This article reviews the treatment options of the twin–twin transfusion syndrome (TTTS). No single therapy is associated with a uniformly improved outcome for the involved twins and success is primarily related to gestational age and severity at diagnosis. Treatment options for severe cases include digitalization, ligation of the umbilical cord, serial amniocenteses, septostomy, laser occlusion of placental vessels, and selective feticide. These modalities are associated with significant risks of complications, and variable results of fetal morbidity and mortality. Therefore, they should be considered when risks of withholding treatment clearly outweigh those associated with intervention.

No randomised controlled trials of treatment of twin-to-twin transfusion syndrome (TTTS) exist. Since severely preterm neonatal survival has increased over time, survival as an outcome measure is confounded by improvements in neonatal care. The diagnosis-to-delivery interval is a measure of success of treatment independent of improvements in neonatal care. We wished to evaluate whether treatment of TTTS is associated with a lengthening of the diagnosis-to-delivery interval. MEDLINE search was performed supplemented by careful reference review. All TTTS series were included where the following information on each patient was available: survival, fetal demise, gestational age at diagnosis and diagnosis-to-delivery interval in days. Inclusion criteria: gestational age at diagnosis < 29 weeks and diagnosis by ultrasound in the absence of maternal symptoms. Cases undergoing multiple types of treatment were excluded. Eight publications met inclusion criteria and included the following cases: controls (n = 16), amnioreduction (n = 61), septostomy (n = 12), and fetoscopic laser occlusion of chorioangiopagus vessels (n = 51). There was no difference in the diagnosis-to-delivery interval, overall survival, at least one survivor, or number of fetal deaths between the four groups. Logistic regression using at least one survivor as the dependent variable revealed a positive association with gestational age at diagnosis and with diagno-sis-to-delivery interval, a negative correlation with fetal death, and no correlation with treatment group. We conclude that there is no difference in diagnosis-to-delivery interval or survival for any treatment for TTTS compared to expectant management. The lack of significance appears to be due to small sample sizes.

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Preterm birth following cervical dilatation is the greatest threat to infants of a multiple pregnancy. Lacking reliable data concerning the effect of prophylactic cerclage, we compared a study group to controls for maternal and perinatal outcome. Sixteen of 94 triplet-, 9 of 18 quadruplet/quintuplet-pregnancies, treated with prophylactic cerclage, were retrospectively compared to those without cervical cerclage respectively. Kruskal-Wallis test and Mann-Whitney-U test were performed as non-parametric one way analysis of variance. For the analysis of frequencies Chi Square test or Fisher’s exact test were performed. Odds ratio with 95% confidence interval was used to compare the need for intravenous tocolysis as well as perinatal morbidity and mortality. Gestational age at delivery was not different from the controls in all studied groups. Birth weight revealed a 200g dominance for the “no cerclage-triplets”, while this significant difference was inverted for quadruplets/quintuplets (1245g vs. 1069g). With respect to gestational age at birth, need for hospitalisation or medical intervention no benefit was achieved. Moreover, perinatal outcome analysed by arterial pH, APGAR-Score and perinatal mortality was not altered by a prophylactic cerclage. Perinatal morbidity for quadruplets and quintuplets was even higher in cerclage pregnancies. Therefore, these retrospective results disclaim a positive impact of cervical cerclage on pregnancy management or perinatal outcome in multifetal pregnancies.

This paper describes the creation of a unique maternal identifier for use in the investigation of perinatal, postneonatal and child outcomes in relation to maternal characteristics. All Midwives’ records of Western Australian (WA) births were routinely linked to registrations of births and deaths for infants born from 1980 to 1992 inclusive, then linked to WA hospital discharge data and to registries of birth defects and cerebral palsy to create a longitudinal health record for each infant. However, since each birth to a woman was recorded as a separate event, there was no way to identify siblings. Probabilistic record linkage, based on information about the mother, was used for this task. Logical inconsistencies within the data were used to test the validity of the linkages between birth records attributed to each mother. Information about the mother from other epidemiological studies and data abstracted from hospital case notes was also used to validate sibships. Linkage of the records of 310,255 births in WA during that period resulted in the formation of 181,133 sibships of one or more children. Pooling the results of all of the validation methods gave an error of 0.9%. Linkage identified 3678 sibships containing multiple births, and 305 sets of maternal twins. Ascertainment of twins and their siblings for an ongoing twin register, the WA Twin Child Health (WATCH) study, was a natural consequence of this process.

The present study aimed to determine a reliable tool to estimate the interval time to delivery in assisted conception twin pregnancies. Mid-gestation cervical length was prospectively measured using transvaginal sonography (TVS) during routine antenatal care. Fifty-seven of 101 suitable women were longitudinally followed and two TVS measurements of their cervical length were obtained, first at approximately 24 weeks gestation and then at approximately 27 weeks gestation. The mean cervical length decreased from 37 ± 12mm at first measurement to 34 ± 11mm at the second one. A linear regression model was found between the time interval of the first (R = 0.656, p < 0.001) and the second (R = 0.435, p < 0.001) assessments and the week of delivery. The current data confirm that the length of the preserved segment of the cervix is an important indicator of its competence. A simple equation using the cervical length (mm) divided by 3 can predict mid gestation scan-to-delivery interval in twin gestation.

Although, in general, twins have higher perinatal mortality rates than singletons, preterm twins have lower perinatal mortality rates than singletons of the same birth weight or gestational age. This study investigated the hypotheses that this paradoxical twin advantage: 1) is due to gestational age distribution differences between the singleton and twin populations, and 2) is due to increased likelihood of birth having occurred in a tertiary perinatal center. A pre-existing, time-limited data set of all births in the province of Ontario in odd years between 1979 and 1985 was chosen for this study because of the large sample size (n = 618,579). Multivariable logistic regression of the relationship between perinatal mortality and twin status was controlled for mother’s age, hospital level and gestational age. Findings confirm the lower mortality of preterm twins. After controlling for level of hospital of birth this difference remained, suggesting that level of hospital of birth was not a major factor responsible for the twin advantage. Analyses in which gestational age was standardized indicate that, for those whose gestational age was less than 2 SD below the mean for their particular group (twin or singleton), twins were actually at higher risk than singletons. These results support hypothesis 1 and do not strongly support hypothesis 2. The results also support earlier authors’ suggestions that the definition of term birth should be different for twins and singletons

There are a growing number of large-scale initiatives for twin registers of children. The Australian Twin ADHD Project (ATAP) is used to illustrate two key limitations which may arise with such studies, namely (1) the importance of including or possibly excluding families in which one or both twins have significant developmental disability, and (2) the selective failure to recruit and/or the selective attrition of families in which parents and children share behavioral difficulties. Initially ATAP excluded 1 in 6 of families whose twins were enrolled in the volunteer-based Australian Twin Registry (ATR), and as more children with significant problems were identified, these families were sequentially excluded. With longitudinal data over ten years, two points about retention were identified: the difficulty of retaining the twins in late adolescence, and the loss of the families whose twins had more ADHD symptoms. We discuss strategies for limiting the loss of families and for ensuring comparability of data across registers with similar interests but different methods of recruitment and exclusion.

Twin–twin transfusion syndrome is the most common complication of monochorionic pregnancies affecting between 5 and 15% of such pregnancies and accounts for 15–77% of perinatal mortality in twins. The management of twin–twin transfusion syndrome is complex and various treatment modalities have been tried. This review critically evaluates the different management options available for the syndrome and recommends some guidelines for future interventional studies.

Assessment of treatment options in twin-twin transfusion should involve a detailed interrogation of the placenta and fetuses prior to treatment, stratification according to response to amnioreduction and careful analysis of quality of survival. Amnioreduction and laser coagulation are not alternative and equivalent modalities for the treatment of twin-twin transfusion. Randomized trials may not be ethical without prior therapeutic/ diagnostic amnioreduction.

The purpose of this study was to create graphs of fundal height parameters in triplet pregnancies compared with those in twin pregnancies, and to investigate whether larger fundal heights in triplet pregnancies would predispose them to earlier delivery (before 34 weeks). The subjects were 727 twin pregnant women and 133 triplet pregnant women, who delivered after 1984. Triplet pregnancies showed significantly higher fundal heights compared with twin pregnancies at each gestational age (weeks). In triplet pregnancies, a single fundal height measurement above the 90th percentile before 34 weeks yielded a sensitivity of 31.3% and specificity of 82.4% for delivery before 34 weeks, with a positive predictive value of 50.0% and a negative predictive value of 68.0%. After adjusting for each associated factor using logistic regression, the risk of preterm labour was not significantly associated with a single fundal height measurement above the 90th percentile recorded before 34 weeks.

The Australian Twin Registry (ATR), established in the late 1970s, is a volunteer registry of over 30,000 pairs of Australian twins of all zygosity types and ages unselected for their health or medical history. The ATR does not undertake research itself but acts as facilitator, providing an important national and international resource for medical and scientific researchers across a broad range of disciplines. Its core functions are the maintenance of an up-to-date database containing basic contact details and baseline information, and the management of access to the resource in ways that enhance research capacity within Australia while protecting the rights of twins. The ATR has facilitated more than 200 studies using a variety of designs, including classic biometrical twin and twin family studies, co-twin control studies, intervention studies, longitudinal studies, and studies of issues relevant specifically to twins. These have yielded more than 300 peer-reviewed publications to date. Areas of major research include studies of behavior, musculoskeletal conditions, teeth and face patterns, cardiovascular risk factors, substance abuse, and risk factors for melanoma and breast cancer. Extensive longitudinal data are available for around 10,000 pairs. DNA samples have been obtained from more than 6000 twins. Considerable efforts are devoted to maintaining the commitment of registry members and recruitment. The ATR hopes to secure funding to expand its activities, including the systematic collection of DNA samples, so that it can continue to play a major role in the development of twin research and contribute to the annotation of the human genome.

The phenomenon of paternally dependent familial twinning has been known in human and animal genetics since the 1920s, but still remains without any theoretical explanation and is indeed a neglected field of inquiry. Over the last two decades investigations in reproduction biology have discovered the significant role of multiple paternally dependent errors in fertilization including androgenic triploidy and moles. We suggest the hypothesis that the fathers of twins in the relevant families carry gene variants that increase the probability of dispermy, diplospermy and male pronucleus heterochrony as well as involvement of two male pronuclei in the fertilization of two female meiotic products. Any resulting twins would be an exceptional intermediate between MZ and DZ twins — and might properly be described as “sesquizygotic” (SZ). Paternal familial twinning may also go together with infertility due to triploidy, moles and chimerism. The hypothesis: (i) places the curiosities of paternally derived twinning within the framework of current knowledge of reproductive genetics and verifiable phenomena; (ii) predicts the existence of families in which twinning is associated with reproductive abnormalities; (iii) predicts an occurrence in relevant families of the third and intermediate category of SZ twins. Families with paternal twinning may thus provide the natural selective system for the search of unusual cases of primary chimeras, the frequency of which is still unknown.

The major morphological types of conjoined twins had all been described by 1600, often in publications that included details of the time and place of birth, morphology, outcome, behaviour, and, on occasion, autopsy findings. These descriptions differ from modern reports in emphasizing the twins’ supposed “meaning” rather than their cause. Understanding the symbolic aspects of these accounts is important for their interpretation. This article summarizes the records of 53 cases of conjoined twins born in 16th-century Europe and examines the cultural background of these accounts and the use of the pediatric autopsy as a means of investigating the pathology of twins. Studies of conjoined twins were central to the debate over whether the possession of separate hearts was a prerequisite for individuality.

Aretrospective study involving 623 twin and 1246 singleton births was conducted to compare the two groups with regard to selected maternal, fetal and labor and delivery characteristics and outcomes. Maternal age and parity were significantly higher for twins. The risks of preterm delivery, arrival in the labor ward in second stage of labor, cesarean births and postpartum haemorrhage were significantly higher in twin than in singleton births. In vaginal deliveries twin mothers were significantly less likely to have had episiotomies or perineal lacerations. There was no difference in the duration of the third stage of labor or in the incidence of retained placentae. Antepartum haemorrhage was a less likely indication for cesarean delivery among twins, while there was no significant difference in the likelihood of severe pre-eclampsia/eclampsia being an indication. Singleton babies were significantly heavier than twins. The incidences of malpresentation, low birth weight, stillbirths and of admission of live births to the neonatal intensive care unit were significantly higher in twins. There was no difference in the rate of instrumental vaginal delivery, or in the route of delivery of fetuses presenting by the breech. There is the need for detailed study of the incidences of antepartum haemorrhage and hypertensive diseases in twin and singleton pregnancies and of the factors determining the mode of delivery when such complications arise. Labor and delivery should also be examined to determine any differences between the two groups, especially in the first and second stages.

Reports over the past seventy years show that twin gestations lead to an increased risk of hypertensive disorders. Numerous studies discuss the incidence of hypertensive disease in twin versus singleton gestations, as well as effects of parity, race, age, income level, smoking, zygosity and heritability on this condition. The range of relative risk of gestational hypertension, preeclampsia and eclampsia for twin compared to singleton gestations is 1.2 to 2.7, 2.8 to 4.4 and 3.4 to 5.1 respectively. Parity, African-American ethnicity, and young maternal age are all factors that increase the relative risk of acquiring hypertensive disease to 4.0, 1.8 and 1.5 in mothers of twin gestations. Factors such as maternal smoking, income level and zygosity have a negligible effect on the relative risk of acquiring hypertensive disease in twin gestations. In addition to twin mothers exhibiting a higher incidence of hypertensive disease compared to their singleton counterparts, they also exhibit an earlier onset of hypertensive disease at both 35 and 37 weeks of gestation comparatively. Uric acid levels measured at 30–31 weeks of gestation in twin mothers predicted the onset of preeclampsia with a sensitivity of 73% and a specificity of 74%. The range of risks presented in the literature is wide and the therapies avocated are diverse. We therefore decided to summarize the risks in a comparative fashion and to review current therapeutic strategies for the convenience of clinicians who confront increasing numbers of multiple pregnancies. The tables bring all recent published risks together in the first comparative analysis in which the data has been converted to relative risks and confidence intervals. Because the literature is relatively silent on specific management of hypertensive disease in twin pregnancies, general management recommendations for singleton gestations should be used by practitioners caring over twin gestations.

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 medicolegal relevance when attributing negligence as the cause of morbidity in a survivor from a multiple pregnancy.

This study investigated the influence of genes and environment on the variation of apolipoprotein and lipid levels, which are important intermediate phenotypes in the pathways toward cardiovascular disease. Heritability estimates are presented, including those for apolipoprotein E and AII levels which have rarely been reported before. We studied twin samples from the Netherlands (two cohorts; n = 160 pairs, aged 13–22 and n = 204 pairs, aged 34–62), Australia (n = 1362 pairs, aged 28–92) and Sweden (n = 302 pairs, aged 42–88). The variation of apolipoprotein and lipid levels depended largely on the influences of additive genetic factors in each twin sample. There was no significant evidence for the influence of common environment. No sex differences in heritability estimates for any phenotype in any of the samples were observed. Heritabilities ranged from 0.48–0.87, with most heritabilities exceeding 0.60. The heritability estimates in the Dutch samples were significantly higher than in the Australian sample. The heritabilities for the Swedish were intermediate to the Dutch and the Australian samples and not significantly different from the heritabilities in these other two samples. Although sample specific effects are present, we have shown that genes play a major role in determining the variance of apolipoprotein and lipid levels in four independent twin samples from three different countries.