STV Analysis Versus Visual Evaluation of Cardiotocography in FGR (SAVEFGR)

Short Term Variation Analysis Versus Visual Evaluation of Cardiotocography in Fetal Growth Restriction

This stepped wedge cluster randomized clinical trial investigates whether in pregnant women with severe, early-onset fetal growth restriction, the use of STV analysis in fetal monitoring improves the chances of perinatal survival, compared with visual evaluation of the cardiotocography.

Study Overview

• Status: Not yet recruiting
• Conditions: Fetal Growth Retardation
• Intervention / Treatment: Device: Visual interpretation; Device: Short term variation

Detailed Description

Severe, early-onset fetal growth restriction (FGR, <32 weeks gestation) is a condition in which the fetus does not reach its growth potential due to placental insufficiency[. This condition affects about 0.3% of pregnancies, accounting for an estimated 15,000 babies in Europe being born premature below 32 weeks gestation. The main clinical dilemma of FGR lies in the timing of birth, given the balance of risks of antenatal mortality and severe damage to organs and the aggravated neonatal effects of prematurity: death or survival with severe neurodevelopmental impairment. The mainstay of clinical management in these cases pivots around the anticipation of the risk of fetal demise from placental oxygenation failure. The monitoring variables that are currently available comprise assessment of the severity of metabolic insufficiency (fetal size and growth, Doppler ultrasound, serum biomarkers) and the early detection of progressive fetal hypoxia with cardiotocography (CTG). The common approach is to deliver the fetus when signs of advanced hypoxia appear on CTG. A delicate balance exists between having the fetus born (too) early and facing the risks of extreme prematurity combined with a very low birthweight; and between delivering the fetus (too) late when the fetus has the disadvantage of hypoxia at birth. The decision when to deliver the fetus, is made mostly based on the CTG. The inter- and intra-observer variability could be overcome by software analysis according to the original Dawes&Redman algorithm. The software calculates the short-term variation (STV) of the inter-beat interval expressed in milliseconds, and a range of secondary calculations. In contrast with repeated decelerations, when fetal hypoxia is considered evident, the place of the software analysis of the fetal heart rate variability is less clear. Although the advantages of mathematized and uniform quantification of the fetal heart rate variability appear self-evident, there are no studies with sufficient power to detect an association of intervention based on STV at any threshold with the most important outcomes: fetal death and long-term infant outcome.

The purpose of this study is to assess the outcomes of monitoring the fetal condition with STV in computerized CTG compared to visual interpretation of the CTG in order to time delivery in pregnant women with severe, early-onset FGR.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wessel Ganzevoort, MD PhD; Phone Number: 003120-5669111; Email: j.w.ganzevoort@amsterdamumc.nl
• Study Contact Backup: Name: Anouk Pels, MD PhD; Phone Number: 003120-5669111; Email: a.pels@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women with a singleton pregnancy between 24 weeks and 0 days and 31 weeks and 6 days with severe, early-onset fetal growth restriction, admitted in hospital or frequently evaluated ambulatory by CTG (according to local protocol) for fetal monitoring.
• Fetal growth restriction is defined in line with the international Delphi consensus as biometric ultrasound measurement of the abdominal circumference (AC) OR a combination of measurements resulting in an estimated fetal weight (EFW) below the 3rd percentile (<p3) OR a combination of EFW <p10 AND uterine artery pulsatility index (PI) >p95 OR umbilical artery Doppler PI >p95.
• Maternal age ≥ 18 years.
• Able to provide written informed consent for collection and use of data on informed consent form in available language.

Exclusion Criteria:

• Known congenital or chromosomal anomalies influencing perinatal outcome.
• Imminent labour or expected maternal indication for delivery < 48 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Visual interpretation of cardiotocography; Monitoring by visual interpretation of cardiotocography	Device: Visual interpretation; Visual interpretation of cardiotocography
Experimental: Short term variation; Short term variation by computer software analysis	Device: Short term variation; Short term variation in computer software analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of pregnancies resulting in perinatal death	Perinatal death is defined as antenatal death or neonatal/infant death before discharge from NICU	Before discharge from neonatal intensive care unit (NICU), up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of children with major neonatal morbidity	Major neonatal morbidity is a composite outcome defined as intraventricular hemorrhage grade 3 or more, periventricular leukomalacia grade 2 or more, moderate or severe bronchopulmonary dysplasia, necrotizing enterocolitis Bell stage 2 or more, or retinopathy of prematurity requiring therapy.	Before discharge from NICU, up to 1 year
Proportion of children with neonatal morbidities	Individual neonatal morbidities of the abovementioned composite outcome and additionally persisting ductus arteriosus, persistent pulmonary hypertension of the newborn (PPHN), respiratory distress syndrome (RDS), period of invasive mechanical ventilation in days, medication need, hypoglycaemia, neonatal jaundice, sepsis and cardiovascular function.	Before discharge from NICU, up to 1 year
Proportion of children with neurodevelopmental impairment	Neurodevelopmental impairment is defined as an abnormal test on Bayley III Dutch version (or version IV if available) (composite cognitive score < 85, composite motor score < 85), cerebral palsy, with a Gross Motor Function Classification System (GMFCS) grade > 1, hearing loss needing hearing aids, or severe visual loss (legally certifiable as blind or partially sighted) assessed at two years of corrected age	At two years of corrected age

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Wessel Ganzevoort, MD PhD, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 24, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: cardiotocography; fetal growth restriction; perinatal death; short term variation
• Additional Relevant MeSH Terms: Pathologic Processes; Fetal Diseases; Pregnancy Complications; Growth Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Growth Retardation
• Other Study ID Numbers: 84591

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no current plan, but data will be available upon collaboration request

Drug and device information, study documents

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