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Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study

BACKGROUND: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypert...

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Autores principales: Huang, Chen, Li, Jiong, Qin, Guoyou, Liew, Zeyan, Hu, Jing, László, Krisztina D., Tao, Fangbiao, Obel, Carsten, Olsen, Jørn, Yu, Yongfu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478255/
https://www.ncbi.nlm.nih.gov/pubmed/34582464
http://dx.doi.org/10.1371/journal.pmed.1003805
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author Huang, Chen
Li, Jiong
Qin, Guoyou
Liew, Zeyan
Hu, Jing
László, Krisztina D.
Tao, Fangbiao
Obel, Carsten
Olsen, Jørn
Yu, Yongfu
author_facet Huang, Chen
Li, Jiong
Qin, Guoyou
Liew, Zeyan
Hu, Jing
László, Krisztina D.
Tao, Fangbiao
Obel, Carsten
Olsen, Jørn
Yu, Yongfu
author_sort Huang, Chen
collection PubMed
description BACKGROUND: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited. METHODS AND FINDINGS: We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare. CONCLUSIONS: Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.
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spelling pubmed-84782552021-09-29 Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study Huang, Chen Li, Jiong Qin, Guoyou Liew, Zeyan Hu, Jing László, Krisztina D. Tao, Fangbiao Obel, Carsten Olsen, Jørn Yu, Yongfu PLoS Med Research Article BACKGROUND: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited. METHODS AND FINDINGS: We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare. CONCLUSIONS: Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring. Public Library of Science 2021-09-28 /pmc/articles/PMC8478255/ /pubmed/34582464 http://dx.doi.org/10.1371/journal.pmed.1003805 Text en © 2021 Huang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Huang, Chen
Li, Jiong
Qin, Guoyou
Liew, Zeyan
Hu, Jing
László, Krisztina D.
Tao, Fangbiao
Obel, Carsten
Olsen, Jørn
Yu, Yongfu
Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study
title Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study
title_full Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study
title_fullStr Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study
title_full_unstemmed Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study
title_short Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study
title_sort maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: a national population-based cohort study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478255/
https://www.ncbi.nlm.nih.gov/pubmed/34582464
http://dx.doi.org/10.1371/journal.pmed.1003805
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