What are the causes of Preterm Premature Rupture of Membranes (PPROM)?

Causes of Preterm Premature Rupture of Membranes (PPROM)

Preterm Premature Rupture of Membranes (PPROM) is primarily caused by infection and inflammation, with microbial dysbiosis being a key underlying mechanism. 1

Infectious Causes

• Microbial infection is a major contributing factor in PPROM, with subclinical intrauterine infection implicated as a primary etiological factor in 25-40% of cases 2
• Bacterial products and pro-inflammatory cytokines trigger altered membrane morphology including marked swelling and disruption of the collagen network 3
• Persistent vaginal dysbiosis characterized by decreased Lactobacilli and increased pathogenic bacteria such as Prevotella and Peptoniphilus is strongly associated with PPROM 1
• Chorioamnionitis is the most frequent infectious complication, with risk increasing with duration of membrane rupture 4

Inflammatory Mechanisms

• Activation of matrix metalloproteinases (MMPs) has been directly implicated in the mechanism of PPROM, leading to degradation of the extracellular matrix in fetal membranes 3
• Inflammatory mediators play a causative role in both disruption of fetal membrane integrity and activation of uterine contractions 3
• Pro-inflammatory cytokines released during infection contribute to membrane weakening and eventual rupture 1

Maternal Risk Factors

• Group B Streptococcus (GBS) colonization increases risk of PPROM, with GBS found in the urine of 2-7% of pregnant women indicating heavy genital tract colonization 5
• Previous history of PPROM significantly increases risk in subsequent pregnancies, suggesting underlying maternal factors 3
• Cervical insufficiency can contribute to PPROM through increased exposure of membranes to vaginal flora 6
• Uterine abnormalities or scarring may increase susceptibility to membrane rupture 4

Membrane-Specific Pathologies

• Altered membrane morphology with marked swelling and disruption of the collagen network is seen with PPROM 3
• Membrane defects can occur in different patterns, including "classic PPROM" with oligo/anhydramnios, "high PPROM" with membrane defects not over the cervical os, and "pre-PPROM" with rupture of only one membrane (chorionic or amniotic) 3
• Iatrogenic causes such as membrane defects following fetoscopy can lead to "high PPROM" syndrome 3

Clinical Presentation and Diagnosis

• PPROM is diagnosed by identification of nitrazine positive, fern positive watery leakage from the cervical canal during speculum examination 3
• More recent diagnostic tests include vaginal swab assay for placental alpha macroglobulin-1 or AFP and IGFBP1 3
• The majority of women with PPROM will deliver within 7 days following rupture 6

Management Implications

• Expectant management of PPROM increases risk of multiple maternal complications including infection, hemorrhage, and death compared to immediate intervention 5
• In cases of previable and periviable PPROM, 60% of patients experience maternal morbidity regardless of management approach 5
• Antibiotic prophylaxis reduces risk of chorioamnionitis (average risk ratio 0.66), neonatal infections (RR=0.67) and abnormal ultrasound scan of neonatal brain (RR=0.67) 3

Understanding these causes is crucial for developing preventive strategies and optimizing management to improve maternal and neonatal outcomes in PPROM.