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Preterm delivery and long term mortality in women: national cohort and co-sibling study.

ABSTRACT: OBJECTIVES:To examine the long term mortality associated with preterm delivery in a large population based cohort of women, and to assess for potential confounding by shared familial factors. DESIGN:National cohort study. SETTING:Sweden. PARTICIPANTS:All 2?189?477 women with a singleton delivery in 1973-2015. MAIN OUTCOME MEASURES:All cause and cause specific mortality up to 2016, identified from nationwide death records. Cox regression was used to calculate hazard ratios while adjusting for confounders, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and environmental) factors. RESULTS:In 50.7 million person years of follow-up, 76?535 (3.5%) women died (median age at death was 57.6). In the 10 years after delivery, the adjusted hazard ratio for all cause mortality associated with preterm delivery (<37 weeks) was 1.73 (95% confidence interval 1.61 to 1.87), and when further stratified was 2.20 (1.63 to 2.96) for extremely preterm delivery (22-27 weeks), 2.28 (2.01 to 2.58) for very preterm delivery (28-33 weeks), 1.52 (1.39 to 1.67) for late preterm delivery (34-36 weeks), and 1.19 (1.12 to 1.27) for early term delivery (37-38 weeks) compared with full term delivery (39-41 weeks). These risks declined but remained significantly raised after longer follow-up times: for preterm versusfull term births, 10-19 years after delivery, the adjusted hazard ratio was 1.45 (95% confidence interval 1.37 to 1.53); 20-44 years after delivery, the adjusted hazard ratio was 1.37 (1.33 to 1.41). These findings did not seem to be attributable to shared genetic or environmental factors within families. Several causes were identified, including cardiovascular and respiratory disorders, diabetes, and cancer. CONCLUSIONS:In this large national cohort of women, the findings suggested that preterm and early term delivery were independent risk factors for premature mortality from several major causes. These associations declined over time but remained raised up to 40 years later.

SUBMITTER: Crump C

PROVIDER: S-EPMC7436341 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Preterm delivery and long term mortality in women: national cohort and co-sibling study.

Crump Casey C Sundquist Jan J Sundquist Kristina K

BMJ (Clinical research ed.) 20200819

<h4>Objectives</h4>To examine the long term mortality associated with preterm delivery in a large population based cohort of women, and to assess for potential confounding by shared familial factors.<h4>Design</h4>National cohort study.<h4>Setting</h4>Sweden.<h4>Participants</h4>All 2 189 477 women with a singleton delivery in 1973-2015.<h4>Main outcome measures</h4>All cause and cause specific mortality up to 2016, identified from nationwide death records. Cox regression was used to calculate h ...[more]

PMID: 32816755

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Project description:BackgroundStroke has a high burden of disease in women, and adverse pregnancy outcomes have been identified as important risk factors for stroke later in life. However, long-term risks of stroke associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment and stroke prevention in women.MethodsA national cohort study was conducted of all 2 188 043 women with a singleton delivery in Sweden in 1973 through 2015 who were followed up for stroke identified from nationwide diagnoses through 2015. Cox regression was used to compute adjusted hazard ratios (aHRs) for stroke associated with pregnancy duration, and cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors.ResultsIn 48.0 million person-years of follow-up, 36 372 (1.7%) women were diagnosed with stroke. In the 10 years after delivery, the aHR for stroke associated with preterm delivery (gestational age <37 weeks) was 1.61 (95% CI, 1.45-1.79) and further stratified was 2.81 (95% CI, 2.02-3.91) for extremely preterm (22-27 weeks), 2.07 (95% CI, 1.74-2.46) for very preterm (28-33 weeks), 1.38 (95% CI, 1.21-1.57) for late preterm (34-36 weeks), and 1.15 (95% CI, 1.06-1.24) for early term (37-38 weeks), compared with full-term (39-41 weeks) delivery. These risks remained similarly elevated at 10 to 19 years after delivery (preterm versus full-term: aHR, 1.61 [95% CI, 1.50-1.74]) and then declined but remained significantly elevated at 20 to 29 years (aHR, 1.35 [95% CI, 1.28-1.44]) and 30 to 43 years (aHR, 1.35 [95% CI, 1.27-1.42]). Preterm delivery was associated with both hemorrhagic (aHR, 1.31 [95% CI, 1.25-1.38]) and ischemic (aHR, 1.54 [95% CI, 1.47-1.61]) stroke across the entire follow-up period (up to 43 years). These findings were not explained by shared determinants of preterm delivery and stroke within families. Stroke risks were higher after either spontaneous or medically indicated preterm delivery, and recurrent preterm delivery was associated with further increases in risk.ConclusionsIn this large national cohort, preterm delivery was associated with higher future risks of both hemorrhagic and ischemic stroke. These associations remained substantially elevated at least 40 years later, and were largely independent of covariates and shared familial factors. Preterm delivery should be recognized as a risk factor for stroke in women across the life course.

Project description:ImportancePreterm delivery has been associated with future cardiometabolic disorders in women. However, the long-term risks of chronic hypertension associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment, clinical monitoring, and cardiovascular prevention strategies in women.ObjectiveTo examine the long-term risks of chronic hypertension associated with preterm delivery in a large population-based cohort of women.Design, setting, and participantsThis national cohort study assessed all 2 195 989 women in Sweden with a singleton delivery from January 1, 1973, to December 31, 2015. Data analyses were conducted from March 8, 2021, to August 20, 2021.ExposuresPregnancy duration identified from nationwide birth records.Main outcomes and measuresNew-onset chronic hypertension identified from primary care, specialty outpatient, and inpatient diagnoses using administrative data. Cox proportional hazards regression was used to compute hazard ratios (HRs) while adjusting for preeclampsia, other hypertensive disorders of pregnancy, and other maternal factors. Cosibling analyses were assessed for potential confounding by shared familial (genetic and/or environmental) factors.ResultsIn 46.1 million person-years of follow-up, 351 189 of 2 195 989 women (16.0%) were diagnosed with hypertension (mean [SD] age, 55.4 [9.9] years). Within 10 years after delivery, the adjusted HR for hypertension associated with preterm delivery (gestational age <37 weeks) was 1.67 (95% CI, 1.61-1.74) and when further stratified was 2.23 (95% CI, 1.98-2.52) for extremely preterm (22-27 weeks of gestation), 1.85 (95% CI, 1.74-1.97) for moderately preterm (28-33 weeks of gestation), 1.55 (95% CI, 1.48-1.63) for late preterm (34-36 weeks of gestation), and 1.26 (95% CI, 1.22-1.30) for early-term (37-38 weeks of gestation) compared with full-term (39-41 weeks of gestation) delivery. These risks decreased but remained significantly elevated at 10 to 19 years (preterm vs full-term delivery: adjusted HR, 1.40; 95% CI, 1.36-1.44), 20 to 29 years (preterm vs full-term delivery: adjusted HR, 1.20; 95% CI, 1.18-1.23), and 30 to 43 years (preterm vs full-term delivery: adjusted HR, 95% CI, 1.12; 1.10-1.14) after delivery. These findings were not explained by shared determinants of preterm delivery and hypertension within families.Conclusions and relevanceIn this large national cohort study, preterm delivery was associated with significantly higher future risks of chronic hypertension. These associations remained elevated at least 40 years later and were largely independent of other maternal and shared familial factors. Preterm delivery should be recognized as a lifelong risk factor for hypertension in women.

Project description:BackgroundPreterm delivery is an independent risk factor for maternal cardiovascular disease. Little is known about the association between preterm delivery and maternal renal function. This study aimed to examine whether women who experience preterm delivery are at increased risk of subsequent chronic kidney disease (CKD) and end-stage kidney disease (ESKD).MethodsUsing data from the Swedish Medical Birth Register, singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Gestational age at delivery was the main exposure and treated as a time-dependent variable. Primary outcomes were maternal CKD or ESKD. Cox proportional hazard regression models were used for analysis.ResultsThe dataset included 1,943,716 women who had 3,760,429 singleton live births. The median follow-up was 20.6 (interquartile range 9.9-30.0) years. Overall, 162,918 women (8.4%) delivered at least 1 preterm infant (< 37 weeks). Women who had any preterm delivery (< 37 weeks) were at increased risk of CKD (adjusted hazard ratio (aHR) 1.39, 95% CI 1.32-1.45) and ESKD (aHR 2.22, 95% CI 1.90-2.58) compared with women who only delivered at term (≥ 37 weeks). Women who delivered an extremely preterm infant (< 28 weeks) were at increased risk of CKD (aHR 1.84, 95% CI 1.52-2.22) and ESKD (aHR 3.61, 95% CI 2.03-6.39). The highest risk of CKD and ESKD was in women who experienced preterm delivery + preeclampsia (vs. non-preeclamptic term deliveries, for CKD, aHR 2.81, 95% CI 2.46-3.20; for ESKD, aHR 6.70, 95% CI 4.70-9.56). However, spontaneous preterm delivery was also associated with increased risk of CKD (aHR 1.32, 95% CI 1.25-1.39) and ESKD (aHR 1.99, 95% CI 1.67-2.38) independent of preeclampsia or small for gestational age (SGA).ConclusionsWomen with history of preterm delivery are at increased risk of CKD and ESKD. The risk is higher among women who had very preterm or extremely preterm deliveries, or whose preterm delivery was medically indicated. Women who experience spontaneous preterm delivery are at increased risk of long-term renal disease independent of preeclampsia or SGA. Preterm delivery may act as a risk marker for adverse maternal renal outcomes.

Project description:BackgroundPreeclampsia and preterm delivery (PTD) are believed to affect women's long-term health including cardiovascular disease (CVD), but the biological underpinnings are largely unknown. We aimed to test whether maternal postpartum metabolomic profiles, especially CVD-related metabolites, varied according to PTD subtypes with and without preeclampsia, in a US urban, low-income multi-ethnic population.MethodsThis study, from the Boston Birth Cohort, included 980 women with term delivery, 79 with medically indicated PTD (mPTD) and preeclampsia, 52 with mPTD only, and 219 with spontaneous PTD (sPTD). Metabolomic profiling in postpartum plasma was conducted by liquid chromatography-mass spectrometry. Linear regression models were used to assess the associations of each metabolite with mPTD with preeclampsia, mPTD only, and sPTD, respectively, adjusting for pertinent covariates. Weighted gene coexpression network analysis was applied to investigate interconnected metabolites associated with the PTD/preeclampsia subgroups. Bonferroni correction was applied to account for multiple testing.ResultsA total of 380 known metabolites were analyzed. Compared to term controls, women with mPTD and preeclampsia showed a significant increase in 36 metabolites, mainly representing acylcarnitines and multiple classes of lipids (diacylglycerols, triacylglycerols, phosphocholines, and lysophosphocholines), as well as a decrease in 11 metabolites including nucleotides, steroids, and cholesteryl esters (CEs) (P < 1.3 × 10-4). Alterations of diacylglycerols, triacylglycerols, and CEs in women with mPTD and preeclampsia remained significant when compared to women with mPTD only. In contrast, the metabolite differences between women with mPTD only and term controls were only seen in phosphatidylethanolamine class. Women with sPTD had significantly different levels of 16 metabolites mainly in amino acid, nucleotide, and steroid classes compared to term controls, of which, anthranilic acid, bilirubin, and steroids also had shared associations in women with mPTD and preeclampsia.ConclusionIn this sample of US high-risk women, PTD/preeclampsia subgroups each showed some unique and shared associations with maternal postpartum plasma metabolites, including those known to be predictors of future CVD. These findings, if validated, may provide new insight into metabolomic alterations underlying clinically observed PTD/preeclampsia subgroups and implications for women's future cardiometabolic health.

Project description:BackgroundPreterm labour and birth (PTL/PTB) is characterised by major health and developmental risks for children, life-changing consequences for their families, and substantial healthcare and economic challenges for wider society. While it is known that PTL/PTB impacts infant healthcare costs in the short and long term in Germany, maternal costs have not been described in detail. The aim of this study was to comprehensively describe costs and resource use among PTL/PTB mothers during pregnancy, at hospitalisation for delivery, and up to three years after delivery-overall and according to gestational age (GA) at delivery.MethodsThis study used data from the Statutory Health Insurance (SHI) sample of the AOK Hessen database in Germany. Mothers aged 12-44 years with deliveries between 2009 and 2013 and > 9 months of medical history prior to delivery were included. PTL/PTB mothers were defined by an International Classification of Diseases, 10th Revision (ICD-10) code for PTL during pregnancy, a diagnosis-related group (DRG) code indicating birthweight < 2500 g, or delivery of an infant < 37 weeks GA. Inpatient and outpatient resource use and total direct medical costs were examined during pregnancy, at delivery hospitalisation, and up to three years post-delivery.ResultsOf all mothers, 2147 (20%) experienced PTL/PTB. During pregnancy, median costs for PTL/PTB mothers were €2130. During delivery hospitalisation, the mean length of stay for all PTL/PTB mothers was 6.0 days, and median costs were €2037. Length of stay and costs declined with increasing GA. Long term, PTL/PTB mothers' total median costs were €607 in Year 1, €332 in Year 2, and €388 in Year 3 post-delivery. In each year after delivery, median costs appeared to be greater for mothers who delivered at lower GAs.ConclusionIn this description of costs and resource use among PTL/PTB mothers in Germany throughout the pregnancy and up to three years after delivery, the greatest costs were noted prior to delivery. Costs appeared to decrease with increasing GA, particularly during the delivery hospitalisation and the first year after delivery.

Project description:OBJECTIVES: We aimed to use simple clinical questions to group women and provide their specific rates of miscarriage, preterm delivery, and stillbirth for reference. Further, our purpose was to describe who has experienced particularly low or high rates of each event. METHODS: Data were collected as part of the Australian Longitudinal Study on Women's Health, a national prospective cohort. Reproductive histories were obtained from 5806 women aged 31-36 years in 2009, who had self-reported an outcome for one or more pregnancy. Age at first birth, number of live births, smoking status, fertility problems, use of in vitro fertilisation (IVF), education and physical activity were the variables that best separated women into groups for calculating the rates of miscarriage, preterm delivery, and stillbirth. RESULTS: Women reported 10,247 live births, 2544 miscarriages, 1113 preterm deliveries, and 113 stillbirths. Miscarriage was correlated with stillbirth (r = 0.09, P<0.001). The calculable rate of miscarriage ranged from 11.3 to 86.5 miscarriages per 100 live births. Women who had high rates of miscarriage typically had fewer live births, were more likely to smoke and were more likely to have tried unsuccessfully to conceive for ≥12 months. The highest proportion of live preterm delivery (32.2%) occurred in women who had one live birth, had tried unsuccessfully to conceive for ≥12 months, had used IVF, and had 12 years education or equivalent. Women aged 14-19.99 years at their first birth and reported low physical activity had 38.9 stillbirths per 1000 live births, compared to the lowest rate at 5.5 per 1000 live births. CONCLUSION: Different groups of women experience vastly different rates of each adverse pregnancy event. We have used simple questions and established reference data that will stratify women into low- and high-rate groups, which may be useful in counselling those who have experienced miscarriage, preterm delivery, or stillbirth, plus women with fertility intent.

Dataset Information

Preterm delivery and long term mortality in women: national cohort and co-sibling study.

Publications

Preterm delivery and long term mortality in women: national cohort and co-sibling study.

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