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

Abstract

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’ versus ‘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 8,307 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=7,397). 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 were calculated from adjusted 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 relative risk of maternal underperfusion lesions in PE was higher than in the control group; 3) the lower the gestational age at delivery, the higher the relative risk 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 suggests 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.

Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary

“…Such early intervention has the greatest potential to decrease early forms of preeclampsia. 32 Women at low risk of preeclampsia have usually been from unselected populations of nulliparous and multiparous women. …”

Hypoxic Patterns of Placental Injury: A Review

“…I regard the abovepresented extravillous trophoblasts lesions, along with the decidual arteriolopathy (both hypertrophic and atherosis), as the complementary criteria for this type of chronic placental hypoxia in histologically borderline cases. 21 The UH and associated histologic findings cluster with severe preeclampsia, but not with mild preeclampsia; gestational hypertension; hemolysis, elevated liver enzymes, and low platelets (HELLP); or eclampsia 56 There is growing evidence that there are basic differences in the pathogenesis of mild and severe preeclampsia, the former usually occurring as a late onset, and the latter, usually having an early onset, [57][58][59][60] to which we recently contributed the molecular basis. 61 The postuterine (PU) (postplacental) pattern of chronic hypoxic placental injury is due to primary villous changes resulting in decreased intake of oxygen from the intervillous space, as in retained stillbirth (Figure 2, C), subsets of FGR (Figure 2, D) and preeclampsia, and fetal thrombotic vasculopathy (only focally) 13,38 (Figure 2, E).…”

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

“…A defect of deep placentation [9][10][11][12][13] is proposed to generate utero-placental ischemia [14][15][16], placental endoplasmic reticulum and oxidative stress [17][18][19][20][21][22], and subsequently systemic intravascular inflammation [23][24][25] and endothelial dysfunction [17,[26][27][28][29][30][31][32][33][34]. The circulating concentrations of pro-inflammatory cytokines, such as interleukin (IL)-1-b and tumor necrosis factor (TNF)-a [35][36][37][38][39], as well as other inflammatory mediators (such as IL-6) [36,[40][41][42] are typically elevated in patients with preeclampsia, although this is not a universal feature [43,44].…”