Placental Lesions Associated With Maternal Underperfusion Are More Frequent in Early-Onset Than in Late-Onset Preeclampsia

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Preeclampsia (PE) has been classified as early- and late-onset disease based on the gestational age at diagnosis or delivery. Early-onset disease is associated with higher perinatal and maternal morbidity and mortality than late-onset disease. It has been suggested that these 2 phenotypic variants may have a different pathophysiology and that differentiating early- and late-onset diseases may have prognostic value. However, no clear gestational age cut-offs have been identified to differentiate early from late disease. Inadequate perfusion of the placenta and the resulting ischemia are considered to be key mechanisms of disease in PE.

The aim of this retrospective nested case-control study was to determine the prevalence of lesions suggestive of maternal underperfusion of the placenta among patients with PE as a function of gestational age. The participants were 8307 pregnant singleton women who delivered after 20 weeks of gestation at a hospital in Chile between 1997 and 2007. PE cases included 910 patients (743 who developed PE and 167 with PE superimposed on chronic hypertension). The control group was composed of 7397 pregnant women without a hypertensive disorder. The prevalence of placental lesions consistent with maternal underperfusion in the 2 groups was compared using criteria of the Society for Pediatric Pathology. Multiple logistic regression was used to estimate associations between PE cases and controls at different gestational ages, adjusting for potential covariates.

Patients in the PE group had a significantly higher prevalence of pathologic findings consistent with maternal underperfusion compared with those in the control group (43.3%


vs. 15.9%


); the unadjusted odds ratio was 4.0, with a 95% confidence interval of 3.5 to 4.7 and the estimated relative risk was 2.8, with a 95% confidence interval of 2.5 to 3.0, P < 0.001. Lowering gestational age of PE at delivery was associated with increased frequency of placental lesions consistent with maternal underperfusion. These differences between cases and controls were found for all gestational age cut-offs examined to define early-onset PE (<32, 33, 34, 35 or 37 weeks) (P < 0.001 for all).

These findings demonstrate that placental lesions consistent with maternal underperfusion are more prevalent in early-onset than in late-onset PE and support the hypothesis that these 2 phenotypic variants have different pathophysiology. The data show no definitive gestational age cutoff at which lesions consistent with underperfusion are not present.

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