New Tool to Predict Risk of Spontaneous Preterm Birth in Asymptomatic High-risk Women

Study Overview
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Brief Summary
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The QUIPP tool integrates information of obstetrical history, quantitative fetal fibronectin (qfFN) and cervical length to predict the risk of sPTB in asymptomatic high-risk women. The aim of this study is to evaluate the QUIPP tool in our setting in order to optimize the management of women at high risk for sPTB and to validate in a randomized clinical trial, whether the use of QUIPP improves efficiently the management of our asymptomatic high-risk women when it is compared with the current clinical management. Design: Randomized controlled trial. Inclusion criteria: Asymptomatic singleton pregnancies 18,0-22,6 weeks at high-risk for sPTB. Sample size: According to a non-inferiority analysis, 129 pregnant women will be needed for each arm. Methodology: Patient selection and who consent to participate in the study will be randomized into two arms: a) Intervention group: QUIPP tool will be used to select and manage patients attending our PBPC: high-risk patients will be followed-up in our PBPC and low-risk patients will be discharged from PBPC and managed in a low-risk unit. b) Control group: Women will be managed according to current clinical practice. Main Outcome: sPTB <34,0 and <37,0 weeks of gestation. Secondary Outcomes: Pregnancy outcomes and a neonatal composite morbidity. Expected Results: Perinatal outcomes are similar in the intervention and control group although the intervention group using the QUIPP tool required less medical resources.

Detailed Description
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Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Women at high-risk of preterm birth are those with a previous spontaneous preterm birth (sPTB) or preterm premature rupture of membranes before 35 weeks of gestation, uterine malformation, surgery on uterine cervix or a short cervical length; these women have a global risk of PTB about 30% but still 75%-85% of these women will deliver at term without any intervention. The availability of a specialized Preterm Birth Prevention Clinic (PBPC) is relevant for the management of these high-risk pregnant women and it results in a reduction in the risk of recurrent sPTB, pregnancy prolongation and a reduction in the rate of major neonatal morbidity. However, it implies higher outpatient care costs as well as trained personnel and intensive follow-up management even for those women not destined to deliver preterm QUIPP is a free smartphone application that integrates the obstetrical history of high-risk women, the cervical length and the value of quantitative fetal fibronectin to predict the risk of preterm birth. QUIPP will determinate the risk of preterm birth in these high-risk women. Patients will be randomized in two groups: Intervention group (QUIPP tool arm): QUIPP tool is applied and patients with a high-risk result will be follow-up in a high-risk unit (PBPC) and patients with a low-risk value will be managed in a low-risk unit. Control group (no QUIPP tool arm): current management in a PBPC will be applied. The use of QUIPP will allow determining which asymptomatic pregnancies with risk factors for sPTB will deliver preterm. Furthermore, we expect to provide the non-specialized clinician with an objective, useful, accurate and efficient tool to manage these women with same pregnancy and neonatal outcomes and using less resource.

Official Title
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New Tool to Predict Risk of Spontaneous Preterm Birth in Asymptomatic High-risk Women

Conditions
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PreTerm Birth

Intervention / Treatment
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* Device: QUIPP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Asymptomatic singleton pregnancies, with at least one of the following: Previous spontaneous preterm delivery or a preterm premature rupture of membranes ≤ 346 weeks of gestation, Previous spontaneous second trimester miscarriage, Previous surgery on uterine cervix, Incidental finding of cervical length less than 25mm, Uterine malformations. Able to sign informed consent form. Exclusion Criteria: Multiple pregnancies. Congenital, chromosomal abnormalities or stillbirth in current pregnancy. No patient consent to participate in the study Women with an obstetrical history of iatrogenic preterm birth indicated for maternal or fetal conditions. Symptomatic high-risk women or preterm prelabor rupture of membranes in current pregnancy. Pregnant women with an indication of prophylactic cervical cerclage due to her own obstetrical history. Pregnant women with a short cervix detected by ultrasound and with an indication to perform a cervical cerclage, prior to study inclusion.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group: QUIPP tool arm<br>In this group, QUIPP tool will be used to select and manage patients attending our PBPC: high-risk patients will be followed-up in our PBPC and low-risk patients will be discharged from PBPC and managed in a low-risk unit. | Device: QUIPP<br>* Information required by QUIPP tool will be introduced ( obstetrical history, cervical length and quantitative fetal fibronectin value) and a percentage of risk of preterm birth will be given. Women with a high-risk value will be managed in Preterm Birth Prevention Clinic and women with low-risk value will be followed-up in a low-risk unit.<br>|
| No Intervention: Control group: no QUIPP tool arm<br>Women will be managed according to current clinical practice. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous preterm birth before 34.0 and 37.0 weeks of gestation | Delivery < 34.0 and <37.0 weeks of gestation ( Yes/No ) | 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational age at delivery | Weeks and days at the moment of delivery | 3,5 years | 
| Hospital admission due to sPTB or PPROM | Number of hospital admission due to a spontaneous preterm labor or a preterm premature rupture of membranes | 3.5 years | 
| Emergency department visits due to uterine contractions | Number of emergency department visits | 3.5 years | 
| Clinical chorioamnionitis | Fever ( >37.8 ºC) and maternal tachycardia ( >100 beats per minute) and /or fetal tachycardia ( >160 beats per minute) and/or maternal leukocytosis ( >15000 leukocites/mm3) and/or uterine contractions and/or malodorous leukorrhea | 3.5 years | 
| Maternal mortality | Maternal death (Yes/No) | 3.5 years | 
| 5 min APGAR score <7 | APGAR test less than 7 at the 5 minuts after birth | 3.5 years | 
| umbilical artery pH at delivery <7.1 | pH artery value less than 7.1 | 3.5 years | 
| NCIU admission | Admission in a neonatal intensive care unit ( Yes/No) | 3.5 years | 
| Need for respiratory support | Administration of respiratory support during the NCIU stay. | 3.5 years | 
| Respiratory distress syndrome | Breathing disorder ( Yes /No) | 3.5 years | 
| Intraventricular haemorrhage | Severe intraventricular haemorrhage grade III/IV | 3.5 years | 
| Necrotizing enterocolitis | Intestinal necrosis in the newborn ( Yes/No) | 3.5 years | 
| Neonatal sepsis | Blood infection of the newborn (Yes/No) | 3.5 years | 
| Neonatal mortality | neonatal death | 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm Birth, Asymptomatic high-risk women, QUIPP, Quantitative fetal fibronectin, Cervical length