Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study

Abstract

ObjectivesPreeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors.MethodsWe recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0–13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population.ResultsThe risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7–11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1–60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1–60.6), intermediate onset (delivery between 34+0–36+6 weeks of gestation) to 25.1-fold (95%CI 3.1–79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0–52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1–3.6). Together with preeclampsia in an earlier pregnancy the risk increased to 11.4 (95%CI 4.5–20.9). Chronic hypertension (n = 60) increased the risk of preeclampsia 5.3-fold (95%CI 2.4–9.8), of severe preeclampsia 22.2-fold (95%CI 9.9–41.0), and risk of early-onset preeclampsia 16.7-fold (95%CI 2.0–57.6). If a woman had chronic hypertension combined with obesity, gestational diabetes and earlier preeclampsia, the risk of term preeclampsia increased 4.8-fold (95%CI 0.1–21.7). Women with type 1 diabetes mellitus had a high risk of all subgroups of preeclampsia.ConclusionThe risk of preeclampsia increases exponentially with respect to the number of risk factors. Early-onset preeclampsia and severe preeclampsia have different risk profile from term preeclampsia.

Postmortem examination protocol and systematic re-evaluation reduce the proportion of unexplained stillbirths

“…This reflects the substantial proportion of high-risk pregnancies referred to our tertiary unit. The incidence of placenta-related pregnancy complications (pre-eclampsia, placental abruption, fetal growth restriction) in our cohort differed from that seen in earlier studies of Finnish pregnant women, such as pre-eclampsia of 2.5% [19], SGA of 2.0% [20], and placental abruption of 0.4% [21]. In our current study population, the rates were nearly four-fold for preeclampsia, nearly 40-fold for placental abruption, and 16-fold for SGA.…”

Pre-eclampsia/Eclampsia

“…21,22 Other changes of risk are chronic hypertension, pregestational diabetes, and systemic lupus erythematosus. 20,23 The association of pre-eclampsia with obesity may stem from the chronic state of systemic inflammation and, as the body mass index (BMI) increases, the activation of inflammatory pathways at the maternalfetal interface is also exacerbated. 21,24,25…”

Pathophysiology and Current Clinical Management of Preeclampsia

“…What is becoming more apparent is that despite the unknown etiology of PE, women with obesity or a high body mass index (BMI: >30 kg/m 2 ) [39, 40], chronic hypertension, diabetes and systemic lupus erythematosus (SLE) prior to pregnancy are more susceptible to the development of PE [41, 42]. As obesity represents a chronic state of low-grade inflammation, is a risk factor for PE [39, 43, 44].…”