INTRODUCTION Cerebral palsy (CP) refers to a heterogeneous group of conditions

involving permanent, nonprogressive motor dysfunction that affects muscle tone, posture,
and/or movement. These conditions are due to abnormalities of the developing fetal or
infantile brain resulting from a variety of causes. Although the disorder itself is not
progressive, the clinical expression may change over time as the central nervous system (CNS)
matures. The motor impairment generally results in limitations in functional abilities and
activity, which can range in severity. Multiple additional symptoms often accompany the
primary motor abnormalities, including altered sensation or perception, intellectual disability,
communication and behavioral difficulties, seizure disorders, and musculoskeletal
complications.

The epidemiology, etiology, and prevention of CP are reviewed here. The classification,
clinical features, evaluation, diagnosis, management, and prognosis of CP are discussed
separately:

●(See "Cerebral palsy: Clinical features and classification".)

●(See "Cerebral palsy: Evaluation and diagnosis".)
●(See "Cerebral palsy: Overview of management and prognosis".)
●(See "Cerebral palsy: Treatment of spasticity, dystonia, and associated orthopedic
issues".)

EPIDEMIOLOGY

Prevalence — The overall prevalence of CP is approximately 2 per 1000 live births [1-5]. The
prevalence of CP is far higher in preterm compared with term infants and increases with
decreasing gestational age (GA) and birth weight (BW) [1,2,6]:
●GA:
•GA <28 weeks – 82 per 1000 live births
•GA 28 to 31 weeks – 43 per 1000 live births
•GA 32 to 36 weeks – 6.8 per 1000 live births
•GA >36 weeks – 1.4 per 1000 live births
●BW:
•<1500 g – 59.2 per 1000 live births
•1500 to 2499 g – 10.2 per 1000 live births
•>2500 g – 1.33 per 1000 live births

Although infants born preterm are at higher risk of developing CP, preterm infants account
for less than one-half of cases of CP. In large epidemiologic studies of children with CP,
approximately 25 percent were very preterm (GA <32 weeks), 10 to 20 percent were
moderately preterm or late preterm (GA 32 to 36 weeks), and 60 percent were born at term
(GA >36 weeks) [2,7].

Risk factors — In addition to prematurity and BW, which are important risk factors for
developing CP, numerous other prenatal and perinatal risk factors have been reported (table
1), though for many of these risk factors, a causal relationship has not been established [2,7-
12]. Potentially modifiable prenatal factors that may contribute to CP risk include heavy
maternal alcohol consumption, maternal smoking, maternal obesity, and infections during
pregnancy [13-17]. CP is most often multifactorial, and multiple risk factors coexist.
(See 'Etiology' below.)

Trends over time — In the 1960s through 1980s, the rate of CP and the extent of disability
among preterm infants increased as survival improved for the most premature [18]. During
the 1980s and 1990s, there was a reversal in this trend, most likely because of improvements
in perinatal care. In one study, the prevalence of CP among very low birth weight (VLBW;
<1500 g) infants declined from 60.6 per 1000 live births in 1980 to 39.5 per 1000 live births in
1996 [19]. This improvement occurred despite overall increases in survival and multiple births
and decreases in mean BW among this group. In another study, the prevalence of CP among
preterm infants (GA 20 to 27 weeks) decreased from 155 per 1000 live births in the early
1990s (1992 to 1994) to 16 per 1000 live births in the early 2000s (2001 to 2003) [20]. This
was in the setting of stable or decreasing mortality during the same time period.

Among term and late preterm infants, the prevalence of CP remained stable during the 1980s
and 1990s [21].

ETIOLOGY The etiology of CP is often multifactorial and can include anything with a

negative impact on the developing fetal or neonatal brain (eg, preterm birth, fetal growth
restriction, multiple gestation, infection, birth asphyxia, untreated maternal hypothyroidism,
congenital malformations, perinatal stroke) [22]. Prematurity is the most common
association; however, in many cases, no specific cause is identified [23].

The multifactorial etiology of CP was illustrated in a series of 213 children diagnosed with CP
in Australia, of whom 98 percent had contributing causes other than intrapartum hypoxia
[24]. The relative frequencies of different contributing causes was as follows (many children
had more than one cause):

●Prematurity (78 percent)

●Intrauterine growth restriction (34 percent)
●Intrauterine infection (28 percent)
●Antepartum hemorrhage (27 percent)
●Severe placental pathology (21 percent)
●Multiple pregnancy (20 percent)

Common causes of CP are described below. The associated causes differ somewhat based
upon the subtype of CP (table 2).

Prematurity — CP develops in approximately 5 to 15 percent of surviving preterm very low

birth weight (VLBW; BW <1500 g) infants [1,6]. In this population, CP is often associated with
the following conditions [25]:
●Periventricular leukomalacia (PVL) – PVL refers to injury of cerebral white matter that
occurs in a characteristic distribution and consists of periventricular focal necrosis, with
 subsequent cystic formation, and more diffuse cerebral white matter injury. PVL is the
major form of brain white matter injury that affects premature infants. (See "Germinal
matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) in the newborn:
Prevention, management, and complications", section on 'White matter injury'.)
●Intraventricular hemorrhage (IVH) – Severe IVH, periventricular hemorrhagic infarction,
and posthemorrhagic hydrocephalus (a potential complication of IVH) may lead to CP
[26]. (See "Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) in
the newborn: Pathogenesis, clinical presentation, and diagnosis" and "Germinal matrix
hemorrhage and intraventricular hemorrhage (GMH-IVH) in the newborn: Prevention,
management, and complications".)
●Bronchopulmonary dysplasia (BPD) – The risk of motor impairment is greater in preterm
infants affected by BPD. The mechanism is not known but may involve the use of
corticosteroids to improve lung disease. This issue is discussed in greater detail
separately. (See "Outcome of infants with bronchopulmonary dysplasia", section on
'Neurodevelopment outcome' and "Prevention of bronchopulmonary dysplasia:
Postnatal use of corticosteroids".)

Perinatal hypoxic-ischemic injury — Perinatal hypoxia and/or ischemia accounts for only a
small minority of cases of CP [27-31]. Reports of the proportion of CP cases caused by birth
asphyxia vary from <3 to >50 percent depending on the definition of birth asphyxia used [30].
In a study using the criteria set forth by the American College of Obstetricians and
Gynecologists (ACOG) and the International Cerebral Palsy Task Force (table 3), an acute
intrapartum hypoxic event was identified in only 1 percent (2 of 213 infants) of children with
CP [24,32]. (See "Etiology and pathogenesis of neonatal encephalopathy", section on 'Acute
events'.)

When severely damaging perinatal hypoxia occurs, it presents as neonatal encephalopathy,

which is a heterogeneous, clinically defined syndrome characterized by disturbed neurologic
function in the earliest days of life in an infant born at term, manifested by a subnormal level
of consciousness or seizures, often accompanied by difficulty with initiating and maintaining
respiration and depression of tone and reflexes [32]. (See "Clinical features, diagnosis, and
treatment of neonatal encephalopathy".)

Neonates with severe intrapartum hypoxia-ischemia may have seizures, coma, hypotonia,
dysfunction of other organ systems, a persistently low Apgar score, and evidence of profound
metabolic acidosis. On magnetic resonance imaging (MRI), two main patterns of hypoxic-
ischemic injury are seen: basal ganglia/thalamic-predominant pattern and a watershed-
predominant pattern (image 1) [33].

Infants with CP caused by an acute intrapartum hypoxic-ischemic event are more likely to
have spastic quadriparesis or dyskinetic CP than other subtypes of CP. (See "Cerebral palsy:
Clinical features and classification", section on 'Cerebral palsy subtypes'.)

Congenital abnormalities — Congenital abnormalities, both structural central nervous

system (CNS) abnormalities and abnormalities outside of the CNS, are more common in
children with than without CP [8,34-37]. Congenital abnormalities are noted in approximately
15 percent of children with CP and are more common in term than preterm infants [8,37]. In
one registry study, the most common CNS anomalies were microcephaly and congenital
hydrocephalus [37]. Non-CNS anomalies included cardiac, urinary, and skeletal
malformations.

Intrapartum events may be influenced by a preexisting abnormality [38,39]. In one report,

congenital anomalies (mostly non-CNS anomalies) occurred more often in term infants with
neonatal encephalopathy than in controls (28 versus 4 percent) [40]. The congenital anomaly
was considered the cause of the encephalopathy in approximately one-third of affected
infants. Infants with congenital anomalies who had encephalopathy were three times more
likely to have CP than those without.

In children with CP due to brain malformations, the biologic basis is usually unknown. Some
result from abnormalities that occur during brain development and affect cell proliferation,
migration, differentiation, survival, or synaptogenesis. Disorders of development occasionally
result from exposure to radiation, toxins, or infectious agents during a critical period of
gestation [41-44]. Some disorders (eg, schizencephaly) are genetic and follow Mendelian
inheritance patterns [45-49]. Certain cerebral malformations can also be associated with
chromosomal abnormalities (eg, holoprosencephaly is associated with both trisomy 13 and
18). Some neurocutaneous syndromes are associated with brain malformations (eg,
hemimegalencephaly and hypomelanosis of Ito or the linear sebaceous nevus syndrome) [50].
(See "Prenatal diagnosis of CNS anomalies other than neural tube defects and
ventriculomegaly", section on 'Schizencephaly' and "Prenatal diagnosis of CNS anomalies
other than neural tube defects and ventriculomegaly", section on
'Holoprosencephaly' and "Congenital cytogenetic abnormalities", section on 'Trisomy 13
syndrome' and "Congenital cytogenetic abnormalities", section on 'Trisomy 18
syndrome' and "The genodermatoses: An overview", section on 'Neurocutaneous
syndromes'.)

Genetic susceptibility — Genetic disorders were historically thought to be uncommon causes

of CP, but with the advent of next-generation genetic testing techniques, they are increasingly
recognized as playing an important role in the etiology of CP [51-53]. In addition, the
aggregation of CP in groups with high consanguinity and observations of increased familial
risk for CP suggests a genetic contribution to CP risk [54-56]. It is important to note that
identification of a genetic diagnosis does not replace the diagnosis of CP [57]. CP is an
umbrella term which includes diverse etiologies, as outlined in this topic.

Genetic testing can sometimes identify inborn errors of metabolism, some of which may be
potentially treatable. These can sometimes go undetected under the guise of a CP diagnosis
[58]. (See "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features".)

In a study using whole-exome sequencing in 183 patients with CP, 14 percent had a potentially
disease-causing gene variant, de novo or inherited [59]. In a study of 52 children with
nonprogressive CP without an identified etiology, genomic testing with chromosomal
microarray analysis identified clinically significant copy number variations in 31 percent [60].

Several genetic polymorphisms have been associated with susceptibility for CP, including
apolipoprotein E [61,62], genes associated with thrombophilia (eg,
prothrombin G20210A mutation) [63,64], and genes involved with inflammation (eg,
inducible nitric oxide synthetase, lymphotoxin alpha, and certain cytokines) [65,66]. However,
only the association with prothrombin G20210A mutation was confirmed by a subsequent
large study [64]. (See "Prothrombin G20210A".)

Hereditary spastic paraplegia (HSP), a mimicker of spastic diplegic CP, is a diverse group of
neurologic disorders that range in phenotype and inheritance pattern [67,68]. HSP is
characterized by progressive lower extremity spasticity. More than 50 corresponding genes
have been linked to HSP. HSP is discussed in greater detail separately. (See "Hereditary spastic
paraplegia".)

Multiple births — The risk of CP is increased among multiple births [69-74]. Causes that may
contribute to this risk include low BW, prematurity, congenital anomalies, cord entanglement,
and abnormal vascular connections [75]. In a study of births in Western Australia from 1980
to 1989, the prevalence of CP was 1.6, 7.3, and 28 per 1000 survivors to one year of age in
singletons, twins, and triplets, respectively [69]. In this report, the increased rates of CP in
multiples were limited to infants of normal BW, although multiples were more likely to have
low BW.

Death of a co-twin greatly increases the risk of CP. In the report from Western Australia, the
risk of CP among twins was greater when one twin died in utero (96 versus 12 per 1000 twin
pairs) compared with both surviving [69]. The mechanism may include release of
thromboplastin and emboli from the dead twin, causing injury to the survivor. It is possible
that some cases of CP in apparent singletons may be due to an unrecognized fetal death of a
co-twin [76].

Postnatal death also increases the risk of CP in the surviving co-twin, and monozygosity
appears to influence this risk. In a study that analyzed birth and death certificate data (1993
to 1995) for different sex (dizygotic) and same sex (dizygotic and monozygotic) twins, and
assessed disability in surviving twins after neonatal death of the co-twin using questionnaires
sent to clinicians, the risk of CP was greater in same sex compared with different sex twin
survivors (167 versus 21 per 1000) for infants of BW 1000 to 1999 g, although the difference
was only marginal for infants of BW <1000 g (224 versus 200 per 1000) [77].

Stroke — Stroke in the perinatal period contributes to CP, especially spastic hemiparesis.
Thromboembolism and prothrombotic disorders contribute to the etiology of this disorder.
Lesions typically are identified by cranial imaging studies following a neonatal seizure.
However, some newborns with stroke are asymptomatic until hemiparesis or other
abnormalities develop later in infancy or childhood. (See "Cerebral palsy: Clinical features and
classification", section on 'Early signs of cerebral palsy'.)

Prenatal causes include hypercoagulable states, vasculopathies, abnormal development of

blood vessels, and emboli secondary to disorders affecting the placenta or fetus [78]. Stroke
that occurs during early infancy may be caused by sepsis, disseminated intravascular
coagulation, venous sinus thrombosis, emboli, and congenital heart disease [79,80]. Some
cases are caused by periventricular atrophy or cerebral dysgenesis. Affected patients with
nondiagnostic neuroimaging may have maldevelopment at a microscopic level [81,82].
(See "Stroke in the newborn: Classification, manifestations, and diagnosis".)

Intracranial hemorrhage — Intracranial hemorrhage (ICH) in term infants is unusual but

frequently results in neuromotor abnormalities. Most are recognized because of the sudden
and dramatic onset of symptoms, including seizures, abnormal movements, apnea, lethargy,
irritability, vomiting, and bulging fontanelle. Diagnosis is made by cranial imaging.

The incidence depends in part upon the method of ascertainment. In one series of 33 term
infants with symptomatic ICH, the regional incidence was estimated to be 0.27 per 1000 live
births [83]. Approximately one-third of cases were related to coagulopathies. In another
report, ICH was diagnosed by ultrasound scan in 54 of 2019 term infants (2.7 percent) treated
in a newborn intensive care unit from 1989 to 1999 [84]. Neurologic impairment developed
in 28 percent.

Thalamic hemorrhage with residual germinal matrix hemorrhage is a common source of ICH
in this population. When no source is apparent, the ICH is thought to originate from the
choroid plexus. In one report, thalamic hemorrhage was identified in 12 of 19 term infants
younger than one month of age with ICH diagnosed by computed tomography (CT) [85].
Thalamic hemorrhage typically occurred in infants with uneventful birth histories and
presentation after one week of age. Many had predisposing factors for cerebral vein
thrombosis (eg, sepsis, congenital heart disease, coagulopathy, electrolyte disturbance). At
18 months of age, the majority had CP, predominantly hemiplegia, and other neurologic
abnormalities such as hydrocephalus and seizures.

Intrauterine infection — Intrauterine infection is associated with an increased risk of CP.

Congenital infections with organisms such as cytomegalovirus, syphilis, Zika virus, varicella
virus, and toxoplasmosis play a role. Bacterial infections are also associated with CP.
(See "Overview of TORCH infections" and "Congenital cytomegalovirus infection: Clinical
features and diagnosis" and "Congenital Zika virus infection: Clinical features, evaluation, and
management of the neonate" and "Clinical features, evaluation, and diagnosis of sepsis in
term and late preterm infants".)

Maternal chorioamnionitis is associated with an increased risk of CP in term infants [86-88].

A 2000 meta-analysis of 26 observational studies found that both clinical and histologic
chorioamnionitis were associated with increased risk of CP (relative risk [RR] 1.9, 95% CI 1.5-
2.5) [89]. Another systematic review in 2003 had similar findings [90], and a subsequent case-
control study also reported a strong association between maternal chorioamnionitis and CP
(odds ratio [OR] 4.1, 95% CI 1.6-10.1) [88]. Another case-control study found that any
maternal infection during pregnancy was associated with increased risk of CP (OR 2.9, 95% CI
1.7-4.8) and that neonatal infection was a strong independent predictor of CP (OR 14.7, 95%
CI 1.7-126.5) [91].

In preterm infants, perinatal infection appears to play a key role in the pathogenesis of PVL
and subsequent CP [92]. (See 'Prematurity' above.)

Acquired postnatal causes — While most cases are due to prenatal or perinatal factors, CP
can also result from insults to the developing brain acquired during infancy and early
childhood. Approximately 10 to 18 percent of cases of CP are acquired after the neonatal
period [9]. Most of these patients have spastic CP. Common causes of postnatally acquired
CP include:
●Stroke − Stroke is uncommon in infants and children and is usually associated with an
underlying disorder (eg, congenital heart disease, prothrombotic disorder, sickle cell
disease, vasculopathy, or metabolic disorder). Stroke typically results in spastic
 hemiparesis. (See "Stroke in the newborn: Classification, manifestations, and
diagnosis" and "Ischemic stroke in children and young adults: Epidemiology, etiology and
risk factors".)
●Trauma. (See "Child abuse: Evaluation and diagnosis of abusive head trauma in infants
and children".)
●Severe hypoxic events such as near-drowning. (See "Drowning (submersion injuries)",
section on 'Neurologic'.)
●Sepsis or meningitis. (See "Clinical features, evaluation, and diagnosis of sepsis in term
and late preterm infants" and "Bacterial meningitis in the neonate: Neurologic
complications".)
●Kernicterus − Infants with severe hyperbilirubinemia are at risk for kernicterus,
permanent neurologic sequelae of bilirubin-induced neurotoxicity that manifests itself
as a type of CP characterized by choreoathetosis, with gaze abnormalities and
sensorineural hearing loss. The disorder results when unconjugated bilirubin enters the
brain and causes focal necrosis of neurons and glia. The regions most often affected
include the basal ganglia and the brainstem nuclei for oculomotor and auditory function,
accounting for the clinical features of this condition. (See "Unconjugated
hyperbilirubinemia in term and late preterm infants: Epidemiology and clinical
manifestations", section on 'Chronic bilirubin encephalopathy (kernicterus)'.)
●Other causes of encephalopathy. (See "Etiology and pathogenesis of neonatal
encephalopathy" and "Acute toxic-metabolic encephalopathy in children", section on
'Specific etiologies of encephalopathy'.)

PREVENTION

Antenatal measures — Antenatal measures to reduce the likelihood of CP include provision

of routine prenatal care, including measures to reduce the likelihood of preterm birth. These
issues are discussed separately. (See "Prenatal care: Initial assessment" and "Prenatal care:
Second and third trimesters" and "Preterm birth: Risk factors, interventions for risk reduction,
and maternal prognosis".)

Magnesium sulfate — There is increasing evidence from clinical trials that antenatal
administration of magnesium sulfate to women at risk for preterm birth decreases the
incidence and severity of CP in their offspring without affecting mortality. This issue is
discussed in greater detail separately. (See "Neuroprotective effects of in utero exposure to
magnesium sulfate".)

Intrapartum measures — Delaying umbilical cord clamping for at least 30 to 60 seconds after
birth in vigorous infants has been shown to reduce the risk of intraventricular hemorrhage
(IVH) in preterm infants and may be associated with improved neurodevelopmental
outcomes. This issue is discussed in greater detail separately. (See "Management of normal
labor and delivery", section on 'Early versus delayed cord clamping'.)

Postnatal measures

Supportive measures — Supportive, neuroprotective measures for neonates at risk of

neurologic injury (ie, preterm very low birth weight [VLBW] infants and infants with neonatal
asphyxia and/or encephalopathy) are aimed at reducing the likelihood of long-term
neurodevelopmental sequelae and include (see "Clinical features, diagnosis, and treatment
of neonatal encephalopathy", section on 'Supportive management'):

●Maintaining adequate ventilation (see "Mechanical ventilation in neonates")

●Maintaining sufficient cerebral perfusion (see "Etiology, clinical manifestations,
evaluation, and management of neonatal shock")
●Maintaining normal metabolic status (see "Fluid and electrolyte therapy in
newborns" and "Management and outcome of neonatal hypoglycemia" and "Neonatal
hyperglycemia", section on 'Management')
●Controlling seizures (see "Treatment of neonatal seizures")
●Treating any underlying causes for encephalopathy (eg, infection or metabolic
derangements) (see "Management and outcome of sepsis in term and late preterm
infants" and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks
gestation" and "Metabolic emergencies in suspected inborn errors of metabolism:
Presentation, evaluation, and management")

Therapeutic hypothermia — For term or late preterm infants with neonatal asphyxia and/or
encephalopathy, therapeutic hypothermia improves survival and neurodevelopmental
outcome at 18 months. (See "Clinical features, diagnosis, and treatment of neonatal
encephalopathy", section on 'Therapeutic hypothermia'.)

SUMMARY

●The prevalence of cerebral palsy (CP) is approximately 2 cases per 1000 children. The
risk is markedly increased among preterm infants with low birth weight (BW).
(See 'Epidemiology' above.)
●The etiology of CP is multifactorial. Most cases are thought to be due to prenatal
factors. The most commonly identified prenatal risk factors for CP are prematurity
and/or low BW. Other commonly associated factors include congenital abnormalities,
multiple pregnancy, placental pathology, and intrauterine infection.
(See 'Etiology' above.)
●CP develops in approximately 5 to 15 percent of surviving very low birth weight (VLBW)
infants. In this population, CP is often associated with the periventricular leukomalacia
(PVL), intraventricular hemorrhage (IVH), and/or bronchopulmonary dysplasia (BPD).
(See 'Prematurity' above.)
●Perinatal hypoxia and/or ischemia likely accounts for only a small minority of cases of
CP. (See 'Perinatal hypoxic-ischemic injury' above.)
●Stroke in the perinatal period may cause CP and is typically manifested as spastic
hemiparesis. Thromboembolism and prothrombotic disorders contribute to the etiology
of this disorder. (See 'Stroke' above and "Stroke in the newborn: Classification,
manifestations, and diagnosis".)
●Preventive measures to reduce the likelihood of CP include (see 'Prevention' above):
•Provision of routine prenatal care, including measures to reduce the likelihood of
preterm birth (see "Prenatal care: Initial assessment" and "Prenatal care: Second
and third trimesters" and "Preterm birth: Risk factors, interventions for risk
reduction, and maternal prognosis")
•Antenatal administration of magnesium sulfate for women at risk for preterm
delivery (see "Neuroprotective effects of in utero exposure to magnesium sulfate")
•Supportive neuroprotective measures for neonates at risk of neurologic injury (ie,
preterm VLBW infants and infants with neonatal asphyxia and/or encephalopathy)
(see "Clinical features, diagnosis, and treatment of neonatal encephalopathy",
section on 'Supportive management')
•Therapeutic hypothermia for term or late preterm infants with neonatal asphyxia
and/or encephalopathy (see "Clinical features, diagnosis, and treatment of
neonatal encephalopathy", section on 'Therapeutic hypothermia')