Public Health Aspects of Preterm Birth. Studies using Scandinavian population-based data

Abstract: Background: Preterm birth is an unresolved serious global health problem. Research must be multi-disciplinary, with assessment of risk factors and causative agents at many levels of observation. Such an important level is the public health aspect of preterm birth. The general aim of this thesis was to describe, assess and explore public health aspects of preterm birth. Material and Methods: Scandinavian population-based data from the three Medical Birth Registers in Sweden, Denmark and Norway, as well as the Swedish Hospital Discharge Register were used. Preterm birth in Sweden during the Birth Register era from 1973 to 2001 was described, and subgroups of preterm birth during 1991-2001 was assessed. The association between spontaneous preterm birth and deviant fetal birth weight from the population mean was explored. We propose to use reference populations as a supplement in international comparison of baseline differences in preterm birth proportions and for time trend surveillance. The outcome of preterm born infants when comparing spontaneous preterm birth with iatrogenic preterm birth was examined. Models for prediction of spontaneous preterm birth <34 and <37 weeks were developed and validated in a test population by combining logistic regression and Bayesian methods. Results: (I) The proportion of preterm birth (<37 weeks) in Sweden decreased from 6.3% in 1984 to 5.6% in 2001 (<0.0001) and was evident among singleton births at 34-36 gestational weeks. The composition of preterm subgroups was similar with findings from populations with higher preterm birth proportions. (II) Associations between smaller than the population mean and spontaneous preterm birth were evident for all gestational age groups. The largest risk was found at 28-31 gestational weeks and birth weight <-3SD (OR: 13.3; 95%CI: 10.3-17.2). Spontaneous preterm infants born at 34-36 gestational weeks weighed 1-1.9 SD (OR: 1.1; 95%CI: 1.1-1.2) or 2-2.9 SD (OR: 1.6; 95%CI: 1.5-1.7) above the expected mean more often. (III) The national preterm delivery rate (<37 weeks) increased in Denmark from 5.3% to 6.1% (p<0.001) and in Norway from 6.0% to 6.4% (p=0.006), but remained unchanged in Sweden, during 1995-2004. In Denmark, the preterm delivery rate in the reference population (5.3% to 6.3%, p<0.001) and the spontaneous preterm delivery rate in the reference population (4.4% to 6.8%, p<0.001) increased significantly. No similar increase was evident in Norway. In Sweden, rates in the reference population remained stable. (IV) Spontaneous preterm infants were at increased risk of experiencing cerebral palsy at gestational age 28-31 weeks (HR: 1.86; 95%CI: 1.12-3.10) and sepsis at gestational age 32-33 weeks (HR: 1.58; 95%CI: 1.28-1.96). Other outcome variables were associated with iatrogenic preterm birth, in particular respiratory and gastrointestinal diagnoses. (V) Six prediction models were developed and the area under the receiver operator curve in the test population ranged from 0.77 (95%CI 0.76-0.77) to 0.59 (95%CI 0.57-0.61) for spontaneous preterm birth <37 weeks and from 0.80 (95%CI 0.79-0.81) to 0.64 (95%CI 0.62-0.67) for spontaneous preterm birth <34 weeks. For each delivery in the test population, the model that to the greatest extent utilized the available information was used, and total area under the receiver operator curve for spontaneous preterm birth <34 weeks (0.74, 95%CI 0.73-0.75) and <37 weeks (0.71, 95%CI 0.7-0.71) were calculated. Conclusions: The proportion of preterm birth in Sweden has decreased since the mid-eighties. Deviation of fetal birth weight from the expected mean is associated with spontaneous preterm delivery. Reference populations may prove to be a valuable supplement to assessments of national preterm delivery proportions in public health surveillance. Spontaneous preterm birth and iatrogenic preterm birth are associated with different paediatric outcomes. Spontaneous preterm birth can be predicted by using the proposed models, which could be applicable in clinical assessment of risk.