Treatment of Classic Mid-Trimester Preterm Premature Rupture of Membranes (PPROM) with Oligo/Anhydramnion between 22 and 26 Weeks of Gestation by Means of Continuous Amnioinfusion: Protocol of a Randomized Multicentric Prospective Controlled TRIAL and Review of the Literature

Michael Tchirikov, Christian Haiduk, Miriam Tchirikov, Marcus Riemer, Michael Bergner, Weijing Li, Stephan Henschen, Michael Entezami, Andreas Wienke, Gregor Seliger, Michael Tchirikov, Christian Haiduk, Miriam Tchirikov, Marcus Riemer, Michael Bergner, Weijing Li, Stephan Henschen, Michael Entezami, Andreas Wienke, Gregor Seliger

Abstract

Background: The classic mid-trimester preterm premature rupture of membranes (PPROM) is defined as a rupture of the fetal membranes prior to 28 weeks of gestation (WG) with oligo/anhydramnion; it complicates approximately 0.4-0.7% of all pregnancies and is associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacterial growth, chorioamnionitis and fetal inflammation. The repetitive amnioinfusion does not work because fluid is lost immediately after the intervention. The continuous amnioinfusion through the transabdominal port system or catheter in patients with classic PPROM shows promise by flushing out the bacteria and inflammatory components from the amniotic cavity, replacing amniotic fluid and thus prolonging the PPROM-to-delivery interval.

Objective: This multicenter trial aims to test the effect of continuous amnioinfusion on the neonatal survival without the typical major morbidities, such as severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis one year after the delivery.

Study design: We plan to conduct a randomized multicenter trial with a two-arm parallel design. Randomization will be between 22/0 and 26/0 SSW. The control group: PPROM patients between 20/0 and 26/0 WG who will be treated with antibiotics and corticosteroids (from 22/0 SSW) in accordance with the guidelines of German Society of Obstetrics and Gynecology (standard PPROM therapy). In the interventional group, the standard PPROM therapy will be complemented with the Amnion Flush Method, with the amnioinfusion of Amnion Flush Solution through the intra-amnial catheter (up to 100 mL/h, 2400 mL/day).

Subjects: The study will include 68 patients with classic PPROM between 20/0 and 26/0 WG.

Trial-registration: ClinicalTrials.gov ID: NCT04696003.

German clinical trials register: DRKS00024503, January 2021.

Keywords: Amnion Flush Method; PPROM; amnioinfusion; anhydramnion; neonatal survival; preterm premature rupture of membranes.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
German tertian perinatal centers taking part in the TRIAL.
Figure 2
Figure 2
Flow diagram of the TRIAL.
Figure 3
Figure 3
The schema of Amnion Flush Method.
Figure 4
Figure 4
(A) Amniocentesis with 22G needle and amnioinfusion 300 mL of Amnion Flush Solution (Serumwerk AG, Bernburg, Germany). (B) Amniocentesis with 18G needle under local anesthesia and introduction of the catheter. (C) The intra-amnial catheter (arrow) is covered by Tagaderm film. The rate of intra-amnial infusion is 100 mL/h (Amnion Flush Solution, Serumwerk AG, Bernburg, Germany).
Figure 4
Figure 4
(A) Amniocentesis with 22G needle and amnioinfusion 300 mL of Amnion Flush Solution (Serumwerk AG, Bernburg, Germany). (B) Amniocentesis with 18G needle under local anesthesia and introduction of the catheter. (C) The intra-amnial catheter (arrow) is covered by Tagaderm film. The rate of intra-amnial infusion is 100 mL/h (Amnion Flush Solution, Serumwerk AG, Bernburg, Germany).

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