Seminar
Cerebral palsy Allan Colver, Charles Fairhurst, Peter O D Pharoah
The syndrome of cerebral palsy encompasses a large group of childhood movement and posture disorders. Severity, patterns of motor involvement, and associated impairments such as those of communication, intellectual ability, and epilepsy vary widely. Overall prevalence has remained stable in the past 40 years at 2–3·5 cases per 1000 livebirths, despite changes in antenatal and perinatal care. The few studies available from developing countries suggest prevalence of comparable magnitude. Cerebral palsy is a lifelong disorder; approaches to intervention, whether at an individual or environmental level, should recognise that quality of life and social participation throughout life are what individuals with cerebral palsy seek, not improved physical function for its own sake. In the past few years, the cerebral palsy community has learned that the evidence of benefit for the numerous drugs, surgery, and therapies used over previous decades is weak. Improved understanding of the role of multiple gestation in pathogenesis, of gene environment interaction, and how to influence brain plasticity could yield significant advances in treatment of the disorder. Reduction in the prevalence of post-neonatal cerebral palsy, especially in developing countries, should be possible through improved nutrition, infection control, and accident prevention.
Introduction In cerebral palsy’s milder forms, individuals present with mild spasticity and contracture in one arm and leg on one side of the body, which interferes with fluid movement and fine manual dexterity. The individual might have some sensory inattention to that side of the body and to that visual field, and might have focal epilepsy. At the other end of the spectrum, an individual can present with involvement of the four limbs, with a mixed picture of spasticity and dyskinesia. The individual can have substantial contractures and scoliosis, and therefore require a wheelchair for mobility. They might also have associated severe learning difficulties, cortical visual impairment, and be prone to chest infections. Cerebral palsy is a syndrome of motor impairment that results from a lesion occurring in the developing brain; the disorder varies in the timing of the lesion, the clinical presentation, and the site and severity of the impairments. The earliest description of the disorder is attributed to the orthopaedic surgeon William Little in 1862.1 Several attempts to define and classify the syndrome have been made. Recently, the International Executive Committee for the Definition of Cerebral Palsy, proposed the following definition: “Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication and behaviour, by epilepsy, and by secondary musculoskeletal problems”. This definition is supplemented by a full explanation of the terms used in the definition.2 The complexity of the syndrome is clear from its various classifications; cerebral palsy can be defined according to the anatomical site of the brain lesion (cerebral cortex, pyramidal tract, extrapyramidal system, or cerebellum); clinical symptoms and signs (spasticity, dyskinesia [dystonic and choreo-athetotic forms], or ataxia); topographical involvement of extremities (diplegia, quadriplegia, or
hemiplegia); timing of presumed insult (prepartum, intrapartum, or postneonatal); and classification of degree of muscle tone (isotonic, hypotonic, or hypertonic).3 Standard classifications are essential for research and transfer of knowledge. The 9th and 10th International Classifications of Disease include many categories of cerebral palsy and substantial inconsistency exists in how clinicians interpret these guidelines.4 A straightforward classification is needed that can be applied reliably by clinicians and used in registers. Such a classification (with categories of unilateral spastic, bilateral spastic, dyskinetic, and ataxic) and an associated decision tree was developed by the Surveillance of Cerebral Palsy in Europe (European network SCPE) and is now widely adopted.5
Published Online November 20, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)61835-8 Institute of Health and Society, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, UK (Prof A Colver FRCPCH); Department of Paediatric Neurosciences, Evelina Children’s Hospital, Guy’s and Saint Thomas’ NHS Foundation Trust, London, UK (C Fairhurst FRCPCH); and University of Liverpool, Liverpool, UK (Prof P O D Pharoah FRCP) Correspondence to: Prof Peter O D Pharoah, University of Liverpool, Liverpool L69 3GB, UK [email protected]
Epidemiology Development of registers for cerebral palsy, with an emphasis on a shared definition of the syndrome and efforts to ensure complete identification of cases, has shown a cerebral palsy prevalence of 2·0–3·5 per 1000 livebirths.6–9 Prevalence in developing countries seems to be similar, but data sources are not well established.10,11 Cerebral palsy prevalence is inversely associated with gestational age and birthweight, with a prevalence ranging from 90 cases per 1000 neonatal survivors weighing less than 1000 g to 1·5 cases per 1000 for those born weighing 2500 g or more.12–14 The upper age limit used for definition of postneonatal cerebral palsy is arbitrary, but in most studies it is considered to be about 5 years. About 10% of all cases of cerebral palsy are classified as postneonatal,15 which are largely attributable to CNS infections such as meningoencephalitis and head
Search strategy and selection criteria References included in this Seminar were identified by the authors based on their respective areas of expertise and supplemented by unsystematic database searches.
www.thelancet.com Published online November 20, 2013 http://dx.doi.org/10.1016/S0140-6736(13)61835-8
1
Seminar
injuries (accidental and non-accidental). Prevalence of cerebral palsy in infants of normal birthweight (≥2500 g) seems not to have changed over time,14 but a decreasing prevalence in low birthweight infants has been noted in Europe (figure 1),16 and a decrease, which then levelled out, was confirmed in an Australian cohort.17 As noted more than a century ago by Sigmund Freud,18 multiple pregnancy is also a risk factor for cerebral palsy. However, comparisons of the risk of cerebral palsy in singleton and multiple births are confounded by the effect of birthweight and gestational age. This problem can be split into two parts: first, the inverse association of the prevalence of cerebral palsy with birthweight and, second, the increasing proportion of multiple births of decreasing birthweights. Compared with singletons, the relative risk of cerebral palsy in twins is 5·6 and in triplets is 12·6.19 When both twins are livebirths, there is a one in 56 probability that one infant has cerebral palsy and a one in 430 probability that both have cerebral palsy.20,21 Most pregnancies are monochorionic (where twins share the same amniotic sac), which is a known risk factor for cerebral palsy22 even in very preterm infants. Population studies suggest a 50–100 times increase in the prevalence of cerebral palsy in a live cotwin of a stillbirth20–23 compared with singleton pregnancies. When both twins are livebirths, infant death of one twin is associated with a significant increase in risk of cerebral palsy in the survivor. The cerebral palsy risk in a same-sex survivor with infant death of the cotwin is 167 per 1000 compared with 21 per 1000 in an unlike pair.24 A risk factor is not necessarily causal and other recently identified risk factors have yielded little in the way of preventive strategies.25 A systematic review26 done in 2013 reported ten risk factors as significantly associated with cerebral palsy: placental abnormalities, major and minor birth defects, low birthweight, meconium aspiration, 100 90 Prevelence per 1000 livebirths
80 70 60 50 40 30 20 10 0 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 Midpoint birth year
Figure 1: Prevalence of cerebral palsy in infants with birthweights of 1000–1499 g from nine European countries in birth years 1980–96 (3 year moving average) Countries are Denmark, France, Germany, Ireland, Italy, The Netherlands, Norway, Sweden, and the UK. Reproduced from Platt and colleagues.16
2
emergency caesarean section, birth asphyxia, neonatal seizures, respiratory distress syndrome, hypoglycaemia, and neonatal infections.
Pathogenesis Although many mechanisms have been proposed to explain the cause, nature, and timing of the definitive cerebral insult, adverse factors might have been present for some time during pregnancy. For every gestation and for each type of cerebral palsy, an optimum birthweight exists; the high rates of cerebral palsy observed in preterm births occur when gestational birthweight deviates from this optimum (figure 2).27 This optimum birthweight effect is especially pronounced when fetal assessment of weights in the womb are used to generate weight standards rather than actual weights of delivered babies. Most cases of cerebral palsy result from an interference in brain development in utero and MRI scanning has helped understanding of these processes. In general, insults during the first trimester are associated with cerebral maldevelopments such as schizencephaly; in the second trimester, with periventricular white matter damage; and in the third trimester, with cortical and deep grey matter damage.28 Neonatal asphyxia was thought to be a key cause of brain damage in preterm or term babies. However, the evidence for asphyxia was applied loosely, and often referred only to the need for administration of oxygen after birth. Asphyxia is now thought to account for 10–20% of cerebral palsy cases29 and attribution of causation now requires evidence of encephalopathy.30 Monochorionicity can have an important role in the pathogenesis of cerebral palsy because the vascular anastomoses in the placenta serve both fetuses and transfusion potentially could occur between fetuses. Embolic theory proposes that the transference of thromboplastin or thromboemboli from the dead fetus to the cotwin leads to cerebral damage;31,32 ischaemic theory suggests that some exsanguination occurs from the surviving fetus into the low resistance dead fetus.33 Although these theories do not seem to help to explain cerebral palsy in singletons or dichorionic multiple pregnancies, obstetric ultrasound has shown that one or more embryos from a multiple conception can be lost early in pregnancy as a vanishing twin or triplet;34,35 therefore, this twin could be the cause of cerebral palsy in some singleton births.36 In developed countries, causes of cerebral palsy are routinely prevented and can go unnoticed. For example, marriage between close family members is not common, mothers receive prompt treatment for rhesus isoimmunisation (in which severe jaundice is an established cause of dyskinetic cerebral palsy), and many immunisations are directed at prevention of infant infections such as meningitis. In some developing countries, iodine deficiency causes a specific type of cerebral palsy.37 A controlled trial of iodinated oil
www.thelancet.com Published online November 20, 2013 http://dx.doi.org/10.1016/S0140-6736(13)61835-8
Seminar
MRI About 85% of children with cerebral palsy have an abnormal MRI scan. An MRI scan can provide an estimate of the timing of the lesion and assist in determination of whether the lesion is responsible for the motor impairment or is an incidental finding.52 An abnormal scan finding is not a prerequisite for diagnosis of cerebral palsy but scans are recommended to assist clinical management.53 Findings could provide families with a more complete explanation of the cause of their child’s cerebral palsy or could show lesions such as bilateral polymicrogyria with implications for genetic counselling. Finally, a normal scan can suggest the need for a more detailed investigation of some genetic conditions such as hereditary spastic paraplegias, doparesponsive dystonias, and metabolic disorders that can mimic cerebral palsy.
Conventional standard
Fetal standard
1000
Number per 1000 livebirths
established that the disease could be prevented, provided supplementation was given before conception.38 In another study, withdrawal of a rich source of dietary iodine precipitated an epidemic of cerebral palsy.39 Maternal infections such as rubella and cytomegalovirus can result in cerebral palsy. Several studies have reported chorioamnionitis to be a risk factor for cerebral palsy, especially in preterm babies.40 To date, however, enhanced identification and treatment of such infections has not been effective. A significant increase in the prevalence of non-cerebral congenital anomalies coexistent with cerebral palsy has been reported.41–43 Undoubtedly, some cases of cerebral palsy that have a fetal origin associated with non-cerebral congenital anomalies42–46 have a genetic or teratogenic cause, but transfusion problems between fetuses might also provide a unified pathogenic mechanism in some cases. Artificial reproductive therapies could play a part in the genesis of cerebral palsy, although these associations are difficult to study because of strict confidentiality regulations in most countries. When studies linking anonymised national datasets have been possible, an increased risk was reported, but was largely attributable to increased risk of multiple pregnancies and preterm births.47,48 Genetic factors are increasingly implicated in our understanding of cerebral palsy. Several single gene Mendelian disorders cause cerebral palsy, including isolated bilateral polymicrogyria and spastic types in closely related families. Single nucleotide polymorphisms, especially clotting abnormalities such as factor V Leiden, are reported to not be predictive of cerebral palsy.49,50 However, complete genome and exome sequencing will probably identify genes and combinations of genes that are predictive of cerebral palsy, and many of these genes could be shared with predictors of other neurodevelopmental disorders such as autism, attention deficit disorder, intellectual impairment, and epilepsy.51
100
10
1
0·1 –3
–2
–1
0
1
42 weeks
Figure 2: Prevalence of cerebral palsy by Z score of weight for gestation Reproduced from Jarvis and colleagues.27
Life expectancy To estimate life expectancy, a register of all cases is needed with dates of birth and regular updates of deaths to allow actuarial analysis. The severities of mental, manual, ambulatory, and visual impairments are significant factors in survival. If all impairment domains are not severe, survival is only marginally less than that of individuals without cerebral palsy.54–56 If severe impairments are present, then life expectancy is reduced approximately in proportion to the number and severity of associated impairments.54 Of individuals with cerebral palsy in the UK who were alive at age 2 years with four severe impairments (intelligence quotient
Cerebral palsy Allan Colver, Charles Fairhurst, Peter O D Pharoah
The syndrome of cerebral palsy encompasses a large group of childhood movement and posture disorders. Severity, patterns of motor involvement, and associated impairments such as those of communication, intellectual ability, and epilepsy vary widely. Overall prevalence has remained stable in the past 40 years at 2–3·5 cases per 1000 livebirths, despite changes in antenatal and perinatal care. The few studies available from developing countries suggest prevalence of comparable magnitude. Cerebral palsy is a lifelong disorder; approaches to intervention, whether at an individual or environmental level, should recognise that quality of life and social participation throughout life are what individuals with cerebral palsy seek, not improved physical function for its own sake. In the past few years, the cerebral palsy community has learned that the evidence of benefit for the numerous drugs, surgery, and therapies used over previous decades is weak. Improved understanding of the role of multiple gestation in pathogenesis, of gene environment interaction, and how to influence brain plasticity could yield significant advances in treatment of the disorder. Reduction in the prevalence of post-neonatal cerebral palsy, especially in developing countries, should be possible through improved nutrition, infection control, and accident prevention.
Introduction In cerebral palsy’s milder forms, individuals present with mild spasticity and contracture in one arm and leg on one side of the body, which interferes with fluid movement and fine manual dexterity. The individual might have some sensory inattention to that side of the body and to that visual field, and might have focal epilepsy. At the other end of the spectrum, an individual can present with involvement of the four limbs, with a mixed picture of spasticity and dyskinesia. The individual can have substantial contractures and scoliosis, and therefore require a wheelchair for mobility. They might also have associated severe learning difficulties, cortical visual impairment, and be prone to chest infections. Cerebral palsy is a syndrome of motor impairment that results from a lesion occurring in the developing brain; the disorder varies in the timing of the lesion, the clinical presentation, and the site and severity of the impairments. The earliest description of the disorder is attributed to the orthopaedic surgeon William Little in 1862.1 Several attempts to define and classify the syndrome have been made. Recently, the International Executive Committee for the Definition of Cerebral Palsy, proposed the following definition: “Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication and behaviour, by epilepsy, and by secondary musculoskeletal problems”. This definition is supplemented by a full explanation of the terms used in the definition.2 The complexity of the syndrome is clear from its various classifications; cerebral palsy can be defined according to the anatomical site of the brain lesion (cerebral cortex, pyramidal tract, extrapyramidal system, or cerebellum); clinical symptoms and signs (spasticity, dyskinesia [dystonic and choreo-athetotic forms], or ataxia); topographical involvement of extremities (diplegia, quadriplegia, or
hemiplegia); timing of presumed insult (prepartum, intrapartum, or postneonatal); and classification of degree of muscle tone (isotonic, hypotonic, or hypertonic).3 Standard classifications are essential for research and transfer of knowledge. The 9th and 10th International Classifications of Disease include many categories of cerebral palsy and substantial inconsistency exists in how clinicians interpret these guidelines.4 A straightforward classification is needed that can be applied reliably by clinicians and used in registers. Such a classification (with categories of unilateral spastic, bilateral spastic, dyskinetic, and ataxic) and an associated decision tree was developed by the Surveillance of Cerebral Palsy in Europe (European network SCPE) and is now widely adopted.5
Published Online November 20, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)61835-8 Institute of Health and Society, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, UK (Prof A Colver FRCPCH); Department of Paediatric Neurosciences, Evelina Children’s Hospital, Guy’s and Saint Thomas’ NHS Foundation Trust, London, UK (C Fairhurst FRCPCH); and University of Liverpool, Liverpool, UK (Prof P O D Pharoah FRCP) Correspondence to: Prof Peter O D Pharoah, University of Liverpool, Liverpool L69 3GB, UK [email protected]
Epidemiology Development of registers for cerebral palsy, with an emphasis on a shared definition of the syndrome and efforts to ensure complete identification of cases, has shown a cerebral palsy prevalence of 2·0–3·5 per 1000 livebirths.6–9 Prevalence in developing countries seems to be similar, but data sources are not well established.10,11 Cerebral palsy prevalence is inversely associated with gestational age and birthweight, with a prevalence ranging from 90 cases per 1000 neonatal survivors weighing less than 1000 g to 1·5 cases per 1000 for those born weighing 2500 g or more.12–14 The upper age limit used for definition of postneonatal cerebral palsy is arbitrary, but in most studies it is considered to be about 5 years. About 10% of all cases of cerebral palsy are classified as postneonatal,15 which are largely attributable to CNS infections such as meningoencephalitis and head
Search strategy and selection criteria References included in this Seminar were identified by the authors based on their respective areas of expertise and supplemented by unsystematic database searches.
www.thelancet.com Published online November 20, 2013 http://dx.doi.org/10.1016/S0140-6736(13)61835-8
1
Seminar
injuries (accidental and non-accidental). Prevalence of cerebral palsy in infants of normal birthweight (≥2500 g) seems not to have changed over time,14 but a decreasing prevalence in low birthweight infants has been noted in Europe (figure 1),16 and a decrease, which then levelled out, was confirmed in an Australian cohort.17 As noted more than a century ago by Sigmund Freud,18 multiple pregnancy is also a risk factor for cerebral palsy. However, comparisons of the risk of cerebral palsy in singleton and multiple births are confounded by the effect of birthweight and gestational age. This problem can be split into two parts: first, the inverse association of the prevalence of cerebral palsy with birthweight and, second, the increasing proportion of multiple births of decreasing birthweights. Compared with singletons, the relative risk of cerebral palsy in twins is 5·6 and in triplets is 12·6.19 When both twins are livebirths, there is a one in 56 probability that one infant has cerebral palsy and a one in 430 probability that both have cerebral palsy.20,21 Most pregnancies are monochorionic (where twins share the same amniotic sac), which is a known risk factor for cerebral palsy22 even in very preterm infants. Population studies suggest a 50–100 times increase in the prevalence of cerebral palsy in a live cotwin of a stillbirth20–23 compared with singleton pregnancies. When both twins are livebirths, infant death of one twin is associated with a significant increase in risk of cerebral palsy in the survivor. The cerebral palsy risk in a same-sex survivor with infant death of the cotwin is 167 per 1000 compared with 21 per 1000 in an unlike pair.24 A risk factor is not necessarily causal and other recently identified risk factors have yielded little in the way of preventive strategies.25 A systematic review26 done in 2013 reported ten risk factors as significantly associated with cerebral palsy: placental abnormalities, major and minor birth defects, low birthweight, meconium aspiration, 100 90 Prevelence per 1000 livebirths
80 70 60 50 40 30 20 10 0 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 Midpoint birth year
Figure 1: Prevalence of cerebral palsy in infants with birthweights of 1000–1499 g from nine European countries in birth years 1980–96 (3 year moving average) Countries are Denmark, France, Germany, Ireland, Italy, The Netherlands, Norway, Sweden, and the UK. Reproduced from Platt and colleagues.16
2
emergency caesarean section, birth asphyxia, neonatal seizures, respiratory distress syndrome, hypoglycaemia, and neonatal infections.
Pathogenesis Although many mechanisms have been proposed to explain the cause, nature, and timing of the definitive cerebral insult, adverse factors might have been present for some time during pregnancy. For every gestation and for each type of cerebral palsy, an optimum birthweight exists; the high rates of cerebral palsy observed in preterm births occur when gestational birthweight deviates from this optimum (figure 2).27 This optimum birthweight effect is especially pronounced when fetal assessment of weights in the womb are used to generate weight standards rather than actual weights of delivered babies. Most cases of cerebral palsy result from an interference in brain development in utero and MRI scanning has helped understanding of these processes. In general, insults during the first trimester are associated with cerebral maldevelopments such as schizencephaly; in the second trimester, with periventricular white matter damage; and in the third trimester, with cortical and deep grey matter damage.28 Neonatal asphyxia was thought to be a key cause of brain damage in preterm or term babies. However, the evidence for asphyxia was applied loosely, and often referred only to the need for administration of oxygen after birth. Asphyxia is now thought to account for 10–20% of cerebral palsy cases29 and attribution of causation now requires evidence of encephalopathy.30 Monochorionicity can have an important role in the pathogenesis of cerebral palsy because the vascular anastomoses in the placenta serve both fetuses and transfusion potentially could occur between fetuses. Embolic theory proposes that the transference of thromboplastin or thromboemboli from the dead fetus to the cotwin leads to cerebral damage;31,32 ischaemic theory suggests that some exsanguination occurs from the surviving fetus into the low resistance dead fetus.33 Although these theories do not seem to help to explain cerebral palsy in singletons or dichorionic multiple pregnancies, obstetric ultrasound has shown that one or more embryos from a multiple conception can be lost early in pregnancy as a vanishing twin or triplet;34,35 therefore, this twin could be the cause of cerebral palsy in some singleton births.36 In developed countries, causes of cerebral palsy are routinely prevented and can go unnoticed. For example, marriage between close family members is not common, mothers receive prompt treatment for rhesus isoimmunisation (in which severe jaundice is an established cause of dyskinetic cerebral palsy), and many immunisations are directed at prevention of infant infections such as meningitis. In some developing countries, iodine deficiency causes a specific type of cerebral palsy.37 A controlled trial of iodinated oil
www.thelancet.com Published online November 20, 2013 http://dx.doi.org/10.1016/S0140-6736(13)61835-8
Seminar
MRI About 85% of children with cerebral palsy have an abnormal MRI scan. An MRI scan can provide an estimate of the timing of the lesion and assist in determination of whether the lesion is responsible for the motor impairment or is an incidental finding.52 An abnormal scan finding is not a prerequisite for diagnosis of cerebral palsy but scans are recommended to assist clinical management.53 Findings could provide families with a more complete explanation of the cause of their child’s cerebral palsy or could show lesions such as bilateral polymicrogyria with implications for genetic counselling. Finally, a normal scan can suggest the need for a more detailed investigation of some genetic conditions such as hereditary spastic paraplegias, doparesponsive dystonias, and metabolic disorders that can mimic cerebral palsy.
Conventional standard
Fetal standard
1000
Number per 1000 livebirths
established that the disease could be prevented, provided supplementation was given before conception.38 In another study, withdrawal of a rich source of dietary iodine precipitated an epidemic of cerebral palsy.39 Maternal infections such as rubella and cytomegalovirus can result in cerebral palsy. Several studies have reported chorioamnionitis to be a risk factor for cerebral palsy, especially in preterm babies.40 To date, however, enhanced identification and treatment of such infections has not been effective. A significant increase in the prevalence of non-cerebral congenital anomalies coexistent with cerebral palsy has been reported.41–43 Undoubtedly, some cases of cerebral palsy that have a fetal origin associated with non-cerebral congenital anomalies42–46 have a genetic or teratogenic cause, but transfusion problems between fetuses might also provide a unified pathogenic mechanism in some cases. Artificial reproductive therapies could play a part in the genesis of cerebral palsy, although these associations are difficult to study because of strict confidentiality regulations in most countries. When studies linking anonymised national datasets have been possible, an increased risk was reported, but was largely attributable to increased risk of multiple pregnancies and preterm births.47,48 Genetic factors are increasingly implicated in our understanding of cerebral palsy. Several single gene Mendelian disorders cause cerebral palsy, including isolated bilateral polymicrogyria and spastic types in closely related families. Single nucleotide polymorphisms, especially clotting abnormalities such as factor V Leiden, are reported to not be predictive of cerebral palsy.49,50 However, complete genome and exome sequencing will probably identify genes and combinations of genes that are predictive of cerebral palsy, and many of these genes could be shared with predictors of other neurodevelopmental disorders such as autism, attention deficit disorder, intellectual impairment, and epilepsy.51
100
10
1
0·1 –3
–2
–1
0
1
42 weeks
Figure 2: Prevalence of cerebral palsy by Z score of weight for gestation Reproduced from Jarvis and colleagues.27
Life expectancy To estimate life expectancy, a register of all cases is needed with dates of birth and regular updates of deaths to allow actuarial analysis. The severities of mental, manual, ambulatory, and visual impairments are significant factors in survival. If all impairment domains are not severe, survival is only marginally less than that of individuals without cerebral palsy.54–56 If severe impairments are present, then life expectancy is reduced approximately in proportion to the number and severity of associated impairments.54 Of individuals with cerebral palsy in the UK who were alive at age 2 years with four severe impairments (intelligence quotient
