| Summary: | Abstract Background The rate of multiple births in the European population has risen in recent decades, due to increasing maternal age at birth , and increasing use of assisted reproductive technologies. This thesis aims to provide a quantitative description of the relationship between multiple births and congenital anomaly. Methods Data analysed was from the EUROCAT network of population-based congenital anomaly registries in 14 European countries. The core study population of 5.4 million births (1984-2007) was extended to 14.8 million with the addition of a national Down Syndrome register for analysis of Down Syndrome cases. Cases include livebirths and fetal deaths or stillbirths from 20 weeks gestation with congenital anomaly, and terminations of pregnancy for fetal anomaly (TOPFA). A total of 148,000 cases were included from the core study population , of which 3.38% were from multiple births. The outcome measures were prevalence and risk I odds in multiple relative to singleton births, estimated using Poisson and Logistic Regression , adjusting for time and country where relevant. Results The prevalence of congenital anomalies from multiple births has risen over time, as has the risk of congenital anomaly in multiple relative to singleton births. In the late 2000s, one in every 1,000 babies were co-affected by congenital anomaly and multiple birth, and 20% of cases from multiple births had a malformed co-twin. Non-chromosomal anomalies were 31% more likely in multiple than in singleton births. Non-chromosomal anomalies from the nervous, cardiac, digestive and genitourinary systems, made up this excess risk. In contrast, chromosomal anomalies were 35% less likely in multiple than in singleton births. For Down Syndrome specifically, the risk of a monozygous twin pair being affected was 31% of the singleton rate. In dizygous pairs, the risk per baby was lower than for singletons, but per pregnancy the risk of one or more babies being affected was slightly higher than the singleton rate. After the age of 45 years, Down Syndrome cases from multiple births are very rare and the risk low. Overall, congenital anomaly cases from multiple births are as likely to be prenatally diagnosed, but more than 50% less likely to be TOPFAs, than singleton cases. Down Syndrome cases from multiple births are less likely to be prenatally diagnosed than singleton cases. Stillbirths and early neonatal deaths were more common among multiple than singleton births with congenital anomaly. Conclusions This thesis identifies areas for further elucidation of the pathogenesis of congenital anomaly among multiple births. The contribution of assisted reproductive technologies to the increase in risk needs further research. The increase in babies from multip le births who are affected by a congenital anomaly has implications for pre and postnatal service provision. A single embryo transfer policy will not change the prevalence of congenital anomalies, but will change pregnancy outcomes for cases. For Down Syndrome specifically, this thesis is unique in providing age-specific risk correction factors that can be used in prenatal counselling of women with twin pregnancies.
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