The aim was to analyse the neonatal mortality related to mode of delivery for twins using a population-based registry. In all, 18,125 twins delivered in Sweden between 1991 and 1997, after excluding those with unknown gestational duration, were used to analyse the differences between groups of twins. Results showed the OR for neonatal death, breech vaginal delivery versus caesarean section (all indications) was 1.47 (95% CI 0.99-2.17). The OR at vaginal delivery for neonatal death, twin I in breech versus cephalic presentation was 5.60 (2.62-11.94) and for twin II the corresponding figures were 1.85 (1.03-3.32). Analyses using population-based registries from other countries are needed to confirm or reject the present findings of an increased neonatal mortality for twins in breech presentation delivered vaginally.

The intrauterine growth patterns for twins are characterized by normal development during the first two trimesters and reduced growth during the third trimester. According to the fetal origins hypothesis this growth pattern is associated with risk factors for cardiovascular morbidity and mortality. We studied cause-specific mortality of 19,986 Danish twin individuals from the birth cohorts 1870–1930 followed from 1952 through 1993. Despite the large sample size and follow-up period we were not able to detect any difference between twins and the general population with regard to all-cause mortality or cardiovascular mortality. Hence, the intrauterine growth retardation experienced by twins does not result in any “fetal programming” of cardiovascular diseases. There is still an important role for twins (and other sibs) to play in the testing of the fetal origins hypothesis, namely in studies of intra-pair differences, which can assess the role of genetic confounding in the association between fetal growth and later health outcome.

Multiple pregnancy represents a challenge for obstetrics and also poses significant psychological, social and economic problems. The chances of a successful outcome may be improved by appropriate preventive, diagnostic and management strategies, by the availability of specific skills and experience and by a multidisciplinary approach. In this paper are indicated and discussed, on the basis of current evidences, what can be considered the ten “commandments” in terms of providing optimal care in multiple pregnancies. In particular in this review we focus on the following topics: psychological support and clinical counseling; diagnosis and characterization of chorionicity; management at referral centers; individualization of care; avoidance of most frequent complications; consideration of specific pathologies; evaluation of fetal anatomy; monitoring of fetuses; planning of time and mode of delivery; monitoring of the mother during postpartum.

The management of multiple pregnancies represents a true challenge for all sub-specialties concerned with perinatal medicine. Many issues were neglected over the years merely because they were rare and therefore considered not sufficiently important to merit clinical trials. This paper discusses a personal selection of controversial issues, such as multifetal pregnancy reduction of triplets and twins, special cases in multifetal preganncy reduction, need for invasive genetic studies, management of twin-twin transfusion, discordant fetal conditions, the definition of “term” in multiples, and the controversy about the mode of delivery.

Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake — indicating glucose intolerance and insulin resistance — among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.

An adverse intra-uterine environment has been associated with abdominal fat distribution in singletons. Twins often have a low birth weight and a short gestation. Therefore, they may have an increased risk to develop abdominal obesity. Furthermore, monozygotic monochorionic twins (MZ MC) have a larger intra-pair birth weight difference compared to monozygotic dichorionic twins (MZ DC). If adult anthropometry is programmed in utero, this may affect the intra-pair correlations in adulthood and, consequently, also the results from the classic twin method to estimate genetic and environmental influences. In the present study, we compared the absolute values, the intra-pair differences, and the intra-pair correlations of body mass, height, BMI, and abdominal fat distribution of 424 MZ MC, MZ DC and dizygotic (DZ) twin pairs (aged 18–34 yrs). DZ, MZ DC and MZ MC twins did not differ for most anthropometric characteristics. Only MZ women tended (p = 0.03) to accumulate more abdominal fat compared to DZ twins. Overall, the contribution of zygosity and chorion type to adult anthropometry was rather low (≤ 1.7%). Although the intra-pair birth weight difference of MZ MC pairs (10.5% in men, 12.3% in women) was significantly larger compared to that of MZ DC pairs (6.9% and 9.2% resp.), the intra-pair differences in adult anthropometry were similar for both MZ twin types. Also the intra-pair correlations of MZ MC and MZ DC pairs were strikingly alike, suggesting no significant influence of the prenatal environment on adult concordance. In conclusion, the substantial difference in the prenatal environment of MZ MC and MZ DC twins did not result in a difference in intra-pair concordance of adult anthropometry and fat distribution. Therefore, we suggest that the chorion type of MZ twins does not bias the twin design and the estimation of the genetic contribution to adult anthropometry.

Programme Committee: Elizabeth Bryan, Isaac Blickstein, Nick Martin, Pat Preedy, Tim Spector

Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (rg = 0.16, p = 0.005) and environmental (re = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.

Aclearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.

It has been proposed that low birth weight is associated with high levels of blood pressure in later life. The aim of this study was to assess the relationship of blood pressure to birth weight and current body size during growth and adulthood. A total of 711 female multiple births, with one group of 244 in their growth phase mean age 12.0 (2.3)(SD) years and the other of 467 adults (mean age 35.2 (12.6) years), had height, weight and both systolic (SBP) and diastolic (DBP) blood pressures measured, and self-reported their birth weight. Regression analyses were performed to assess the cross-sectional and within-pair associations of blood pressure to birth weight, with and without adjustments for current body size. Within-pair analysis was based on 296 twin pairs. Cross-sectionally, a reduction in birth weight of 1 kg was associated with 2 to 3 mm Hg higher age-adjusted SBP, which was of marginal significance and explained about 2% of the population variance. Adjustment for body mass index did not significantly change this association. Within-pair analyses found no association between birth weight and SBP or DBP, even after adjusting for current body size. After age, current body size was the strongest predictor of systolic BP. The weak association of blood pressure to birth weight cross-sectionally is of interest, but any within-pair effect of birth weight on blood pressure must be minimal compared with the effect of current body size.

The hypothesis was tested that monozygotic (MZ) and dizygotic (DZ) twins, with their lower average birth weight, have higher adult blood pressure than their singleton brothers or sisters. From the Netherlands Twin Registry, 261 twin families were recruited from a young adult and an older adult cohort with mean ages of 26.2 and 50.4 respectively. These families yielded 204 MZ twins with 71 singleton siblings and 271 DZ twins with 103 of their singleton siblings. Anti-hypertensive medication use of these 649 participants was assessed twice with a two-year interval. Resting blood pressure was measured thrice during a standardized laboratory protocol. In spite of a significant difference in birth weight (1036 gram), no differences were found in anti-hypertensive medication use at both time points between twins and singletons nor between their resting laboratory diastolic or systolic blood pressure. These results applied to each gender and to both age cohorts. Limiting the analyses to matched twin-sibling pairs of the same families and taking current weight and height into account did not change the results; no evidence was found for a twin-singleton difference. It was concluded that estimates of genetic and environmental contributions to blood pressure deriving from twin studies do not appear to be biased and may be generalized to singletons. Our results suggest that the lower birth weight in twins does not reflect the intrauterine disadvantage described by the Barker hypothesis.

Previous studies have suggested that perinatal factors influence the risk for asthma but population studies on perinatal factors and risk for hay fever are few. We studied the effect of perinatal factors on the risk for hay fever among adolescent twins by a questionnaire study involving five consecutive nation-wide birth cohorts of 16-year-old twins and their parents. The risk for parent-reported, doctor-diagnosed hay fever in the adolescents associated with several perinatal characteristics was assessed with logistic regression analysis among individuals and by a discordant pair analysis. In the univariate analysis of the birth factors, the risk for hay fever increased with increasing birth weight (p for trend = 0.048, OR for those ≥ 3000g 1.35, 95% CI 0.91–2.02 compared to those < 2000g) and gestational age (p for trend = 0.04, OR for those born after 40 weeks of gestation 2.24, 95% CI 1.03–4.86, compared to those born before 33 weeks of gestation) and was lower in those subjects hospitalised in the neonatal period (OR 0.74, 95% CI 0.58–0.93). Because of significant interactions between parental hay fever status and birth factors (ponderal index, p = 0.03 and maternal age p = 0.04), stratified analysis were performed. The positive association between birth weight and hay fever was most obvious among adolescents with no parental history of hay fever (p for trend = 0.03). Similar, though not significant, trends were found with other birth factors among these families, whereas no such trend was found among adolescents with parental hay fever, suggesting that gestational maturity increases the risk for hay fever in the absence of genetic predisposition. However, of the perinatal factors only neonatal hospitalisation (OR 0.75, 95% CI 0.59–0.96) remained a significant risk factor for the development of hay fever, when adjusted for non-perinatal factors.