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OBJECTIVE: To compare specific maternal and clinical characteristics and contributing factors among the five leading causes of pregnancy-related mortality to develop focused clinical and public health prevention programs. METHODS: California pregnancy-related deaths from 2002-2005 were identified with enhanced surveillance using linked birth and death certificates. A multidisciplinary committee reviewed medical records, autopsy reports, and coroner reports to determine cause of death, clinical and demographic characteristics, chance to alter outcome, contributing factors (at health care provider, facility, and patient levels), and quality improvement opportunities. The five leading causes of death were compared with each other and with the overall California birth population. RESULTS: Among the 207 pregnancy-related deaths, the five leading causes were cardiovascular disease, preeclampsia or eclampsia, hemorrhage, venous thromboembolism, and amniotic fluid embolism. Among the leading causes of death, we identified differing patterns for race, maternal age, body mass index, timing of death, and method of delivery. Overall, there was a good-to-strong chance to alter the outcome in 41% of deaths, with the highest rates of preventability among hemorrhage (70%) and preeclampsia (60%) deaths. Health care provider, facility, and patient contributing factors also varied by cause of death. CONCLUSION: Pregnancy-related mortality should not be considered a single clinical entity. Reducing mortality requires in-depth examination of individual causes of death. The five leading causes exhibit different characteristics, degrees of preventability, and contributing factors, with the greatest improvement opportunities identified for hemorrhage and preeclampsia. These findings provide additional support for hospital, state, and national maternal safety programs. [ABSTRACT FROM AUTHOR]