Multimodal Monitoring of Fetal Risk of Inflammation in Preterm Premature Rupture of Membranes

Completed

• Conditions: Infection of Amniotic Cavity; Early Onset Neonatal Sepsis; Preterm Premature Rupture of Membranes; Fetal Inflammatory Response Syndrome
• Interventions: Other: single arm

• Registration Number: NCT02702297
• Lead Sponsor: Martin-Luther-Universität Halle-Wittenberg

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.

Study Timeline

• Study Start: 2016-01-07
• Study First Submitted: 2016-02-22
• Study First Submitted QC: 2016-03-02
• Study First Posted: 2016-03-08
• Primary Completion: 2018-02-28
• Status Verified: 2018-11
• Study Completion: 2018-11-10
• Last Update Submitted: 2018-11-12
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 57

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

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Single arm	single arm	daily multimodal monitoring during pregnancy after PPROM, Analysis of neonatal routine parameters and histologic examination of placenta

Primary Outcome Measures

Name	Time	Method
Odds ratio for severe fetal/early onset neonatal Infection	postpartum one point assessment/ first three days post partum	combined outcome - rate of: early onset neonatal sepsis, elevated IL6 concentration in cord blood sample, histological signs of funisitis

Secondary Outcome Measures

Name	Time	Method
necrotizing enterocolitis	28 days	NEC
Severe neonatal cerebral hemorrhage	28 days	IVH II+IV°
combined neonatal adverse outcome	28 days	rate of severe intraventricular hemorrhage, necrotizing enterocolitis, late onset sepsis, white matter damage within the first 28 days of life
late onset neonatal sepsis	28 days	clinical Sepsis after first 72h of life
umbilical cord blood IL 6 concentration	first day after delivery	IL-6-concentration in cord blood sample after delivery or in fetal Serum during first hour of life
neonatal early onset sepsis	3 days	clinical Sepsis during first 72h of life
histological funisitis	first day after delivery	redline maternal stage \>1, fetal stage \>0

Trial Locations

Locations (4)

Maternity Clinic/Perinatal Treatment Center, university hospital, Martin-Luther-Universität Halle-Wittenberg; 🇩🇪 Halle (Saale), Sachsen-Anhalt, Germany

St. Elisabeth Hospital Halle; 🇩🇪 Halle, Sachsen-Anhalt, Germany

Maternity clinic, University of Leipzig; 🇩🇪 Leipzig, Saxony, Germany

Maternity Clinic, Jena University Hospital; 🇩🇪 Jena, Thüringen, Germany