STV Analysis Versus Visual Evaluation of Cardiotocography in FGR

Study Overview
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Brief Summary
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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.

Detailed Description
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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 cCTG compared to visual interpretation of the CTG in order to time delivery in pregnant women with severe, early-onset FGR.

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

Conditions
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Fetal Growth Retardation

Intervention / Treatment
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* Device: Short term variation
* Device: Visual interpretation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Stepped wedge cluster randomized clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Visual interpretation of cardiotocography<br>Monitoring by visual interpretation of cardiotocography | Device: Visual interpretation<br>* Visual interpretation of cardiotocography<br>|
| Experimental: Short term variation<br>Short term variation by computer software analysis | Device: Short term variation<br>* Short term variation in computer software analysis<br>|

What is the study measuring?
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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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fetal growth restriction, cardiotocography, perinatal death, short term variation