Cerebral palsy.

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.

The influence of gestational age on severity of impairment in spastic cerebral palsy.

OBJECTIVE: To investigate the association between severity of impairment and gestational age in unilateral and bilateral spastic cerebral palsy, and to determine whether the influence of gestational age is independent of deviations from optimal birth weight. STUDY DESIGN: The study group was a United Kingdom cohort of 4772 cases of spastic cerebral palsy born between 1960 and 1997, with information on birth demographics and severity of impairment. Generalized additive models were used to determine the proportions of cases severely impaired, by gestational age, and to determine whether gestational age or deviations from optimal birth weight better predicts severity of impairment. RESULTS: For unilateral spastic cerebral palsy, the proportions of severe impairments did not vary with gestational age. In contrast, for bilateral spastic cerebral palsy, the proportions of severe motor or cognitive impairments increased with increasing gestational age (e.g., from 20% to 50% between weeks 30 and 40 for cognitive impairment). For spastic cerebral palsy, gestational age is at least as good as deviation from optimal birth weight in predicting severity. CONCLUSIONS: The severity of impairment increases with increasing gestational age in bilateral spastic cerebral palsy. This suggests differing etiologies in term and preterm infants and supports the theory that the developing brain is better able to compensate after a cerebral insult.

Sudden infant death syndrome in twins and singletons.

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.

Vanishing twin: a possible cause of cerebral impairment.

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.

Comparative development of surviving co-twins of vanishing twin conceptions, twins and singletons.

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.

Prevalence and pathogenesis of congenital anomalies in cerebral palsy.

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.

Fetal death registration in multiple births: anomalies and clinical significance.

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.

Risk of cerebral palsy in multiple pregnancies.

Multiple compared with singleton gestations have a five- to tenfold increased risk of CP. The increased risk associated with MC placentation has been variously ascribed to transfer of thromboplastin or thromboemboli from the dead to the surviving fetus, exsanguination of the surviving fetus into the low pressure reservoir of the dead fetus, or hemodynamic instability with bidirectional shunting of blood between the two fetuses. An increased risk of CP in assisted reproductive technology gestations is to be expected because of the higher proportion of preterm births. The increase in risk of CP associated with monochorionic placentation will not be observed except for the minority of assisted reproductive technology gestations that undergo monozygotic splitting.

Long-term survival for a cohort of adults with cerebral palsy.

The aim of this study was to investigate long-term survival and examine causes of death in adult patients with cerebral palsy (CP). A 1940-1950 birth cohort based on paediatric case referral allows for long-term survival follow-up. Survival is analyzed by birth characteristics and severity of disability from age 20 years (and age 2y for a subset of the data). Survival outcome compared with that expected in the general population based on English life tables. The main cohort consisted of 341 individuals, with 193 males and 148 females. Conditional on surviving to age 20 years, almost 85% of the cohort survived to age 50 years (a comparable estimate for the general population is 96%). Very few deaths were attributed to CP for those people dying over 20 years of age. Females survived better than males. However, females faced a greater increase in risk relative to the general population than did males. We conclude that survival outlook is good though lower than in the general population. The relative risk of death compared with the UK population decreases with age, although it shows some indication of rising again after age 50 years. Many more deaths were caused by diseases of the respiratory system among those dying in their 20s and 30s than would be expected in the general population. Many fewer deaths than expected in this age group are caused by injuries and accidents. For those people who die in their 40s and 50s, an increase in deaths due to diseases of the circulatory system and neoplasms is observed. More deaths than expected in this age group are due to diseases of the nervous system.

Causal hypothesis for some congenital anomalies.

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).

Risk of cerebral palsy in multiple pregnancies.

Multiple compared with singleton gestations have a five- to tenfold increased risk of CP. The increased risk associated with MC placentation has been variously ascribed to transfer of thromboplastin or thromboemboli from the dead to the surviving fetus, exsanguination of the surviving fetus into the low pressure reservoir of the dead fetus, or hemodynamic instability with bidirectional shunting of blood between the two fetuses. An increased risk of CP in assisted reproductive technology gestations is to be expected because of the higher proportion of preterm births. The increase in risk of CP associated with monochorionic placentation will not be observed except for the minority of assisted reproductive technology gestations that undergo monozygotic splitting.

Cerebral palsy in triplet pregnancies with and without iatrogenic reduction.

UNLABELLED: Iatrogenic fetal reduction is undertaken to try and improve the outcome of multiple pregnancies by reducing the rate of severe preterm delivery. In twin pregnancies, however, spontaneous death of one of the fetuses is associated with increased risk of cerebral palsy (CP) in the survivor. The aim of this study was to determine whether iatrogenic fetal reduction might also increase the prevalence of CP. The database of a tertiary fetal medicine unit was interrogated to identify women with trichorionic triplet pregnancies who had either given birth to three live infants or two live infants following selective fetal reduction. A questionnaire was sent to the women's general practitioners asking them to report whether any of the children had CP. The results of the questionnaire revealed that the CP prevalence (13.8 per 1000) of 72 children from trichorionic triplet pregnancies reduced to twins by selective termination was similar to that of 111 children from trichorionic triplet pregnancies with no loss (18 per 1000), but the pregnancies with selective termination delivered at a later gestation (P = 0.004). CONCLUSION: a lower cerebral palsy rate might have been expected in the pregnancies with selective termination given that they were delivered at a later gestational age; these data, therefore, emphasise the importance of further investigating the impact of selective reduction on the prevalence of cerebral palsy.

Errors in birth registrations and coding of twins and higher order multiples.

Dizygotic compared with monozygotic conceptions are at decreased risk of fetal and infant death and serious morbidity in surviving infants. Different sex twin maternities must be dizygotic but miscoding and incorrect registration of sex and number of fetuses may lead to an incorrect assignment of zygosity. The aim of the study was to validate the coding and registration of number and sex of births in multiple pregnancies. Fetal and infant death registrations from all multiple maternities in England and Wales 1993-1998 were examined. There were 51,792 twin, 1627 triplet and 51 higher order multiple maternities that were registered. Among these there were 1926 fetal deaths, 58 of which were registered as being of indeterminate sex but were coded as male in 56 and female in 2 cases. A fetus papyraceous was registered as male in 19 and as female in 19 cases. Other fetal deaths weighing >/= 100g, with no mention of papyraceous on the death certificate, nevertheless, likely to be of indeterminate sex, were registered as male in 26 and as female in 23 cases. In 13 maternities, the number of infants registered at birth was less than the number mentioned on the registration certificate. It cannot be assumed that multiple births of different registered sex are dizygotic. As surviving infants from a monozygotic multiple birth are at much greater risk of infant death and serious morbidity than dizygotic multiple births, incorrect assignment of sex has important implications for parental counselling and may have medico-legal relevance when attributing negligence as the cause of morbidity in a survivor from a multiple pregnancy.