Predicting EONS in PPROM Patients

Study Overview
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Brief Summary
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An EONS occurred in nearly 14-22 % of the preterm infant of pregnant women with PPROM. To this day no risk prediction is established. The main aim of this pilot study is generating primary data with a focus on the vaginal microbiome to set-up a prospective, multi-centre trial investigating the role of the vaginal microbiome for future EONS risk prediction. The planned PEONS pilot trial is subdivided in three Work packages: Recruitment, sample collection and routine clinical diagnostics Microbiome analysis by 16S rRNA Microbiome/ Metagenome analysis by Nanopore (proof-of-principle) and will enroll women with a PPROM event hospitalized between 22+0 and 34+0 weeks of gestation and neonates with signs of EONS (Subgroup 1) and without signs of EONS (Subgroup 2).

Official Title
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Prediction of Early-Onset Neonatal Sepsis (EONS) in Pregnant Women With Preterm Premature Rupture of Membranes (PPROM) by Vaginal Microbiome Analysis - a Pilot Study

Conditions
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PPROM, Early-Onset Neonatal Sepsis

Intervention / Treatment
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* Diagnostic Test: microbiome analysis
* Diagnostic Test: Conventional cultures
* Diagnostic Test: CAAP48 measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: full age pregnant woman with PPROM and their born preterm infants hospitalization between 22+0 and 34+0 weeks of gestation multipara possible Exclusion Criteria: hospitalization with PPROM before limit of viability are reached intrauterine fetal death no study agreement not able to consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| neonates with signs of EONS<br> | Diagnostic Test: microbiome analysis<br>* From all full age pregnant women with PPROM enrolled in this study vaginal smear samples will be taken at three time points: directly after hospitalization 5-7 days after beginning of antibiotic treatment 24 h before birth The microbiome of the neonates of these women will be analysed out of pharyngeal and rectal swabs and umbilical cord blood taken directly after birth and additionally out of the first Meconium.<br>Diagnostic Test: Conventional cultures<br>* For every sample taken for microbiome analysis, a conventional culture is taken as control.<br>Diagnostic Test: CAAP48 measurement<br>* CAAP48 is an identified sepsis marker in adult patients. The samples are taken dependent on clinical monitoring to compare CAAP48 with established inflammation markers (CRP, IL-6, White blood cell count, Procalcitonin).<br>|
| neonates without signs of EONS<br> | Diagnostic Test: microbiome analysis<br>* From all full age pregnant women with PPROM enrolled in this study vaginal smear samples will be taken at three time points: directly after hospitalization 5-7 days after beginning of antibiotic treatment 24 h before birth The microbiome of the neonates of these women will be analysed out of pharyngeal and rectal swabs and umbilical cord blood taken directly after birth and additionally out of the first Meconium.<br>Diagnostic Test: Conventional cultures<br>* For every sample taken for microbiome analysis, a conventional culture is taken as control.<br>Diagnostic Test: CAAP48 measurement<br>* CAAP48 is an identified sepsis marker in adult patients. The samples are taken dependent on clinical monitoring to compare CAAP48 with established inflammation markers (CRP, IL-6, White blood cell count, Procalcitonin).<br>|
| pregnant women with PPROM<br> | Diagnostic Test: microbiome analysis<br>* From all full age pregnant women with PPROM enrolled in this study vaginal smear samples will be taken at three time points: directly after hospitalization 5-7 days after beginning of antibiotic treatment 24 h before birth The microbiome of the neonates of these women will be analysed out of pharyngeal and rectal swabs and umbilical cord blood taken directly after birth and additionally out of the first Meconium.<br>Diagnostic Test: Conventional cultures<br>* For every sample taken for microbiome analysis, a conventional culture is taken as control.<br>Diagnostic Test: CAAP48 measurement<br>* CAAP48 is an identified sepsis marker in adult patients. The samples are taken dependent on clinical monitoring to compare CAAP48 with established inflammation markers (CRP, IL-6, White blood cell count, Procalcitonin).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of EONS | Primary outcome is the development of EONS defined as the presence of confirmed or suspected sepsis at ≤3 days after birth for which prolonged neonatal antibiotic treatment beyond 72 hours. Confirmed sepsis is established by positive blood cultures whilst suspected sepsis is diagnosed in the presence of clinical suspicion of sepsis (lethargy, apnoea, respiratory distress, hypotension (mean arterial blood pressure (MAD) < gestational age), hypoperfusion and shock) supported by elevated neonatal C-reactive protein (CRP), interleukin-6 (IL6) or blood film suggestive of bacteraemia. | 3 days after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vaginal CST in PPROM | the specific patterns of vaginal CST and vaginal microbiota composition (microbiome) in PPROM | until delivery | 
| neonatal microbial colonisation | neonatal microbial colonisation (microbiome) on 1st and 2nd day of life | up to 2 days after delivery |