Health-Related Quality of Life, emotional and behavioural difficulties and perception of pain after extreme preterm birth – a population-based longitudinal cohort study

Appendices 2-4 is is not available in BORA due to publisher restrictions.Background: Rates of preterm birth vary widely among countries, proportions ranging from around 6% in Scandinavia, 12% in the United States to 18% in some African countries. Due to progress in perinatal medicine, there has been a substantial increase in survival after extreme preterm birth (gestational age < 28 weeks) over the past decades, accounting for about 0.4% of births in Norway. Extreme preterm birth poses tremendous challenges to neonates and their families from the very beginning. Preterm birth may have lifelong consequences for neurodevelopmental functioning in terms of motor, cognitive and psychosocial skills, and may contribute to development of various chronic diseases. When investigating these possible effects, researchers typically employ traditional measures of morbidity (i.e., objective measures of function). Self-reported opinions of health and well-being and how they vary throughout life have received less research attention. Aims: The overall aim of this dissertation work was to investigate how extreme preterm birth affects health and well-being throughout childhood and early adulthood. We compared the developmental trajectories of health-related quality of life (HRQoL), emotional and behavioural patterns, and perception of and responses to pain of subjects born preterm to those of matched control subjects born at term. Methods: This was a population-based longitudinal matched controlled cohort study of subjects born at a gestational age of ≤ 28 weeks or with a birth weight of ≤ 1000 grams and of gender- and age-matched term-born (TB) controls. The participants were born within a defined region of Western Norway during two periods: 1982-1985 (46 preterm babies) and 1991-1992 (35 preterm babies). The Child Health Questionnaire and Child Behaviour Checklist were applied when the children reached the age of 10 years and in late adolescence (18 years), supplemented with the Youth Self-Report, General Self-Efficacy, and health complaints questionnaire at 18 years; and the Short Form Health Survey-36 and health complaints questionnaire in young adulthood (24 years). At 18 years of age, their pain tolerance and pain perception were measured using a standardized Cold Pressor Task (hand in ice water). Results: The longitudinal response rates were high at 89% and 84%, respectively, for the preterm-born subjects, and 83% and 87%, respectively, for the control term-born subjects. The parents of the 1991-1992 preterm-born cohort reported that their children had inferior HRQoL in nearly all domains at 10 years of age, including the family and parent domains, and more emotional and behavioural difficulties compared to age-matched TB children. The differences were especially evident for preterm-born boys, but minor for preterm-born girls. When these children reached adolescence (age 18), the parents reported improved HRQoL and behaviour for the preterm-born boys, achieving scores approaching those of the TB boys. The girls, however, remained relatively unchanged. Early emotional and behavioural difficulties predicted less improvement in HRQoL for all participants. The preterm-born adolescents reported their HRQoL, behaviour, and pain perception to be relatively similar to those of their TB peers, but their actual pain tolerance was inferior, especially the preterm-born boys. General Self-Efficacy was associated with better HRQoL, behaviour, and pain tolerance for all participants. Also the 1982-1985 preterm-born cohort reported HRQoL and health complaints to be relatively similar to those of their TB peers when in their adolescence (age 17), except for inferior physical functioning for the impaired preterm-born subjects. At adulthood (age 24), the healthy preterm-born subjects reported poorer psychosocial functioning and more psychological health complaints compared to their TB peers. Conclusion: These findings demonstrate that extremely preterm-born subjects have inferior HRQoL and more behaviour problems in childhood, as reported by their parents. These characteristics improved through adolescence, especially for the boys. Severe behaviour problems in childhood predicted less improved HRQoL through puberty. At 18 years, extreme preterm-born subjects reported relatively similar HRQoL and behaviour as term-born controls, whereas in adulthood a tendency for inferior psychosocial HRQoL became apparent, particularly in those without disabilities. We also found lower pain tolerance but similar perception of pain at 18 years. Our findings underscore the importance of obtaining subjective knowledge of health and well-being, both from the perspective of parents and the preterm-born subjects. Moreover, it is important to observe changes through critical developmental phases in life, such as puberty, and to further explore the observed effects of gender that may be of importance. Finally, health professionals treating subjects who were born prematurely should be aware of a potential for unexpected pain responses in these individuals