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

Date Published: March 28, 2017

Publisher: Public Library of Science

Author(s): Pia M. Villa, Pekka Marttinen, Jussi Gillberg, A. Inkeri Lokki, Kerttu Majander, Maija-Riitta Ordén, Pekka Taipale, Anukatriina Pesonen, Katri Räikkönen, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Nandor Gabor Than.


Preeclampsia 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.

We 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.

The 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.

The 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.

Partial Text

Preeclampsia affects 3%[1] of all pregnancies. It is a systemic disease with a multifactorial background. Preeclampsia is diagnosed when a pregnant woman develops hypertension and proteinuria after 20 weeks of gestation. Recent recommendation by the American College of Obstetricians and Gynecologists [2] further proposes that in the absence of proteinuria, preeclampsia could be diagnosed when newly diagnosed hypertension occurs in association with thrombocytopenia, impaired liver function, new development of renal insufficiency, pulmonary edema, or new-onset cerebral or visual disturbances.

Of the 903 women 86 (9.5%) developed preeclampsia. Of those with preeclampsia 10 (11.6%) had early-onset disease and 36 (41.9%) severe disease. 465 women (51.5%) did not meet any of the primary or secondary outcome criteria whereas 438 (48.5%) had one or more of these pregnancy complications (Table 3).

In this study the risk of preeclampsia increased exponentially as the number of risk factors increased. Women who developed preterm or severe preeclampsia had a different risk profile than those who developed term preeclampsia. Previous preeclampsia, chronic hypertension, and type 1 diabetes mellitus were strong risk factors for severe and preterm preeclampsia in our cohort. SGA newborn in an earlier pregnancy was a strong risk factor for early-onset preeclampsia. Obesity increased the risk of term preeclampsia and severe preeclampsia. Neither age below 20 years nor age over 40 years, gestational diabetes or fetal demise as a sole risk factors predicted increased risk.




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