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"Pharoah, Peter O. D."
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Cerebral palsy
2014
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.
Journal Article
Prevalence and pathogenesis of congenital anomalies in cerebral palsy
by
Pharoah, Peter O D
in
Cerebral Palsy - embryology
,
Cerebral Palsy - epidemiology
,
Cerebral Palsy - etiology
2007
Background:It has been hypothesised that cerebral palsy (CP) and other congenital anomalies are attributable to feto–fetal transfusion problems in a monochorionic multiple gestation. Thus more than one organ could be compromised leading to the coexistence of two or more anomalies in a fetus. Such anomalies in a singleton birth may be attributable to early demise of the co-conceptus as a vanishing twin.Aim:To determine whether the coexistence of congenital anomalies and CP is greater than a chance finding by comparing the prevalence of congenital anomalies in children with CP with that in the general population of children.Methods:A population-based register of children with CP born in 1966–1991 in the counties of Merseyside and Cheshire, UK, comprised the index population. Coexisting congenital anomalies were recorded. For comparison the population prevalence of congenital anomalies was obtained from eight congenital malformation registers in the UK.Results:Children with CP were found to have highly significant increases in risk for microcephaly, isolated hydrocephaly, congenital anomalies of the eye, congenital cardiac anomalies, cleft lip and/or palate and congenital dislocation of the hips and talipes (p<0.001) and atresias of the oesophagus (p<0.001) and intestines (p<0.01). The relative risks ranged from 3.1 (95% CI 1.9 to 4.8; p<0.001) for congenital malformations of the cardiac septa to 116.09 (95% CI 84.0 to 162.3; p<0.001) for microcephaly.Conclusions:Congenital anomalies in children with CP are found much more frequently than expected by chance. A common pathogenic mechanism may account for the coexistence of disparate congenital anomalies. A hypothesis is proposed for such a common pathogenic mechanism.
Journal Article
Causal Hypothesis for Some Congenital Anomalies
2005
Congenital anomalies are a major cause of fetal and neonatal death and of childhood morbidity. Chromosomal and other genetic abnormalities, environmental teratogens and some nutritional deficiencies account for some congenital anomalies but the majority are of unknown etiology. The hypothesis is here proposed that a significant proportion of congenital anomalies and cerebral palsy of unknown etiology are attributable to a monozygotic multiple conception with monochorionic placentation and that these anomalies, even in singletons, may be explained by early, unrecognized or unrecorded loss of one conceptus in a monochorionic monozygotic conception. The pathological mechanism is hemodynamic instability with episodes of acute feto–fetal transfusion that produce ischemic organ impairment in either or both twins. The resultant clinical abnormality will depend on range of severity (fetal death, infant death, congenital anomaly, normal infant), site or combination of sites (which organ[s] present[s] with the congenital anomaly) and timing (early, middle or late in gestation as shown by variation in brain pathology that is observed).
Journal Article
Sudden Infant Death Syndrome in Twins and Singletons
2007
Twins compared with singletons and monozygous (MZ) compared with dizygous (DZ) twins are at increased risk of fetal and infant death, cerebral palsy and many congenital anomalies. The aim of this study is to investigate whether zygosity is a risk factor for the sudden infant death syndrome (SIDS). Birth registration data and draft infant death certificates for all multiple births in England and Wales 1993 to 2003 were provided by the Office for National Statistics. As a partial proxy for zygosity, same-sex was compared with opposite-sex twins for birthweight-specific mortality and mortality attributed to SIDS. Data on singleton infants were obtained by subtraction of multiple births from routinely published population births and infant deaths. SIDS mortality among low birthweight infants was significantly less in twins than singletons. The twin-singleton relative risk was reversed in infants of normal birthweight. Among infants of normal birthweight, neonatal SIDS was significantly more common in same- compared with opposite-sex pairs. Among infants of low birthweight, postneonatal SIDS was significantly more common in same- compared with opposite-sex pairs. The difference in birthweight distribution of same- compared with opposite-sex twins for neonatal SIDS suggests that zygosity is a risk factor for SIDS. As congenital cerebral anomalies are a feature of many monozygous twin conceptions, a detailed macro- and microscopical examination of the brain in twin SIDS may indicate an otherwise unrecognised pathology.
Journal Article
Vanishing Twin: A Possible Cause of Cerebral Impairment
by
Anand, Dhullipala
,
Pharoah, Peter O. D.
,
Platt, Mary Jane
in
Brain
,
Cerebellar Diseases - etiology
,
Cerebellar Diseases - physiopathology
2007
Fetal death in a twin conception during second and third trimester is associated with increased risk of cerebral injury in the surviving twin. The aim of this study is to test the hypothesis that even early fetal losses as a ‘vanishing’ twin may be associated with an increased risk of cerebral impairment in the surviving twin. The study population comprised 362 pregnant women attending Liverpool Women's Hospital recruited between 1999 and 2001. Women were classified according to the first ultrasound scan into 3 groups: vanishing twin, twin and singleton. The vanishing twin group was further subdivided into ‘definite’ and ‘probable’. Children from these pregnancies were assessed at 1 year of age for their development and neurological function using the Griffiths Mental and Developmental Scales and Optimality score. Children from 229 pregnancies (63.2%) attended the assessment. Information on children from a further 21 (5.8%) pregnancies was obtained through a review of hospital records. Cerebral impairment was found in 2 children from the vanishing twin group, 2 from the twin group and none from the singleton group. When cases with definite vanishing twin are considered there is a significant difference between the vanishing twin and singleton group (relative risk 6.1; 95% confidence interval 1.5–8.3; p = .03). An additional study with an increased sample size would enable a more robust conclusion.
Journal Article
Comparative Development of Surviving Co-Twins of Vanishing Twin Conceptions, Twins and Singletons
by
Anand, Dhullipala
,
Pharoah, Peter O. D.
,
Platt, Mary Jane
in
Birth Weight
,
Child Development
,
Children
2007
Early loss of one fetus in a multiple gestation as a ‘vanishing’ twin is a well recognized phenomenon. It is uncertain whether this has an impact on the development of the surviving co-twin. The aim of this study is to compare the development of singletons, twins and the surviving co-twins of a vanishing twin. The 324 children born to 229 women who were recruited into the study between 1999 and 2001 formed the study population. Children were assessed at 1 year of age with Griffiths Mental and Developmental Scales. A neurological examination was performed using an optimality score to exclude those with severe neurodisability. Three hundred and five children (92 singletons, 180 twins and 33 survivors with a vanishing twin) were included. The sub- and general quotient scores in singletons and surviving co-twins of a vanishing twin did not differ significantly. Twins had significantly lower scores than singletons in all areas of development and were more likely to be born early with lower birthweights. Following adjustment for gestation and birthweight, the difference between the two groups was nullified suggesting that the slower development of twins is related to their prematurity and lower birthweight.
Journal Article
Fetal Death Registration in Multiple Births: Anomalies and Clinical Significance
2006
Trends in the civil registration of fetal death in multiple gestations that has occurred before, but expelled from the womb after, 24 weeks' gestation are examined using England and Wales 1993–2004 registration obtained from the Office for National Statistics. Count was made of fetal death registrations in which fetus papyraceous, fetal death before 24 weeks' gestation or fetocide before 24 weeks' gestation was recorded. There were 3700 fetal death registrations among 217,595 twin, triplet and higher order multiple births in England and Wales between 1993 and 2004. In 354 (9.6%) of these fetal deaths, death was recorded as having occurred before 24 weeks' gestation. There has been a threefold increase in such fetal death registrations. It is a legal requirement of parents to register a fetal death. The definition of a fetal death that meets formal registration criteria is that the fetus is expelled from the womb after 24 weeks' gestation. However, if the fetal death occurs before 24 weeks, there is confusion, nationally and internationally, whether or not registration is legally required. Fetal death in a multiple gestation has serious clinical implications for a surviving co-conceptus and failure to inform parents of an early death in a multiple gestation may have important repercussions. Legal definition for the registration of fetal death requires international agreement and application.
Journal Article
Life expectancy in children with cerebral palsy
by
Hutton, J L
,
Cooke, T
,
Pharoah, P O D
in
Birth Weight
,
Cerebral palsy
,
Cerebral Palsy - mortality
1994
Abstract Objective : To determine life expectancy of children with cerebral palsy. Design : Cohort analysis, by means of register compiled from multiple sources of ascertainment, of all children with cerebral palsy born during 1966-84 to mothers resident in Mersey region. Status of children was determined by flagging through NHS central register. Subjects : 1258 subjects with idiopathic cerebral palsy, of whom 1251 were traced and included in analysis. Main outcome measures : Effect of functional ability (ambulation, manual dexterity, and mental ability), sex, birth weight, and gestational age on survival. Results : 20 year survival for whole cohort was 89.3% for females and 86.9% for males. For subjects with no severe functional disabilities 20 year survival was 99% (95% confidence interval 98% to 100%), while subjects severely disabled in all three functional groups had 20 year survival of 50% (42% to 58%). Subjects with birth weight <=2500 g had 20 year survival of 92% (89% to 95%), while those with birth weight <2500 g had survival of 87% (84% to 89%). Subjects with gestational age of <37 weeks had 20 year survival of 93% (91% to 96%), while those with gestational age >=37 weeks had survival of 85% (83% to 88%). Birth weight and gestational age were less predictive of survival than functional disability. Best statistical model used gestational age and number of severe functional disabilities as predictors. Conclusions : Life expectancy of this cohort of children with cerebral palsy was greater than has been suggested in some previous studies. This has important implications for social, educational, and health services.
Journal Article
Differential effects of preterm birth and small gestational age on cognitive and motor development
by
Pharoah, Peter O D
,
Cooke, Richard W I
,
Hutton, Jane L
in
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
,
Babies
,
Biological and medical sciences
1997
AIMS To determine the differential effects of preterm birth and being small for gestational age on the cognitive and motor ability of the child. METHODS A longitudinal cohort of all infants of gestational age ≤ 32 weeks born to mothers resident in the counties of Cheshire and Merseyside in 1980-1 was studied. The children were assessed at the age of 8 to 9 years using the Wechsler Intelligence Scale for Children, the Neale analysis of reading ability, and the Stott-Moyes-Henderson test of motor impairment. Adequacy of fetal growth was determined by the birthweight ratio—that is, the ratio of the observed birthweight to the expected birthweight for a given gestational age. Children with clinically diagnosed motor, learning or sensory disabilities were excluded. Information on social variables was obtained by a questionnaire completed by the parents. Of the 182 children, 158 were assessed. RESULTS IQ was positively correlated with birthweight ratio but not with birthweight or gestational age. Motor ability was associated with birthweight, gestational age, and birthweight ratio. Reading comprehension was associated with birthweight ratio, but reading rate and accuracy were best explained by social variables and sex. IQ remained associated with birthweight ratio, after adjusting for maternal education, housing status, and number of social service benefits received. Reading ability was related to these social variables but motor ability was not. CONCLUSIONS The effects of SGA and preterm birth differed: SGA was associated with cognitive ability, as measured by IQ and reading comprehension; motor ability was additionally associated with preterm birth. Reading rate and accuracy were not associated with SGA or preterm birth but were socially determined. Key points Preterm birth and being small for gestational age differ in their effects on motor and cognitive development Cognitive ability, as measured by IQ and reading comprehension, was negatively associated with the degree of fetal growth retardation Motor ability was positively associated with gestational age and negatively associated with the degree of fetal growth retardation Reading rate and reading accuracy were not associated with either gestational age or the degree of fetal growth retardation, but were socially determined
Journal Article
Fetal death registration in multiple births: anomalies and clinical significance
2006
Trends in the civil registration of fetal death in multiple gestations that has occurred before, but expelled from the womb after, 24 weeks' gestation are examined using England and Wales 1993-2004 registration obtained from the Office for National Statistics. Count was made of fetal death registrations in which fetus papyraceous, fetal death before 24 weeks' gestation or fetocide before 24 weeks' gestation was recorded. There were 3700 fetal death registrations among 217,595 twin, triplet and higher order multiple births in England and Wales between 1993 and 2004. In 354 (9.6%) of these fetal deaths, death was recorded as having occurred before 24 weeks' gestation. There has been a three-fold increase in such fetal death registrations. It is a legal requirement of parents to register a fetal death. The definition of a fetal death that meets formal registration criteria is that the fetus is expelled from the womb after 24 weeks' gestation. However, if the fetal death occurs before 24 weeks, there is confusion, nationally and internationally, whether or not registration is legally required. Fetal death in a multiple gestation has serious clinical implications for a surviving co-conceptus and failure to inform parents of an early death in a multiple gestation may have important repercussions. Legal definition for the registration of fetal death requires international agreement and application.Trends in the civil registration of fetal death in multiple gestations that has occurred before, but expelled from the womb after, 24 weeks' gestation are examined using England and Wales 1993-2004 registration obtained from the Office for National Statistics. Count was made of fetal death registrations in which fetus papyraceous, fetal death before 24 weeks' gestation or fetocide before 24 weeks' gestation was recorded. There were 3700 fetal death registrations among 217,595 twin, triplet and higher order multiple births in England and Wales between 1993 and 2004. In 354 (9.6%) of these fetal deaths, death was recorded as having occurred before 24 weeks' gestation. There has been a three-fold increase in such fetal death registrations. It is a legal requirement of parents to register a fetal death. The definition of a fetal death that meets formal registration criteria is that the fetus is expelled from the womb after 24 weeks' gestation. However, if the fetal death occurs before 24 weeks, there is confusion, nationally and internationally, whether or not registration is legally required. Fetal death in a multiple gestation has serious clinical implications for a surviving co-conceptus and failure to inform parents of an early death in a multiple gestation may have important repercussions. Legal definition for the registration of fetal death requires international agreement and application.
Journal Article