Computerized Cardiotocography Monitoring of Fetuses With pPROM (COCA-PROM)

Computerized Cardiotocography Monitoring in Fetuses With Preterm Premature Rupture of Membranes

Preterm premature rupture of membranes (PPROM) is associated with neonatal complications leading to a high rate of cerebral palsy, sepsis, and death. Choosing the best time of delivery is crucial to improve fetal outcome. The balance is between a premature delivery exposing the infant to all the risk of prematurity, and keeping the baby in utero, prolonging the exposure to an adverse intrauterine milieu. There are no objective and reproducible tools to help in this decision-making process. Techniques most frequently used for fetal surveillance are biased by high inter- and intra-observer variability. Computerized cardiotocography (cCTG) identifies several objective parameters related to fetal heart rate (FHR) to determine fetal well-being. cCTG has been successfully used in fetuses with intrauterine growth restriction, but it has never been used in prospective studies to assess its role in the management of fetuses with PPROM. The investigators designed a case control study to highlight cCTG differences in PPROM pregnancies versus physiological pregnancies, to establish the effectiveness in predicting adverse outcome, and to develop a score to predict neonatal outcome.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Premature Birth; Premature Rupture of Membrane; Cardiotocography; Rupture of Membranes; Premature
• Intervention / Treatment: Diagnostic test: Computerized cardiotocography

Detailed Description

Preterm premature rupture of membranes (PPROM) occurs in 2 to 3% of pregnancies and is associated with higher maternal and neonatal morbidity and mortality. Neonatal complications are primarily due to prematurity and to ascending infection of the amniotic cavity (chorioamnionitis), leading to a high rate of cerebral palsy, intracranial hemorrhage, sepsis, pneumonia, and death. Every physician is confronted with an extremely difficult and at the same time of paramount importance decision, when it comes to establish the timing of the delivery of a premature fetus with PPROM. The balance is between delivering a premature infant exposed to all the risk of prematurity, and keeping the baby in utero, prolonging the exposure to an adverse intrauterine milieu. At present, there are no objective and reproducible tools to help in this decision-making process. The technique most frequently used for fetal surveillance is cardiotocography (CTG). Assessment of the fetal heart rate is classified subjectively as 'reassuring' or 'not reassuring'. Dawes and Redman have suggested computerized CTG (cCTG), which eliminates inter- and intra-observer variability, identifying several objective parameters to determine fetal well-being. After the multicentre TRUFFLE-Study, cCTG became the best tool to manage fetuses with intrauterine growth restriction (IUGR). However, the use of cCTG has never been investigated in prospective studies to assess its role in the management of fetuses with PPROM. Of note, amniotic fluid concentration of glucose, lactate, interleukin-6 (IL-6), and matrix metalloproteinase-8 (MMP-8) have been associated with neonatal septicemia, chorioamnionitis, preterm birth, and/or fetal inflammatory response syndrome in women with pPROM.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Maddalena Morlando, MD; Phone Number: +39 333 426 3110; Email: madmorlando@gmail.com
• Study Contact Backup: Name: Fabiana Savoia, MD; Email: dott.fabianasavoia@gmail.com

Study Locations

• Italy
  • Naples, Italy, 80138
    • Recruiting
    • University of Campania "Luigi Vanvitelli"
    • Contact: Maddalena Morlando, MD; Phone Number: +39 333 426 3110; Email: madmorlando@gmail.com
    • Contact: Fabiana Savoia, MD; Email: dott.fabianasavoia@gmail.com
    • Sub-Investigator: Antonio Schiattarella, MD
    • Sub-Investigator: Anna Conte, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Singleton pregnancies admitted for pPROM to the Obstetrics ward of this Hospital will be recruited after informed consent.

Description

Inclusion Criteria:

• pPROM between 24 and 34 weeks (w)

Exclusion Criteria:

• multiple pregnancy, structural fetal anomalies, preexisting or gestational diabetes mellitus and\or hypertension, intrauterine growth restriction.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
pPROM; Singleton pregnancies admitted for pPROM to the Obstetrics ward	Diagnostic test: Computerized cardiotocography; To compare Dawes and Redman indices as determined by computer analysis of the fetal heart tracing
Control group; Healthy pregnant women matched for gestational age	Diagnostic test: Computerized cardiotocography; To compare Dawes and Redman indices as determined by computer analysis of the fetal heart tracing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Preterm birth rate	Less than 37 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age at delivery		Time of delivery
Preterm birth rates		Less than 24, 28, 34 weeks gestation
Birth weight	Weight of the baby at the time of delivery	Time of delivery
Low birth weight rate	Birth weight <2500g	Time of delivery
Neonatal death rate		Between birth and 28 days of age
Composite adverse neonatal outcomes	Number of neonates who will have at least one of the following: necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) (grade 3 or higher), respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), retinopathy (ROP), blood-culture proven sepsis and neonatal death	Between birth and 28 days of age
Maternal outcomes	Number of mothers who will have at least one of the following: sepsis, histological chorioamnionitis, hysterectomy, intensive care unit admission.	Between birth and 28 days after the birth
Dawes and Redman indices	determined by computer analysis of the fetal heart tracing	between 24 and 34 weeks of gestation

Collaborators and Investigators

• Sponsor: University of Campania "Luigi Vanvitelli"
• Investigators: Study Chair: Antonio Schiattarella, MD, University of Campania "Luigi Vanvitelli"

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Anticipated): March 30, 2021
• Study Completion (Anticipated): July 30, 2021

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: premature birth; cardiotocography; Premature Rupture of Membrane; computerized cardiotocography
• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Rupture; Premature Birth; Fetal Membranes, Premature Rupture
• Other Study ID Numbers: 8452 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No