Clinical trial NCT02702297: Multimodal Monitoring of Fetal Risk of Inflammation in Preterm Premature Rupture of Membranes
Official title: Multimodales Monitoring Des Fetalen Inflammationsrisikos Bei frühem Vorzeitigen Blasensprung (PPROM)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preterm Premature Rupture of Membranes
Fetal Inflammatory Response Syndrome
Early Onset Neonatal Sepsis
Infection of Amniotic Cavity
Keywords: Preterm premature rupture of the membranes
PPROM
PROM
fetal membranes
premature rupture
neonatal early onset sepsis
amniotic fluid
amniotic infection
fetal inflammatory response syndrome
adverse neonatal outcome
FIRS
Lead sponsor: Martin-Luther-Universität Halle-Wittenberg
Sponsor class: OTHER
Collaborators: name: Jena University Hospital
name: University of Leipzig
name: St. Elisabeth Hospital Halle
First posted: 2016-03-08
Enrollment: 57
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with PPROM-complicated pregnancies who referre to one of the participating tertiary referreal care centers.

Brief summary: The purpose of this study is to examine whether the value of vaginal fluid cytokine levels as well as computerized fetal ECG analysis are suitable clinical parameters to detect an imminent intra-amniotic inflammation with a high risk of fetal inflammatory response syndrome (FIRS) or a neonatal early onset sepsis (EOS) and whether these parameters can be determined on a daily basis in the clinical monitoring of pregnancies complicated by PPROM.

Detailed description: Preterm premature rupture of membranes (PPROM) is one of the leading causes for preterm birth and adverse neonatal outcome. Between 24 0/7 and 34 0/7 weeks of gestation the prolongation of pregnancy is the recommended course of action to reduce the risks of prematurity in most countries. An intra-amniotic infection resulting in fetal inflammatory response syndrome (FIRS) or early onset neonatal sepsis (EOS) is often associated with high morbidity and mortality.

Standard monitoring includes the maternal response to inflammation (i.e. maternal serum parameters) as well as fetal signs of acute FIRS (i.e. fetal tachycardia, high cytokine level in amniotic fluid obtained by amniocentesis). Changes of fetal ECG-parameters are also a sign of an acute FIRS.

Currently, there is no adequate parameter for the surveillance of a possible ongoing intra-amniotic infection. Other studies have reported a correlation between vaginal fluid interleukine 6 (IL6) collected noninvasively and the risk of FIRS and EOS. Information obtained by computerized fetal ECG analysis might be suitable to detect early signs of fetal infection before the manifestation of FIRS.

With the implementation of a vaginal fluid collector it is possible to detect the vaginal fluid cytokine in clinical everyday routine. With the improvement of fetal ECG monitoring it is possible to record the fetal ECG daily. This study examines the correlation between these new parameters and the onset of fetal infection before the manifestation of a severe systemic fetal inflammation.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of preterm rupture of the fetal membranes
* Pregnancy between 24 0/7 and 34 0/7 weeks of gestation
* Ability to give informed consent in german or english

Exclusion Criteria:

* Sign of acute amniotic infection syndrome
* independent indication for urgent delivery
* Active labor
* Missing informed consent

Primary outcomes:
measure: Odds ratio for severe fetal/early onset neonatal Infection
timeFrame: postpartum one point assessment/ first three days post partum
Secondary outcomes:
measure: combined neonatal adverse outcome
timeFrame: 28 days
measure: late onset neonatal sepsis
timeFrame: 28 days
measure: Severe neonatal cerebral hemorrhage
timeFrame: 28 days
measure: necrotizing enterocolitis
timeFrame: 28 days
measure: umbilical cord blood IL 6 concentration
timeFrame: first day after delivery
measure: neonatal early onset sepsis
timeFrame: 3 days
measure: histological funisitis
timeFrame: first day after delivery
Other outcomes:
Locations:
city: Halle (Saale)
country: Germany
facility: Maternity Clinic/Perinatal Treatment Center, university hospital, Martin-Luther-Universität Halle-Wittenberg
state: Sachsen-Anhalt
city: Halle
country: Germany
facility: St. Elisabeth Hospital Halle
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: Maternity clinic, University of Leipzig
state: Saxony
city: Jena
country: Germany
facility: Maternity Clinic, Jena University Hospital
state: Thüringen
Study officials:
affiliation: Maternity Clinic/Perinatal Treatment Center, Halle university hospital, Martin-Luther-Universität Halle-Wittenberg
name: Gregor Seliger, Dr. med
role: PRINCIPAL_INVESTIGATOR
affiliation: Maternity Clinic/Perinatal Treatment Center, Halle university hospital, Martin-Luther-Universität Halle-Wittenberg
name: Michael Bergner
role: PRINCIPAL_INVESTIGATOR
affiliation: Maternity Clinic; Jena University Hospital
name: Uwe Schneider, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Maternity Clinic/Perinatal Treatment Center, Halle university hospital, Martin-Luther-Universität Halle-Wittenberg
name: Michael Tchirikov, Prof.
role: STUDY_CHAIR
affiliation: Department of Laboratory Medicine; Halle university hospital, Martin-Luther-Universität Halle-Wittenberg
name: Frank Bernhard Kraus, PD; PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pediatrics; Halle university hospital, Martin-Luther-Universität Halle-Wittenberg
name: Roland Haase, PD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maternity clinic, University of Leipzig
name: Holger Stepan, Prof.
role: PRINCIPAL_INVESTIGATOR
References: