Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome

Abstract

Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long-and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/anhydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane -either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intraamniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR) = 0.66), neonatal infections (RR = 0.67) and abnormal ultrasound scan of neonatal brain (RR = 0.67)]. The positive effect of continuo...

Preterm premature rupture of membranes: Which criteria contraindicate home care management?

“…PPROM was diagnosed on a visualization of amniotic fluid loss and/or was confirmed by the use of a PROM test (Actim PROM®, Medix Biochemica, Espoo, Finland) . We did not differentiate “classic” or “high” PPROM, as recently proposed by Tchirikov et al Gestational age was determined from the first‐trimester ultrasound. The latency period was set between the date of PPROM occurrence and the date of delivery.…”

“…It is associated with quite important perinatal morbidity and mortality, especially prematurity . In the absence of severity criteria, current guidelines are based on hospital surveillance in an adequate maternity ward, up to 36 weeks of gestation, for labor induction …”

Human β‐defensin‐1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra‐amniotic infection

“…Intra-amniotic infection was defined as the presence of MIAC with intra-amniotic inflammation 77, 118, 120, 121, 124–138 . Preterm prelabor rupture of membranes (pPROM) had to occur prior to the onset of labor before 37 weeks and was diagnosed by vaginal pooling of amniotic fluid, amniotic fluid ferning patterns, and a positive nitrazine test 139–142 .…”

“…77,118,120,121,[124][125][126][127][128][129][130][131][132][133][134][135][136][137][138] Preterm prelabor rupture of membranes (pPROM) had to occur prior to the onset of labor before 37 weeks and was diagnosed by vaginal pooling of amniotic fluid, amniotic fluid ferning patterns, and a positive nitrazine test. [139][140][141][142] glucose concentration, 143 Gram stain, 144 and IL-6 concentration. 118…”

Microbial burden and inflammasome activation in amniotic fluid of patients with preterm prelabor rupture of membranes

“…Positive culture with low IL-6 (n = 14) defined as amniorrhexis confirmed by vaginal pooling, ferning, or a positive nitrazine test prior to the onset of labor before 37 weeks of gestation [117][118][119][120]. Intra-amniotic inflammation was defined using an established cutoff for amniotic fluid concentrations of IL-6 [14], where concentrations >2.6 ng/mL indicate intra-amniotic inflammation and concentrations <2.6 ng/mL are considered as no inflammation.…”