Placental lesions associated with maternal underperfusion are more frequent in early-onset than in late-onset preeclampsia

Objective: Preeclampsia (PE) has been classified into early- and late-onset disease. These two phenotypic variants of PE have been proposed to have a different pathophysiology. However, the gestational age cut-off to define early vs. late PE has varied among studies. The objective of this investigation was to determine the prevalence of lesions consistent with maternal underperfusion of the placenta in patients with PE as a function of gestational age. Study design: A nested case-control study of 8307 singleton pregnant women who deliver after 20 weeks of gestation was constructed based on a cohort. Cases were defined as those with PE (n=910); controls were pregnant women who did not have a hypertensive disorder in pregnancy (n=7397). The frequency of maternal underperfusion of the placenta (according to the criteria of the Society for Pediatric Pathology) was compared between the two groups. Logistic regression was used for analysis. Estimated relative risks (RRs) were calculated from odds ratios. Results: 1) The prevalence of lesions consistent with maternal underperfusion was higher in patients with PE than in the control group [43.3% vs. 15.9%, unadjusted odds ratio 4.0 (95% CI 3.5-4.7); P<0.001]; 2) the estimated RR of maternal underperfusion lesions in PE was higher than in the control group [RR=2.8 (95% CI 2.5-3.0)]; 3) the lower the gestational age at delivery, the higher the RR for these lesions; 4) early-onset PE, regardless of the gestational age used to define it (<32, 33, 34, 35 or 37 weeks) had a significantly higher frequency of placental lesions consistent with maternal underperfusion than late-onset PE (P<0.001 for all). Conclusions: 1) The earlier the gestational age of preeclampsia at delivery, the higher the frequency of placental lesions consistent with maternal underperfusion; 2) our data suggest that demonstrable placental involvement as determined by pathologic examination differs in early-and late-onset preeclampsia; and 3) this phenomenon appears to be a continuum, and we could not identify a clear and unambiguous gestational age at which lesions consistent with underperfusion would not be present.