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Overall in the last two decades there has been a decrease in the average gestational age at delivery. Gestation at delivery is important as it is associated with both short and long-term outcomes for the baby. The gestation the baby is born at affects the risk of perinatal mortality with increased perinatal mortality rates with preterm delivery but also in cases of prolonged pregnancy. In the longer-term, the gestation at delivery can affect the cognitive and school outcomes of the child, especially if born prematurely. Optimising the timing of delivery is therefore an important balance between short and long-term childhood outcomes. This thesis aimed to investigate the impact of timing of delivery on short and long-term outcomes in both singleton and twin pregnancies and the differences between the two using routinely collected maternity data. In singleton pregnancies, preterm delivery is the largest cause of perinatal and infant mortality with 10% of neonates worldwide born prematurely (< 37 weeks). One of the main challenges with preterm delivery is that the aetiology is so wide and largely unknown that implementing the correct interventions for prevention is not yet possible. In this thesis a population cohort study was used to determine the effect of geographical and environmental influences on preterm birth rates in an attempt to identify potential new mechanisms driving preterm birth. In a study of 1,335,802 singleton births, marked differences in the preterm delivery rate were observed across the country with longer gestational ages in urban areas suggesting the effect of urbanity as a potential area for future research. The association of late preterm birth (34-36 weeks) and early term births (37-38 weeks) with long-term cognitive outcomes in the offspring was investigated in the form of a systematic review. In four studies of 35,711 children, infants born at 39-41 weeks had higher cognitive outcome scores than those born at early term (37-38 weeks). This study adds to the growing body of evidence regarding the need to consider both short and long-term outcomes associated with gestation at delivery when planning timing of delivery. In twin pregnancies the optimum timing of delivery is largely unknown. The short and long-term outcomes according to gestation at delivery were explored initially in a subset of the Scottish population (n=7421) and then in the full Scottish population of 43,133 twins. Short term outcomes investigated included perinatal mortality and long-term outcomes were investigated by record linking the maternity data to the school census data of the child. The optimum gestation for delivery of uncomplicated twin pregnancies is 37 weeks. To investigate the differences in perinatal mortality between twins and singletons a population cohort study of 2,002,587 infants was performed. Overall twins had a higher rate of stillbirth compared to singletons at all gestational ages from 24 weeks. Neonatal death was higher in twins in the extreme preterm period but lower between 29 and 37 weeks. In conclusion determining optimum timing of delivery should consider both short and long-term infant outcomes and this information should be used to inform policy makers and when counselling women and families about timing of delivery.

Increasing time trends in the recorded incidence of childhood cancer have been reported in many different settings. The extent to which these trends reflect real changes in incidence, rather than improvements in methods for diagnosis and registration, is controversial. Using data from the National Registry of Childhood Tumours (NRCT), this thesis investigates time trends in cancer diagnosed under age 15 in residents of Britain during 1966-2005 (54650 cases), and considers potential sources of artefact in detail. Several different methods are used to estimate completeness of NRCT registration. The history of methods for diagnosis and registration of childhood cancers in Britain is described, and predictions are made for effects on recorded incidence. For each of the 12 main diagnostic groups, Poisson regression is used to fit continuous time trends and ‘step’ models to the annual age-sex-standardised rates by year of birth and year of diagnosis. Age-specific rates by period, and quinquennial standardised rates for diagnostic subgroups, are shown graphically. For three broad groups (leukaemia, CNS tumours and other cancer), geographical variation is compared by period of diagnosis. The results of these analyses are discussed in relation to the predicted artefacts. The evidence for a positive association between affluence and recorded incidence of childhood leukaemia is briefly reviewed. A special form of diagnostic artefact, the ‘fatal infection’ hypothesis, is proposed as an explanation of both this association and the leukaemia time trend. This hypothesis is examined in a novel test based on clinical data. The recorded incidence of childhood cancer in Britain increased in each of 12 diagnostic groups during 1966-2005 (from 0.5% per year for bone cancer to 2.5% for hepatic cancer, with 0.7% for leukaemia). Evidence presented here suggests that these increases are probably artefacts of diagnosis and registration. The potential implications for epidemiological studies of childhood cancer should be considered.