Cardiovascular events following pregnancy complicated by pre‐eclampsia with emphasis on comparison between early‐ and late‐onset forms: systematic review and meta‐analysis
Authors: Dall'Asta A. , D'Antonio F. , Saccone G. , Buca D. , Mastantuoni E. , Liberati M. , Flacco M. E. , Frusca T. , Ghi T. 
Published: June 2020

ABSTRACTObjectiveTo elucidate whether pre‐eclampsia (PE) and the gestational age at onset of the disease (early‐ vs late‐onset PE) have an impact on the risk of long‐term maternal cardiovascular complications.MethodsMEDLINE, EMBASE and Scopus databases were searched until 15 April 2020 for studies evaluating the incidence of cardiovascular events in women with a history of PE, utilizing combinations of the relevant MeSH terms, keywords and word variants for ‘pre‐eclampsia’, ‘cardiovascular disease’ and ‘outcome’. Inclusion criteria were cohort or case–control design, inclusion of women with a diagnosis of PE at the time of the first pregnancy, and sufficient data to compare each outcome in women with a history of PE vs women with previous normal pregnancy and/or in women with a history of early‐ vs late‐onset PE. The primary outcome was a composite score of maternal cardiovascular morbidity and mortality, including cardiovascular death, major cardiovascular and cerebrovascular events, hypertension, need for antihypertensive therapy, Type‐2 diabetes mellitus, dyslipidemia and metabolic syndrome. Secondary outcomes were the individual components of the primary outcome analyzed separately. Data were combined using a random‐effects generic inverse variance approach. MOOSE guidelines and the PRISMA statement were followed.ResultsSeventy‐three studies were included. Women with a history of PE, compared to those with previous normotensive pregnancy, had a higher risk of composite adverse cardiovascular outcome (odds ratio (OR), 2.05 (95% CI, 1.9–2.3)), cardiovascular death (OR, 2.18 (95% CI, 1.8–2.7)), major cardiovascular events (OR, 1.80 (95% CI, 1.6–2.0)), hypertension (OR, 3.93 (95% CI, 3.1–5.0)), need for antihypertensive medication (OR, 4.44 (95% CI, 2.4–8.2)), dyslipidemia (OR, 1.32 (95% CI, 1.3–1.4)), Type‐2 diabetes (OR, 2.14 (95% CI, 1.5–3.0)), abnormal renal function (OR, 3.37 (95% CI, 2.3–5.0)) and metabolic syndrome (OR, 4.30 (95% CI, 2.6–7.1)). Importantly, the strength of the associations persisted when considering the interval (< 1, 1–10 or > 10 years) from PE to the occurrence of these outcomes. When stratifying the analysis according to gestational age at onset of PE, women with previous early‐onset PE, compared to those with previous late‐onset PE, were at higher risk of composite adverse cardiovascular outcome (OR, 1.75 (95% CI, 1.0–3.0)), major cardiovascular events (OR, 5.63 (95% CI, 1.5–21.4)), hypertension (OR, 1.48 (95% CI, 1.3–1.7)), dyslipidemia (OR, 1.51 (95% CI, 1.3–1.8)), abnormal renal function (OR, 1.52 (95% CI, 1.1–2.2)) and metabolic syndrome (OR, 1.66 (95% CI, 1.1–2.5).ConclusionsBoth early‐ and late‐onset PE represent risk factors for maternal adverse cardiovascular events later in life. Early‐onset PE is associated with a higher burden of cardiovascular morbidity and mortality compared to late‐onset PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.