Cerebral palsy in the surviving twin associated with infant death of the co-twin

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.     

Childhood pregnancy (10-14 years old) and risk of stillbirth in singletons and twins

OBJECTIVE: To clarify the association between childhood pregnancy and risk of stillbirth. STUDY DESIGN: We analyzed singleton and twin pregnancies that occurred in children (10-14 years old) in the United States from 1989 to 2000. We estimated the absolute and relative risks of stillbirth by using 15- to19-year-old and 20- to 24-year-old mothers as comparison groups. RESULTS: The analysis involved 17.8 million singletons and 337,904 individual twins. The rate of stillbirth was highest in pediatric mothers for both singletons (12.8/1000) and twins (56/1000) compared with adolescent (6.8/1000 in singletons and 29/1000 in twins) and mature (5.5/1000 in singletons and 20/1000 in twins) mothers. After adjusting for confounding characteristics, pediatric mothers continued to exhibit significantly elevated risk for stillbirth in both singletons (odds ratio, 1.57; 95%CI, 1.49-1.66) and twins (odds ratio, 1.97; 95%CI, 1.42-2.73). Preterm birth rather than small size for gestational age was revealed by means of sequential modeling to account for the excess risk of stillbirth observed in pediatric gravidas. CONCLUSION: Pregnancy in childhood is a risk factor for stillbirth; shortened gestation rather than reduction in fetal growth is the mediating pathway.     

Sudden infant death syndrome among twins.

BACKGROUND: Sudden infant death syndrome (SIDS) is a major contributor to infant mortality. Previous studies have suggested that infants born of twin pregnancies are at greater risk for SIDS and that a twin who survives after a co-twin dies is at increased risk for SIDS. OBJECTIVE: To attempt to confirm the increased risk of SIDS among and within twin pairs through the use of US vital statistics data. METHODS: We analyzed data from the US-linked birth and infant death certificate tapes for the years 1987 through 1991 to determine the risk of SIDS in twin births compared with singleton births and to describe the characteristics of twin pairs in whom SIDS occurred. The analysis was limited to live births with weights of 500 g or more and gestational ages of 24 weeks or more. We used an algorithm to match co-twins (infants within a twin pair) to measure sex and birth weight concordancy, to identify twin pairs, in which one or both twins died of SIDS; and to examine, when both twins died, whether they died on the same day. RESULTS: There were 23464 singleton SIDS deaths and 1056 twin SIDS deaths during the 5-year period. The crude relative risk for SIDS among twins compared with singleton births was 2.06 (95% confidence interval, 1.94-2.19). The adjusted relative risk independent of birth weight and sociodemographic variables was 1.13 (95% confidence interval, 0.97-1.31). We successfully matched the co-twins of 172029 twin pregnancies. Of these, 767 were twin pregnancies in which one or both twins died of SIDS. Among the 767 twin pregnancies in which one or both twins experienced SIDS, there were only 7 in which both twins died of SIDS (rate ratio, 4.0 per 100000 twin pregnancies). In only 1 of these 7 did both twins die on the same day (rate ratio, 0.58 per 100000 twin pregnancies). The relative risk for a second twin dying of SIDS was 8.17 (90% confidence interval, 1.18-56.67). CONCLUSIONS: Independent of birth weight, twins do not appear to be at greater risk for SIDS compared with singleton births. In addition, the occurrence of both twins dying of SIDS is uncommon, and the occurrence of both twins dying on the same day is extremely uncommon.     

Cerebral palsy: effects of twinning, birthweight, and gestational age.

AIMS: To determine the effects of birthweight and gestational age on the risk of cerebral palsy for multiple and singleton births. METHODS: Children on the North East Thames Regional Health Authority Interactive Child Health System, born between 1 January 1980 and 31 December 1986, and notified as having cerebral palsy, were included. Cases of postneonatal onset, of known progressive, or non-cerebral pathology and with only mild signs were excluded. Rates and relative risks were calculated using the most complete data, which related to 1985-86, and comprised 102,059 singletons and 2367 twins. Logistic regression was used to examine the associations between being a twin, gestational age, and birthweight. RESULTS: The crude rate per 1000 survivors at 1 year of age was 1.0 in singletons and 7.4 in twins. The relative risk was greatest in twins weighing more than 2499 g (4.5). However, after adjusting for reduced birthweight of twins it was the relative risk of twins weighing less than 1400 g that was significantly increased. Logistic regression confirmed that lower fetal growth, lower gestational age, and being a twin are all independent risk factors for cerebral palsy. CONCLUSION: The increased risk to twins of cerebral palsy is not entirely explained by their increased risk of prematurity and low birthweight.     

Cerebral palsy and multiple births.

AIM: To compare the birthweight specific prevalence of cerebral palsy in singleton and multiple births. METHODS: Registered births of babies with cerebral palsy born to mothers resident in the counties of Merseyside and Cheshire during the period 1982 to 1989 were ascertained. RESULTS: The crude prevalence of cerebral palsy was 2.3 per 1000 infant survivors in singletons, 12.6 in twins, and 44.8 in triplets. The prevalence of cerebral palsy rose with decreasing birthweight. The birthweight specific prevalence among those of low birthweight < 2500 g was not significantly different in singleton than in multiple births. Among infants weighing > or = 2500 g, there was a significantly higher risk in multiple than in singleton births. The higher crude cerebral palsy prevalence in multiple births is partly due to the lower birthweight distribution and partly due to the higher risk among normal birthweight infants. CONCLUSIONS: Multiple birth babies are at increased risk of cerebral palsy. There is also an increased risk of cerebral palsy within a twin pregnancy if the co-twin has died in utero.     

Cerebral palsy in twins: a national study

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.     

Language assessment of non‐handicapped twins at 5 years of age

Background: The aim of the present study was to determine language levels in twins and singletons born after at least 34 weeks gestation and without identifiable neurological abnormality and to evaluate whether in vitro fertilization (IVF) affects language development in twin pregnancies. Methods: A prospective study of a large cohort of all children born between 1 January 2001 and 31 December 2003 was carried out at Gazi University Hospital. All live‐born twin pairs in which both twins survived were identified, and a comparable sample of families with pairs of singletons were chosen. The Stanford–Binet Intelligence Scale Form and the translated Turkish form of the Peabody Picture Vocabulary Test were completed at 60 months. Results: Even after excluding the most premature twins and those with diagnosable neurological damage, twins performed worse than singletons on language development tests. Twin girls had better scores than twin boys. A statistically significant difference was found between the scores of term and preterm twins. No significant difference was noted when compared according to birth order. Appropriate for gestational age (AGA) twins did better than small for gestational age (SGA) twins in the test scores. All twin girls did not differ from singleton girls, but all twin boys performed worse than singleton boys. Term twins had similar results with term singletons, but preterm twins had lower scores than preterm singletons. SGA singletons had better scores than SGA twins, while AGA twins and singletons did not differ. When the children were compared with regard to method of conception, IVF children had significantly lower scores on the tests than those in the spontaneous conception group. Conclusion: It is hoped that the present findings could lead to a more precise assessment of children for speech impairment and, above all, to more efficient preventive intervention. Whatever mechanisms are involved, the present results indicate that twins born as a result of IVF, are at a disadvantage in terms of language development in comparison with spontaneously conceived twins.     

Are twins growth restricted?

It is now well established that IUGR is associated with an increased risk of a range of adult onset diseases, including cardiovascular disease, obesity, and type 2 diabetes. Infants from twin pregnancies are generally born smaller than singletons; therefore, it has been suggested that twins represent a naturally occurring model of IUGR. Although twin gestations contribute significantly to the population burden of preterm birth and small size at birth, whether twins have the same long-term health consequences as IUGR singletons remains unclear. The purpose of this review is to consider what is currently known about the clinical implications of twinning, the differences that exist between the growth and developmental profiles of singleton and twin fetuses, and to use this as a basis for exploring the question of whether fetuses conceived as twins are analogous to IUGR singletons of similar birthweight and gestation. This question is increasingly important in both the clinical and research settings, because the incidence of twinning is increasing and the long-term implications of reduced size at birth are mostly investigated in species which bear multiple offspring.     

National birthweight percentiles by gestational age for twins born in Australia

OBJECTIVE: To develop national charts of birthweight percentiles by gestational age and infant sex for liveborn twins born in Australia. METHODOLOGY: National data on live twin births to non-Indigenous Australian-born mothers during 1991-94 were derived from perinatal data collected by midwives in each State and Territory. RESULTS: During 1991-4 there were 20,075 liveborn twin infants. Of these births, missing data included: birthweight 36 (0.2%) births, gestational age 95 (0.5%) births, and sex (missing or indeterminate) 13 (0.06%) births. These births were excluded from the study. An additional 0.6% births were excluded because the recorded birthweights were extreme outliers for the recorded gestational ages. Forty-seven per cent of live twin births were preterm (< 37 weeks). At all gestational ages, the median birthweight of male twins was higher than that of female twins. At model gestational age of 38 weeks, the difference in the median birthweight was 130 g. CONCLUSIONS: The charts produced as a result of the study provide birthweight percentiles by gestational age for twins based on national data in Australia. They provide current population norms for the use of Australian clinicians and researchers.     

Mortality of twin and singleton livebirths under 30 weeks' gestation: a population-based study

OBJECTIVE: To determine the mortality rates of liveborn twins compared with singletons of less than 30 weeks' gestation in relation to gestational age, mode of delivery and year of birth in a geographically defined population. STUDY DESIGN: Comparison of early neonatal, late neonatal and infant death rates in 479 twin babies and 1538 singletons, liveborn between 23 and 29 completed weeks of gestation in the north of England over two epochs, 1998-2001 and 2002-5. RESULTS: Twins and singletons had similar mortality rates except at the extreme of gestation (23-25 weeks) where twins had higher infant mortality (OR 2.04, 95% CI 1.37 to 3.02). This higher rate was attributable to early and late neonatal deaths (OR 1.86, 95% CI 1.28 to 2.72, and 2.11, 95% CI 1.13-3.94, respectively). When analysed in two epochs, the excess mortality was confined to babies born in 1998-2001. There was no effect of gender or chorionicity. CONCLUSIONS: The excess mortality among twins of less than 30 weeks' gestation was confined to neonatal deaths in babies of 25 weeks or less, and to the earlier epoch (1998-2001). In the modern era, there appears to be no excess mortality in neonates less than 30 weeks' gestation when compared with singletons.     

Physical and mental development of Turkish twins

BACKGROUND: Multiple gestations are known to bring some risks in the prenatal and natal period, but whether it is a risk for development in childhood is a matter of debate. The aim of the present study was to evaluate physical and mental development of Turkish twins and then to assess whether being a twin poses risks for their development. METHODS: Fifty-two twin pairs (104 children) aged between 1 and 5 years were enrolled in the study. The control group consisted of 91 singletons, who were matched according to age, sex, gestational week and maternal educational level. The Denver Developmental Screening Test (DDST) was administered to assess cognitive development. Student t-test and chi2 test were used to compare the two groups. RESULTS: The mean age of the mothers of twins did not differ from that of singleton mothers (P > 0.05). Twins were more frequently born in cases of assisted fertilization and were more often born via cesarean section. The birthweights of twins were lower and they were more frequently hospitalized after birth. The breast feeding period was shorter in twins and they had more chronic diseases than singletons (P < 0.05). Mothers of twins needed more help while caring for their infants. Physical development of twins and singletons did not differ statistically (P > 0.05). Twins had more suspect and delayed results in the DDST, especially in the language section of the test. CONCLUSION: Physical and mental development of twins does not differ significantly from singletons except that twins might have a tendency towards slow language acquisition.     

Respiratory distress syndrome and birth order in premature twins

OBJECTIVE: To determine the effect of birth order on respiratory distress syndrome (RDS) in the outcome of twins in a large premature population managed in a modern neonatal intensive care unit. METHODS: An historical cohort study design was used to analyse the neonatal outcomes of 301 premature liveborn twin sibling pairs of between 23 and 31 weeks gestation from the Australia and New Zealand Neonatal Network 1995 database. RESULTS: Among the 56 twin sibling pairs who were discordant for RDS, the second twin was affected in 41 cases (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.5 to 5.3). The excess risk of RDS in the second twin increased with gestation and was statistically significant for twins above 29 weeks gestation (OR 4.4, 95% CI 1.6 to 15). CONCLUSIONS: There is a significant increased risk of RDS associated with being the second born of premature twins, which appears to depend on gestation.     

Excess risk of mortality in very low birthweight triplets: a national,population based study

BACKGROUND: Neonatal morbidity and mortality differ between singletons, twins, and triplets. OBJECTIVE: To evaluate whether plurality is associated with excess risk of neonatal morbidity and poor outcome (death, chronic lung disease, or adverse neurological findings) in very low birthweight (VLBW) infants from a national, population based cohort. METHODS: The Israel national VLBW infant database has prospectively collected extensive perinatal and neonatal data on all liveborn VLBW infants since 1995. The study sample (n = 5594) consisted of all singletons (n = 3717) and all complete sets of twins (n = 1394) and triplets (n = 483) born during 1995-1999. To account for differences in case-mix, both univariate and multivariate comparisons that included confounding variables such as antenatal steroid treatment and mode of delivery were performed for each of the outcome variables. RESULTS: There was a small inverse correlation between gestational age (GA) and birth weight (BW) and the number of fetuses (singletons: GA 28.9 (2.6) weeks, BW 1096 (269) g; twins: GA 28.4 (2.3) weeks, BW 1062 (271) g; triplets: GA 28.5 (2.4) weeks, BW 1049 (259) g). Triplets were significantly more likely to have been conceived following fertility treatments, to have received antenatal steroids, and to be delivered by caesarean section. Respiratory distress syndrome was significantly more common in twins and triplets in spite of the increased exposure to antenatal steroids. Multivariate logistic regression analysis using all significant perinatal covariates showed that triplets were at increased risk of death (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.13 to 2.11), but not of adverse neurological outcome (OR 1.29, 95% CI 0.91 to 1.85) or chronic lung disease (OR 0.69, 95% CI 0.46 to 1.02). CONCLUSION: Despite considerable differences in the incidence of confounding variables between the groups, VLBW triplets are at increased risk of death compared with twins and singletons. In addition, VLBW twins and triplets more often have respiratory distress syndrome but not chronic lung disease or adverse neurological findings.     

No correlation in post-neonatal deaths for twins. A study of the early mortality of twins based on the Norwegian Medical Birth Registry

The records of 10,204 pairs of twins born in Norway 1967-84 in the Norwegian Birth Registry were examined. The probabilities of stillbirth, neonatal death and post-neonatal death, conditional on the fate of the cotwin, were calculated. The neonatal death rate was four times increased when the cotwin was stillborn. When the cotwin died neonatally, the probability of postneonatal death was increased ninefold. The concordance rate for stillbirth and for neonatal death was above 0.4. In striking contrast, there was no correlation in postneonatal death for members of a twin pair. This finding suggests that genetic or common environmental factors play a minor role in the aetiology of post-neonatal death.     

Neurological outcome in twins

Twins are at greater risk of death and severe morbidity than singletons which is in excess of that attributable to their greater prematurity. Monozygous, specifically monochorionic, twins are at greater risk than dichorionic twins. The major morbidity is neurological impairment usually presenting as cerebral palsy or severe learning disability and frequently, but not always, associated with fetal death of a co-twin. The likely pathogenesis of the neurological impairment is ischaemia attributable to haemodynamic imbalance via placental vascular anastomoses. In addition to the neurological impairment, congenital cardiac, renal, intestinal and other anomalies are more common but discordant in monozygous twins. It has been hypothesized that cerebral palsy and other neurological impairment in apparently singleton infants is attributable to early loss of a twin, the ‘vanishing’ twin phenomenon. It is also postulated that other congenital anomalies in singletons may be attributable to the same phenomenon.     

Preterm twin and triplet pregnancies are at increased risk for the development of cystic periventricular leukomalacia

BackgroundAn increased risk of cerebral palsy in multiples has been reported.AimsTo determine the risk for the development of periventricular leukomalacia (PVL) of twin and triplet pregnancy.Study designRetrospective single-centre study at a tertiary care university hospital.SubjectsInfants ≤35 weeks gestational age born between 1988 and 2008.Outcome measuresRisk of twin and triplet compared to singleton pregnancy regarding development of PVL in one offspring.ResultsOf 6195 infants 117 singletons and 39 multiples were diagnosed as having cystic PVL. Perinatal data did not differ as did not ultrasonographic findings and neurologic outcome. The relative risk (RR) of a twin pregnancy resulting in at least one infant with PVL when born prior to 36 weeks was 2.181 (CI 95% 1.474–3.228, p < .0001), and 6.793 (CI 95% 2.470–13.108, p < .0001) of a triplet pregnancy. In-vitro fertilisation was present in 3% of affected twins compared to 100% in triplets (p < .001).ConclusionWe found an increased risk for PVL in preterm twin and triplet pregnancies.     

Mortality from birth to adult life: a longitudinal study of twins

We have examined mortality from birth through adult life in a cohort of 2562 twins born in Birmingham, UK, between 1950 and 1954. Their birthweights and obstetric details had been recorded as part of a longitudinal study of births in Birmingham. There were a total of 151 perinatal deaths (perinatal mortality rate = 116 per 1000 births) and 227 infant deaths (infant mortality rate = 94 per 1000 live births). 70 deaths occurred after the age of one year. In comparison with national mortality rates in the UK, overall mortality in the twins was high (standard mortality rate, SMR = 259, 95% CI 221-300). Mortality was highest in the first year of life and, although it then declined progressively, it remained significantly higher that that of the general population until age 5 years. The excess mortality was largely due to conditions originating in the perinatal period but there were excess rates of congenital abnormalities, diseases of the respiratory system, digestive system and nervous and sensory organs. A Cox proportional Hazards analysis showed that the risk of death was related to low birthweight, prematurity and male sex. Death of the co-twin was highly predictive of mortality throughout the period of follow up. These studies not only underline the excess mortality associated with twin birth but show for the first time that this excess mortality extends into childhood.     

Relation between size of delivery unit and neonatal death in low risk deliveries: population based study

AIM: To examine risk of neonatal death after low risk pregnancies in relation to size of delivery units. METHODS: A population based study of live born singleton infants in Norway with birthweights of at least 2500 g was carried out. Antenatal risk factors were adjusted for. RESULTS: From 1972 to 1995, 1.25 million births fulfilled the criteria. The neonatal death rate was lowest for maternity units with 2001-3000 annual births and steadily increased with decreasing size of the maternity unit to around twice that for units with less than 100 births a year (odds ratio 2.1; 95 % confidence interval 1.6 to 2.8). Institutions with more than 3000 deliveries a year also had a higher rate (odds ratio 1.7; 95% CI 1.4 to 2.0), but analyses suggest that this rate is overestimated. CONCLUSION: Around 2000 to 3000 annual births are needed to reduce the risk of neonatal deaths after low risk deliveries.     

Fetal or infant death in twin pregnancy: neurodevelopmental consequence for the survivor

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.