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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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The majority of cases of cerebral palsy (CP) have their pathogenesis during fetal development and are a form of congenital anomaly, the aetiology of which is uncertain. Anomalous development of other organs evident at birth is also a congenital anomaly. A small proportion of these are known to be caused by chromosomal or gene abnormalities, environmental teratogens and dietary deficiencies. The majority are of unknown aetiology., Methods: A review of monochorionic (MC) monozygotic (MZ) placentation in the pathogenesis of congenital anomalies and CP was conducted using the PubMed, MEDLINE, EMBASE and Cochrane databases., Results: Zygote division and MC placentation have serious implications for the development of both conceptuses. Most reports observe predominantly cerebral abnormalities in one or both conceptuses. These cerebral abnormalities often present as CP or other disabilities attributable to central nervous system impairment. In addition to the anomalies in central nervous system development, anomalies in the fetal development of a wide variety of other organs have been reported with MC MZ twinning., Conclusions: CP and congenital anomalies share a common pathogenic mechanism attributable to MZ twinning. These abnormalities in singletons are coincident with very early loss of one conceptus. The quantitative contribution of monozygosity and monochorionicity to the genesis of CP and congenital anomalies needs to be made.

Background: Congenital anomalies are more common in twins than singletons but in the majority, aetiology is not known. Our aim was to test the hypothesis that survivors of an early loss in a multiple conception, compared with all singletons, are at increased risk of congenital anomaly., Methods: Data were abstracted from the UK population-based Northern Multiple Pregnancy Register and Northern Congenital Abnormality Survey, 1998-2004., Results: Among 3311 twin conceptions, both conceptuses were lost at <16 weeks gestation in 67, and one conceptus in 142 conceptions. Of the 142 singleton survivors, two died in infancy, two were terminated for a congenital anomaly and 11 of 138 had a congenital anomaly (prevalence 915.5 per 10,000 births). There were 197 congenital anomalies among 5948 registered twin births (331.2 per 10,000). The relative risk (RR) of congenital anomalies in a singleton with early loss of a conceptus and twins was 2.40 [95% confidence interval (CI): 1.34-4.29]. There were 4265 infants with a congenital anomaly among the 206 914 singletons [206.1 per 10,000 births: RR twin:singleton 1.61 (95% CI 1.40-1.89)]., Conclusions: A highly significant increase in the risk of congenital anomaly in survivors from a multiple conception following early loss of a conceptus supports the hypothesis that many congenital anomalies are associated with monozygotic multiple conceptions.

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.

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.

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.

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.

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.

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.

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 comprises an important component of paediatric and obstetric practice and has major medico-legal implications. The prognosis for survival in cerebral palsy determines the financial provision made in cases that come to litigation. Issues of data quality and estimation methods are critical. Estimating the probability of survival in cerebral palsy based on clinical experience is liable to serious error unless numerical data can be produced. Only an actuarial analysis based on a standard life table of cases of cerebral palsy will enable a valid estimate of survival. Construction of the table requires a total cohort of cases of cerebral palsy with their date of birth. Each case must conform to a specified definition of the syndrome. Notification of all those who die, with their date of death is mandatory. Estimating the probability of survival according to the severity of functional disability requires specific definitional criteria for each severity category and for those categories to be mutually exclusive. Survival is significantly poorer in those with severe disability. Severe cognitive, motor (manual and ambulatory), and visual disabilities have independent effects on the probability of survival. Severe hearing disability does not add additional information when the other four functional disability categories are included.

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.

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).

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.

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., (Copyright 2004 Springer-Verlag)

Aim: To compare children of very low birth weight with matched controls for their performance in the General Certificate of Secondary Education (GCSE)., Methods: GCSE examination results of 167 children of birth weight < or =1500 g attending mainstream schools and without clinical disability and 167 individually matched classroom controls were analysed., Results: In 143 instances, both children of a matched pair were entered for examination in one or more GCSE subjects. The total points score obtained was greater in the comparison group than in the index cases (difference between means 4.45: 95% CI 0.95 to 7.94; p = 0.01). The mean point score per examination subject was also significantly greater in the comparison group than in the index cases (mean of differences 0.43: 95% CI 0.12 to 0.73; p < 0.01)., Conclusions: As the children were closely matched for school and several social variables, factors acting during fetal or early postnatal development of very low birthweight infants probably compromise performance in the GCSE examination to a greater extent than school or childhood social environmental factors.

Aims: To determine if very low birth weight (VLBW; birth weight <1500 g) is associated with reduced lung function and respiratory health in adolescence and, if it is, whether this impairment is associated with prematurity or intrauterine growth restriction., Methods: A geographically defined cohort of 128 VLBW infants and an age, sex, and school matched comparison group born in 1980/81 were studied. The cohort and comparison group were assessed at 15 years of age. The birth weight ratio of the index cases (observed birth weight/expected birth weight for the gestation) was determined to assess the degree of growth restriction. Respiratory support received during the neonatal period was obtained from hospital records. Smoking habits and respiratory morbidity were obtained through questionnaires. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory flow when 25-75% of FVC is expired (FEF(25-75%)) were measured using a portable spirometer. The values are expressed as percentage predicted for height, age, and gender using standard reference values. Adjustments were made for smoking habits of mother and children., Results: The differences in means between index and comparison groups for FEF(25-75%) (-12.42%; p < 0.001) and FEV1/FVC (-3.53%; p < 0.001) ratio were statistically significant. The differences in FVC and FEV1 were not significant. No correlation was found between the birth weight ratio and lung function among the index cohort. Chronic cough, wheezing, and asthma were more common among the index cohort than in the comparison group. Within the index group, there was no difference in lung function between those who received and those who did not receive respiratory support., Conclusion: Adolescents who were VLBW compared with matched controls showed medium and small airways obstruction. This was associated with prematurity rather than intrauterine growth restriction or having received respiratory support during the neonatal period. The index VLBW cohort compared with their controls were also more prone to chronic cough, wheezing, and asthma.

Background: Twins compared to singletons are at increased risk of sudden infant death syndrome (SIDS)., Aims: To compare the epidemiology of SIDS in twins and singletons and to test the hypothesis that monozygous (MZ) were at greater risk of SIDS than dizygous (DZ) twins., Methods: Data from the Office for National Statistics on all registered live births and infant deaths with registered cause of death "sudden unexpected death in infancy" in England and Wales from 1993 to 1998 were obtained, together with the registered birth weight and, for twins, whether they were of like or unlike sex., Results: The crude relative risk of SIDS in twins is twice that in singletons. There has been a significant temporal decline in SIDS mortality. There is also a significant increase in risk with decreasing birth weight for both twins and singletons. The birth weight specific risk of SIDS in all except for those > or =3000 g is greater in singletons than in twins. There is no significant difference in risk of SIDS in like compared with unlike sex twins., Conclusions: In spite of a lower risk of SIDS in twins compared with singletons for each birth weight group <3000 g, one component of the higher crude relative risk of SIDS in twins is attributable to the higher proportion of twins that are of low birth weight. A second component is the higher risk in twins compared with singletons for those of birth weight > or =3000 g. Like sex are at no greater risk than unlike sex twins, which suggests that zygosity is not a significant factor in SIDS.

Background: Cerebral palsy is more common in twins than singletons. Among twins, if one twin suffers a fetal death or dies in infancy, the prevalence of cerebral palsy in the surviving co-twin is considerably increased, and those from like-sex pairs are particularly at high risk., Aim: To compare birthweight specific cerebral palsy prevalence in like-sex and unlike-sex twins where both twins survive infancy and to provide a comparative and composite picture of cerebral palsy prevalence according to whether a co-twin died or where both twins survived., Methods: Parents of twins born in England and Wales in 1994 and 1995 completed a booklet with open ended questions asking whether their twins had any medical, physical, visual, genetic, or chromosomal problems. Any mention of cerebral palsy, hemiplegia, diplegia, or quadriplegia allowed the child to be included as a case of cerebral palsy. Birthweight specific prevalence rates of cerebral palsy were determined for like and unlike-sex twins in birthweight groups < 1000 g, 1000-1499 g, 1500-1999 g, 2000-2499 g, and > or = 2500 g., Results: When both twins survived infancy, like-sex were at greater risk of cerebral palsy than unlike-sex twins, but the difference was not statistically significant. If both twins survived infancy, the birthweight specific prevalence of cerebral palsy was significantly less than if the co-twin had died., Conclusions: Among the generality of twins, like-sex compared with unlike-sex twins are at greater risk of cerebral palsy particularly if one twin suffers a fetal or infant death. Although it is not possible to subdivide the twins according to zygosity, it is postulated that monozygosity and, specifically, monochorionicity may be the crucial feature that leads to the higher prevalence of cerebral impairment among like-sex twins.

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.

Background: Cerebral palsy presents with a range of severity of cognitive, motor, and sensory disabilities, which might affect survival., Aims: To quantify the effects of motor, cognitive, and sensory disabilities, year of birth, birth weight, and gestational age on survival in cerebral palsy., Methods: A cohort of children with cerebral palsy born between 1966 and 1989 to mothers resident in a defined geographical region was subdivided into early impairment (EICP: cerebral insult prenatally or within 28 days of birth) or late impairment (LICP: insult at least 28 days after birth). Deaths are notified by the National Health Service Central Register. Birth and disability details were obtained from clinical records. Survival analyses were carried out., Results: Severe motor disability was associated with a 30 year survival of 42% and severe cognitive disability with a 30 year survival of 62%. Severe visual disability was associated with a 30 year survival of 38%, but the association of survival with hearing disability was weak. EICP had better survival than LICP but the difference was not significant after allowing for severity of functional disabilities. Normal birth weight infants (>/= 2500 g) showed no birth cohort effect, but the 10 year survival of low birth weight (<2500 g) infants declined from 97% for 1966 to 89% for 1989 births., Conclusions: Survival in cerebral palsy varies according to the severity and number of functional disabilities and by birth weight. Among low birth weight children, survival declined steadily from 1966 to 1989 after allowing for disability. The disabilities reported do not capture all the factors affecting survival of preterm infants.

Aim: To determine the neurodevelopmental morbidity in the surviving twin after fetal or infant death of the co-twin., Methods: Twin pregnancies with an antepartum or infant death delivered between 1981 and 1992 were identified from the Northern Perinatal Mortality Survey. Information on the neurodevelopmental morbidity of infant survivors of a deceased co-twin was obtained by a questionnaire sent to the community paediatrician or general practitioner., Results: A total of 111 children who survived infancy after the fetal death of the co-twin (group 1) and 142 from liveborn twin pairs in which one twin died in infancy (group 2) were traced. Responses were received from 97 (87%) and 130 (92%) respectively. In group 1, the cerebral palsy prevalence was 93 (95% confidence interval (CI) 43 to 169) per 1000 infant survivors; it was more common in like-sex pairs (8/70) with a prevalence of 114 (95% CI 51 to 213) compared with 45 (95% CI 1 to 228) per 1000 infant survivors in unlike-sex pairs (1/22). The overall prevalence of neurodevelopmental morbidity (including developmental delay) was 175 (95% CI 106 to 266) per 1000. In group 2, the cerebral palsy prevalence was 154 (95% CI 84 to 223) per 1000 infant survivors in like-sex (16/104) and 77 (95% CI 9 to 251) in unlike-sex (2/26) survivors; the overall prevalence of neurodevelopmental morbidity was 246 (95% CI 172 to 320) per 1000., Conclusions: The risk of cerebral palsy is increased in the surviving twin after a fetal or infant co-twin death compared with the general twin population. Like-sex twins are at greater risk than unlike-sex. The probable cause, in addition to the consequences of prematurity, is twin-twin transfusion problems associated with monochorionicity.

Assisted reproductive techniques have led to an increase in the proportion of maternities that are multiple. Though predominantly dizygotic, they are at greater risk of monozygotic division than those spontaneously conceived. England and Wales data 1974-99 on stillbirths and livebirths were analysed for 4 periods: 1974-80 (pre-assisted reproduction; 1982-8; 1989-91 (pre-redefinition of stillbirth); 1993-9 (post-redefinition of stillbirth). For twin data, Weinberg's rule was applied to estimate the proportions that were mono- (MZ) and dizygotic (DZ). Compared with the period before assisted reproduction, the most recent period shows an increase in twin maternities of 3.81 per 1,000 comprised of 3.22 (95% CI 3.10 to 3.33; p < 0.0001) DZ and 0.60 (95% CI 0.51 to 0.68; p < 0.0001) MZ twins. It is estimated that 15.7% of assisted reproduction twins are MZ. Higher order multiple births showed an increase of 3.06 (95% CI 2.85 to 3.29; p < 0.0001) per 10,000 maternities. Stillbirth rates in MZ twins are of the same order of magnitude as those in higher order multiple births but higher than those in DZ twins. The improvement in stillbirth rates over the 26 year study period is of the same order magnitude in singletons, DZ and MZ twins and higher order multiples. Assisted reproduction has led to a significant increase in the proportion of MZ twins. These are at high risk of fetal death and this needs to be considered when local stillbirth and perinatal mortality rates are used in auditing obstetric services.

In a national follow-up study of twin births, monozygous compared with dizygous twins were at significantly increased for both to die in utero, one to die in utero and the co-twin to die in infancy, or both to be livebirths but both die in infancy. The prevalence of cerebral palsy among survivors of a co-twin fetal death was 80.2 and other cerebral impairment was 107.0 per 1000. Many apparently singleton cases of cerebral palsy and impairment may be due to fetal death of a twin that has not been recognized or has been recognized but not registered.

Background: Monozygotic twins are at greater risk of dying and of serious morbidity than dizygotic twins, and both are at greater risk than singletons. This is only partly explained by the higher proportion of low birthweight infants among twins., Aim: To compare, in same sex and different sex twins, birth weight specific neonatal death rates and cerebral palsy prevalence rates in the surviving twin when the co-twin has died in infancy., Methods: Analysis of birth and death registration data for same sex and different sex twins for England and Wales 1993-1995 where both were live births. Death certificates of all liveborn twins who died were obtained from the Office for National Statistics. A questionnaire was sent to the general practitioners of all surviving co-twins to determine if the child had any disability., Results: The neonatal death rate in same sex twins was 25.4 and in different sex twins 18.0 per 1000 live births (death rate difference 7.4; 95% confidence interval 4.7 to 10.1; p < 0.001). The higher neonatal death rate in same sex compared with different sex twins is attributable to the higher proportion of same sex twins with low birth weight. Prevalence of cerebral palsy in the low birthweight group (< 1000 g) was marginally higher in same sex (224 per 1000) than different sex (200 per 1000) twin survivors. In the birth weight group 1000-1999 g, same sex twin survivors were at a significantly higher risk of cerebral palsy than those of different sex: 167 v 21 per 1000; difference 145 (95% confidence interval 44 to 231; p < 0.01) per 1000 infant survivors., Conclusion: There are two components to the cause of cerebral palsy in twins. Immaturity per se predisposes to cerebral damage. Also, same sex twins may sustain cerebral damage that is in excess of that due to immaturity.

Aims: To test the null hypotheses that finger and palm prints have no relation with fetal growth or adolescent blood pressure., Methods: All 128 singleton, unimpaired, very low birth weight (VLBW; < or =1500 g) infants born to mothers resident in the county of Merseyside in 1980 and 1981 were studied retrospectively. The comparison group consisted of 128 age, sex, and school matched children. Main outcome measures were blood pressure at age 15 years, birth weight ratio, fingerprint patterns, and palmar AtD angles., Results: The VLBW index population had a significantly higher systolic blood pressure than the comparison group (mean difference 3.2 mm Hg). The difference in diastolic blood pressure between the VLBW index and the matched comparison group was not significant. No significant differences were found in the palmar AtD angles or in the fingerprint proportions of arches, loops, and whorls and no correlation was found between fingerprint patterns and blood pressure. Among the VLBW index population, both height and right palmar AtD angle were independently and significantly correlated with and explained 12.1% of the variance in the systolic blood pressure. Birth weight ratio, as a measure of fetal growth restriction, had no significant correlation with systolic blood pressure., Conclusions: The higher systolic blood pressure of adolescents who were of very low birth weight compared with the matched comparison group is not associated with fingerprint patterns or birth weight ratio as markers for fetal growth restriction.

Background: Birth weight mortality statistics are important for examining trends and monitoring the outcomes of neonatal care., Aim: To determine the effects of errors in the registered birth weight on birth weight specific mortality., Methods: All twins born in England and Wales during 1993-95 comprise the denominator population. For those twins that died, the Office for National Statistics (ONS) provided copies of the death certificates. From the information on the death certificates, the registered birth weight was validated and amended using predetermined rules. The neonatal, postneonatal, and infant mortality rates were recalculated., Results: In 2.5% of cases the registered birth weight was "not stated" and in others there were miscoding errors. Important differences between published and amended birth weight specific mortality rates especially in <500 g and >/=3500 g groups were evident., Conclusions: The bias arising from these errors should be taken into account in interpreting mortality rates and their trends.

Background: Twins have a higher mortality and morbidity than singletons and, among twins, the surviving co-twin of a fetus that dies in utero is particularly at risk. We did a cohort study to quantify mortality and serious morbidity in co-twin survivors of fetuses that died in utero., Methods: We collected data of all registered twin births in England and Wales between 1993 and 1995 in which one twin was registered as having died in utero. Copies of all death certificates of these fetuses and death certificates of live-born co-twins of fetuses that died in utero were obtained from the Office for National Statistics. A questionnaire was sent to the general practitioners of all surviving co-twins to find out if the child had any disability., Findings: There were 434 fetal death/live-birth same-sex twin pairs. Among the live births, there were 59 neonatal deaths, seven postneonatal deaths (first 28 days), and five infant deaths (<1 year). In three of the five deaths, the cause of death was cerebral palsy. Ten of the children who survived infancy were lost to follow up. Responses were received from general practitioners for 241 of 353 survivors (68% response). Of the 241 respondents, 23 had cerebral palsy and 28 had other cerebral impairment. Among the children who survived to infancy, the prevalence of cerebral palsy was 106 (95% CI 70-150) per 1000 and prevalence of other cerebral impairment was 114 (80-160) per 1000. There were 163 fetal death/live-birth different-sex twin pairs. Of the live births, 13 died in the neonatal period and four were lost to follow up. Of the 146 survivors, responses were received from the general practitioners for 102 (70% response). Three of the 102 had cerebral palsy and 12 had other cerebral impairment. The prevalence of cerebral palsy was 29 (95% CI 6-83) per 1000 and of other cerebral impairment 118 (62-196) per 1000 infant survivors., Interpretation: The live-birth co-twin of a fetus that died in utero is at increased risk of cerebral impairment, the overall risk is 20% (95% CI 16-25). The gestational-age-specific prevalence of cerebral palsy after fetal death of the co-twin is much higher than that reported for the general twin population.

Background: Cause specific research on death certification in chronic disease has rarely involved cerebral palsy., Aims: To evaluate cause of death information in people known to have cerebral palsy by: describing the cause of death distribution; determining case ascertainment using death certification as the data source; and analysing the choice of wording and its arrangement in the "cause of death statement". STUDY CASES AND SETTING: People with early or late impairment cerebral palsy who died by 30 June 1998, on the population based Mersey Cerebral Palsy Register born 1966-91 to mothers resident locally., Study Design: Descriptive study of the multiply coded cause of death statements from National Health Service Central Register flagging., Results: Death certificate copies were acquired for all 282 (13.4%) of the 2102 registered cases who died. Cerebral palsy was the most common "underlying cause of death" (95 of 282; 33.7%) and was mentioned in a further 61 cases. The underlying cause of death was more likely to be cerebral palsy with increasingly severe disability and was derived from Part II in 16 of 95 cases., Conclusions: The potential of death certification for case ascertainment of cerebral palsy is important, but limited, even with multiple cause coding. Mortality data need careful interpretation as a proxy source for examining trends and patterns in cerebral palsy.

Aim: To compare the prevalence of childhood and adolescent behavioural problems in low birthweight infants with matched controls., Methods: A cohort study of a geographically defined population of survivors of

Aim: To quantify the level of risk for stillbirth and infant death in singleton compared with twin pregnancies, using national data; to determine the independent effects of zygosity, sex, and birthweight on these risks in twin pregnancies., Methods: A retrospective national study was carried out of all singleton and twin birth and death registrations in England and Wales 1982-91, according to sex and birthweight group. Weinberg's rule was applied to the twin pairs to differentiate mono- from dizygotic twins. Relative risks for mono- compared with dizygous twins for both twins being stillbirths and for one of the pair being a stillbirth were determined. For twins where one was stillborn and the other live born, the relative risk of neonatal and infant mortality in the surviving co-twin was determined., Results: There were 6 563 834 registered singletons and 70772 registered twin pairs for the period under study. Monozygotic twins had a relative risk of: 18.91 (95% CI 12.48-28.64) for both twins being stillborn; 1.63 (95% CI 1.48-1.79) for one twin being a stillbirth; and 2.26 (95% CI 1.45-3.52) for the live born co-twin dying as a neonate. When both twins were live born and among singletons, the odds ratio for neonatal mortality of being male was 1.41 (95% CI 1.37-1.45) and there was a highly significant negative association with birthweight. After adjusting for birthweight group and sex, twins had a reduced neonatal mortality compared with singletons: odds ratio 0.91 (95% CI 0.85-0.96)., Conclusions: Fetal death in one of monozygotic twins has serious implications for survival of the co-twin. Monochorionicity is probably the essential feature of the increased risk to the co-twin. It is imperative that all fetal deaths in multiple pregnancies are recorded and chorionicity determined if parents are to be adequately counselled.

The influence of gestational age, the neonate's birthweight, and maternal age, weight, height and parity on transplacental antibody transfer was assessed in 141 mothers from Sri Lanka and their neonates. Paired blood samples were collected from the mothers and the umbilical cords of the newborns. The sera separated from these samples were categorized as: preterm but adequate birthweight (< 37 weeks' gestation and birthweight > or = 2500 g); term but low birthweight (> or = 37 weeks' gestation and birthweight < 2500 g); or term and adequate birthweight (> or = 37 weeks' gestation and birthweight > or = 2500 g). Neonatal and maternal sera were assessed, in ELISA, for specific IgG antibodies against measles virus (MeV), herpes simplex virus type-1 (HSV1), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), tetanus toxoid (TT), diphtheria toxoid (DT), and Streptococcus pneumoniae (Pn) and Haemophilus influenzae type-b (Hib) capsular antigens. Placental antibody transfer to certain antibody specificities was significantly lower in preterm neonates than term neonates. Thus the ratios between geometric mean cord antibody levels and geometric mean maternal antibody levels (the antibody-transfer ratios) were lower in preterm sera than term sera, for MeV (1.51 v. 2.03; P = 0.03), HSV1 (1.29 v. 1.76; P = 0.04), VZV (0.96 v. 2.50; P = 0.01), TT (1.13 v. 1.33; P = 0.04), DT (1.03 v. 2.39; P = 0.02), Pn (0.68 v. 0.98; P = 0.01) and Hib (0.58 v. 0.98; P = 0.00). Geometric mean levels of antibody to MeV, VZV, TT, DT and Pn were also significantly lower in preterm neonates than term. Compared with the values for 'adequate-birthweight' sera, low birthweight was independently associated with significantly lower levels of antibody transfer, for MeV (with antibody-transfer ratios of 1.51 v. 2.03; P = 0.02), VZV (0.99 v. 2.50; P = 0.03), TT (1.01 v. 1.33; P = 0.04) and DT (1.16 v. 2.39; P = 0.04) and significantly lower levels of antibodies to MeV, HSV1, VZV, TT, DT and Pn in the neonates. Maternal age, weight, height and parity had no independent influence on placental IgG transfer for antibodies to any of the pathogens investigated. These results demonstrate that prematurity and low birthweight may influence the level of maternally acquired immunity in Sri Lankan neonates.

Aims: To compare the blood pressure of very low birthweight infants with that of normal birthweight controls in adolescence., Methods: A cohort of all infants of birthweight < or = 1500 g born to women resident in the county of Merseyside in 1980-1 was followed up at age 15 years with age, sex, and school matched controls. Growth indices and blood pressures were measured under standard conditions. The smoking history of mothers and children and their status for several socioeconomic variables were documented. In a matched pairs analysis systolic and diastolic blood pressures were compared for cases and controls before and after adjusting for height, weight, and body mass index., Results: There were 172 singleton 15 year old survivors of birthweight < 1500 g out of 40,321 live births of Merseyside residents in 1980-1. Of the 172 survivors, 128 (74%) who had no clinical disability and 11 (6%) with a clinical disability but attending normal schools, were assessed with individually matched age, sex, and school controls. Twenty three (13%) had a clinical disability and were attending special schools; these were assessed without controls. Ten (6%) children refused or were unavailable for assessment. The systolic blood pressure was significantly higher in cases than in controls; the mean of the difference was 3.2 mm Hg. The diastolic blood pressure was also higher in the cases, but the difference was not significant. The controls were significantly heavier (4.4 kg), taller (4.0 cm), with larger head circumference (1.5 cm) than the cases. The difference in body mass index was not significant. Adjusting for height, weight, or body mass index increased the difference in systolic blood pressure between cases and controls. There were no significant differences in the socioeconomic variables, but what differences did exist favoured the controls. There was also a higher prevalence of smoking among the children and the mothers of the cases than the controls., Conclusions: The study supports the hypothesis that in adolescents variation in systolic blood pressure has its origins in fetal development. Some of the variation could be attributed to socioeconomic differences.

Aims: To report on the epidemiology of cerebral palsy in England and Scotland, to provide information on the prevalence of cerebral palsy and the severity of the disability or any co-morbidity., Methods: Cerebral palsy registers were compiled from multiple sources of ascertainment covering all of Scotland and the counties of Merseyside, Cheshire, Berkshire, Buckinghamshire, Northamptonshire and Oxfordshire in England. All cases of cerebral palsy born in 1984 to 1989, to mothers resident in the area, were included. Denominator number of live births and neonatal deaths for determining birthweight specific prevalence were obtained from birth and death registrations. Learning, manual, and ambulatory disabilities were graded for severity. Any co-existing sensory (hearing or visual) morbidity was also graded for severity., Results: There were 789,411 live births in 1984-9, with 3651 neonatal deaths (neonatal mortality 4.6 per 1000 live births) and 1649 cases of cerebral palsy--a cerebral palsy prevalence of 2.1 per 1000 neonatal survivors. The birthweight specific cerebral palsy prevalence ranged from 1.1 per 1000 neonatal survivors in infants weighting > or = 2500 g to 78.1 in infants weighing < 1000 g. There was no significant time trend in prevalence of cerebral palsy in any of the birthweight groups, in contrast to the fall in neonatal mortality observed in all birthweight groups. Of the 1649 cases of cerebral palsy, 550 (33.4%) had severe ambulatory disability (no independent walking), 390 (23.7%) had severe manual disability (incapable of feeding or dressing unaided), 381 (23.1%) had severe learning disability (IQ < 50), 146 (8.9%) had severe visual disability (vision < 6/60 in the better eye) and 12 had severe hearing disability (> 70 dB loss)., Conclusions: Registers fill an important gap left by the lack of routine data on the prevalence of disability in children. The ability to record trends in the prevalence and the severity of the disability should inform those who have responsibility for providing services for children with disabilities.