E H Yeung1, A Saha2, C Zhu3, M H Trinh4, S N Hinkle4, A Z Pollack5, K L Grantz4, J L Mills4, S L Mumford4, C Zhang4, S L Robinson4, M W Gillman6, J Zhang7, P Mendola8, R Sundaram2. 1. Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. Electronic address: edwina.yeung@nih.gov. 2. Biostatistics and Bioinformatics Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. 3. Glotech, Inc, Rockville, MD, USA. 4. Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. 5. Global and Community Health Department, College of Health and Human Services, George Mason University, 4400, University Drive MS5B7, Fairfax, VA, USA. 6. Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health, Bethesda, MD, USA. 7. Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 8. Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA; Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
Abstract
INTRODUCTION: Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as a risk factor for future CVD mortality in mothers. METHODS: Longitudinal study of 33,336 women from the Collaborative Perinatal Project (CPP; 1959-1966) linked to mortality information through December 2016. Pathologists took extensive morphological and histopathological measures. Apart from assessing associations with morphological features, we derived an overall composite score and specific inflammation-related, hemorrhage-related, and hypoxia-related pathologic placenta index scores. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality adjusting for covariates. RESULTS: Thirty-nine percent of women died with mean (standard deviation, SD) time to death of 39 (12) years. Mean (SD) placental weight and birthweight were 436 g (98) and 3156 g (566), respectively. Placenta-to-birthweight ratio was associated with all-cause mortality (adjusted HR 1.03: 1.01, 1.05 per SD in ratio). In cause-specific analyses, it was significantly associated with respiratory (HR 1.06), dementia (HR: 1.10) and liver (HR 1.04) related deaths. CVD, cancer, diabetes and kidney related deaths also tended to increase, whereas infection related deaths did not (HR 0.94; 0.83, 1.06). Placental measures of thickness, diameters, and histopathological measures grouped by inflammatory, hemorrhagic, or hypoxic etiology were not associated with mortality. DISCUSSION: Placental weight in relation to birthweight was associated with long-term maternal mortality but other histopathologic or morphologic features were not.
INTRODUCTION: Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as a risk factor for future CVD mortality in mothers. METHODS: Longitudinal study of 33,336 women from the Collaborative Perinatal Project (CPP; 1959-1966) linked to mortality information through December 2016. Pathologists took extensive morphological and histopathological measures. Apart from assessing associations with morphological features, we derived an overall composite score and specific inflammation-related, hemorrhage-related, and hypoxia-related pathologic placenta index scores. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality adjusting for covariates. RESULTS: Thirty-nine percent of women died with mean (standard deviation, SD) time to death of 39 (12) years. Mean (SD) placental weight and birthweight were 436 g (98) and 3156 g (566), respectively. Placenta-to-birthweight ratio was associated with all-cause mortality (adjusted HR 1.03: 1.01, 1.05 per SD in ratio). In cause-specific analyses, it was significantly associated with respiratory (HR 1.06), dementia (HR: 1.10) and liver (HR 1.04) related deaths. CVD, cancer, diabetes and kidney related deaths also tended to increase, whereas infection related deaths did not (HR 0.94; 0.83, 1.06). Placental measures of thickness, diameters, and histopathological measures grouped by inflammatory, hemorrhagic, or hypoxic etiology were not associated with mortality. DISCUSSION: Placental weight in relation to birthweight was associated with long-term maternal mortality but other histopathologic or morphologic features were not.
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