What is the pathophysiology of postpartum preeclampsia in women with or without a history of preeclampsia during pregnancy?

Pathophysiology of Postpartum Preeclampsia

Postpartum preeclampsia results from the same fundamental pathophysiologic mechanisms as antepartum preeclampsia—placental hypoxia triggering excessive anti-angiogenic factor release and systemic endothelial dysfunction—but manifests after delivery due to withdrawal of placental vasodilatory hormones, rapid volume shifts, and persistent vascular injury that unmasks or exacerbates the underlying disease process. 1

Core Pathophysiologic Mechanisms

The pathophysiology operates through a two-stage process that continues into the postpartum period:

Stage 1: Placental Origin (Initiated During Pregnancy)

• Abnormal placentation occurs with shallow cytotrophoblast invasion and incomplete spiral artery remodeling, creating high-resistance uteroplacental circulation and placental hypoxia 1, 2
• This placental ischemia triggers release of pathogenic factors including excessive soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) into maternal circulation 1
• These anti-angiogenic proteins antagonize vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), creating an angiogenic imbalance that persists even after placental delivery 2

Stage 2: Maternal Systemic Response (Continues Postpartum)

• The angiogenic imbalance causes widespread endothelial dysfunction affecting kidneys (glomerular endotheliosis with proteinuria), liver (hepatic ischemia with elevated transaminases), brain (cerebral edema causing headaches and seizures), and vasculature (systemic vasoconstriction) 1, 2
• Systemic inflammation and oxidative stress perpetuate endothelial injury beyond delivery 2
• Deficient natriuretic peptide signaling contributes to impaired vascular adaptation and volume regulation 1

Postpartum-Specific Pathophysiologic Factors

Hemodynamic Changes After Delivery

• Withdrawal of placental vasodilatory hormones (progesterone, relaxin, natriuretic peptides) after placental delivery causes increased systemic vascular resistance and rising blood pressure 1
• Peak systolic BP occurs on postpartum days 3-5 and peak diastolic BP on days 5-7, explaining the typical timing of postpartum preeclampsia presentation 1
• Rapid mobilization of interstitial fluid into the vascular space increases circulating volume, challenging already compromised endothelial function 1

Persistent Vascular Injury

• Endothelial dysfunction initiated during pregnancy does not immediately resolve after placental delivery, with circulating anti-angiogenic factors and inflammatory mediators remaining elevated 2
• The stressed endothelium has reduced capacity to produce vasodilators (nitric oxide, prostacyclin) due to ongoing sFlt-1 antagonism of VEGF 2
• Attenuated reductions in systemic vascular resistance and impaired tolerance to volume shifts persist postpartum 1

Iatrogenic Contributions

• Administration of IV fluids for postpartum hemorrhage can precipitate hypertensive crisis in women with compromised endothelial function 1
• Ergot derivatives used for uterine atony cause vasoconstriction that may unmask or worsen underlying preeclamptic pathophysiology 1

Additional Pathophysiologic Contributors

Renin-Angiotensin System Dysregulation

• Circulating AT1 receptor autoantibodies present in >95% of preeclamptic women induce vasoconstriction, hypertension, and increased coagulation, with effects persisting postpartum 2
• These antibodies bind the AT1 receptor, triggering downstream signaling that promotes endothelial dysfunction 2

Genetic and Constitutional Factors

• Maternal genetic susceptibility influences whether placental dysfunction progresses to clinical disease, with family history conferring 2.9-fold increased risk 2
• Women with underlying cardiovascular vulnerability (insulin resistance, thrombophilias, chronic inflammation) are more likely to manifest postpartum preeclampsia when stressed by pregnancy-induced vascular changes 2

Coagulation Abnormalities

• Activation of the coagulation cascade with fibrin deposition in hepatic sinusoids and other vascular beds contributes to organ dysfunction 1
• Microangiopathic changes can progress postpartum, particularly in HELLP syndrome 1

Clinical Implications of Pathophysiology

Timing and Presentation

• Most postpartum preeclampsia occurs within 7-10 days after delivery, coinciding with peak postpartum BP and maximal volume shifts 3, 4
• De novo postpartum preeclampsia (occurring in women without antepartum disease) represents 55% of cases, suggesting the pathophysiologic substrate was present but subclinical during pregnancy 5
• Cases can occur up to 6 weeks postpartum, though late presentations beyond 4 weeks are uncommon 6, 3

Organ System Manifestations

• Neurologic symptoms (headache, visual changes) are most common, reflecting cerebral edema from endothelial dysfunction 5, 3
• Renal involvement manifests as proteinuria and decreased GFR, with glomerular endotheliosis as the pathognomonic lesion 2, 7
• Hepatic dysfunction causes right upper quadrant pain and elevated liver enzymes from ischemic injury 1, 8
• Pulmonary edema can occur from capillary leak and volume overload in severely compromised endothelium 4

Risk Amplification

• Women with recurrent preeclampsia have more severe endothelial injury and 3-fold higher cardiovascular risk, indicating cumulative vascular damage 2
• Severe preeclampsia features during pregnancy predict more profound postpartum pathophysiology 2

Long-Term Pathophysiologic Sequelae

• The endothelial dysfunction and vascular remodeling associated with preeclampsia do not fully resolve, contributing to 75% increased lifetime cardiovascular mortality 2
• Accelerated atherosclerosis develops, with women showing higher coronary artery calcium scores and 2.5-fold increased coronary disease risk 2
• Persistent microvascular dysfunction increases risk of chronic kidney disease, stroke, and metabolic syndrome 1, 8, 7