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Aims To examine changes in health-related quality of life throughout the course of pregnancy and among three pairs of consecutive periods (pre-pregnancy to early pregnancy, early to middle pregnancy and middle to late pregnancy), as well as to identify associated obstetric factors during the entire period of pregnancy. Background Only sparse data are available concerning the profiles of health-related quality of life throughout pregnancy. Design A within-subject comparison was undertaken. Methods In total, 358 women completed the Taiwanese version of the Medical Outcomes Study Short Form-36 Health Questionnaire and a demographic-obstetric questionnaire at three stages of pregnancy at a medical centre. The participants were recruited between 2009-2010. A generalized estimating equation regression model was employed for the repeated measures. Results The scores for physical component summary decreased significantly throughout early, middle and late pregnancy. The scores for mental component summary increased. The scores for physical, mental component summary and the eight domains of health-related quality of life decreased significantly from pre-pregnancy to early pregnancy. After adjusting for demographic and clinical factors, significant factors predicting physical component summary during pregnancy included stage of pregnancy and previous infertility. The factors predicting mental component summary included stage of pregnancy, parity and medical condition. Conclusions The results revealed the dynamic pattern of perceived health status by the Taiwanese pregnant women in their surrounding socio-cultural context and identified the stage of pregnancy and obstetric factors predicting health-related quality of life. [ABSTRACT FROM AUTHOR]