevelopments (9%): Including lissencephaly, pachygyria, cortical dysplasia, polymicrogyria, or schizencephaly—these suggest genetic or early prenatal disruptions 1
Important Clinical Caveats
- The lack of a clinically reliable indicator of impaired fetal-placental gas exchange limits confidence that birth asphyxia plays a true causal role in many cases historically attributed to it 4
- Some prenatally damaged infants manifest clinical signs suggestive of birth asphyxia in the perinatal period, making causation difficult to establish 4
- The increased survival of very small infants from newborn intensive care may augment the contribution of prematurity to CP incidence in the future 4
- Identifying a specific genetic or acquired cause does not exclude the CP diagnosis, as CP is a clinical diagnosis based on motor dysfunction 6